HY Immunology

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HY IMMUNO
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HY Immuno
The purpose of this review is not to be a 600-page immuno textbook with superfluous discussion of minutiae that will
never get tested. The purpose of this doc is to focus strictly on what will increase your USMLE Step 1 score based on what
shows up on NBME and Step exams. I had to try and strike a balance between sufficient background discussion of key
concepts and just focusing on where your HY points are (i.e., saving you time).
- “What do I need to know about MHC molecules for USMLE?”
Simplified comparison of MHC I and MHC II for USMLE

MEHLMANMEDICAL MHC I MHC II
Antigen-presenting cells (APCs)
Located on which cell
All nucleated cells (not RBCs) – i.e., dendritic cells,
surfaces?
macrophages, B cells
Interact with which cell? CD8+ T cell CD4+ T cell
Bind to what? T cell receptor (TCR) + CD8 TCR + CD4
Following release of invariant
How is antigen loaded onto on Associated with b2-
chain within acidified
the MHC molecule? microglobulin and TAP protein
endosome
Displays phagocytosed
Displays intracellular pathogen
extracellular pathogen to T
Purpose? to T cells (viruses, some
cells (most bacteria, fungi,
bacteria)
parasites)
Bortezomib is a proteasome
Gold salts used as antiquated
inhibitor that ¯ ability of MHC I
Associated drugs Tx for rheumatoid arthritis
to present antigen to CD8+ T
inhibit both MHC I and II
cells (on NBME).
- What do I need to know about innate vs adaptive immunity for USMLE?”
Innate vs Adaptive immunity HY points

MEHLMANMEDICAL Innate Adaptive
Cells + molecules Neutrophils, macrophages, NK
B cells, T cells, antibodies
involved? cells, complement proteins
Mechanism? Germline-encoded Created via V(D)J recombination
Onset? Occurs rapidly (minutes to hours) Occurs slowly (days)
Short-lived; no memory cells Longer-lived; memory cells
Duration?
produced produced
- “What do I need to know about natural killer (NK) cells?”
o Part of innate immunity; stimulated by IL-12.
o NK cells, B cells, and T cells are the three types of lymphocytes (all derived from lymphoid
progenitors).
o Kill viral-infected and tumor cells based on variation in cell surface protein expression (e.g.,
by identifying downregulation of cellular MHC I expression).
o CD16 on NK cells enable a process called antibody-dependent cell-mediated cytotoxicity:
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§ Antibodies produced by plasma B cells bind to antigen at their Fab regions, leaving
Fc regions of the antibody facing outward.
§ CD16 on NK cells binds Fc regions of antibody.
§ Crosslinking of CD16 molecules occurs, causing the NK cell to release of granzymes,
granulysins, and perforins, which induces apoptosis in target cell.
- “What do I need to know about B cells?”
o Main cell of humoral immunity; differentiates into antibody-secreting plasma cell.
o Undergoes somatic hypermutation and affinity maturation, enabling increased antibody
specificity for antigen.
o Areas within lymph nodes and the spleen where B cells proliferate and differentiate are
known as germinal centers.
o Type of antigen-presenting cell (APC), meaning it can phagocytose extracellular pathogen
and present it to CD4+ T cells on MHC II.
- “What do I need to know about T cells?”
o Two main types to know for USMLE: CD8+ and CD4+.
o Cytotoxic CD8+ T cells kill intracellular organisms (i.e., mostly viruses, some bacteria). Its T
cell receptor (TCR) binds to MHC I on all nucleated cells. Once activated, it will release
cytotoxic granzymes, granulysins, and perforins, causing apoptosis of the target (infected)
cell.
o CD4+ T cells have many types. Th0 is an upstream CD4+ T cell subtype. This can differentiate
into, most importantly, Th1 and Th2. Th1 primarily activates macrophages. Th2 primarily
stimulates B cells, enabling antibody production.
- “What do I need to know about T cell activation?”
o When a cell loaded with antigen on MHC I or II comes into contact with a CD8+ T cell (aka
cytotoxic T cell) or CD4+ T cell (aka Helper T cell), respectively, the primary signal is merely
the binding of MHC to both TCR and the CD molecule. In other words:
§ MHC I binds to TCR + CD8.
§ MHC II binds to TCR + CD4.
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o A secondary signal then ensues: B7-1 (CD80) or B7-2 (CD86) on the nucleated cell / APC binds
to CD28 on the naive T cell. The T cell is now activated. In other words, the second step is:
§ B7-1/-2 (CD80/86) binds to CD28.
§ This second step is the same for both CD4+ and CD8+ T cells.
o Activation of the T cell results in:
§ CD8+ cytotoxic cells directly kill nucleated cells that have antigen loaded on MHC I.
§ CD4+ T cells are able to exert a variety of effects, depending on their differentiation
(discussed below). The activation of the CD4+ T cell usually occurs after its
differentiation.
o So the quick summary of T cell activation:
§ Primary signal = MHC binds to TCR/CD.
§ Secondary signal = B7 protein binds to CD28.
- “What do I need to know about T cell differentiation?”
o For USMLE purposes, this applies to just CD4+ T cells. In other words, they want you to know
mostly about how Th0 can become Th1 and Th2 cells. As mentioned earlier, a Th0 cell is an
upstream type of CD4+ T cell that has not yet differentiated. CD8+ T cells are more simplistic
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and are merely activated to kill target cells, but CD4+ T cells undergo various routes of
differentiation in addition to their activation.
o Th0 can become Th1, Th2, Th17, and Treg (regulatory) cells.
o Th1 cells stimulate macrophages, which kill phagocytosed pathogens and (if necessary)
organize into granulomas.
o Th2 cells stimulate B cells to become plasma cells, which make antibodies that kill
extracellular pathogens.
o Th17 cells stimulate neutrophilic production and recruitment.
o Treg cells prevent autoimmunity (i.e., are a suppressive type of T cell).
o Th0 à Th1 occurs via stimulation with IL-12 and IFN-l. IL-12 is secreted by macrophages.
IFN-γ is secreted by Th1 cells. Once a Th0 cell becomes a Th1 cell, it activates macrophages
via IFN-γ. Macrophages then secrete even more IL-12, which continues to stimulate more
Th0 à Th1 cells. This IL-12-IFN-γ loop is HY for Step 1.
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o Stimulated macrophages may or may not go on to form granulomas, which are dense
clusters of organized macrophages that appear if inflammation is chronic. Activated
macrophages composing a granuloma are called histiocytes, or epithelioid macrophages.
§ In short: IL-12/IFN-γ à Th1 lineage à macrophage activation.
§ Macrophages that organize into granulomas are called histiocytes, or epithelioid
macrophages.
o Th0 à Th2 occurs via stimulation with IL-4 and IL-10. The Th2 cell has a ligand on its cell
surface called CD40 ligand (CD40L). This binds to CD40 on the B cell, activating it and
facilitating its differentiation into a plasma cell. The plasma cell (or plasma B cell) then makes
copious antibodies that neutralize extracellular pathogen (humoral immunity).
§ In short: IL-4/IL-10 à Th2 = B cell activation à plasma cells à Abs.
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o It should be noted that Th1 cells also co-stimulate macrophages via CD40L-CD40 interaction,
however on USMLE, this CD40L-CD40 interaction is specifically HY with respect to Th2
activation of B cells.
o The plasma B cell is able to dramatically increase the specificity of the antibodies it produces
via processes called somatic hypermutation and affinity maturation.
§ Somatic hypermutation refers to mutation rates in the genes of immunoglobulins
that are 1,000,000 times greater than in other cell lines.
§ This results in affinity maturation, which means antigen-binding regions (Fab) of
immunoglobulins (antibodies) are capable of generating increasingly greater affinity
for pathogens.
§ Do not confuse somatic hypermutation and affinity maturation (B cell processes)
with V(D)J recombination, which refers to B and T cells early in their maturation
process generating antibodies and TCR, respectively, that bear a diverse array of
combinations, specificities, and affinities.
o The Th1 and Th2 differentiation pathways are considered to be in opposition. When one
activates, the other is suppressed. IL-12/IFN-γ suppress the Th2 lineage; IL-4 and IL-10
suppress the Th1 lineage. In other words:
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§ IL-12/IFN-γ à Th1 lineage + ¯ Th2 lineage.
§ IL-4/IL-10 à Th2 lineage + ¯ Th1 lineage.
- “Can you explain T cell migration through the thymus? What do I need to know?”
o T cells migrate into the thymic cortex first as CD4 and CD8 negative. They then differentiate,
still in the thymic cortex, into T cells that are both CD4+ and CD8+ (i.e., each T cell has both
CD4 and 8 on its surface). Positive selection occurs in the cortex, where only T cells capable
of binding self-MHC antigen survive (i.e., they’re capable of generating an immune
response).
o As T cells migrate from the cortex into the medulla, they lose either a CD4 or CD8, so the
thymic medulla has CD4+ and CD8+ T cells (i.e., they don’t simultaneously express both
antigens anymore). Negative selection occurs in the medulla, where T cells capable of
binding self-MHC antigen undergo apoptosis. This is a check to prevent autoimmunity.
o The CD8+ T cell then leaves the thymic medulla for the lymph node, where it becomes a
cytotoxic T cell. It will bind to MHC I on all nucleated cells via its T cell receptor (TCR).
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o The CD4+ T cell leaves the thymic medulla for the lymph node, where it becomes a Helper T
cell (Th cell; [Th0 initially]), which then can become many different subtypes of CD4+ T cells,
including Th1, Th2, Th17, and Treg (regulatory T cells). The TCRs on these cells bind to MHC II
on antigen-presenting cells (APC).
- “What is the difference between cell-mediated and humoral immunity?”
MEHLMANMEDICAL.COM Cell-mediated immunity Humoral immunity

