Disorders of Immunity Hypersensitivity Reactions: Dr. Mehzabin Ahmed

Disorders of Immunity
Hypersensitivity Reactions
Dr. Mehzabin Ahmed

THE IMMUNE SYSTEM IN HEALTH & DISEASE
 The immune system enables  The most common clinical

us to recognize self from problems are:
non-self and thereby confer  Overactivity of the
protection against disease
 It is made up of complex
immune response
network of leading to allergic and
 Lymphocytes
autoimmune disease.
 Underactivity -
 in tonsils, lymphnodes,
thymus, spleen and resulting in
bone marrow, immunodeficiency.
 Monocytes and  Inappropriate activity
macrophages of the immune system
 Plasma proteins resulting in
 Cytokines (Chemical autoimmune disorders
messengers)
The immune system in health:
 Innate immunity: Consists of the rapidly acting (front line) host
defense mechanism and includes both physical as well as elements
of immune system. They are:
a) Physical or chemical barriers: Skin and mucus membrane,
Gastric acid, lactoferrin, nitric oxide in secretions
b) Mechanical removal: Sneezing, coughing, Secretions and urine,
Ciliary escalator of respiratory mucosa
c) Non specific immune system: Phagocytes, NK cells,
Complement, Interferon
d) Colonization resistance: Present in the skin and G.I.T. of
normal flora preventing colonization by pathogenic organism.
Phagocytes:
 They provide the first line of defense.

a) Neutrophils - is microbe killing phagocyte. These
cells are released in the large numbers during
acute infection.
b) Eosinophils - used selectively for fighting
parasitic infection. Eosinophils also participate in
immediate hypersensitivity (allergic) reactions.
c) Macrophages – destroy bacteria and foreign
bodies
Disorders of the Immune System
1. Hypersensitivity reactions
2. Autoimmune diseases
3. Immunologic deficiency syndromes
4. Amyloidosis
Hypersensitivity reactions
1. Type I hypersensitivity (Immediate Hypersensitivity)
2. Type II hypersensitivity (Antibody-mediated disorder)
3. Type III hypersensitivity (Immune complex-mediated disorder)
4. Type IV hypersensitivity (Cell-mediated immune disorder)

Immediate, or Type I, Hypersensitivity
 occurring within minutes after the
combination of an antigen with an
IgE antibody bound to mast cells in
individuals previously sensitized to
the antigen
 Activation of the mast cells in type I
hypersensitivity causes release of
their mediators
 Common examples are bronchial
asthma, urticaria/ hives,
anaphylactic shock
Many local type I hypersensitivity reactions have
two well-defined phases
 The immediate, or initial, response within 5 to 30 minutes is characterized by

 vasodilation,
 vascular leakage, and
 smooth muscle spasm or
 glandular secretions.
 Due to release of primary mediators.
 The late-phase reaction sets in 2 to 24 hours later is characterized by

 infiltration of tissues with eosinophils, neutrophils, basophils, monocytes, and
CD4+ T cells as well as
 tissue destruction, typically in the form of mucosal epithelial cell damage due to
release of secondary mediators.
Type II hypersensitivity
 Type II hypersensitivity is mediated by antibodies
directed toward antigens present on cell surfaces or

extracellular matrix.
 Three different antibody-dependent mechanisms
involved in this type of reaction are described.

1. Opsonin and Complement-and Fc
Receptor-Mediated Phagocytosis
When antibodies are deposited on the surfaces of cells, they may

activate the complement system (if the antibodies are of the
IgM or IgG class).
Complement activation on cells also leads to the formation of the

membrane attack complex, which causes lysis of the cells
In addition, cells opsonized by IgG antibodies are recognized by

phagocyte Fc receptors, which are specific for the Fc portions
of some IgG subclasses. The net result is the phagocytosis of
the opsonized cells and their destruction
A. Complement-dependent reactions that lead to lysis of
cells or render them susceptible to phagocytosis.
Clinically, antibody-mediated cell destruction and
phagocytosis occur in the following situations:
(1) transfusion reactions
(2) erythroblastosis fetalis
(3) autoimmune hemolytic anemia,

agranulocytosis, and thrombocytopenia
(4) certain drug reactions

2. antibody-dependent cellular cytotoxicity (ADCC)
 Antibody-mediated
destruction of cells may
occur by another
process
 IgG coated target cells

are killed by cells that
bear Fc receptors for
IgG (e.g., NK cells,
macrophages).
3. Antibody-Mediated Cellular Dysfunction
 In some cases, antibodies directed against cell-surface receptors impair

or dysregulate function without causing cell injury or inflammation.
 For example, in myasthenia gravis,
 antibodies reactive with acetylcholine receptors in the motor end-
plates of skeletal muscles impair neuromuscular transmission and
therefore cause muscle weakness.
 The opposite i.e., antibody-mediated stimulation of cell function is noted
in Graves disease.
 In this disorder, antibodies against the thyroid-stimulating hormone
receptor on thyroid epithelial cells stimulate the cells, resulting in
hyperthyroidism.
Antireceptor antibodies disturb the normal function of receptors.
In this example, acetylcholine receptor antibodies impair neuromuscular

transmission in myasthenia gravis.
Type lll hypersensitivity reaction
 Two general types of antigens cause immune complex-mediated
injury:
(1) The antigen may be exogenous, such as a foreign protein, a

bacterium, or a virus; or
(2) Under some circumstances, the individual can produce antibody

against self-components-endogenous antigens
Examples of Immune Complex-Mediated Diseases
Clinicopathologic
Disease Antigen Involved Manifestations
Systemic lupus DNA, nucleoproteins, others Nephritis,
erythematosus arthritis, vasculitis
Polyarteritis nodosa Hepatitis B virus surface antigen (in some cases) Vasculitis
Poststreptococcal Streptococcal cell wall antigen(s); may be Nephritis

