Basic Immunology
and Disorders of The Immune System
Francisco G. La Rosa, MD

III. Immune mechanisms of tissue injury

A. Type I: Anaphylaxis or Immediate Hypersensitivity Reactions
B. Type II: Cytolytic Antibody Reactions
C. Type III: Immune Complex Mediated Reactions
D. Type IV: Cell Mediated Reactions

Although the immune system generally is protective, the same immunologic mechanisms that defend the host at times may result in severe damage to tissues and, occasionally, may cause death. Cell and Coombs have classified these damaging immunologic reactions (also called hypersensitivity reactions) into four major types: immediate hypersensitivity (type I) reactions, cytotoxic (type II) reactions, immune complex-mediated (type III) reactions, and delayed hypersensitivity (cell-mediated, type IV) reactions.

A. Type I: Anaphylaxis or Immediate Hypersensitivity reactions

Immediate hypersensitivity reactions involve the release of pharmacologically active substances, or mediators, from mast cells or basophils, a mechanism which is triggered by antigens reacting with preformed, cell-bound IgE molecules.

Allergens are antigens that induce production of specific IgE antibodies in humans.

IgE antibody (reagin). IgE production is firmly under the control of IgE-specific T cells, which can produce both IgE-potentiating and IgE-suppressing factors.


1. Histamine. It causes smooth muscle contraction and increased capillary permeability

2. Slow-reacting substance of anaphylaxis (SRS-A) contracts smooth muscle and increases capillary permeability, in a more prolonged manner.

3. Bradykinin. It causes smooth muscle contraction in a slow, prolonged manner, increases vascular permeability, and increases mucus secretion by mucous glands.

4. Serotonin (5-hydroxytryptamine) an important mediator of anaphylaxis in animals other than humans.

5. Eosinophil chemotactic factor of anaphylaxis (ECF-A). It attracts eosinophils to areas of allergic inflammation.

6. Platelet activating factor (PAF). It causes platelet aggregation and release of vasoactive amines, leading to increased vascular permeability, smooth muscle contraction, and bronchoconstriction.

7. Prostaglandins are products of cyclooxygenase metabolism of arachidonic acid. Prostaglandin E1 (PGE1) and PGE2 are potent bronchodilators and vasodilators. PGI2 (also called prostacyclin) disaggregates platelets.

Genetic factors: Hay fever, asthma, and food allergies, show familial tendency.

Clinical features:

1. Anaphylaxis refers to an immediate hypersensitivity response that is inducible in a normal host of any given species upon appropriate antigenic exposure (called sensitization). The response may be either systemic (anaphylactic shock) or local but in all species is primarily characterized by smooth muscle contraction and increased capillary permeability.

2. Atopy refers to an immediate hypersensitivity response that occurs only in genetically predisposed hosts upon sensitization to specific allergens. This condition differs from anaphylaxis in that it cannot be induced in normal hosts.


1. Avoidance

2. Hyposensitization

3. Administration of modified allergens, or "allergoids".

4. Drug treatment

a. Diphenhydramine

b. Corticosteroids

c. Epinephrine

d. Sodium cromolyn

e. Theophylline

B. Type II: Cytolytic antibody Reactions

Cytotoxic reactions involve primarily either the combination of IgG or IgM antibodies with epitopes on cell surface or tissue or the adsorption of antigens or haptens to tissue or cell membrane, with subsequent attachment of antibodies to the adsorbed antigens. Either mechanism may lead to one of the following destructive processes.

Activation of complement, with subsequent lysis or inactivation of target cells.

Phagocytosis of target cells, with or without complement activation.

Lysis or inactivation of target cells via effector lymphoid cells (e.g., ADCC)

Type II hypersensitivity reactions:

1. Transfusion reactions: Intravascular hemolysis of red blood cells usually is associated with ABO system incompatibility.

2. Extravascular hemolysis of red blood cells almost invariably is associated with Rh incompatibility.

3. Hemolytic disease of the newborn: Erythroblastosis fetalis occurs when Rh-negative mother gives birth to an Rh-positive infant, the Rh antigen having been acquired from an Rh-positive father. Sensitization may occur during pregnancy, if fetal blood leaks into the maternal circulation. After sensitization, IgG antibodies to the Rh0 (D) antigen are produced, which may cross the placenta and destroy fetal cells. The first child usually is not affected, but the chance sensitization increases with subsequent pregnancies.

4. Autoimmune hemolytic disease. Warm antibody hemolytic anemia, cold antibody hemolytic anemia, and paroxysmal cold hemoglobinuria.

5. White blood cell lysis

a. Systemic lupus erythematosus (SLE)

b. Granulocytopenia

c. Idiopathic thrombocytopenic purpura (ITP)

6. Nephrotoxic nephritis. Goodpasture's syndrome

7. Bullous diseases. Characterized by antibody and complement deposition in squamous intercellular spaces and along the basement membrane of the skin.

Therapy for cytotoxic reactions:

1. Suppression of the immune response.

2. Removal of offending antibodies.

3. Withholding the offending antibodies.

4. Nephrectomy.

C. Type III: Immune Complex Mediated Reactions

The pathogenesis of immune complex disorders involves an interplay of antigen, antibody, complement, and neutrophils.

Soluble immune complexes: Generally occurs in the region of antigen excess. Virtually any antigen that induces a detectable antibody response will serve. The antibodies involved are primarily precipitating IgG and IgM capable of fixing complement.

Immune adherence: Being soluble, the immune complexes escape phagocytosis, penetrate the endothelium of blood vessel walls (probably with the aid of vasoactive amines released from platelets and basophils), and are deposited on the vascular basement membrane.

Complement activation: In the formation of immune complexes, complement is activated with the release of factors that are chemotactic for neutrophils (i.e., C5a and C5b67); the neutrophils then infiltrate the area and release lysosomal enzymes that destroy the basement membrane of the vessels.

1. Arthus reaction

2. Serum sickness

3. Hypersensitivity pneumonitis

4. Poststreptococcal glomerulonephritis

5. Autoimmune disease. Rheumatoid arthritis and SLE.

D. Type IV: Cell Mediated Reactions

Delayed hypersensitivity (cell-mediated) tissue damage results from the interaction between sensitized T cells and specific antigen, which leads to the release of soluble effector substances called lymphokines, direct cytotoxicity, or both. This reaction is independent of antibody and complement but is dependent upon two types of functioning T cells: T4 + cells. Cells for delayed hypersensitivity and cells that help to produce cytotoxic/suppressor and T8 + cells.

Mediators of delayed hypersensitivity: It is known how many biochemically distinct lymphokines exist; however, the following are among those functionally recognized:

1. Migration inhibition factor (MIF) inhibits migration of macrophages.

2. Macrophage activation factor (MAF) enhances microbicidal and cytolytic activity of macrophages (gIFN).

3. Macrophage chemotactic factor stimulates infiltration of macrophages.

4. Transfer factor

5. Leukocyte inhibition factor (LIF) inhibits random migration of neutrophils.

6. Interleukin-2 stimulates growth of activated T cells; it is a mitogenic factor.

7. Lymphotoxin has the ability to lyse certain tumor cells.

8. Gamma interferon functions similarly to MAF.

a. Rejection of grafted tissues and organs.

b. Contact dermatitis

c. Autoimmune disease

Modulation of delayed hypersensitivity.

1. Suppressant agents

a. Corticosteroids

b. Antilymphocyte, or antithymocyte, serum

c. Cytotoxic immunosuppressive drugs

2. Enhancing agents

a. Thymic hormones

b. Levamisole

c. Isoprinosine

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