TB, M. leprae,
Most bacteria, Polio
HY pathogens Most viruses; Listeria Leishmania,
virus
Pneumocystis, Candida
Pathogen location Cytoplasm Vesicles of macrophages Extracellular fluid (ECF)
Th1 CD4+ T cell,
Main cells involved CD8+ T cell Th2 CD4+ T cell, B cell
macrophages
Induces apoptosis of
Effector T cell role Activates macrophages Activates B cells
infected cell
MHC I on infected MHC II on macrophage MHC II on B cell or
MHC association
nucleated cell or dendritic cell dendritic cell
1) MHC II binds to TCR
on CD4+ Th1 (or Th0)
cell; CD4 + CD3 on T cell
also bind to MHC II
1) MHC II binds to TCR
2) B7-1/7-2 (CD80/86) on CD4+ Th2 (or Th0)
on macrophage or cell; CD4 + CD3 on T cell
dendritic cell binds to also bind to MHC II
CD28 on CD4+ Th1 (or
Th0) cell 2) B7-1/7-2 (CD80/86)
1) MHC I binds to TCR
on B cell or dendritic cell
on CD8+ T cell; CD8 +
3a) Th1 cell secretes binds to CD28 on CD4+
CD3 on T cell also bind
IFN-γ, which activates Th2 (or Th0) cell
to MHC I
macrophages to secrete
IL-12, which further 3a) Th2 cell secretes IL-4
2) B7-1/7-2 (CD80/86)
activates Th1 to secrete and IL-10, which
on nucleated cell binds
HY steps IFN-γ + stimulates more activate more Th0 to
to CD28 on CD8+ T cell
Th0 à Th1 Th2
3) Activated CD8+ T cell
3b) IL-12 and IFN-γ 3b) IL-4 and IL-10 inhibit
induces apoptosis in
inhibit Th2 response Th1 response
infected cell by releasing
granzymes, granulysins,
4) Th1 cell CD40L binds 4) Th2 cell CD40L binds
and perforins
to CD40 on to CD40 on B cells,
macrophages causing facilitating
further activation + IL-12 differentiation to
secretion (but on plasma cells for Ab
USMLE, this CD40L- production and isotype
CD40 interaction is class-switching
most important for B
cell activation by Th2
cells)
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Choose “deficiency of
Choose cell-mediated immunity for viruses and
HY USMLE disease humoral immunity” for
Listeria. For chronic mucocutaneous candidiasis,
associations IgA deficiency and
choose “deficiency of cell-mediated immunity”
Bruton XLA
o Humoral immunity means antibodies are involved in the killing of the organism. If antibodies
are not involved, then the process does not relate to humoral immunity.
§ Plasma B cells produce antibody and hence are the main cell of humoral immunity.
§ B cells are one type of APC that presents antigen to Th2 CD4+ T cells via MHC II.
§ Th2 cells activate B cells to become plasma cells + induce B cell isotype class-
switching via CD40L-CD40 interaction (CD40L on the Th2 cell; CD40 on the B cell).
§ Therefore B cells and Th2 CD4+ T cells are integral cells in humoral immunity.
§ USMLE wants you to know that X-linked agammaglobulinemia (XLA) and IgA
deficiency are deficiencies of humoral immunity – i.e., the vignette sounds like XLA,
but rather than “XLA” as the answer, you will simply select “deficiency of humoral
immunity.”
o Cell-mediated immunity means “T cell-mediated” immunity that does not involve antibodies
in order to kill the organism.
§ Cytotoxic CD8+ T cells kill nucleated cells that present intracellular antigen on MHC I
molecules, where the CD8+ T cell releases granzymes, granulysins, and perforins,
inducing apoptosis of the target cell. This does not involve antibody and is therefore
cell-mediated, not humoral, immunity.
§ Th1 CD4+ cells activate macrophages via the IFN-γ-IL-12 loop to kill phagocytosed
organisms. No antibody is made in relation to this process.
§ CD8+, Th1 CD4+ T cells, and macrophages are therefore part of cell-mediated
immunity.
§ Dendritic cells are another type of APC that are part of both humoral and cell-
mediated immunity, depending on if the MHC II-TCR interaction results in a Th1
(cell-mediated) or Th2 (humoral) response.
o In short:
§ Humoral immunity = B cells and Th2 CD4+ T cells.
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§ Cell-mediated immunity = CD8+, Th1 CD4+ T cells, and macrophages.
§ It is inaccurate to say the difference between cell-mediated and humoral immunity
is strictly CD4+ vs CD8+. This is because CD4+ Th1 cells contribute to cell-mediated
immunity; CD4+ Th2 contribute to humoral immunity.
- “What do I need to know about the different antibody types and their structure?”
Antibody types + HY points

Ab Binds Crosses
In breastmilk? Function / HY points
type complement? placenta?
- Primary immune responses (i.e., first Ab to
appear); therefore indicates acute infection.
If Q asks what would best reflect a Dx of
congenital Toxo in a neonate, choose IgM
titers in the neonate.
- Pentameric in structure, therefore greatest
avidity (i.e., has the most binding sites – 10
IgM Yes No No total [2 per Fab])
- Hyper-IgM syndrome à caused by
deficiency of CD40L on Th2 CD4+ T cells,
leading to ¯ binding of CD40 on B cells à
differentiation into plasma B cells + ¯
isotype class-switching (i.e., plasma B cell is
“stuck” at IgM and cannot make other types
of Ig)
- Secondary immune responses (i.e., rises the
most in re-infections) and chronic infections
- Has greatest affinity (i.e., binds most
strongly to Ag); used in passive immunity
IgG Yes Yes No (e.g., RhoGAM, HepB/VZV IVIG)
- Ability for IgG to cross placenta is
responsible for hemolytic disease of the
newborn
- Most abundant Ab in serum (~80%)
- Most common Ab found in mucosal
secretions, respiratory tract, and GIT
- Secreted as a dimer adjoined together by a
J-chain (very pedantic detail that for some
magical reason is HY for IgA)
- Gut-associated lymphoid tissue (GALT)
consists of Peyer’s patches, or aggregates of
lymphoid tissue in the gut responsible for
protection against intra-luminal pathogens;
IgA No No Yes
Peyer’s patches are the predominant source
of IgA-producing cells
- IgA deficiency à one of the highest yield Qs
for step; most common hereditary
immunodeficiency; recurrent sinopulmonary
infections, atopy (i.e., seasonal allergies,
asthma, eczema), risk of Giardia;
associated with other autoimmune disorders
like vitiligo; anaphylaxis with blood
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transfusion is HY detail but often omitted

from NBME Qs because it’s too easy
- For IgA deficiency Qs, the answer will often
just be “deficiency of humoral immunity,” or
“deficiency of mucosal immunoglobulin”
- IgA deficiency will yield false-negative Celiac
screening; patients with Celiac have 15x
greater simultaneous prevalence of IgA
deficiency (as per above, association with
other autoimmune disorders)
- Located on surface of mast cells; crosslinks
in type I hypersensitivity responses and
leads to mast cell degranulation, with
release of histamine and tryptase
- Associated with allergies and eosinophilia
- Increased in helminth infections (activate
IgE No No No eosinophils, which kill helminths by secreting
major basic protein)
- Hyper-IgE (Job) syndrome à FATED à
abnormal Facies, Staphylococcal “cold”
Abscesses, retained deciduous Teeth, hyper-
IgE, Dermatologic findings (i.e., eczematoid
skin lesions)
- Part of B cell receptor
IgD No No No - Considered to be “obscure” and the “least
important” Ab for USMLE
- “Can you quickly explain passive vs active immunity?”
Passive vs active immunity

MEHLMANMEDICAL Passive Active
Mechanism of acquisition Receiving pre-formed antibodies Real-life exposure to antigen
Onset Fast (minutes to hours) Slow (hours to days)
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Short; dependent on half-life of

Duration Long (memory cells)
pre-formed Abs (weeks)
Post-exposure IVIG given for
HepB, VZV, tetanus, botulism,
HY associations for USMLE Vaccinations; real-life infection
diphtheria, rabies; IgA in
breastmilk; transplacental IgG
- “What do I need to know about the complement cascade/pathways? I hear about complement a lot
but I’m not really sure what it does. Can you explain that.”
o No, you do not need to memorize / draw out the complement pathways for Step 1. Waste of
time. You just need to have a broad sense of the role complement plays in the innate
immune system + some factoids about the different complement molecules.
o Complement proteins are acute phase proteins produced by the liver. There are three
pathways for complement activation; they all lead to target cell death via formation of the
membrane attack complex (MAC), composed of C5b-C9 complement proteins, or via
stimulating opsonization and phagocytosis.
o Three main pathways: classic, alternative, and lectin:
§ Classic à when complement (C1) binds to the Fc region of IgM and IgG, it flags the
antigen bound to the Ab’s Fab for opsonization and phagocytosis, or cell death via
MAC.
§ Alternative à triggered by C3b binding directly to the microbial cell surface.
§ Lectin à triggered by mannose-binding lectin (a type of carbohydrate-binding
protein instrumental in innate immunity) binding to the microbial cell surface.
o C3b and IgG are the immune system’s two major opsonins (which means they bind to
antigen and flag it for phagocytosis).
§ Do not confuse this with IgM and IgG’s ability to bind complement. Phagocytes do
not have an Fc receptor for IgM, making IgM a poor opsonin. In other words, whilst
IgM and IgG bind complement, it is IgG and C3b that are the immune system’s
major opsonins.
o C3 goes down in post-streptococcal glomerulonephritis (PSGN) and SLE flares.
o C4 goes down in cryoglobulinemia (discussed later).
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o C3a, C4a, and C5a are known as anaphylatoxins, which can trigger degranulation of mast
cells, causing anaphylaxis.
o C5a is a neutrophilic chemotactic molecule (as with IL-8, LTB-4, kallikrein, platelet-activating
factor, and bacterial products).
o Terminal complement deficiency (C5-9) is associated with recurrent Neisseria infections
(both gonococcal and meningococcal).
o C1 esterase inhibitor deficiency (not C1 esterase; C1 esterase inhibitor) is associated with
hereditary angioedema.
o Paroxysmal nocturnal hemoglobinuria is caused by “increased complement-mediated lysis”
of RBCs. It is caused by deficiency of GPI anchor, which “anchors” CD55 (decay-acceleratory
factor) and protectin (CD59) to the RBC cell surface. CD55/59 protect the RBC from
complement-mediated lysis.
- “Can you explain thymus-independent vs thymus-dependent antigens?”
o Thymus-independent means an antigen is not displayed on MHC molecules. Therefore there
is no resultant T cell response.
o Thymus-dependent means an antigen is displayed on MHC molecules. Therefore there is a
resultant T cell response.
o Antigens need to be proteinaceous in order to be displayed on MHC molecules and generate
a T cell response. In other words, if a Q asks what kind of molecule could induce a T cell
response, choose whatever answer is the protein, even if it sounds weird (e.g., poly-D-
glutamic acid capsule of C. anthracis).
o If an antigen is not proteinaceous (e.g., the polysaccharide capsule of H. influenzae type B, or
lipopolysaccharide from gram-negative bacteria), then it will not be expressed on MHC
molecules (i.e., thymus-independent antigen). USMLE wants you to know that H. influenzae
type B vaccine is a polysaccharide vaccine (on NBME 27 for Step 1), not a toxoid.
o Toxoid vaccines involve the conjugation of a protein to a non-proteinaceous substrate so
that a T cell response can be elicited. Typical examples are diphtheria and tetanus vaccines,
where protein is conjugated to the toxins to enhance presentation on MHC II molecules for
interaction with T cells.
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o Thymus-independent response involves an antigen binding to B cell receptor (BCR), followed
by the B cell making antibody against the antigen without phagocytosing + expressing it on
MHC II to Th2 cells. This process does not result in any type of memory cell being produced,
so immunity is short-lived.
o In contrast, thymus-dependent responses lead to the production of memory cells, so the
immunity is longer-lived.
- “What do I need to know about the various cytokines?”
o Memorize macrophages as secreting, most importantly: TNF-a, IL-1, IL-6, IL-8, and IL-12.
o Memorize IL-2 as a T cell stimulator.
o Memorize TNF-a and IL-1 as the two associated with sepsis: TNF-a causes low BP; IL-1 causes
fever.
o Memorize IL-8 as a neutrophilic chemotactic molecule.
o Interferons can broadly facilitate with viral infections by inhibiting viral replication.
Cytokine HY points for USMLE

