Hypersensitivity

Assistant professor of
Microbiology and Medical Immunology

‫طه النصاري‬.‫ ) مناعت سريرة وامصال) د‬4 ‫مختبراث طبيت مستوى‬

 IMMUNOLOGICAL DISORDERS
Introduction
A. There are three types of immunological
disorders
1. Hypersensitivity
2. Autoimmune disease
3. Immunodeficiency
B. Hypersensitivity reactions to usually harmless
substances are often called allergies or allergic
reactions
IMMUNOLOGICAL DISORDERS

Type I Hypersensitivity
Definition :
Hypersensitivity refers
to the injurious
consequences in the
sensitized host
,Following contact
with specific Antigen
Allergens: antigens that cause allergic reactions
Hypersensitivity diseases: are conditions in which
tissue damage is caused by immune responses.
Classified by Gell & Coombs according to:
1. Antibody involved
2. Type of cell mediating the response
3. Nature of the antigen
4. Duration of the reaction
CLASSIFICATION

Most allergic reactions fall into one of four major

types depend on Coombs and Gell classification:
1. Type I: Immediate IgE-mediated
2. Type II: Cytotoxic(antibody-dependent)
3. Type III: Immune complex-mediated
4. Type IV: Delayed cell-mediated
 TYPE I HYPERSENSITIVITY
A. Also called IgE Mediated Hypersensitivity
B. Mechanism:
1. First exposure to antigen induces an IgE
antibody response leading to sensitization
A) Antigen is taken up by dendritic cells (APC)
and merged with MHC molecules
 TYPE I HYPERSENSITIVITY
B) APC presents the antigen to T-cells
C) Activated T-cells release cytokines that stimulate B-cells to
produce plasma cells which secrete large amounts of IgE
D) IgE antibodies bind to mast cell receptors and the individual is
now “sensitized”
TYPE I HYPERSENSITIVITY
 TYPE I HYPERSENSITIVITY
2. During the subsequent exposures, antigens
activate IgE antibodies on the mast cell causing
it to degranulate
A) Histamines, leukotrienes, prostaglandins, and/or cytokines are
released
B) These chemicals are the cause of hives, hay fever, asthma and
anaphylactic shock
3. Reactions generally occur within 30 minutes
of exposure
THE MEDIATORS OF TYPE I HYPERSENSITIVITY
 TYPE I HYPERSENSITIVITY
C. Localized Anaphylaxis
1. Hives – an allergic skin condition characterized by the formation
of a wheal and flare pattern
A) Frequently the result of seafood allergies
B) These reactions are due to the release of
histamine which causes dilation of tiny
blood vessels and the leaking of plasma
into the area
 TYPE I HYPERSENSITIVITY
2. Hay fever – itchy, teary eyes, sneezing, and
runny nose; occurs when allergic person
inhales an antigen rather than ingests it
A) also mediated by histamine
3. Asthma – inhaled allergen causes chemical
mediators from IgE to stimulate increased
mucus secretions and spasms of the bronchi
A) leukotrienes and prostaglandins are responsible
 TYPE I HYPERSENSITIVITY
D. Generalized Anaphylaxis
1. Antigen enters the bloodstream and becomes
widespread and the reaction affects almost the
entire body (systemic)
2. Loss of fluid from the blood vessels into tissues
causes swelling and possibly shock
3. Reactions may be fatal within minutes
4. Bee sting, peanut, and penicillin allergies
account for most cases
5. Can usually be controlled by epinephrine
injections
 Allergic Diseases Due to Specific Allergens and Their Clinical
Manifestations
Allergic Disease Allergens Clinical Findings
Allergic rhinitis Trees, grasses, Edema, irritation, mucus
(hay fever) dust, cats ,dogs, in nasal mucosa
mites
Systemic Insect stings, drug Bronchial and tracheal
anaphylaxis reactions constriction, complete
vasodilation and death
Food allergies Milk, eggs, fish, Hives and gastrointestinal
cereals, problems
grains
Asthma inhaled materials Bronchial and tracheal
constriction, edema, mucus
production, massive
inflammation
 TYPE I HYPERSENSITIVITY
E. Immunotherapy
1. Desensitization or immunotherapy is
often effective in decreasing the Type I
hypersensitivity state
E. Immunotherapy

