Med I: Hypersensitivities

Hypersensitivity reactions

exaggerated or inappropriate immune responses to benign antigens

in response to external, or “non-self,” antigens

autoimmune reactions occur in response to internal, or “self,” antigens.

Hypersensitivity reactions are antigen-specific, meaning that the first contact with the antigen sensitizes the immune system (i.e., primes the adaptive immune system)

subsequent contacts elicit the hypersensitive (allergic) response. reactions can become more severe with time

Four main types

Reactions I-III are antibody mediated

Reaction IV is cell mediated

Immediate and delayed hypersensitivity

Immediate (anaphylactic) hypersensitivity

• immediate immunoglobulin (Ig) E-mediated reactions

• occurs when an antigen (allergen) binds to IgE on the surface of mast cells, resulting in the release of several mediators

Delayed hypersensitivity

• caused by T lymphocytes, not antibody

• starts hours or days after contact with the antigen and often lasts for days

Anaphylaxis

most severe form of type I hypersensitivity

Life threatening due to severe bronchoconstriction and hypotension

Likely requires Medical ICU intervention with pressors and intubation

Caused by massive doses of antigen-IgE complexes on mast cells

Symptoms include wheezing, hoarseness, laryngeal edema, pruitis, andnurticaria

Common environmental causes include peanuts, shellfish, bee venom, and drugs such as penicillin

Histamine and mast cells

• Histamine is one of several mediators. It is stored in granules of tissue mast cells and basophils

• Eosinophils release histamine

• Can lead to bronchospasm

• Histamine release leads (vasodilation, Increased capillary permeability, Smooth muscle contraction)

Hypersensitivity I

• Immediate anaphylactic hypersensitivity

• Characterized by IgE/ IgE mediated

• Sensitization via antigen (allergen) induces IgE antibody that binds to mast cells and basophils.

• Immunological reaction involves repeat exposure to the allergen followed by allergen cross links that bind IgE onto those cells. This leads to degranulation and release of mediators like histamine.

• Manifests as hives, urticaria, pruritis

Environmental allergies cause Type I hypersensitivity reactions

Hypersensitivity II

• Cytotoxic

• IgG mediated

• Sensitization occurs by antigens on a cell surface that elicit Tfh and Bcell activation.

• Immunological activation: Antibody binding to cell membrane antigens leads to

  complement mediated lysis of the cells (e.g., transfusion or Rh reactions) or autoimmune hemolytic anemia.

• OB clinical correlation - Prevented by Rhogan (bind to antigen& avoid immune driven reaction)

Hypersensitivity III

• Immune complex

• Mediated by multiple types of antibodies

• Sensitization via soluble antigens that elicit Tfh and Bcells activation

• Immunological activation: Antigen –antibody immune complexes are deposited in tissues and neutrophils are attracted to the site. They release lysosomal enzymes, causing tissue damage. In the case of IgM or IgG, complement is also involved.

• Clinical correlations

  • Systemic Lupus Erythematosus (SLE): Autoantibodies against double stranded DNA, histones, nucleolar

    proteins, and other components of the cell nucleus; deposits in kidney,

    skin and joints

  • Rheumatoid arthritis (RA): autoantibodies (IgM, called rheumatoid factors) formed against IgG;

    deposits in synovial membranes

  • IgA nephropathy: IgA containing immune complexes are found lining the glomeruli causes

    glomerulonephritis

Hypersensitivity IV

• Delayed

• T cell mediated

• Sensitization via CD4 and/or CD8 T cells sensitized by protein antigens

• Immunological activation by memory T cells that release cytokines upon second exposure with same antigen. The cytokines induce inlammation and activate macrophages which release inflammatory mediators.