- Increases vascular permeability; causes low
BP in septic shock; if the USMLE asks which
cytokine is most responsible for patient’s
presentation of septic shock, TNF-a is the
TNF-a
answer.
- Also known as cachexia factor à is the
main cytokine responsible for weight loss in
the setting of malignancy (HY).
- Causes fever.
- If the Q tells you a guy with sepsis has low
BP and fever, they want TNF-a and IL-1 as
the two cytokines responsible; if you’re
forced to choose only one cytokine for
septic shock, choose TNF-a, but if they ask
specifically about the fever, choose IL-1.
- Also known as osteoclast-activating factor;
can contribute to post-menopausal
IL-1 osteoporosis and lytic lesions of bone in the
setting of metastases and multiple
myeloma; USMLE Q might show you a pic
of an osteoporotic vertebra, and then the
answer is just “increased IL-1 activity.” IL-6
also plays a role in osteoporosis, but NBME
for Step 1 has IL-1 as many answers.
- If the Q tells you an NSAID is used to
decrease fever, choose prostaglandin, not
IL-1, as the molecule responsible for fever.
- Stimulates T cells; when you think of IL-2,
IL-2
the first thing that should come to mind is,
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“Ok, that’s the one that broadly activates T

cells.”
- Cyclosporin and tacrolimus are HY drugs
that decrease transcription of IL-2 via
inhibiting calcineurin.
- Sirolimus decreases responsiveness to IL-2.
- Aldesleukin is a recombinant IL-2 used in
the Tx of RCC and metastatic melanoma
(essentially, T cell response helps fight
cancer, and IL-2 T cell response).
- Stimulates myeloid lineage (i.e., mostly
IL-3 neutrophils); think of IL-3 as similar to GM-
CSF.
- Both IL-4 and IL-10 stimulate Th0 à Th2,
and inhibit Th0 à Th1.
- Therefore IL-4 functions to ultimately
IL-4
increase CD4+ activation of B cells.
- This means this cytokine is important for
supporting humoral immunity.
- Stimulates eosinophil maturation.
- Mepolizumab and reslizumab are
monoclonal Abs against IL-5 used in severe
IL-5
asthma accompanied by eosinophilia.
- Benralizumab is a monoclonal Ab against IL-
5 receptor.
- Stimulates acute-phase protein release
from the liver (i.e., CRP, hepcidin).
- Can cause osteoporosis.
IL-6 - Tocilizumab is a monoclonal Ab against IL-6
receptor used in severe rheumatoid
arthritis.
- IL-6 and TGF-b stimulate Th0 à Th17.
- Neutrophilic chemotactic molecule
- IL-8, C5a, LTB-4, platelet-activating factor,
IL-8
kallikrein, and bacterial products all
stimulate neutrophilic chemotaxis.
- HY as an anti-inflammatory cytokine that
plays a role in suppressing various immune
responses. If the USMLE asks which
cytokine can decrease an immune
response, choose IL-10 (or TGF-b).
IL-10 - Both IL-10 and IL-4 stimulate Th0 à Th2,
- Therefore IL-10 functions to ultimately
increase CD4+ activation of B cells.
- This means this cytokine is important for
supporting humoral immunity.
- Stimulates platelets.
- Oprelvekin is a recombinant IL-11 that can
IL-11
be used to stimulate thrombopoiesis post-
chemotherapy.
- Both IL-12 and IFN-γ stimulate Th0 à Th1,
IL-12 - Stimulates Th1 cells to make IFN-γ.
- IL-12 receptor deficiency is associated with
TB infections (i.e., ¯ IL-12 response à ¯
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IFN-γ à ¯ macrophage activity à risk for

TB infections); treat with IFN-γ.
- Stimulates NK cells.
- HY cytokine produced by Th1 CD4+ T cells
that stimulates macrophages.
- Macrophages stimulated by IFN-γ produce
IL-12.
IFN-γ
- Both IFN-γ and IL-12 stimulate Th0 à Th1,
- Used in the Tx of NADPH oxidase deficiency
(chronic granulomatous disease).
- Used between flares of multiple sclerosis
IFN-b
(for acute flares gives steroids).
- Anti-inflammatory cytokine, similar to IL-10
(i.e., when you think of TGF-b and IL-10,
TGF-b think ¯ inflammation).
- TGF-b and IL-6 stimulate Th0 à Th17.
- TGF-b stimulates Th0 à Treg.
- “What should I know about various cell surface markers?”
Cell surface marker HY points for USMLE

CD1a Marker in Langerhan cell histiocytosis
Generic T cell marker; associated with TCR; binds to
CD3
target cell MHC in addition to CD4/CD8
Marker for T helper cells (Th0, Th1, Th2, Th17, Treg);
CD4
binds to MHC II on APCs
Seen in CLL (sounds low-yield and pedantic but I’ve
CD5 + CD23
seen these on a few NBME Step 1 Qs)
Marker for cytotoxic T cells; binds to MHC I on
CD8
nucleated cells
CD10 Associated with ALL
On macrophages; associated with toll-like receptor
4; binding of LPS endotoxin to CD14 results in
macrophage release of TNF-a + IL-1 à septic shock
CD14
caused by endotoxin (do not confuse with septic
shock caused by S. aureus TSST superantigen
bridging TCR and MHC II à toxic shock syndrome)
CD15 + CD30 Seen on Reed-Sternberg cells in Hodgkin disease
Both on NK cells; CD16 binds Fc region of IgG and
causes antibody-dependent cell-mediated
CD16 + CD56
cytotoxicity à lysis of target cell by NK cell; CD56 is
just a specific NK cell marker
CD18 is a subunit of LFA-1 integrin found on various
CD18 WBCs; deficiency of CD18/LFA-1 integrin causes
leukocyte adhesion deficiency
Specific B cell markers; rituximab is a monoclonal Ab
against CD20; Q might mention a virus invading cells
CD19 + CD20
that are CD19/20 (+) and the answer is EBV (invades
B cells)
CD21 Receptor for EBV entrance into B cells
CD25 Regulatory T cell (Treg) marker
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On T cells; bound by B7-1/7-2 (CD80/86) on

CD28 nucleated cells/APCs as secondary signal following
MHC primary interaction
Ubiquitous on hematopoietic stem cells (i.e., not
CD34
specific marker for, but found on all)
Found on macrophages and B cells; activated by
CD40L on Th1 and Th2 cells, respectively; CD40L-
CD40 CD40 interaction between Th2 and B cells is
responsible for isotype class-switching + B cell
differentiation into plasma cells
CD55/59 Deficient in paroxysmal nocturnal hemoglobinuria
Also known as B7-1/7-2; found on nucleated
CD80/86 cells/APCs; bind to CD28 on T cells as secondary
signal following primary MHC interaction
- “What autoantibodies do I need to know for USMLE?”
HY autoantibodies for USMLE

HY disease association HY antibodies
Anti-b2-microglobulin; anti-cardiolipin; lupus
anticoagulant (the latter is the name for either of
the former two if the patient happens to have SLE);
Antiphospholipid syndrome
Abs associated with recurrent miscarriage; can
cause false-positive syphilis screening (e.g., SLE
patient who gets positive syphilis VDRL test)
Anti-hemidesmosome (bullous pemphigoid antigen);
Bullous pemphigoid hemidesmosomes connect the dermis to epidermis;
cause a linear immunofluorescence on skin biopsy
Anti-desmosome (anti-desmoglein 1 and 3);
Pemphigus vulgaris desmosomes connect adjacent cells in epidermis;
cause a net-like immunofluorescence on skin biopsy
Anti-collagen IV (anti-GBM; glomerular basement
membrane); causes linear immunofluorescence on
Goodpasture syndrome
renal biopsy; don’t confuse with Alport syndrome,
which is mutations in type IV collagen (not Ab)
c-ANCA; anti-proteinase 3 (PR3); dumb mnemonic I
Granulomatosis with polyangiitis (Wegener) created that helps some of my students: Water
Closet (Wegener C-ANCA)
Eosinophilic granulomatosis with polyangiitis
p-ANCA (anti-myeloperoxidase)
(Churg-Strauss)
Microscopic polyangiitis p-ANCA (anti-myeloperoxidase)
Anti-double-stranded DNA (dsDNA); anti-Smith
(ribonucleoprotein); anti-hematologic cell line Abs;
should be noted that dsDNA goes up in acute flares
+ best reflects renal prognosis; anti-Smith is more
Systemic lupus erythematosus (SLE) specific than anti-dsDNA; thrombocytopenia is an
exceedingly HY finding in SLE due to Abs; if all cell
lines are down in SLE, aplastic anemia (¯ bone
marrow production) is wrong answer; choose
“increased peripheral destruction” as answer
Anti-histone; caused by various drugs (Mom is HIPP)
Drug-induced lupus (DIL) à Minocycline, Hydralazine, INH, Procainamide,
Penicillamine
Anti-post-synaptic acetylcholine receptor;
Myasthenia gravis
sometimes a paraneoplastic of thymoma
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Anti-presynaptic voltage-gated calcium channel;

Lambert-Eaton
sometimes a paraneoplastic of small cell lung cancer
Anti-Hu/-Yo; ataxia in someone with small cell lung
Small cell cerebellar dysfunction
cancer and negative CNS imaging
Polymyositis / Dermatomyositis Anti-Jo1; can be a paraneoplastic of ovarian cancer
Limited-type systemic sclerosis / scleroderma Anti-centromere
Diffuse-type systemic sclerosis / scleroderma Anti-topoisomerase I (Scl-70)
Primary biliary cirrhosis Anti-mitochondrial
Autoimmune hepatitis Anti-smooth muscle
Rheumatoid factor (an IgM against the Fc region of
Rheumatoid arthritis IgG); anti-cyclic citrullinated peptide (CCP); anti-CCP
is more specific than rheumatoid factor
Sjogren syndrome Anti-SS-A (anti-Ro); anti-SS-B (anti-La)
Anti-TSH receptor (this antibody is called thyroid-
Graves disease stimulating immunoglobulin, or TSI, and activates
the TSH receptor)
Anti-thyroperoxidase (anti-microsomal); anti-
Hashimoto thyroiditis
thyroglobulin
Pernicious anemia Anti-parietal cell; anti-intrinsic factor
Anti-endomysial (aka anti-gliadin); anti-tissue
Celiac disease transglutaminase IgA; antibody screening will yield
false-negatives if patient also has IgA deficiency
Anti-glutamic acid decarboxylase(anti-GAD); anti-
Type I diabetes mellitus
zinc transporter 8
Primary membranous glomerulonephritis Anti-phospholipase A2 receptor
Anti-ADAMTS13 (a matrix metalloproteinase that
Thrombotic thrombocytopenic purpura
cleaves vWF multimers)
Anti-platelet factor 4-heparin complex (anti-PF4-
Heparin-induced thrombocytopenia (HIT)
heparin)
Addison disease Anti-21-hydroxylase
Anti-myosin; anti-valve-derived proteins; should be
noted that these Abs are formed against S. pyogenes
Rheumatic heart disease
M protein and almost always cross-react with the
mitral valve (molecular mimicry)
IgM against RBCs (CMV and Mycoplasma are HY
infectious associations; also as associated with
Cold autoimmune hemolytic anemia
chronic lymphocytic leukemia); will result in positive
Coombs test
IgG against RBCs (various miscellaneous drugs and
Warm autoimmune hemolytic anemia
infections); will result in positive Coombs test
- “What about hemolytic disease of the newborn? That’s antibody-mediated but isn’t technically
autoimmune right?” Correct. Because it’s not against one’s own cells, tissues, or receptors.
Anti-rhesus factor (Rh); mechanism is: Rh(-) mom in

first pregnancy is exposed to fetal blood whose
Hemolytic disease of the newborn (Rh type) Rh(+); mom makes Ab against Rh; subsequent
pregnancy results in IgG against Rh crossing placenta
and targeting fetal Rh(+) RBCs
IgG crossing the placenta and binding to fetal A and
B RBC antigens; mechanism is: most anti-A and -B
Hemolytic disease of the newborn (ABO type) Abs are inherently IgM, but people with O blood can
have fractional IgG; if mother with O blood has
higher % of anti-A and -B Abs that are IgG, fetus can
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be symptomatic; USMLE will give you O+ mom

usually in first pregnancy and A or B fetus (can occur
in Rh- women in second pregnancies, but the USMLE
wants to assess you specifically know the ABO type
of HDN, so they’ll give O+ mom in first pregnancy)
- “Aren’t the transfusion reactions high-yield? Most are antibody-related right?”
High-yield Transfusion Reactions