Desensitization or immunotherapy
A) Repeated injections of very small amounts of
antigen are given over several months
B) This regimen leads to the formation of specific
IgG antibodies
C) The IgG reacts with antigen before it can bind
to IgE and therefore it blocks the IgE reaction
that might result in allergic reactions
Hypersensitivity II & III

Assistant professor of
Microbiology and Medical Immunology

‫طه النصاري‬.‫ ) مناعت سريرة وامصال) د‬4 ‫مختبراث طبيت مستوى‬

 Type II Hypersensitivity
A. Also called Cytotoxic Hypersensitivity
because it utilizes antibodies that can
destroy normal cells by complement lysis or
by antibody-dependent cellular cytotoxicity
(ADCC)
B. Generally occur within hours after
exposure
C. Transfusion Reactions – the ABO blood
groups are the major cause of hemolytic
anemia in blood transfusion patients
 Type II Hypersensitivity
1. Recall that persons with A type blood
possess the A antigen and the natural
antibody anti-B
2. Persons with B type blood possess the B
antigen and the natural antibody anti-A
3. Persons with O type blood lack both the A
and B antigens but possess both the natural
antibodies anti-A and anti-B
 Type II Hypersensitivity
4. Persons with AB type blood possess both the A
and B antigens but posses no natural antibodies
5. In the case of ABO incompatibility, the antibodies
cause reactions that include fever, low blood
pressure, pain, nausea, and vomiting
6. Cross-matching the bloods and other techniques
are used to ensure compatibility of donor and
recipient
 Type II Hypersensitivity
D. Hemolytic Disease of the Newborn
1. Also called Erythroblastosis fetalis
2. Results when mother is Rh- and baby is
Rh+
3. Upon delivery, Rh+ antigens are transferred
to the mother’s bloodstream which causes
her to produce anti-Rh antibodies
Transfusion
Reactions
are Type II
Reactions
Hemolytic Disease of the New Born is Caused by Type II Reactions
4. If the mother becomes pregnant again with an Rh+
child, the antibodies cross the placenta, enter the
circulation of the fetus, and cause extensive fetal
erythrocyte damage
5. RhoGAM may be administered to prevent this
reaction
A) contains Rh antibodies and prevents the
mother’s natural production of them
B) widely used at 28 weeks and after delivery
during all susceptible pregnancies
 Type III Hypersensitivity
A. Also called Immune Complex-Mediated
Hypersensitivity
B. Occurs within hours or days after exposure
C. When there is a slight excess of antigen,
the antigen-antibody complexes activate complements
and stimulate neutrophil and basophil degranulation
 Type III Hypersensitivity
1. Results in vasodilation, increased vascular
permeability, and inflammation
D. Small antigen-antibody complexes are often
deposited in the walls of small blood vessels in
skin, joints and kidneys where they continue to
cause inflammation and eventually tissue
damage
 Type III Hypersensitivity
E. The complexes can also precipitate causing clots to
form in the small blood vessels leading to failure or
death of the organ
1. Known as disseminated intravascular coagulation
F. Examples of Type III Hypersensitivity are:
1. Arthus reaction – localized tissue death
A) ex. Chronic Obstructive Pulmonary Disease
(COPD)
2. Serum sickness – seen in individuals
immunized/treated with animal serum
Immune-Complex Diseases
Formation of circulating immune complexes contributes to
the pathogenesis of a number of conditions other than
serum sickness. These include the following:
1. Autoimmune diseases
■ Systemic lupus erythematosus (SLE)
■ Rheumatoid arthritis
2. Drug reactions
■ Allergies to penicillin and sulfonamides
3. Infectious diseases
■ Post streptococcal glomerulonephritis
■ Meningitis
■ Hepatitis
■ Infectious mononucleosis
■ Malaria
■ Trypanosomiasis
Type III Localized Type III Reaction
- Arthus Reaction
Hypersensitivit
y
tissue
damage
Generalized Type III Reaction – Serum
Sickness
fever, weakness, rashes,
edema, erythema,
arthritis,
glomerulonephritis
 Type IV Hypersensitivity

