43. Immunopathology. Allergies (hypersensitivity reactions). Mechanism of Rapid and delayed type hypersensitivity reactions.

Immunopathology & Hypersensitivity Reactions

• Immunopathology refers to pathological immune responses that cause disease. It occurs when the immune system is inadequate, inappropriate, or misdirected. This often results in tissue damage. Immunopathology includes hypersensitivity disorders, immune deficiency diseases, and autoimmune diseases.

• Hypersensitivity Reactions (Allergies) are exaggerated or inappropriate immune responses against an antigen (allergen). They happen when a person previously exposed to an antigen has a 'hypersensitive' reaction upon subsequent exposure. There are four main types.

Type I Hypersensitivity (Rapid)

• Also Known As: Immediate hypersensitivity or IgE-mediated.
• Mediators: Primarily IgE antibodies and release of mast cell mediators (e.g., histamine). Does not involve complement.
• Mechanism:
• Sensitization: First exposure to allergen causes B cells to produce IgE antibodies, which bind to mast cells and basophils.
• Re-exposure: Subsequent exposure to the same allergen binds to IgE on sensitized mast cells/basophils, causing them to activate and release inflammatory mediators. These mediators cause vasodilation, smooth muscle contraction, etc..
• Onset: Rapid, occurs within minutes to 30 minutes.
• Clinical Manifestations: Swelling, inflammation, urticaria (whealing), rhinitis, asthma, diarrhea, and potentially severe anaphylactic shock. Reactions can be systemic or local. Atopic individuals are more susceptible. Penicillin allergy can be IgE mediated.
• Diagnosis/Treatment: In vitro tests like RIA, RIST, RAST. Treatment includes antihistamines, corticosteroids, epinephrine for emergencies. Desensitization involves repeated allergen exposure.
• Type II (Antibody-Mediated/Cytotoxic): Involves IgM and IgG antibodies binding to cell surface antigens, leading to cell destruction via complement activation, phagocytosis, or cell recruitment. Examples include blood transfusion reactions and autoimmune hemolytic anemia.
• Type III (Immune Complex Mediated): Involves IgG antibodies binding to soluble antigens, forming circulating immune complexes. These complexes deposit in tissues (e.g., blood vessels, joints, kidneys), activating complement and attracting neutrophils, causing local inflammation and tissue damage. This can lead to chronic inflammation. Examples include Lupus and Rheumatoid Arthritis.

Type IV Hypersensitivity (Delayed Type)

• Also Known As: Cell-mediated hypersensitivity or DTH.
• Mediators: Mediated by T lymphocytes (CD4+ TH1 and CD8+ cytotoxic T-cells) and macrophages. Does not involve antibodies.
• Mechanism:
• Sensitization: Initial exposure activates T lymphocytes, forming memory cells.
• Re-exposure: Re-exposure activates memory T cells, which release cytokines. Cytokines activate macrophages and other cells, causing local inflammation and tissue damage. CD8+ T cells can also kill target cells directly.
• Onset: Delayed, typically 48-72 hours after re-exposure.
• Clinical Manifestations: Usually a localized reaction, often affecting skin or lungs. Can appear as dermal thickening after injection of soluble antigen.