MEHLMANMEDICAL Signs/symptoms Mechanism Management Notes
“Pre-formed
Acetaminophen is the
antibodies against
Febrile Non-hemolytic answer on IM form 5; Coombs test is
Fever, chills, malaise leukocyte antigens”
Transfusion reaction steroids is the wrong negative
(answer on NBME
answer
exam)
ABO incompatibility;
Fever, chills, flank pain,
Hemolytic Transfusion pre-formed Stop transfusion + Coombs test is
hypotension,
Reaction antibodies against administer IV fluids positive
hemoglobinuria
donor RBC antigens
Prior transfusion or
pregnancy results in
Presence of amnestic
Ab production;
Delayed Transfusion antibodies against
¯ Hb + bilirubin Supportive care hemolysis not
Reaction minor RBC antigens
immediate because
(i.e., Kell, Duffy, Kidd)
Ab titers against Ag
usually very low
Donor antibodies Stop transfusion + Alveolar damage
Transfusion-Related Lung Bilateral pulmonary
against MHC I/II or provide airway caused by activated
Injury (TRALI) infiltrates; dyspnea
neutrophil antigens support neutrophils
Transfusion-Associated Supportive; diuretics; Usually seen in
Dyspnea, pulmonary Rapid expansion of
Circulatory Overload prevent with slower elderly with heart
edema, peripheral edema plasma volume
(TACO) transfusion failure
- “Can you explain the hypersensitivity types?”
HY Hypersensitivity reaction points for USMLE

Type Mechanism HY disease associations
- Immediate (within minutes): Antigen binds to Fab
region of IgE on mast cell; adjacent IgE crosslink; mast - Anaphylaxis (i.e., bee
I cell degranulates and secretes histamine + tryptase sting, peanut allergy)
- Late (within hours): Cytokines recruit inflammatory - Atopy / asthma
cells (e.g., eosinophils) à further inflammation
- Graves disease
- Hashimoto thyroiditis
- Goodpasture
- Pernicious anemia
- HIT
II Antibody production against cells, tissues, receptors
- Rheumatic fever
- Myasthenia gravis
- Lambert-Eaton
- Bullous pemphigoid
- Pemphigus vulgaris
- PSGN
Antibody-antigen complexes (i.e., antibodies simply bind to
- Polyarteritis nodosa
III antigen and deposit; the antibodies do not target cells, tissues,
- SLE
or receptors)
- Arthus reaction
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- Serum sickness
- PPD skin test for TB
T cell response (only HS type not associated with antibodies);
IV - Contact dermatitis
can be mediated by either CD8+ or CD4+ T cells
- Graft-vs-host disease
- “What about vaccine types? Are those important?” Yeah.
o Killed vaccines:
§ RIPP Always à Rabies, Influenza (IM), Polio (Salk; IM), Pertussis, Hep A.
§ A TRIPP could Kill you à Hep A, Typhoid (IM), Rabies, Influenza (IM), Polio (Salk;
IM), Pertussis, Killed vaccines.
§ Will generate a humoral (antibody) response via expression on MHC II following
phagocytosis, since cannot directly invade nucleated cells for expression on MHC I.
o Live-attenuated:
§ Yellow fever, varicella, rotavirus (oral), influenza (intranasal), Polio (Sabin; oral),
MMR, Typhoid (oral).
§ Will be expressed on MHC I by nucleated cells à generates CD8+ T cell-mediated
response.
§ MMR and varicella can be given to patients with HIV if CD4 count >200 cells/uL.
o Recombinant: HPV, HBV.
o Toxoid: Diphtheria, tetanus.
- “What are the highest yield points about the immunodeficiencies?”
Immunodeficiencies HY points
- X-linked recessive most common à
usually due to common gamma chain
mutation, or mutation in IL-2 receptor
- Autosomal recessive type less common
à due to deficiency in adenosine
deaminase (ADA)
- Combined T and B cell deficiency
- T cell deficiency à absent thymic
Severe-combined immunodeficiency (SCID) shadow
- B cell deficiency à scanty/absent lymph
nodes and tonsils
- Q will give you sick kid who’s had
infections of all different types (i.e., viral,
fungal, bacterial, protozoal) since birth
- This contrasts with Bruton XLA, which will
be just bacterial infections (usually since
6 months of age)
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- Tx = bone marrow transplant

- X-linked recessive (as name implies) à
caused by mutation in Bruton tyrosine
kinase
- Isolated B cell deficiency
- Scanty/absent lymph nodes + tonsils
- Kid will have ¯ immunoglobulins of all
classes (because B cells make Ab)
- Q will almost always be a boy who’s had
only bacterial infections since 6 months
of age (if they mention bacterial and
viral, fungal, and/or protozoal, the Dx is
SCID)
Bruton X-linked agammaglobulinemia (XLA) - There is a Q on a Peds 2CK form where
they say “bacterial infections since birth,”
but you’re able to eliminate the other
answers (literally 14/15 Qs will say from
~5-7 months-onward, so this is a highly
annoying point to have to make, but I
have to communicate it because it’s on
the NBME)
- Tx on NBME is “monthly infusion of
immunoglobulin”
- Answer on USMLE will often be
“deficiency of humoral immunity,” rather
than just “Bruton XLA”
- One of the highest yield conditions for
the Step (hence I mention it repeatedly in
this doc; purposeful redundancy)
- Most common hereditary
immunodeficiency
- 9/10 Qs will give you recurrent
sinopulmonary infections in someone
between high school and 30s; one 2CK
Peds Q has it in a kid; the Q might say the
patient has a sore cheek (sinusitis) + Hx
of pneumonia
- Anaphylaxis with transfusion of blood
products is ultra-HY detail but often
omitted from real NBME Qs because it’s
IgA deficiency too easy/buzzy
- Atopy is really HY (asthma, seasonal
allergies, eczema)
- Hx of Giardia infection
- Associated with other autoimmune
diseases (i.e., vitiligo, Celiac)
- Celiac Ab screen falsely negative in IgA
deficiency
- IgA deficiency can be associated with
false-positive pregnancy tests (yes,
fucking weird, but due to heterophile Ab
production apparently, with zero relation
to EBV)
- Answer on USMLE will often be
“deficiency of mucosal immunoglobulin”
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or “deficiency of humoral immunity,”

rather than just “IgA deficiency”
- T cell deficiency caused by 22q11
deletion
- Failure of development of 3rd and 4th
pharyngeal pouches (not arches) à 3rd
becomes thymus + two inferior
parathyroids (these structures form a
triangle à 3rd); 4th becomes two superior
parathyroids
- Absent thymic shadow
- Hypocalcemia due to
DiGeorge syndrome
hypoparathyroidism (positive Chvostek
and Trousseau signs of hypocalcemia)
- Tetralogy of Fallot (VSD, overriding aorta,
pulmonic stenosis, RVH) and truncus
arteriosus are HY cardiac anomalies
- Cleft lip/palate may or may not be
mentioned
- Patient will have normal antibody levels
(even though T cells activate B cells,
choose normal Ab levels)
- T cell dysfunction
- Recurrent candidal skin infections since
birth
- Choose “deficiency of cell-mediated
immunity”
- Associated with other autoimmune
Chronic mucocutaneous candidiasis
diseases (i.e., T1DM, thyroiditis)
- 17F + recurrent candidal skin infections
since birth + one year Hx of autoimmune
thyroiditis + 2-yr Hx of T1DM; mechanism
for infections? à answer = “deficiency of
cell-mediated immunity”
- X-linked recessive
- First enzyme of the respiratory burst;
converts molecular O2 à superoxide
- Recurrent infections with catalase (+)
organisms: Serratia, Pseudomonas,
Aspergillus, Candida, E. coli, Staph, H.
Chronic granulomatous disease pylori
(NADPH oxidase deficiency) - Condition results in ¯ ability of patient to
synthesize enough H2O2 to overwhelm
catalase (+) organisms
- Diagnose with dihydrorhodamine test
(tetrazolium blue assay is atavistic and
the wrong answer if both are listed, as
per Step 1 NBME)
- Last enzyme in respiratory burst;
converts H2O2 à hydroxyl-halide radicals
(bleach)
Myeloperoxidase deficiency - Q will literally give you a one-liner telling
you someone can’t produce hydroxyl-
halide radicals, and the answer is
myeloperoxidase deficiency
Wiskott-Aldrich syndrome - X-linked recessive (WAS gene)
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- T cell cytoskeletal dysfunction

