HYPERSENSITIVITY

dr R. Lia K. Iswara, MS, SpMK (K)

HYPERSENSITIVITY
A damage to host mediated by preexisting an abnormal immune response to self or foreign antigen

Reaksi Hypersensitivitas Tipe I-II-III-IV

Hypersensitivity (Allergy): Four Types of Hypersensitivity Reactions:

Type I: Anaphylactic/Immediate Reactions Type II: Cytotoxic Reactions Type III: Immune Complex Reactions Type IV: Cell-Mediated/delayed Reactions

Type I (Anaphylactic) Reactions

Occur

within minutes of exposure to antigen Antigens combine with IgE antibodies IgE binds to mast cells and basophils, causing them to undergo degranulation and release several mediators:

Type I (Anaphylactic) Reactions

Histamine:

Dilates and increases permeability of blood vessels (swelling and redness), increases mucus secretion (runny nose), smooth muscle contraction (bronchi). Prostaglandins: Contraction of smooth muscle of respiratory system and increased mucus secretion. Leukotrienes: Bronchial spasms.
Anaphylactic

shock: Massive drop in blood pressure. Can be fatal in minutes.

Mast Cells and the Allergic Response

Role of Mast Cells & Basophils

Mast cells located in the connective tissue of all organs (in lungs, skin, GI and genital tract) Basophils circulate in blood into tissues Each cell can bind 10,000-40,000 IgE Cytoplasmic granules contain active cytokines, histamine, etc Cells degranulate when stimulated by allergen

Chemical mediators

Mast Cells and the Allergic Response

Mechanism of Type I

Sensitizing dose first contact with allergen (specific B cells form IgE which attaches to mast cells and basophils) Provocative dose - subsequent exposure with the same allergen (binds to the IgE-mast cell complex) Degranulation : releases mediators with physiological effects (vasodilation and bronchoconstriction) Symptoms : rash, itching, redness, increased mucous discharge, pain, swelling, and difficulty breathing

Systemic Anaphylaxis
Sudden

respiratory and circulatory disruption that can be fatal in a few minutes Allergen and route are variable Bee stings, antibiotics or serum injection

Strategies for circumventing allergic attacks

Blocking Ab

Type II (Cytotoxic) Reactions

Involve

activation of complement by IgG or IgM binding to an antigenic cell. Antigenic cell is lysed. Transfusion reactions:
ABO

Blood group system: Type O is universal donor. Incompatible donor cells are lysed as they enter bloodstream.

Type II (Cytotoxic) Reactions

Rh

Blood Group System: 85% of population is Rh positive. Those who are Rh negative can be sensitized to destroy Rh positive blood cells.
Hemolytic disease of newborn: Fetal cells are destroyed by maternal anti-Rh antibodies that cross the placenta.

Immunopathology Definition - Type II reaction

Cytotoxic antibodies of IgM or IgG subtype formed against an antigen on a cell surface, or more rarely, against a component of the extracellular matrix. Usually, the binding of the antibody to the cellular antigen causes complement fixation (activation). The membrane attack complex (MAC) of complement then kills the cell.

Type III (Immune Complex) Reactions

Involve

reactions against soluble antigens circulating in serum. Antibody-Antigen immune complexes are deposited in organs, activate complement, and cause inflammatory damage.
Glomerulonephritis:

Inflammatory kidney

damage.
Occurs

with slightly high antigen-antibody ratio is present.

Immunopathology Definition - Type III reaction

Type III reactions involve immune complexes of antibody and antigen. Antibodies are of IgM or IgG type, but the antigen is usually a soluble antigen. Antibodies form immune complexes with these antigens, and the complexes are deposited in tissue activate complement. Kidney and skin are most often affected.

Immunopathology Type III hypersensitivity reaction

Immune complexes of ideal size are usually formed with slight antigen excess. Larger complexes removed by the mononuclear phagocyte system. Complexes likely induce disease by attaching to the Fc or C3b receptors on polymorphs, and trigger release of cytokines, attracting more PMNs, and initiating more complement fixation.

Immune Complex Mediated Hypersensitivity

SYSTEMIC LUPUS ERYTHEMATOSUS

Detection of immune complexes in serum

Type IV (Cell-Mediated) Reactions

Involve
First

reactions by TD memory cells.

contact sensitizes person. Subsequent contacts elicit a reaction.

Reactions
Delay

are delayed by one or more days (delayed type hypersensitivity).

is due to migration of macrophages and T cells to site of foreign antigens.

Type IV (Cell-Mediated) Reactions

Reactions

are frequently displayed on the skin: itching, redness, swelling, pain.

Tuberculosis skin test Poison ivy Metals Latex in gloves and condoms (3% of health care workers)

Anaphylactic

shock may occur.

Type IV Hypersensitivity
Cell-mediated A delayed response to Ag involving activation of and damage by T cells Delayed allergic response skin response to allergens tuberculin skin test, contact dermititis from plants, metals, cosmetics Graft rejection reaction of cytotoxic T cells directed against foreign cells of a grafted tissue; involves recognition of foreign HLA

Immunopathology
Transplant rejection
Mechanisms

involved in transplant

rejection
T

cell mediated delayed type hypersensitivity

Direct

pathway via recipient CD4+ and CD8+ recognition of MHC Class I antigens on donor APCs Indirect pathway whereby processing of antigen by the recipients APCs is required
Antibody

mediated immediate hypersensitivity

Allergic Contact Dermatitis Response to Poison Ivy Hapten

Contact dermatitis reaction to leather

Granuloma in a leprosy

Delayed hypersensitivity

Mechanism of damage in contact hypersensitivity

Comparison of hypersensitivity