glomerulonephritis "planted" in glomerular basement membrane
Acute Bacterial antigens (Treponema); parasite antigens Nephritis

glomerulonephritis (malaria, schistosomes); tumor antigens
Reactive arthritis Bacterial antigens (Yersinia) Acute arthritis
Arthus reaction Various foreign proteins Cutaneous vasculitis
Serum sickness Various proteins, e.g., foreign serum (anti- Arthritis,

thymocyte globulin) vasculitis, nephritis
The pathogenesis of systemic immune complex disease
can be divided into three phases
(1) formation of antigen-antibody

complexes in the circulation;
(2) deposition of the immune complexes

in various tissues, thus initiating; and
(3) an inflammatory reaction at the sites

of immune complex deposition
Schematic illustration of the three sequential phases in
the induction of systemic type III (immune complex) hypersensitivity.
Circulating immune Complexes (CIC)
 Large complexes formed in great antibody excess are
rapidly removed from the circulation by the

mononuclear phagocyte system and are therefore
relatively harmless.
 The most pathogenic complexes are of small or
intermediate size (formed in slight antigen excess),

which bind less avidly to phagocytic cells and
therefore circulate longer.
Deposition of CICs
 In addition to the renal glomeruli, the favored sites of
immune complex deposition are joints, skin, heart,
serosal surfaces, and small blood vessels.
 They produce vasculitis, arthritis, endocarditis,
glomerulonephritis, pericardial and pleural effusions

Cell-Mediated (Type IV) Hypersensitivity
 The cell-mediated type of hypersensitivity is initiated by
antigen-activated (sensitized) T lymphocytes.

 It includes the
 delayed type hypersensitivity reactions mediated by CD4+

T cells
 direct cell cytotoxicity mediated by CD8+ T cells.

Delayed type hypersensitivity reactions
 The reaction is mediated by CD4+
helper T cells
 T cell–derived cytokines give rise
to the formation of granuloma

in type IV hypersensitivity
reactions.
 Commonly seen in TB, Leprosy

A section of a lymph node shows several granulomas, each
made up of an aggregate of epithelioid cells and
surrounded by lymphocytes. The granuloma in the center
shows several multinucleate giant cells.
Mantoux Test
 The classic example of delayed hypersensitivity is the
tuberculin reaction,
 It is produced by the intracutaneous injection of
tuberculin, a protein-lipopolysaccharide component of
the tubercle bacillus.
 In a previously sensitized individual, reddening and
induration of the site appear in 8 to 12 hours, reach a
peak in 24 to 72 hours, and thereafter slowly subside.

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What are the different types of hypersensitivity reactions?

What are the different types of hypersensitivity reactions?

What are the phases of immune complex mediated disease?

What are the phases of immune complex mediated disease?

Disorders of Immunity

Dr. Mehzabin Ahmed

 The immune system enables  The most common clinical

 They provide the first line of defense.

3. Immunologic deficiency syndromes

1. Type I hypersensitivity (Immediate Hypersensitivity)

2. Type II hypersensitivity (Antibody-mediated disorder)

3. Type III hypersensitivity (Immune complex-mediated disorder)

4. Type IV hypersensitivity (Cell-mediated immune disorder)

 The immediate, or initial, response within 5 to 30 minutes is characterized by

 The late-phase reaction sets in 2 to 24 hours later is characterized by

 Type II hypersensitivity is mediated by antibodies

directed toward antigens present on cell surfaces or

 Three different antibody-dependent mechanisms

involved in this type of reaction are described.

When antibodies are deposited on the surfaces of cells, they may

Complement activation on cells also leads to the formation of the

In addition, cells opsonized by IgG antibodies are recognized by

(1) transfusion reactions

(2) erythroblastosis fetalis

(3) autoimmune hemolytic anemia,

(4) certain drug reactions

 IgG coated target cells

 In some cases, antibodies directed against cell-surface receptors impair

In this example, acetylcholine receptor antibodies impair neuromuscular

 Two general types of antigens cause immune complex-mediated

(1) The antigen may be exogenous, such as a foreign protein, a

(2) Under some circumstances, the individual can produce antibody

Poststreptococcal Streptococcal cell wall antigen(s); may be Nephritis

Acute Bacterial antigens (Treponema); parasite antigens Nephritis

Reactive arthritis Bacterial antigens (Yersinia) Acute arthritis

Arthus reaction Various foreign proteins Cutaneous vasculitis

Serum sickness Various proteins, e.g., foreign serum (anti- Arthritis,

(1) formation of antigen-antibody

(2) deposition of the immune complexes

(3) an inflammatory reaction at the sites

 Large complexes formed in great antibody excess are

rapidly removed from the circulation by the

 The most pathogenic complexes are of small or

intermediate size (formed in slight antigen excess),

immune complex deposition are joints, skin, heart,

serosal surfaces, and small blood vessels.

 They produce vasculitis, arthritis, endocarditis,

glomerulonephritis, pericardial and pleural effusions

 The cell-mediated type of hypersensitivity is initiated by

antigen-activated (sensitized) T lymphocytes.

 delayed type hypersensitivity reactions mediated by CD4+

 direct cell cytotoxicity mediated by CD8+ T cells.

 The reaction is mediated by CD4+

 T cell–derived cytokines give rise

to the formation of granuloma

 Commonly seen in TB, Leprosy

 It is produced by the intracutaneous injection of

tuberculin, a protein-lipopolysaccharide component of