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Hypersensitivity

Altered immunologic response to an antigen that results in disease or damage to the host

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Hypersensitivity (cont’d)

Allergy Deleterious effects of hypersensitivity to

environmental (exogenous) antigens Autoimmunity

Disturbance in the immunologic tolerance of self-antigens

Alloimmunity Immune reaction to tissues of another

individual

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Hypersensitivity (cont’d)

Characterized by the immune mechanism: Type I

• IgE mediated Type II

• Tissue-specific reactions Type III

• Immune complex mediated Type IV

• Cell mediated

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Hypersensitivity (cont’d)

Immediate hypersensitivity reactions Anaphylaxis Delayed hypersensitivity reactions

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Type I Hypersensitivity

IgE mediated Against environmental antigens (allergens) IgE binds to Fc receptors on surface of

mast cells (cytotropic antibody) - “sensitized”

Histamine release H1 and H2 receptors Antihistamines

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Type I Hypersensitivity (cont’d)

Manifestations: Itching Urticaria Conjunctivitis Rhinitis Hypotension Bronchospasm Dysrhythmias GI cramps and malabsorption

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Type I Hypersensitivity (cont’d)

Genetic predisposition- atopic Tests:

Food challenges Skin tests Laboratory tests

Desensitization Cautiously

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Type I Hypersensitivity (cont’d)

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Type II Hypersensitivity

Tissue specific Specific cell or tissue (tissue-specific antigens)

is the target of an immune response

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Type II Hypersensitivity (cont’d)

Five mechanisms: Cell is destroyed by antibodies and

complement Cell destruction through phagocytosis Soluble antigen may enter the circulation and

deposit on tissues; tissues destroyed by complement and neutrophil granules

Antibody-dependent cell-mediated cytotoxicity (ADCC)

Causes target cell malfunction (e.g., Graves)

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Type III Hypersensitivity

Immune complex mediated Antigen-antibody complexes are formed in

the circulation and are later deposited in vessel walls or extravascular tissues

Not organ specific Serum sickness Raynaud phenomena Arthrus

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Type IV Hypersensitivity

Does not involve antibody Cytotoxic T lymphocytes or lymphokine

producing Th1 cells Direct killing by Tc or recruitment of phagocytic

cells by Th1 cells Examples:

Acute graft rejection

Skin test for TB

Contact allergic reactions

Some autoimmune diseases

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Allergy

Most common hypersensitivity and usually type I

Environmental antigens that cause atypical immunologic responses in genetically predisposed individuals Pollens, molds and fungi, foods, animals, etc.

Often allergen is contained within a particle too large to be phagocytosed or is protected by a nonallergenic coat

Bee stings

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Autoimmunity

Breakdown of tolerance Body recognizes self-antigens as foreign Self-antigens not normally seen by the immune

system Infectious disease (e.g., rheumatic fever,

glomerulonephritis) Antigenic mimicry

Neoantigen Haptens become immunogenic when they bind

to host proteins

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Autoimmune Examples

Systemic lupus erythematosus (SLE) Chronic multisystem inflammatory disease Autoantibodies against:

• Nucleic acids• Erythrocytes• Coagulation proteins• Phospholipids• Lymphocytes• Platelets, etc.

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Autoimmune Examples (cont’d)

Systemic lupus erythematosus (SLE) Deposition of circulating immune complexes

containing antibody against host DNA More common in females

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Systemic Lupus Erythematosus

Clinical manifestations: Arthralgias or arthritis (90% of individuals) Vasculitis and rash (70%-80%) Renal disease (40%-50%) Hematologic changes (50%) Cardiovascular disease (30%-50%)

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Systemic Lupus Erythematosus (cont’d)

Eleven common findings:

Serial or simultaneous presence of at least four indicates SLE

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Alloimmunity

Immune system reacts with antigens on the tissue of other genetically dissimilar members of the same species Transplant rejection and transfusion reactions:

• Major histocompatibility complex (MHC)• Human leukocyte antigens (HLC)

Transfusion reactions• ABO blood groups

Rh incompatibility• Hemolytic disease of newborn

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Graft Rejection

Transplant rejection is classified according to time Hyperacute

• Immediate and rare• Preexisting antibody to the antigens of the graft

Acute• Cell-mediated immune response against unmatched

HLA antigens

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Graft Rejection (cont’d)

Transplant rejection is classified according to time Chronic

• Months or years• Inflammatory damage to endothelial cells of vessels

as a result of a weak cell-mediated reaction against minor HLA antigens

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Graft-Versus-Host Disease (GVHD)

Immunocompromised individuals are at risk for CVHD T cells in the graft are mature and capable of

cell-mediated destruction tissues within the recipient

Not a problem if patient is immunocompetent