- Triad of: immunodeficiency, eczematoid
skin lesions, thrombocytopenia
- serum IgA/IgE; ¯ IgM
- 12M + Pneumocystis infection + Hx of
nosebleeds + eczema; Q asks what cell is
dysfunctional? à answer = T cell
- Answer can be “deficiency of cell-
mediated immunity”
- Deficiency of CD18/LFA-1 integrin
- ¯ ability of leukocytes to leave blood
vessels for sites of infection à ¯ pus
Leukocyte adhesion deficiency (LAD) - Classically associated with delayed
separation of umbilical cord
- Answer can be “defective leukocyte
chemotaxis” instead of just “LAD”
- Phagolysosomal fusion disorder with
disruption of microtubule function
- Melanosome function also impaired à
Chediak-Higashi syndrome
partial albinism / fairer skin than siblings
- Giant granules in phagocytes in
neutrophils and eosinophils
- Failure of double-stranded DNA break
repair
- Cerebellar atrophy à ataxia
Ataxia-telangiectasia
- Telangiectasias
- susceptibility to radiation à risk of
leukemia and lymphoma
- Deficiency of CD40L on CD4+ T cells
- ¯ activation of CD40 on B cells à ¯ B cell
Hyper-IgM syndrome activation à ¯ ability to differentiate
into plasma B cells + isotype class-switch
à Ab isotype “stuck” at IgM
- STAT3 mutation
- FATED à abnormal Facies,
Hyper-IgE (Job) syndrome staphylococcal cold Abscesses, retained
primary Teeth, hyper IgE, Dermatologic
findings (e.g., eczematoid lesions)
- Recurrent TB infections
- Important point for USMLE is that Th1
CD4+ T cells and macrophages activate
each other in a cyclical loop via IL-12 and
IL-12 receptor deficiency
IFN-γ. Th1 cell lacking IL-12 receptor
cannot get activated and therefore does
not secrete IFN-γ à macrophages not
activated à ¯ granuloma formation
- Normal B cell number but defective
maturation into plasma cells
- ¯ immunoglobulin production
- Will be the answer if the Q gives you an
Common variable immunodeficiency (CVID) adult who has had recurrent
sinopulmonary infections (similar to IgA
deficiency), except ¯ Ig not limited to IgA;
in addition, if vignette gives you atopy or
Giardia, answer is IgA deficiency not CVID
Terminal complement deficiency - Deficiency of C5-C9 complement proteins
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- Cannot form membrane attack complex

(MAC)
- Recurrent Neisseria infections (both
gonococcal and meningococcal)
- Q will often have deficiency of “C7” or
“C8” as the answer (i.e., they choose a
random terminal complement protein),
or “terminal complement deficiency,” or
“complement-mediated
immunodeficiency”
- 4F + has her MHC class I molecules investigated; which of the following processes is most likely to be
seen? à answer = “binding of peptides from endocytic pathway”; MHC I has antigen peptides loaded
in the RER before being transported to cell surface with b2-microglobulin; wrong answers are
“association with invariant chain,” and “antigen loaded following release of invariant chain within
acidified endosome,” which refer to MHC II molecules. MHC I is present on all nucleated cells
(therefore not RBCs) and presents intracellular antigens (virus) to CD8+ T cells; MHC II is present only
on antigen-presenting cells (i.e., macrophages, dendritic cells, Langerhan cells, B cells) and presents
exogenous antigen (bacterial products) to CD4+ T cells.
- Researcher investigating an immune structure that naturally concentrates within endosomes,
lysosomes, and phagolysosomes + directly kills organisms (e.g., TB) + increasing pH within
phagolysosomes decreases efficacy of the structure; Q asks, which of the following processes is
primarily affected? à answer = “MHC II molecule peptide loading.” If you think about it, since MHC II
is expressing phagocytosed extracellular antigen, it makes sense that that’s the MHC where
endosomes play a role.
- Transgenic rats + incapable of expressing b2-microglobulin; which of the following host defenses is
most likely to be altered? à answer = cytotoxic T cells; b2-microglobulin is associated with MHC I,
which interacts with T cell receptor on CD8+ cytotoxic T lymphocytes.
- 4F + thymus is investigated using laser scanning microscopy; what is most likely to be seen? à
answer = T lymphocyte antigen receptor selection.
- 3M + bacterial infections since 6 months of age + scanty lymph nodes/tonsils; what mechanism best
explains this patient’s condition? à answer = “deficiency of humoral immunity”; diagnosis is X-linked
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agammaglobulinemia à mutation in Bruton tyrosine kinase à decreased B cell function à
decreased immunoglobulins.
- 19F + Hx of recurrent sinopulmonary infections since elementary school + asthma + Hx of Giardia
infection; what mechanism best explains this patient’s condition? à answer = “deficiency of humoral
immunity,” OR “deficiency of mucosal immunoglobulin”; diagnosis is IgA deficiency.
- 17F + Hx of cutaneous candida infections since childhood + 2-year Hx of type I diabetes mellitus + Hx
of autoimmune thyroiditis; Dx? à answer = chronic mucocutaneous candidiasis à answer = “T cell
dysfunction” = “impaired cell-mediated immunity” (both answers); although candida infections can be
seen in diabetes, the durations don’t match up here, so you know the Dx is CMC.
- 2F + numerous infections of skin + oral mucosa since birth + P/E shows numerous superficially
ulcerated skin lesions + WBC 20,000 (75% neutrophils) + biopsy of skin lesion shows no neutrophils
within the dermis or epidermis + culture of lesion shows S. aureus; Q asks, this patient’s recurrent
infections are most likely due to defective production of what? à answer = integrin; diagnosis is
leukocyte adhesion deficiency (LAD), caused by deficient CD18/LFA-1 integrin. LFA-1 is a type of
integrin; CD18 is a common subunit of integrins. LAD Qs need not mention delayed separation of
umbilical cord or absence of pus (although these are two HY descriptors); sometimes the answer will
be “defective leukocyte chemotaxis” instead of simply “LAD.”
- 3M + severe skin infections caused by S. aureus since birth + no pus at infection sites + previous
laboratory studies showed leukocytosis even in the absence of infection; which mechanism is
impaired in this patient? à answer = “leukocyte adhesion and migration”; diagnosis is LAD.
- Researcher investigating leukocyte extravasation + chemotaxis; Q asks, which molecule is necessary
for margination + rolling of leukocytes; answer = selectin; wrong answer is integrin.
Leukocyte extravasation + chemotaxis