Assistant professor of
Microbiology and Medical Immunology

‫طه النصاري‬.‫ ) مناعت سريرة وامصال) د‬4 ‫مختبراث طبيت مستوى‬

 Type IV Hypersensitivity
 Also called Delayed Cell-Mediated
Hypersensitivity
1. occurs within days after exposure
 T-cells rather than antibodies are involved
with this type
 Examples of delayed hypersensitivity are:
1. Tuberculin skin test
2. Contact hypersensitivity
3. Delayed hypersensitivity to infectious diseases
(Granulomatous Lesion)
 Type IV Hypersensitivity
Pathogenesis:
 T- cell cause tissue injury either by :
A. Triggering DTH reaction by TH1 cell.
B. Directly killing target cells by CD8 T cell.
 Both cells secret cytokines (IFN- and TNF) Leading to :
1. Attract lymphocytes.
2. Activate macrophages.
3. Induce inflammation
 The tissue damage occurs within days after exposure
Mechanisms of T cell-mediated tissue injury
 Example of Type IV Hypersensitivity
1. Tuberculin skin test:
– a positive test results when circulating antibodies (which are
only present if the person has been exposed) bind to the protein
antigens of the tuberculosis bacteria introduced under the skin
(PPD: purified protein derivative of tubercle bacilli)
A) Local induration area appears after 48- 72 hours after
exposure to PPD protein.
B) the redness results mainly from sensitized T-cell reactions,
the release of cytokines and the influx of macrophages to
the injection site
C) false positive tests can result from exposure to another
species of Mycobacterium or use of the BCG vaccine
Example of Type IV Hypersensitivity
Tuberculin skin test
 Example of Type IV Hypersensitivity

2. Contact hypersensitivity :
– mediated by T-cells that release cytokines when they come
into contact with the same antigen
 the cytokines cause inflammation which attracts WBC
to the site
 these then release chemicals that result in allergic
dermatitis or contact dermatitis (eczema, rash and
vesicular eruptions)
 Examples:
1. Poison Ivy,
2. Poison Oak,
3. Nickel Reactions,
4. And Latex Reactions
5. Hair dyes
6. Neomycin skin ointment
7. Soaps
Example of Type IV Hypersensitivity
Contact Dermatitis
Allergic Contact Dermatitis Response to Poison Ivy
 Example of Type IV Hypersensitivity

3. Delayed hypersensitivity to infectious diseases:

 Due to intracellular organisms that resist destruction by macrophages
such as the following:
1. Leprosy,
2. Tuberculosis,
3. and Herpes Simplex Infections
4. Schistosomiasis
 The persistent antigens in tissue especially in macrophages lead
to :
1. Stimulate a chronic local delayed hypersensitivity
2. Continues release of cytokines
3. Formed epitheloidal and giant cell
4. Then granuloma formation----------- appear as caseation and
cavitation in tissues
– as T-cells destroy macrophages and sick body cells, tissue damage results
Granuloma Formation from DTH
Mediated by Chronic Inflammation
 Clinical
Type Fig 5Reaction
time
appearanc
Histology
Antigen and site
e

epidermal (
lymphocytes,
organic
followed by
chemicals,
Contact 48-72 hr eczema macrophag
poison ivy,
es; edema
heavy metals,
of epidermis
etc.)
lymphocytes,
local intradermal
Tuberculi monocytes,
48-72 hr indurati (tuberculin,
n macrophag
o lepromin, etc.)
es
macrophages, persistent antigen
epitheloid or foreign body
Granulom 21-28
hardening and giant presence
a days
cells, (tuberculosis,
Introduction to Autoimmunity

Assistant professor of
Microbiology and Medical Immunology

‫طه النصاري‬.‫مختبراث طبيت ) مناعت طبيت) د‬

Introduction to Autoimmunity
 Autoimmunity is a condition when the body
produces autoantibodies and immunologically
competent T lymphocytes against its own tissues.

