Anda di halaman 1dari 25

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.


• Neutrophils - is microbe killing phagocyte. These
cells are released in the large numbers during
acute infection.
• Eosinophils - used selectively for fighting
parasitic infection. Eosinophils also participate in
immediate hypersensitivity (allergic) reactions.
• 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

• Type I hypersensitivity (Immediate Hypersensitivity)

• Type II hypersensitivity (Antibody-mediated disorder)

• Type III hypersensitivity (Immune complex-mediated disorder)

• 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:

• transfusion reactions

• erythroblastosis fetalis

• autoimmune hemolytic anemia,


agranulocytosis, and thrombocytopenia

• 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

• formation of antigen-antibody
complexes in the circulation;

• deposition of the immune complexes


in various tissues, thus initiating; and

• 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.

Anda mungkin juga menyukai