BIO401 Immunobiology Immunobiology

BOOK – Kuby 6th Edition* • Office hour – After class or by appointment

EXAMS - 4 exams = 450 points
• 1 hour exams
- Cumulative Final = • Trip to Washington DC
Dr. Nieto?
- Quizzes – 50 points
• Exams
returned within 1 week
TOTAL: 500 points • If concerns - 1 week to check with me.
FINAL GRADE: Follow the syllabus’s guidelines!!
Lab: 25% (300 points) • Review the whole exam
Lecture: 75% (500 points)
• No cell phones
• Be on time – back door!

Questions? Readiness Exam

1. Mention a difference between a Gram (+) and
Gram (-) bacteria
2. Provide one example of innate immunity?
3. What is a difference between an antigen and an
antibody?
4. What cells produce antibodies?
5. What cell(s) carry out phagocytosis?

The immune system:

How important is the
“A system of cells, tissues, and fluids that function to immune system?
protect the body from invasion by a wide range of
organisms - including viruses, bacteria, protozoans, fungi Individuals with significant
and worm”
defects in immunity (e.g.
AIDS, genetically inherited
E.coli bacteria adhering to
epithelial cells of the urinary tract. syndromes - “boy in the
- bubble”) - succumb rapidly
to infection.

- Gamma chain
- ADA (adenosine
deaminase)

David Vetter

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 The Immune System
Vaccination
Immunology
Functions:
-1) Recognition ----------- Effector Response
Smallpox
• Organism?
-2) Two Immunity Systems: • History
a) Innate
b) Acquired/Adaptive • Vaccination

14th – 17th centuries : variolation

used in China

-Powdered scabs of smallpox

pustules were inhaled (or rubbed
into scratches in the skin) to
protect from smallpox

17th century – practice spread to

Turkish regions
http://www.immunisation.org.uk/history.html

1718 – Lady Mary Wortley Montagu, wife of the British

ambassador to Constantinople, allowed her children to
be treated with this procedure
Europe

Edward Jenner

Variolation

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 Edward Jenner
- Meanwhile, it was commonly believed that
milkmaids who had had cowpox were resistant to
smallpox.

- Cowpox is a relatively benign disease in both

humans and cows.
Vaccination vs. variolation
- 1774 – Edward Jenner inoculated individuals with
- No risk of smallpox
cowpox in order to protect them from smallpox.
- Fewer side effects
Individuals receiving the cowpox did not develop
smallpox in subsequent outbreaks of the By 1800, vaccination was widely accepted.
disease. Why?
http://www.immunisation.org.uk/history.html

1880 - Pasteur experiment – fowl cholera

http://www.medinfo.ufl.edu/other/profmed/slides/pm012599/

1880 - Pasteur experiment – fowl cholera Pasteur’s Contributions:

-Vaccine (vacca= cow)

-Attenuated vaccines = cholera,
anthrax, rabies

Attenuated Vaccines!! http://www.medinfo.ufl.edu/other/profmed/slides/pm012599/

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 Early Studies of Humoral and
Cellular Immunity

Why do we still have measles, diphtheria, etc in the USA?

Experiments of von Behring and Kitasato - tetanus toxin

Protection can be transferred with serum.

Implication?
1

Shibasaburo Kitasato Emil von Behring

(1852-1931) (1854-1917)
3

SUMMARY:
1890 – Serum from animals previously immunized with diphtheria
could transfer the immune state to immunized animals
Serum – Liquid component of coagulated blood
2
TOXOID – modified toxin, unable to cause toxic effect but highly
antigenic
http://www.medinfo.ufl.edu/other/profmed/slides/pm012599/

Elvin Kabat
• Activity in serum associated with a fraction
1883 -Phagocytosis of microorganisms
called gamma globulin
• Gamma globulin fraction is also known as
immunoglobulin (Ig), which is also called
antibody (Ab)
Elie Metchnikoff
• Antibodies contained in body fluids (humor) (1845-1916)
– humoral immunity
http://pw1.netcom.com/~aguldo/agga/bt/pix/phagocytosis.jpg

Passive Immunity?
Cell-mediated immunity

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 Cellular Immunity Immunity
• 1940 – Merrill Chase transferred immunity
against tuberculosis by using white blood
cells Nonspecific mechanisms Specific mechanisms
• Lymphocytes: 2 types Innate Immunity Acquired Immunity

Humoral Cell-mediated
(Antibody mediated)
Antigen?