What the leukocyte is doing Important molecules required
Margination + rolling on endothelium L-, E-, P-selectins
Adhesion to endothelium Integrins (CD18/LFA-1 integrin for LAD)
Diapedesis (extravasation) PECAM-1
IL-8, C5a, LTB-4, kallikrein, platelet-activating
Chemotaxis to desired site
factor, bacterial products
- 23F + one week of difficulty walking + blurry vision in left eye + MRI shows white matter lesions in
cerebellum; which of the following immune mechanisms best describes the pathogenesis in this
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patient? à answer = “CD4+ T cells are activated by myelin basic protein” (MBP); diagnosis is multiple
sclerosis (MS); MBP is a component of myelin. As one proposed mechanism for MS, T cells will attack
MBP, via molecular mimicry, following HHV-6 infections. If you are asked to pick the cell that T cells
attack in a USMLE Q for MS, answer is oligodendrocyte. For Guillain-Barre, choose Schwann cell.
- 45M + bilateral crackles + fever of 102F + Legionella grown from sputum culture; Q asks, which
mechanism is most integral to clearing the organism from his alveoli? à answer = “T cell-mediated
immunity”; Legionella is facultative intracellular; CD8+ cell-mediated immunity is helpful in clearing
Legionella for this reason; very fucking HY detail for Step 1.
- 29M + splenectomy following motor vehicle accident + now has target cells; this is due to loss of
what? à answer = red pulp à part of spleen (~75%) that normally clears out senescent RBCs;
asplenia is rare cause of target cells for USMLE, although this shows up on one NBME Q (target cells
almost always thalassemia). White pulp of the spleen (~25%) is composed of lymphoid tissue, where
opsonization + phagocytosis occurs.
- 29M + splenectomy + must now receive which three vaccines? à S. pneumo, Haemophilus influenzae
type B, Neisseria meningitides à encapsulated organisms à increased risk because normally
encapsulated organisms are removed via opsonization + phagocytosis, and the spleens plays a major
role in carrying out that function. C3b and IgG are two major opsonins à once bound to cell, cell now
labeled for phagocytosis.
- What will be seen on blood smear post-splenectomy (or with auto-splenectomy)? à answer =
Howell-Jolly bodies (RBC nuclear remnants) + target cells (although the latter usually thalassemia).
- How does the spleen relate to platelets? à splenomegaly can sequester platelets and cause
thrombocytopenia; splenectomy can cause transient thrombocytosis.
- 16F + has fever and confusion + CSF culture shows gram (-) diplococci + younger brother had similar
infection last year; which of the following immune disorders does this patient have? à answer = “late
component of complement deficiency” à terminal complement deficiency (C6-C9) leads to recurrent
Neisseria infections (both meningococcus and gonococcus) à defective membrane attack complex
(MAC); sometimes the answer will simply just be “C7,” or “C8”; sounds random, but if you know these
are terminal complement then it’s easy.
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- 7M + three infections with Neisseria meningitides the past year; which of the following is most likely
to be abnormal in this patient? à answer = “total hemolytic complement activation.”
- 40F + receives new chemotherapeutic drug that causes myelosuppression; Q asks, in order to follow
for risk of infectious complications, what should be monitored? à answer = neutrophil counts à
agranulocytosis (neutropenia) is often seen with chemotherapy; also seen with various drugs such as
the thionamides (propylthiocuracil + methimazole, for hyperthyroidism), ganciclovir (for CMV),
methotrexate (for RA), clozapine (for schizophrenia), ticlopidine (anti-platelet); agranulocytosis will
frequently present on USMLE as mouth ulcers (mucositis), sore throat, and fever; or they can just tell
you the patient has a WBC count of, e.g., 3000/uL (NR 4-11,000) following the administration of a
neutropenia-inducing agent, so you can infer the drug has dropped the WBCs.
- 35M + red spots on shins, joint pain, and fatigue + HepC + urine protein and blood; which
hypersensitivity type is responsible for the renal damage? à answer = type III; diagnosis is
cryoglobulinemia (immunoglobulins / Ag-Ab complexes that precipitate below 37C), causing skin
lesions/ulcers, Raynaud phenomenon, muscle pain, and glomerulonephritis.
- 4F + leukocytes fail to express CD40 ligand; the immunoglobulin that predominates in this patient’s
serum has which biologic property? à answer = “complement activation” à diagnosis is hyper-IgM
syndrome à caused by failure of expression of CD40 ligand on T cells à therefore B cells cannot be
activated for immunoglobulin isotype class-switching (i.e., cannot switch from IgM to IgD, IgG, IgE,
IgA). Wrong answers are: “ability to cross the placenta” = IgG; “attachment to Fc receptors on mast
cells” = IgE; “secretion across mucosal epithelial cells” = IgA; “activation of B cells” = IgD.
- 42M + inflammatory bowel disease + trial of monoclonal antibody is begun; what does it most likely
target? à answer = tumor necrosis factor; anti-TNF-a agents such as infliximab, adalimumab, and
etanercept can be used for IBD non-responsive to NSAIDs and steroids.
- 38F + rheumatoid arthritis + treatment with NSAIDs, prednisone, and methotrexate not effective; the
most appropriate next step in pharmacology blocks which cytokine? à answer = TNF-a; sounds
similar to above IBD Q, but these are distinct immuno NBME Qs (let that emphasize yieldness).
- 35F + SLE + has diffuse proliferative glomerulonephritis; what is the most likely immunological
mechanism associated with this patient’s disease? à answer = anti-DNA/DNA immune complex
deposition in the glomeruli.”
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- 41M + infection of dorsolateral foot that ascends lymphatically; Q asks, what is the most likely source
of drainage? à answer = popliteal lymph nodes (HY). Other HY lymph node drainage points:
o Testes + ovaries à para-aortic.
o Foregut, midgut, hindgut à celiac, superior mesenteric, inferior mesenteric, respectively.
o Cervix + body of uterus à external iliac.
o Anal canal above pectinate line + bladder à internal iliac.
o Anal canal below pectinate line + scrotum à superficial inguinal.
o Right arm + right side of trunk above diaphragm à right lymphatic duct.
o Left side of body (entire) + right side of body below diaphragm à thoracic duct.
o Right lymphatic + thoracic ducts drain into the confluence of the subclavian and internal
jugular veins on that respective side.
o “Yeah but Michael, you didn’t mention x, y, and z locations.” Relax. As I said, the objective
here is to get you HY points, not to list off minutiae that’s not likely to be tested.
- 29M + HIV + receives drug that blocks viral entry into the cell; which of the following is the molecular
target of this drug? à answer = chemokine receptor à refers to CCR5 as the target of maraviroc,
which is an HIV entry inhibitor. Don’t confuse this with enfuvirtide, which targets Gp41 and functions
as an HIV fusion inhibitor.
- An investigator is comparing the live-attenuated (Sabin) vs killed (Salk) Polio vaccines; what is a
common feature of these vaccines that accounts for their efficacy? à answer = “neutralizing
antibodies in the circulation.” The live-attenuated is given oral; it enters cells and is expressed on
MHC I for interaction with CD8+ T cells for cell-mediated immunity; there is production of neutralizing
secretory IgA antibodies and activated CD8+ T cell effector in the gut, neutralizing IgG antibodies and
activated CD8+ T cell effectors in the circulation, and CD8+ memory T cells; in contrast, killed vaccine
does not cause cell-mediated immunity so will only cause neutralizing IgG antibodies in the
circulation.
- 20F + healthy + painful swelling on the chest wall inferior to right breast + physician identifies it as a
nipple; biopsy of the specimen is most likely to show what? à answer = “epithelial cells” (i.e., normal
finding) à supernumerary nipples are common in women; yes, this is on the NBME for Step 1.
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- 33F + shortness of breath + fever + sputum shows gram (+) diplococci; which of the following enzymes
is most likely to initiate intracellular killing of the organism? à answer = “lysosomal hydrolases.”
- 5-month-old girl + recurrent sinopulmonary infections since birth + hypopigmentation of skin, eyes,
and hair + peripheral smear shows giant granules in neutrophils and eosinophils; what’s the most
likely diagnosis? à answer = Chediak-Higashi syndrome; phagolysosomal fusion disorder with
disruption of microtubule function; melanosome function also impaired.
- 4F + immunodeficiency + fairer skin than siblings + giant granules seen in phagocytes; Dx? à answer =
Chediak-Higashi syndrome; phagolysosomal fusion disorder with disruption of microtubule function;
melanosome function also impaired.
- 2M + immunodeficiency + delayed separation of umbilical cord; Dx? à answer = leukocyte adhesion
deficiency à deficiency of LFA-1/CD18 integrin.
- 2M + viral, fungal, bacterial, protozoal infections since birth + absent thymic shadow + scanty/absent
lymph nodes/tonsils; Dx? à answer = severe-combined immunodeficiency (SCID) à XR type is most
common and due to common gamma-chain mutation or IL-2 receptor deficiency; AR is due to
adenosine deaminase (ADA) deficiency; Tx is bone marrow transplant; absent thymic shadow means T
cell deficiency; scanty/absent lymphoid tissue means B cell deficiency.
- 2M + bacterial infections from ~6 months of life + scanty/absent lymph nodes/tonsils; Dx? à answer
= “deficiency of humoral immunity” (Bruton X-linked agammaglobulinemia); it must be pointed out
that a Q on one of the newer Peds forms has Bruton as the answer for a kid who has bacterial
infections since birth (which throws a dagger in the classic contrast with SCID); therefore the stronger
emphasis must be that Bruton is bacterial only, whereas SCID is all types of infections (viral, fungal,
bacterial, protozoal); Tx = “monthly infusion of immune globulin.”
- 5-month-old boy + severe diarrhea and pneumonia + thymus decreased in size + Pneumocystis jiroveci
is isolated + decreased serum immunoglobulin concentrations + karyotype normal; diagnosis? à
answer = severe combined immunodeficiency (SCID); wrong answer is DiGeorge;
hypogammaglobulinemia has not been reported in DiGeorge; also, DiGeorge would have 22q11
deletion identified on karyotype analysis.
- 3M + sore throat + grey membrane at back of throat; immunization with which of the following would
have prevented this? à answer = toxoid vaccine; Corynebacterium diphtheriae is a toxoid vaccine;
MEHLMANMEDICAL.COM
presents classically with grey pseudomembrane in oropharynx and myocarditis, although vignette
need not mention these.
- 34F + septic shock caused by gram (-) rod; which of the following is responsible for her low BP? à
answer = “lipopolysaccharide stimulating production of tumor necrosis factor” à lipid A of
lipopolysaccharide (LPS) will stimulate macrophages to release cytokines à IL-1 causes fever; TNF-
alpha causes vascular permeability and low BP. Important to note that lipid A of LPS in gram (-) sepsis
is an endotoxin that binds to toll-like receptor 4 (CD14 co-receptor) on macrophages; this is in
contrast to TSST toxin in toxic shock syndrome that is a superantigen that bridges MHC II and TCR.
- 16M + nose bleeding in car accident + has nasal packing + now gets low BP; what are the
immunological receptor(s) bound? à answer = MHC II and TCR à toxic shock syndrome from the
cotton packing; CD14 (toll-like receptor 4 is co-receptor) is wrong answer, since that is endotoxic
shock from gram (-) sepsis.
- 2M + mental retardation + fairer skin than siblings + deficiency of hydroxylase enzyme; how could this
patient’s presentation have been prevented? à answer = “routine newborn screening” via heel-prick
test at birth for phenylketonuria (PKU; autosomal recessive; deficiency of phenylalanine hydroxylase)
à tyrosine becomes essential; phenylalanine must be avoided in diet; malignant PKU =
tetrahydrobiopterin (THB) deficiency (cofactor for phenylalanine hydroxylase).
- 8-month-old girl + oropharyngeal candidiasis + Hx of parainfluenza infection + 3/6 harsh systolic
murmur at left sternal border; what does she have a deficiency of? à answer = T lymphocytes à
possibly DiGeorge syndrome in this case (tetralogy of Fallot with murmur being a mix of VSD and
pulmonary stenosis); T lymphocyte deficiency will cause viral, fungal and protozoal infections; if the
USMLE wants B cell deficiency as part of answer, they’ll mention bacterial infections.
- 8-day-old newborn + truncus arteriosus + serum calcium of 7mg/dL + no thymic shadow; Dx? à
answer = hypoparathyroidism (DiGeorge; 3rd and 4th pouch agenesis à 3rd = thymus and inferior
parathyroids; 4th = superior parathyroids).
- An 8-month-old boy has recurrent respiratory tract infections since birth + hypocalcemia + broad
nasal bridge; deficiency of which of the following is responsible for this patient’s condition? à answer
= T cell; diagnosis is DiGeorge à 22q11 deletion.
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- 16F + 3-day Hx of pain and pressure over left cheek + Hx of strep pneumonias at age 6 and 10 +
seasonal allergies; Dx? à answer = “impaired humoral immunity” or “deficiency of mucosal
immunoglobulin”; Dx is IgA deficiency (one of the highest yield presentations for not just the Peds
shelf but also USMLE); sore cheek = sinusitis; presents as recurrent sinopulmonary infections; also
associated with Hx of Giardia infection, autoimmune diseases (e.g., vitiligo), and atopy (dry cough in
winter [cough-variant asthma], hay fever in spring, eczema in summer); anaphylaxis with blood
transfusion is “too easy” for most 2CK IgA deficiency Qs but will rarely show up, yes.
- 3M + recurrent OM + recently underwent placement of tympanostomy tube + mom HIV negative; Dx?
à answer = “antibody deficiency” à IgA deficiency.
- 8F + fever + purpuric lesions over trunk and extremities + brother died of fulminant meningococcemia
four years ago; Dx? à answer “complement system immunodeficiency” à terminal complement
deficiency (C5-9) is associated with recurrent Neisseria infections (gonococcal and meningococcal).
- 18M + African American + Neisseria meningitides infection + had similar infection two years ago +
vignette gives no other info; Q asks, this patient should be examined for which of the following
conditions? à answer = “complement deficiency”; wrong answer = sickle cell disease; no reason to
suspect asplenia from sickle cell.
- “What do I need to know about the respiratory burst and chronic granulomatous disease (CGD; aka
NADPH oxidase deficiency)?”
o Respiratory burst is a process by which phagocytes such as neutrophils and macrophages can
produce hydrogen peroxidase and hydroxy-halide radicals (bleach) to kill microbes.
o CGD is caused by NADPH oxidase deficiency à decreased H2O2 production à increased
susceptibility to catalase-positive organisms.
o Catalase is the enzyme that breaks down H2O2.
o Humans without CGD: Production of H2O2 via respiratory burst is >>> catalase produced by
organisms → organisms are overwhelmed + die.
o Human with CGD: Production of H2O2 via respiratory burst is < catalase produced by
organisms → organisms can tolerate phagocyte environment + survive.
o Organisms that produce catalase are able to neutralize small amounts of H2O2, but not large
amounts. So in a typical person who does not have NADPH oxidase deficiency, the amount of
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hydrogen peroxide he or she produces far exceeds what catalase (+) organisms can handle,
so therefore there's no innate susceptibility to these organisms.
o A general mnemonic for catalase-positive organisms is C SHAPES or SPACESHip:
§ Candida, Serratia, H. pylori, Actinomyces, Pseudomonas, E. coli, S. aureus.
§ Staph, Psuedomonas, Actinomyces, Candida, E. coli, Serratia, H. pylori.
- 6M + recurrent Staph infections + diarrhea; Dx? à answer = “neutrophil oxidation burst” à chronic
granulomatous disease (NADPH oxidase deficiency) à infections with catalase (+) organisms (Staph
infections are signature complication); SPACES à Staph, Psuedomonas, Actinomyces, Candida, E. coli,
Serratia; Aspergillus most common fungal infection seen in CGD; 2CK has Q where child gets Serratia
sepsis as part of CGD.
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- 5F + life-threatening Staph infections since age 3 months + WBCs normal + serum immunoglobulins
normal; which of the following will best help establish the Dx? à NBME answer = “NADPH oxidase
test”; if the Q gets specific, dihydrorhodamine test is now correct over tetrazolium blue assay; this is
on either retired NBME 15 or 16 for Step 1, where the latter is wrong; the former is correct.
- 19M + type I diabetes + recurrent yeast infections + analysis shows deficiency of myeloperoxidase; Q
asks most likely cause of infection susceptibility in this patient; answer = “decreased ability to
produce hydroxy-halide radicals” à Dx is myeloperoxidase deficiency; enzyme normally converts
hydrogen peroxide into bleach (hydroxy-halide radicals).
- 32F + has PPD test performed + large area of induration; which cell type is predominant in this area of
induration? à answer = macrophages; wrong answer = cytotoxic T lymphocytes; macrophages
phagocytose the TB antigen and express it on MHC II to CD4+ T cells (humoral immunity); cytotoxic T
cells are CD8+ and will interact with virus expressed on MHC I (cell-mediated immunity).
- 60M + undergoes chemotherapy + has fever of 102F + neutrophil count is low + antibiotics are
administered; which of the following should be given to this patient to improve his neutrophil count?
à answer = granulocyte-macrophage colony-stimulating factor (GM-CSF; molgramostim), or G-CSF
(filgrastim).
- 3-week-old boy born at term + experienced two weeks of respiratory distress following birth + mom
has myasthenia gravis; this patient’s transient respiratory distress was due to transplacental transfer
of which of the following antibody types? à answer = IgG (only one that crosses the placenta).
- 14M + fever + stiff neck + non-blanching purpura on abdomen + BP of 60/35 + IV fluids and
norepinephrine have limited effect; Tx? à answer = hydrocortisone; Dx = Waterhouse-Friderichsen
syndrome; hemorrhagic necrosis of adrenal cortices secondary to meningococcal septicemia; non-
blanching rash in the setting of meningitis = meningococcus; hydrocortisone is the answer because
cortisol is deficient in this setting à cortisol normally needed to upregulate alpha-1 receptors on
arterioles, thereby permitting NE and E to do their job; that’s why NE has limited effect.
- 1-month-old male + diffuse white plaques in oral cavity that bleed when scraped + papular
erythematous rash with satellite lesions over the diaper area; mechanism? à answer = “decreased T
lymphocyte activity” à chronic mucocutaneous candidiasis.
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- 8M + super high IgM on lab report; what’s the mechanism? à answer = deficiency of CD40 ligand on
T cells (can’t activate CD40 on B cells to induce isotype class switching) à Dx = Hyper IgM syndrome.
- 6F + recurrent Staph abscesses + eczematoid skin lesions + abnormal dentition; Dx? à answer =
hyper IgE syndrome (Job syndrome) à FATED à abnormal Facies, staphylococcal cold Abscesses,
retained primary Teeth, hyper IgE, Dermatologic findings (e.g., eczematoid lesions).
- 12M + eczematoid skin lesion on forehead + nosebleeds + Hx of infections; Q asks which cell is
dysfunctional à answer = T cell; Dx = Wiskott-Aldrich syndrome (XR) à classic triad of eczematoid
skin lesions + thrombocytopenia + immunodeficiency.
- 3F + dilated superficial blood vessels on face + wobbly gait; mechanism? à answer = failure of
double-stranded DNA break repair” à Dx = ataxia-telangiectasia.
- 17M + 3-wk Hx of lymphadenopathy, fever, and loose stools + hepatosplenomegaly + low RBCs and
WBCs + high IgM and IgG; Dx? à answer = HIV infection; wrong answers are CVID, IgA deficiency,
SCID, DiGeorge, Bruton (so you can eliminate to get there); CVID is can rarely occur as young as
adolescence but Dx is with IgG and IgA >2SD less than the mean (IgG high in this stem).
- 47M + farmer + nodule on nose + biopsy shows invasive melanoma with features of regression; which
of the following best explains the mechanism of regression? à answer = “T lymphocyte-mediated
cytotoxicity” à T cells can recognize and destroy cancer cells; aldesleukin is a recombinant IL-2 used
for melanoma that stimulates T cells.
- 20M + Crohn disease + treated with prednisone + recovers; the mechanism of this pharmacologic
therapy is suppression of which of the following? à answer = T lymphocytes; steroids lead to
suppressed T cell responses; wrong answers are antibody binding, complement activity, mast cell
degranulation, neutrophil function.
- 28F + squamous cell carcinoma of the cervix + biopsy of tumor cells shows HPV-18; which of the
following cell types is most important for killing these virally infected cells? à answer = T cells; CD8+
T cells kill virus-infected cells; wrong answers are dendritic cells, macrophages, and plasma cells.
- 45M + has tuberculosis + which cytokine concentration is most likely to be increased in this patient?
à answer = interferon-gamma (IFN-γ); IFN-γ from CD4+ T cells stimulates macrophages in order to
form granulomas.
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- 25M + receives bone marrow transplant + one week later develops rash, diarrhea, and increased LFTs;
what’s the most likely mechanism for this patient’s condition? à answer = “Donor T cells reacting
against host cells”; diagnosis is graft vs host disease à usually seen in bone marrow transplants, but
sometimes in liver transplants; donor (graft) T cells recognize the host (recipient) antigens as foreign +
cause immune response.
- 45M + bone marrow transplant 7 weeks ago + now has increased LFTs; Q asks, which of the following
hypersensitivity types is most responsible? à answer = cell-mediated; graft-vs-host disease is
considered to be cell-mediated hypersensitivity; wrong answers are antibody-mediated, immediate,
and immune complex.
- 46F + receives liver transplant + the vessels supporting the graft appear to necrose within 15 minutes
of transplantation; what’s the mechanism? à answer = preformed antibodies; hyperacute rejection
(graft rejection on the operating table). Acute rejection on USMLE will be up to several months;
chronic rejection will be >6 months; for both acute and chronic, USMLE wants T cell response.
- 52M + infiltrating parietal lobe mass identified as astrocytoma; impaired activity of which of the
following is most likely responsible? à answer = p53; this is often the answer if the USMLE asks about
what needs to be mutated for there to be cancer invasion; effect of p53 mutation is “defective DNA
repair”; p53 normally facilitates DNA repair by halting the cell cycle to allow time for cellular
machinery to restore molecular stability.
- 31M + cellulitis + goes on to develop fever, confusion, tachycardia, and low BP + WBC 18,000/uL;
which two cytokines are responsible for his condition? à answer = IL-1 and TNF-a. Really HY Q for
USMLE à IL-1 causes fever associated with sepsis; TNF-a causes low BP (increased vascular
permeability). If the Q gives you a vignette of sepsis and forces you to choose one molecule, the
answer is TNF-a. Should be noted that students memorize IL-1 as causing fever, but this only applies
to infection/sepsis; if the vignette tells you aspirin or ibuprofen is given to decrease fever, answer =
decreased effect of prostaglandin, not IL-1 (sounds easy, but I’ve seen students get this wrong).
- 52F + breast cancer + lost 20 lbs past month + no appetite; what is responsible for this patient’s loss
of appetite? à answer = “effect of cytokine” à TNF-a causes cachexia.
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- Researcher compares two cell lines; one cell line has an IL-2 gene transfected; the other does not; the
transfected group generates a stronger immune response; what kind of cell is responsible for this
difference? à answer = T lymphocyte; IL-2 stimulates T cells.
- 40M + has a wound surgically repaired; Q asks, which of the following inflammatory mediators is most
likely released from aggregated platelets in this patient during wound repair? à answer =
thromboxane A2 (I guess more of a heme/onc Q, but life moves on doesn’t it).
- 65F + fever of 102F + muscle pain + non-productive cough + shortness of breath; which vaccine would
have prevented these findings? à answer = influenza virus.
- 20M + fever of 100.8F + non-productive cough + pale conjunctivae + blood sample agglutinates while
waiting for transport to laboratory; which of the following antibody isotypes most likely caused the
agglutination? à answer = IgM; Mycoplasma pneumoniae can cause atypical pneumonia, as well as
cold autoimmune hemolytic anemia (pale conjunctivae); cold AIHA is associated with IgM targeting
RBCs (cold = “Mmm ice cream” = IgM); agglutination of RBCs occurs <37C; can also be caused by
CMV; warm AIHA is IgG against RBCs and is caused classically by chronic lymphocytic leukemia (CLL).
- 61M + goes hiking + has linear vesicles on his leg; this finding is most likely caused by activation of
which of the following cell types? à answer = T cells à contact dermatitis (type IV hypersensitivity)
caused by poison ivy/sumac; “linear vesicles” is HY for brushing up / walking past weeds; if Q asks
how to avoid this condition, answer = “avoidance of contact with weeds.”
- Researcher makes a cell line that produces an inactive form of caspase. What’s most likely to be the
result of this? à answer = continued proliferation of cells; caspases enable apoptosis.
- 50F + has flow cytometry performed showing CD3 50%; CD4 40%; CD8 10%; CD20 50%; surface kappa
48%; surface lambda 3%; what is most predictive of clonal lymphoid proliferation in this patient? à
answer = “surface kappa/lambda ratio”; CD3 = T cell marker; CD20 = B cell marker (so we know the
analysis is showing us 50% T cells and 50% B cells); CD4 and CD8 are T cell markers (so 80% of the
patient’s T cells are CD4, and 20% are CD8); surface kappa and lambda are expressed on B cells,
where the ratio can be heavily slanted in leukemia/lymphoma. The point of this Q is to 1) be able to
infer the heavy ratio of kappa/lambda means the pathology is related to this, and 2) to be aware of
various T and B cell markers. Should be noted CD19 is another important B cell marker, and that
rituximab is a monoclonal antibody against CD20.
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- 4F + bloody diarrhea caused by Salmonella; which of the following factors is most responsible for
neutrophil recruitment to intestinal cells? à answer = IL-8; neutrophilic chemotactic molecules
include IL-8, kallikrein, platelet-activating factor, C5a, LTB-4, and bacterial products.
- 72M + fever 101 + WBCs 15,000 + CXR shows patchy infiltrate; which endogenous chemoattractant
primarily causes leukocytic recruitment to his site of acute inflammation? à answer = C5a. Don’t get
pulled into weird distractors like filamin or N-formyl methionine terminal amino acid peptides.
- 2-month-old girl + feeding and developing well + pregnancy uncomplicated + temperature of 99.8F +
hematocrit, platelets, and WBC count normal, but neutrophils 5%; diagnosis? à answer = congenital
neutropenia”; neutrophils should be 50-55%; asked on the NBME.
- 22F + vesicular lesions on lower lip + recurrences most likely caused by viral latency where? à answer
= sensory neurons.
- 4F + fever 102F + crackles and rhonchi heard in the lungs + CXR shows dextrocardia and right-sided
gastric bubble; deficiency of which of the following is responsible for this patient’s disorder? à
answer = dynein; Dx is primary ciliary dyskinesia (Kartagener syndrome); patients present with situs
inversus, sinopulmonary infections, and immotile sperm / ectopic pregnancy. Sometimes the answer
can be “dynein arm” or “cilium.”
- 4M + lymphadenopathy + absent granulomata seen on lymph node biopsy + acid-fast bacilli identified
as Mycobacterium avium intracellulare + normal serum immunoglobulin concentrations and B and T
cells; the patient most likely has defective expression of which of the following? à answer =
interferon-gamma (IFN-γ) receptor à IFN-γ needed for granulomas.
- 60F + fever + night sweats + PPD test positive; sputum culture is most likely to show organisms inside
which of the following cells? à answer = macrophages; T cells are wrong answer because they help
facilitate granulomas, but the TB are phagocytosed by alveolar macrophages.
- 28F + AIDS + develops tuberculosis + which cell types is most likely to have deficient function in the
tuberculous areas of lung? à answer = macrophages; CD4+ T cells normally activate macrophages via
IFN-gamma, and macrophages stimulate CD4+ T cells via IL-12; wrong answers = eosinophils,
neutrophils, fibroblasts, Langerhan cells.
- 29M + PPD test positive + IFN-γ administered improves his condition; diagnosis? à answer = IL-12
receptor deficiency à causes increased susceptibility to TB infections; macrophages and CD4+ T cells
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have an IL-12-IFN-γ stimulatory loop à macrophages secrete IL-12, which stimulates CD4+ T cells to
make IFN-γ, which in turn stimulates the alveolar macrophages to form granulomas to contain TB.
- 2-month-old girl + given vaccine that converts T cell-independent antigens into T cell-dependent
antigens; which vaccine was given? à answer = Haemophilus influenzae type B (HiB). Only proteins
can be expressed on MHC molecules in order to induce T cell response; HiB has polysaccharide
capsule that will alone will not get expressed on MHC, so it is conjugated to a protein (toxoid vaccine),
which in turn can be expressed on MHC, generating a T cell response.
- 2M + scaly, seborrheic eruption over scalp, palms, and diaper region + hepatosplenomegaly +
generalized lymphadenopathy + x-ray of skull shows osteolytic legions + biopsy of skin lesion shows a
tennis racquet-shaped bilamellar granule in cytoplasm + immunohistochemistry shows cells are CD1a
positive; the abnormal cells in this patient are most likely derived from which of the following? à
answer = dendritic cells; Dx = Langerhan cell histiocytosis; tennis racquet-shaped granules are called
Birbeck granules. Langerhan cells are a type of dendritic cell found in the skin. Dendritic cells are
antigen-presenting cells found throughout the body that, once exposed to antigen, travel to lymph
nodes for interaction with B and T cells.
- 34M + chronic HepC; what mechanism best describes any hepatic damage in this patient? à answer
= “Cytotoxic T cell response”; wrong answer is “direct viral cytopathic effects.” Hepatitis viruses
(except HepD) primarily cause hepatic damage by inducing a T cell-mediated immune response to
hepatocytes; direct viral cytopathic effect is seen more with hepatitis D.
- 26M + lower back pain worse in the morning + gets better throughout the day + eczematoid lesion on
his forehead; what is most likely to be seen in this patient? à answer = HLA-B27 positivity; HLA-B27
à PAIR à Psoriasis, Ankylosing spondylitis, IBD, Reactive arthritis; never choose HLA-B27 for
diagnostic purposes; USMLE just wants you to know the immunologic link for these PAIR conditions.
- 14M + abdominal mass just left to the umbilicus + chylothorax + biopsy of mass shows “starry sky
appearance”; Q shows an arrow pointing to a macrophage and asks the process occurring here;
answer = apoptosis; Burkitt lymphoma can be of the jaw or intra-abdominal; “starry sky appearance”
refers to a background of lymphocytes with interspersed macrophages; the latter are called “tingible
body macrophages,” (not tangible) which are macrophages within germinal centers containing large
amounts of apoptotic debris. Sounds outrageous and pedantic but it’s on the NBME for Step 1.
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- 47M + cystic fibrosis + receives bilateral lung transplant + on immunosuppressive agents for several
months + now has higher fasting glucose levels; Q asks why; answer = adverse effect of medication
(tacrolimus) à HY drug that causes diabetes; tacrolimus binds to to FK506 à decreases intracellular
calcineurin à decreases IL-2 transcription (cyclosporin also decreases IL-2 transcription; in contrast,
sirolimus decreases responsiveness to IL-2).
- 42M + receives intramuscular antibiotic + three days later has rash in his arm where the drug was
administered; Q asks, what kind of hypersensitivity is this? à answer = type III à diagnosis is Arthus
reaction à localized skin reaction due to immune complex deposition; can be distinguished from type
I hypersensitivities because type III require 3-5 days after exposure to be seen. Arthus reaction is a
localized form of serum sickness; the latter is also a type III hypersensitivity due to drugs, but rather
than localized to the skin, serum sickness often presents as arthritis and erythema nodosum (redness
of the shins due to panniculitis [inflammation of subcutaneous fat]).
- 16F + starts taking TMP/SMX for UTI + three days later has polyarthritis; Q asks, what kind of
hypersensitivity is this? à answer = type III; diagnosis is serum sickness due to sulfa drug. Serum
sickness can also occur as result of infections, notably HepB/C, Rubella, Yersinia, and Chlamydia
(reactive arthritis).
- 17M + leukemia + neoplastic cells do not express CD4 and CD8, however they do express T
lymphocyte receptor b-chain D and J segments; Q asks, which of the following best refers to these
malignant cells? à answer = “T cell thymocytes localized to thymic cortex.” Recall that T cell
precursors first migrate into the thymic cortex as CD4 and CD8 negative, before differentiating into
CD4 and CD8 positive cells. Pedantic, but asked on NBME.
- “I always get confused about the immunosuppressants. Can you consolidate some of what I need to
know?”
Cyclosporine vs tacrolimus vs sirolimus