 Conditions where the mechanisms of self-tolerance

fail are termed as autoimmune disorders and the
Phenomenon is called autoimmunity.
 Tolerance:
is a state of specific immunological unresponsiveness
to a certain antigen or epitope.
 Mechanisms of Tolerance
Both T cells and B cells participate in tolerance, but it
is T-cell tolerance that plays a major role.
◗ T-cell tolerance
T-cell tolerance is explained by theories of (a) clonal
deletion,(b) clonal anergy, and (c) clonal ignorance.
◗B-cell tolerance
B cells become tolerant to self-antigens also by (a)
clonal deletion of B-cell precursors while they are in
the bone marrow and (b)clonal anergy of B cells in the
periphery.
 Pathogenesis of Autoimmunity

 Mechanisms
The following mechanisms have been proposed for
pathogenesis of autoimmunity:
1. Release of sequestrated antigens
2. Antigen alteration
3. Epitope spreading
4. Molecular mimicry
◗ Release of sequestrated antigens
 Certain tissues, such as
1. Sperm.
2. Central nervous system.
3. And the lens and uveal system of the eye.
are sequestrated or hidden.
 These sites are normally never exposed to the
immune system for various reasons.
 These are called immunologically privileged
sites.
◗ Antigen alteration
 Certain
1. physical,
2. chemical,
3. or biological factors
may alter tissue antigens, resulting in formation of new
cell surface antigens called neoantigens.
 These neoantigens are no longer recognized as self,
therefore, appear foreign to immune system, thereby
eliciting an immune response.
 Procainamide-induced SLE is an example of an
autoimmune disease caused by this mechanism.
 ◗ Epitope spreading
 Epitope spreading:
 is the term used to describe the new exposure of
sequestrated autoantigens as a result of damage to
cells caused by viral infections.
 It is another process that is believed to contribute to
pathogenesis of autoimmunity.
 These newly exposed autoantigens or epitopes
stimulate autoreactive
 Molecular mimicry
Molecular mimicry is a process in which
infection by particular microbial pathogen is
associated with the subsequent development of
specific autoimmune diseases.
Examples:
- Acute Rheumatic Fever
due to group A streptococcus.
- Stromal keratitis
due to herpes simplex virus type I
- SLE due Epstein-Barr virus
cross reactive with nuclear Sm antigen
-Lyme arthritis due Borrelia burgdorferi reactive with
LFA-1 (lymphocyte function antigen-1)
Autoimmune Pathological Process
 The autoimmune pathological process may be
initiated and maintained by:
(a) Autoantibodies,
(b) Immune complexes containing
autoantigens,
(c) Autoreactive T lymphocytes.
 The autoimmune diseases can be broadly
classified as
(a) Organ-specific autoimmune disease and
(b) Systemic autoimmune diseases
 Organ-specific autoimmune disease
 These are diseases in which autoantibodies are produced
targeting only the tissue of a single organ.
 Examples:
• Addison’s disease, autoimmune hemolytic anemia,
• Goodpasture’s syndrome, Graves’ disease,
• Hashimoto’s thyroiditis, idiopathic thrombocytopenic
purpura,
• insulin-dependent diabetes mellitus, myasthenia gravis,
• pernicious anemia, poststreptococcal glomerulonephritis,
 These diseases can be further sub grouped on the basis of
tissue damage as diseases mediated by :
(a) The action of cell mediated immunity and
(b) The action of autoantibodies.
Organ-specific autoimmune disease
Systemic autoimmune diseases
Definition of transplantation:
The practice of grafting tissues or organs from
one individual to another or from one part of the
body to another in the same individual.
IMPORTANCE:
Replacement of a non-functional organ by
another healthy one . transplantation may be
life saving.
 Types of graft