Infection and Immunity Innate Immunity

• I. Anatomic Barriers:
– Skin: keratin (waterproof), sebum (low pH),
• Pathogens – organisms that cause disease sweat (lysozyme)
• Opportunistic pathogens – decreased – Mucus membranes: mucus (X adherence),
immune function normal flora (space, nutrients, immunity), cilia
– Candida albicans – “thrush”
systemic
RIP (removes microorganisms), antimicrobial
– Pneumocystis pneumonia peptides (defensins)
• Respiratory, Genitourinary, Digestive.
• Immune system must deal with: viruses, • MUCUS – 4L/day
worms, fungi, bacteria, protozoa, toxins

Innate Immunity Adaptive or Acquired or Specific

• II. Physiologic Barriers: Immunity
– Chemical mediators:
• Lysozyme - (cell wall),
• Interferons - (anti-viral proteins),
• Complement - (lysis, phagocytosis, inflammation),
• Characteristics:
• Collectins - (detergent activity) a) highly specific (antigen),
• Pattern Recognition Receptors – (i.e Toll receptors –
recognition and activation)
b) diversity (109-11)potential recognitions,
• III. Phagocytic Barriers: c) memory,
– Phagocytosis – neutrophils, monocytes/ macrophages, d) self/non-self recognition (MHC molecules,
dendritic cells e) self-regulation (turning off responses)
• IV. Inflammation

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 Acquired Responses
Immune Response
(two phases) a) B cells:
- Originate and mature in bone marrow
• A) Recognition – Highly specific! - Mature B cells a unique receptor = antibody
molecule (Immunoglobulin = Ig)
- Membrane antibody molecule recognizes antigen
• B) Response (Effector Response)– through alone/intact
cells and molecules - 105 Ig molecules on membrane
- “Activated B cell”
polyclonal activation

– MEMORY!!! Plasma Cells
Secreted antibody.
**Memory B cells are generated in every
response

Acquired Responses
T cells:
- Originate in BM and mature in thymus
- In thymus they acquire a unique membrane receptor = T
cell receptor (TCR). The TCR recognizes antigen
ONLY when bound or presented by major
histocompatibility complex (MHC) molecules
- MHC restriction.
- Antigen + MHC
“Activated T cell”
polyclonal
activation
Memory T cells + Effector T Cells (cytokines
or cytotoxicity)
**Memory T cells are generated in every response

Acquired Responses
T cells subpopulations:
a) T helper (Th) and T cytotoxic (Tc)
- Th subpopulations:
- Tregs (regulatory T cells)
- Th17
b) T helper (Th) express a CD4 membrane marker
c) T cytotoxic (Tc) express a CD8 membrane marker

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 Acquired Responses
T cells subpopulations:
- T cytotoxic (Tc) express a CD8 membrane marker
- T helper (Th) express a CD4 membrane marker
- T helper (Th) cells interact with antigen presented
by MHC-II molecules
- Activation lead to secretion of cytokines

multiple effects
- T cytotoxic (Tc) cells interact with antigen
presented by MHC-I molecules
- Activation lead to cell killing (cytotoxicity)

MHC molecules Antigen presenting cells (APC)

• Three types: Macrophages, Dendritic cells
• Highly polymorphic genetic complex with and B cells
multiple loci
• Goal: processing, presentation and
• MHC loci encodes 2 surface molecules: activation of T cells
– Class I (MHC-I) – all nucleated cells
• Requirement:
– Class II (MHC-II) – ONLY in APC
– 1) Express MHC-II
• Role: – 2) Provide co-stimulatory signal for activation
– Self-recognition!
– 3) Cytokines for activation
– Bind antigen (peptides) and present it to T cells

Effector Response:
APC -B cells: Abs

-T cells:
Th cytokines APC

T helper Tc killing
1 a
2 c

b
4

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- T cell activation
-“Cross-presentation”
Clonal Selection Theory
- Antigenic peptides!!!
• Specificity of recognition receptors in B
(surface antibody) and T cells (T cell
receptor) is acquired in primary lymphoid
organs through a complex gene re-
arrangement event
• Mature T or B cells encounter the antigen and
only that cell with the respective “specificity”
is selected to undergo activation & expansion
leading to effector responses and memory
cell production
What T cells will be activated in each case?

Always! Primary and Secondary responses

Lucky
one!!!

Plasma cells

- Ab levels 100-1000-fold higher
more plasma cells generated!!!!

When things go wrong!

• Immune dysfunction can lead to:
– a) Allergy and Asthma: Sensitization to allergen
leading to allergic response
– b) Graft rejection and Graft versus host disease:
non-self rejection mediated by MHC molecules
– c) Autoimmune Disease: loss of self-recognition
leading to immunological attack (Crohn’s
disease, Rheumatoid arthritis, Multiple sclerosis)
– d) Immunodeficiency: loss of components from
innate and acquired immunity (AIDS)
- Natural VS Acquired

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 Conclusion

• The Innate and Adaptive immune systems

DO NOT operate independently.
• They are highly interactive and cooperative
systems whose combines responses is more
effective than either branch by itself.