MEHLMANMEDICAL Cyclosporine Tacrolimus Sirolimus
Binding site Cyclophilin FK506 mTOR
Effect on IL-2? ¯ transcription ¯ transcription ¯ responsiveness
¯ intracellular calcineurin? Yes Yes No
Causes diabetes? Yes Yes No
Nephrotoxic? Yes Yes No
Neurotoxic? Yes Yes No
Gingival hyperplasia,
Other HY adverse effects Diabetes highest yield Dyslipidemia
HTN, hypertrichosis
MEHLMANMEDICAL.COM
- “What about monoclonal antibodies? What are some worthy of memorizing for USMLE?”
Highest yield monoclonal antibodies for USMLE (i.e., sans the superfluousness)
Drug name(s) Molecular target Therapeutic utility HY points
*Etanercept is the odd one out
à it is a recombinant TNF-a
Infliximab,
receptor that mops up TNF-a,
Adalimumab, Soluble TNF-a Severe rheumatoid arthritis; IBD
whereas the others are
Etanercept*
monoclonal antibodies against
TNF-a
risk of progressive multifocal
Rituximab CD20 on B cells Lymphoma
leukoencephalopathy (PML)
Trastuzumab HER2/neu HER2/neu (+) breast cancer Cardiotoxic
Percutaneous coronary Students often confuse with
Abciximab Platelet GpIIb/IIIa
intervention (PCI) adalimumab
Omalizumab IgE Severe asthma with IgE
Denosumab RANKL Advanced osteoporosis
Prevents RSV syncytia
formation; always wrong
answer for Tx on USMLE (i.e.,
RSV bronchiolitis in very rare /
Palivizumab RSV F protein always choose “supportive
limited cases
care” for RSV Tx, but just be
aware the drug exists + its
MOA)
Natalizumab a4-integrin Multiple sclerosis risk of PML
Tocilizumab IL-6 receptor Severe rheumatoid arthritis
Daclizumab is another
monoclonal Ab against IL-2
Basilixumab IL-2 receptor Transplant rejection receptor that was once used
for MS but has been
discontinued
Complement Paroxysmal nocturnal Lowest yield one in this chart
Eculizumab
protein C5 hemoglobinuria (PNH) (i.e., “LY of the HY”)
MEHLMANMEDICAL.COM
MEHLMANMEDICAL
HY IMMUNO
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MEHLMANMEDICAL