Allograft Xenograft
Autograft Isograft (homograft ) (heterograft)
Barriers to transplantation:
- The main obstacle of transplantation is the occurrence of
genetic and antigenic disparity between individuals of the
same species.
- This antigenic difference leads to stimulation of an
immune response that cause rejection of the transplanted
organ.
- Rejection is due to mainly recognition by the immune
system of the recipient of the MHC class I and II antigens
of the donated organ.
- Minor histocompatiblity antigens.
GRAFT REJECTION:
Rejection is an immune response against the
grafted tissue. The process can be divided into
two stages :
Sensitization phase:
lymphocytes of the recipient recognize and
proliferate in response to alloantigens on the
graft (recognition phase)
Effector stage:
in which immune destruction of the graft takes
place (rejection phase) .
Sensitization PHASE:
- T cells have the central role in rejection.
- T cells recognize the donor MHC molecules
and the associated peptides.
- Donor MHC may be presented by either of 2
ways:
1- on donor APCs which are present in the
grafted organ as passenger leucocytes
(interstitial dendritic cells) (direct pathway)
2- by the host APCs that enter the graft (indirect
pathway).
REJECTIN PHASE :
- activated TH cells produce cytokines:
*IL-2 + INFy activate TC cell direct
damage of the graft .
*INFy + TNFβ activate macrophages,
cellular infiltration destruction of the
graft (delayed hypersensitivity reaction ).
• macrophages release TNFα direct graft
damage.
• IFNy and TNF induce MHC expression,
increasing APCs activity
- B cells recognize foreign antigens on the graft
and with the help of TH lymphokines IL2, IL 4,5,6
become activated Abs which bind to
grafted cells:
● fix complement lysis
● opsonization
● ADCC (type II hypersensitivity reaction).
- immune complex deposition on vessel walls,
damage for endothelium by neutrophils,
hemorrhage, platelet aggregation, graft thrombosis,
ischemia and necrosis of the graft ( type III HR
 According to the speed of graft damage,
rejection is classified into

1- Hyper acute rejection : occurs minutes or

hours after grafting in patients with preformed
antibodies either due to ABO incompatibility or
previous sensitization by blood transfusion,
multiple pregnancies or the rejection of a
previous transplant . Mechanism of damage is
through type II hypersensitivity
2- accelerate rejection: occurs within few
days. It is due to presence of presensitized T
Cells (type IV H).
3- acute rejection: takes weeks to few
months and is due to the primary activation
of T cells (type IV H).
4- chronic rejection: occurs slowly over a
period of months or years . it may be cell
mediated , antibody mediated or both
 Hyper
acute
rejection

Types
Chronic Acute
of
rejection rejection
rejection

Accelerate
rejection
Graft versus host (GVH) reaction:
- occurs when immunologically competent graft
e.g. bone marrow is transplanted into
immunologically suppressed recipient. T cells
in the transplant see the host as "foreign" and
proceed to mount a widespread attack against
the tissues of the host.
Symptoms:
fever, diarrhea, weight loss, rash, pancytopenia,
hepatosplenomegaly, jaundice and death .
Acute GVH disease:
occurs within days to weeks after transplantation .
Chronic GVH disease:
may follow the acute syndrome or may occur insidiously.
• Cord blood, another source of stem cells, presents less
risk of serious GVHD even from a donor with HLA
molecules not present in the recipient as cord blood does
not contain mature T cells.
Prevention:
- Removal of T cells from marrow graft using Ant-CD3
monoclonal antibodies.
- Immunosuppressive drugs
 PREVENTION OF
GRAFT REJECTION