- “What do I need to know about MHC molecules for USMLE?”

Simplified comparison of MHC I and MHC II for USMLE

- What do I need to know about innate vs adaptive immunity for USMLE?”

Innate vs Adaptive immunity HY points

- “What do I need to know about natural killer (NK) cells?”

o Part of innate immunity; stimulated by IL-12.

by identifying downregulation of cellular MHC I expression).

o CD16 on NK cells enable a process called antibody-dependent cell-mediated cytotoxicity:

Fc regions of the antibody facing outward.

§ CD16 on NK cells binds Fc regions of antibody.

§ Crosslinking of CD16 molecules occurs, causing the NK cell to release of granzymes,

granulysins, and perforins, which induces apoptosis in target cell.

- “What do I need to know about B cells?”

o Main cell of humoral immunity; differentiates into antibody-secreting plasma cell.

o Undergoes somatic hypermutation and affinity maturation, enabling increased antibody

specificity for antigen.

known as germinal centers.

o Type of antigen-presenting cell (APC), meaning it can phagocytose extracellular pathogen

and present it to CD4+ T cells on MHC II.

- “What do I need to know about T cells?”

o Two main types to know for USMLE: CD8+ and CD4+.

stimulates B cells, enabling antibody production.

- “What do I need to know about T cell activation?”

§ MHC I binds to TCR + CD8.

§ MHC II binds to TCR + CD4.

§ B7-1/-2 (CD80/86) binds to CD28.

o Activation of the T cell results in:

o So the quick summary of T cell activation:

§ Primary signal = MHC binds to TCR/CD.

§ Secondary signal = B7 protein binds to CD28.

- “What do I need to know about T cell differentiation?”

differentiation in addition to their activation.

organize into granulomas.

o Th17 cells stimulate neutrophilic production and recruitment.

o Treg cells prevent autoimmunity (i.e., are a suppressive type of T cell).

Th0 à Th1 cells. This IL-12-IFN-γ loop is HY for Step 1.

clusters of organized macrophages that appear if inflammation is chronic. Activated

macrophages composing a granuloma are called histiocytes, or epithelioid macrophages.

§ In short: IL-12/IFN-γ à ­ Th1 lineage à ­ macrophage activation.

§ Macrophages that organize into granulomas are called histiocytes, or epithelioid

copious antibodies that neutralize extracellular pathogen (humoral immunity).

§ In short: IL-4/IL-10 à ­ Th2 = B cell activation à ­ plasma cells à ­ Abs.

however on USMLE, this CD40L-CD40 interaction is specifically HY with respect to Th2

via processes called somatic hypermutation and affinity maturation.

§ Somatic hypermutation refers to mutation rates in the genes of immunoglobulins

that are 1,000,000 times greater than in other cell lines.

§ This results in affinity maturation, which means antigen-binding regions (Fab) of

immunoglobulins (antibodies) are capable of generating increasingly greater affinity

§ Do not confuse somatic hypermutation and affinity maturation (B cell processes)

combinations, specificities, and affinities.

suppress the Th1 lineage. In other words:

§ IL-12/IFN-γ à ­ Th1 lineage + ¯ Th2 lineage.

§ IL-4/IL-10 à ­ Th2 lineage + ¯ Th1 lineage.

of binding self-MHC antigen survive (i.e., they’re capable of generating an immune

binding self-MHC antigen undergo apoptosis. This is a check to prevent autoimmunity.

on antigen-presenting cells (APC).

- “What is the difference between cell-mediated and humoral immunity?”

MEHLMANMEDICAL.COM Cell-mediated immunity Humoral immunity

in order to kill the organism.

§ In short: IL-12/IFN-γ à Th1 lineage à macrophage activation.

§ In short: IL-4/IL-10 à Th2 = B cell activation à plasma cells à Abs.

§ IL-12/IFN-γ à Th1 lineage + ¯ Th2 lineage.

§ IL-4/IL-10 à Th2 lineage + ¯ Th1 lineage.

IFN-γ à ¯ macrophage activity à risk for