POST ORATIVE
IMMUNOSUUREESIVE
PROPER CHOICE ANTIGEN SPECIFIC
OF DONOR IMMUNOSUPPRESSION
DRUG

ABO blood group Tissue typing

Serologic typing MLR

Molecular HLA typing

Cross matching
A- Proper choice of donor:
1- ABO blood group compatibility.
2- Tissue typing for histocompatibility antigen
a- Serologic typing ( lymphocytotoxicity assay):
- For MHC class I as well as class II DQ and
DP proteins.
- Done by reacting lymphocyte from donor and
recipient with antibodies against HLA in the
presence of complement . Lysis of lymphocytes
indicates that they contain the antigen .
b– Mixed lymphocyte reaction ( MLR ):
- When lymphocytes from an individual are cultured
with lymphocytes from an unrelated individual,
they are stimulated to proliferate due to a disparity
in the class II MHC (DR) antigens.
used for studying the degree of histocompatibility:
- T lymphocytes from the recipient are mixed in
cell culture with irradiated or mitomycin C treated
leukocytes from the donor, containing B-
lymphocytes and monocytes (stimulator cells) for
4-6 days.
• Contin. Mixed lymphocyte reaction ( MLR ):
- when responder T cells recognize foreign class II
antigens on the donor, they undergo
transformation, DNA synthesis and proliferation.
These changes are recorded by the addition of
radioactive thymidine into the culture and
monitoring its incorporation into DNA.

• Can be used to determine class II MHC DR

proteins using the homozygous cell typing.
c- Molecular HLA typing (genotyping of transplant
epitopes):
- the most commonly used technique.
- based on amplification of DNA segments on
chromosome 6 carrying the genes for HLA
class I and II by PCR . The amplified product
may be further identified by DNA probes or by
sequencing.
* Tissue typing is usually limited to looking
for 6 HLA antigens: the two each at HLA-A,
HLA-B, and HLA-DR.
3- Cross matching:
is used to test the recipient's serum for the
presence of preformed antibodies (cytotoxic
antibodies) against the donor's HLA antigens.

Recipient preparation
- The recipient must be infection-free and must not
be hypertensive.
- about five transfusions of 100-200 ml whole
blood from the donor at 1-2 week intervals
improves the graft survival.
B– Postoperative immunosuppressive therapy
1- Immunosuppressive drugs:
a) Anti–inflammatory corticosterids given at
large doses after transplantation and reduced to
small doses to maintain therapy. Corticosteroids
interfere with a transcription factor needed to
turn on the genes for T cells to become
activated.
b) Cyclosporine A (neoral) and tacrolimus (FK-
506) natural products isolated from certain fungi.
They inhibit the signaling pathway used by T cells
for genes activation, e.g., for IL-2 secretion.
b) Rapamycin (rapaimmun) is a macrolide
antibiotic produced by an actinomycete and
inhibits T cell proliferation by blocking IL2-
IL2R signaling.
d) Mycophenolate mofetil (cellcept): block
lymphocytes peoliferation and maturation
through inhibition of an enzyme needed by B and
T cells for purine synthesis. Other types of cells
are not dependent on this enzyme with few toxic
effects.
e) Antimitotic drugs (purine analogue) as
azathioprine (immuran) and methotrexate
2- Monoclonal antibodies:
1- OKT3, anti-CD3 monoclonals. These lyses T cells and
block their function .
2- Daclizumab and basiliximab. Anti-IL-2 receptor
antibodies and thus inhibit only activated T cells.
3- Alemtuzumab (Campath-1H). Binds to CD52, a molecule
found on lymphocytes and depletes both T cells and B
cells.
4- anti-CD40L antibody which blocks T cell proliferation
by blocking co-stimulatory molecules
C– Antigen specific immunosuppression
by induction of tolerance to the graft antigen (under
trial).
- Hyper acute :
only by removal of the organ immediately .
- Chronic :
irreversible and can not be prevented only
treatment is a new transplant after 10 years .
- Acute :
1- high dose corticosteroids
not enough
2- repeated
not enough
3- triple therapy
 Tumor Immunology

Assistant professor of
Microbiology and Medical Immunology

‫طه النصاري‬.‫مختبراث طبيت ) مناعت طبيت) د‬

Tumor Immunology
 Tumor immunology has been defined as part of
immunology that deals with the antigens on tumor
cells and the immune response to them.

 A tumor that is not capable of indefinite growth and

does not invade the healthy surrounding tissue
extensively is benign.
 A tumor that continues to grow and becomes
progressively invasive is malignant; the term cancer
refers specifically to a malignant tumor.
 Features of Malignant Cells
Malignant cells show the following features:
1. Once cells become malignant, they stop functioning
normally and add to the burden on the body by competing
with the normal cells for space and nutrition.
2. The more “undifferentiated” a cell is, the lesser its
functionality and more its malignant nature.
3. They undergo rapid and uncontrolled division.
4. They lose their homing instinct and start invading the
basement membrane and enter the vasculature to spread to
dissimilar tissues, leading to metastasis and spread of cancer.
 ◗ Tumor Antigens

 Tumor cells also express unique molecules

that can be classified into two groups:

 1. Tumor-specific antigens
 2. Tumor-associated transplantation antigens
◗Tumor-specific antigens

 The tumor-specific antigens (TSAs), also called tumor-specific

transplantation antigens, are unique to tumors.
 They are not found on other cells of the body. They are usually
the products of mutated genes seen in the cancer cells.
 Cytosolic processing of the abnormal proteins yields peptides that
are unique and when presented by the appropriate MHC class I
molecules elicit a cell-mediated immune response.
 Another mode through which the tumor cells may express unique
and novel antigens “is by” integration with proviral genomes.
 ◗Tumor-associated transplantation antigens
 Tumor-associated transplantation antigens (TATAs)
are the other class of tumor antigens. These antigens
are expressed by
 (a)tumor cells and also by
 (b) normal cells at low levels or only during the
process of differentiation.
Antigens of tumors that are capable of eliciting an immune
response may be one of the following nature:
■ First, these antigens are uniquely expressed by tumor cells
alone. Also, there are the products of genes that have been
mutated during the process of transformation, leading to
the expression of abnormal products.
■ Second, certain antigens expressed by tumors are present
only when normal cells are undergoing the process of
differentiation and these are also readily recognized by the
Immune system.
■ Finally, the antigens that are overexpressed by the tumor
cells elicit a good immune response.
Immune Reactions against Tumors
Tumor antigens are capable of eliciting a comprehensive
immune response involving both the cellular and humoral
immune responses.
 ◗ Cellular immune responses
T lymphocytes play an important role in tumor immunity.
They act both as cytotoxic effector cells and as central
modulating cells.
Through these effector cells, they control the specific cell
mediated antitumor immune responses and up regulate
nonspecific killing mechanisms.
The activation of T lymphocytes by tumor cell products as a
consequence of antigen recognition may result in the
secretion of nonspecific immunoregulatory factors.
 Nonspecific immunoregulatory factors
■These factors are capable of “upregulating” the tumor
killing function of mononuclear phagocytes, NK cells, and
granulocytes.

■ These factors also enhance the ability of NK cells and

monocytes to participate in ADCC against tumor cells.
■ Macrophages also play an important role in tumor
response. Clustering of macrophages around tumor cells
is associated with tumor regression and seen in the case of
numerous cancers.
 ◗ Humoral immune responses
 B lymphocytes produce tumor-specific antibodies,
which may induce complement-dependent cytotoxicity
of tumor cells or may mediate ADCC.
 ADCC can be mediated by a variety of cells expressing
Fc receptors (NK cells, monocytes or macrophages, and
granulocytes) by recognizing and destroying IgG-
coated tumor cells.