(4.7) HYPERSENSITIVITY

Hypersensitivity Reactions

• Hypersensitivity reactions are the consequence of an adaptive immune response.
• An initial stimulus (allergen/innocuous antigen) is required.
• Hypersensitivity is an overreaction of the immune system.
• Recognition of self and non-self antigens is crucial for immune function. Misidentification can lead to autoimmunity.
• Hypersensitivity reactions can be categorized, also known as Types I-IV based on the Gell and Coombs classification.

Objectives

• Diagram the pathophysiology of hypersensitivity reactions.
• Identify immune components, antigen types, mechanisms, and timing involved in hypersensitivity reactions.
• Correlate disorders with the appropriate hypersensitivity reaction type.

What is Hypersensitivity?

• The immune system can overreact to harmless substances, leading to hypersensitivity reactions.
• Examples include reactions to cat hair, allergies, and various other stimuli.

Normal Role of the Immune System

• The innate immune system provides a first line of defense through normal flora, skin, mucosal surfaces, and chemical factors.
• Components like complement and phagocytes (neutrophils, macrophages, and dendritic cells) are involved in local immune defense.
• Amplification of the immune response occurs through phagocytes, cytokines, and migration of dendritic cells.
• The adaptive immune system (B cells, specific antibodies, CD4 and CD8 T cells, and macrophages) contributes to clearing infections.

The True Nature of the Immune System

• The immune system defends against both friend (self) and foe (foreign).
• It works by recognizing antigens, including self-antigens that can trigger autoimmunity.
• Oversensitivity to innocuous or otherwise harmless antigens leads to hypersensitivity reactions.

Hypersensitivity & Allergies Fundamentals

• All hypersensitivities are a consequence of an adaptive immune response.
• An initiating antigen (e.g., allergen/innocuous antigen) triggers this overreaction.
• Adaptive immune response leads to the development of memory, enabling subsequent reactions.

Gell and Coombs Classification

• Type I: IgE-mediated (anaphylaxis)
• Type II: Antibody-dependent cellular cytotoxicity (e.g., Hemolytic disease of the newborn)
• Type III: Immune complex-mediated (e.g., serum sickness, SLE)
• Type IV: Cell-mediated (delayed-type) (e.g., contact dermatitis, PPD)

Type I Hypersensitivity (Anaphylaxis)

• Antigens are typically soluble (e.g., peanuts, pollen, animal dander).
• Initial exposure introduces innocuous antigens, recognized as foreign.
• Type I response involves IgE generation, binding to mast cells/basophils via FcεRI receptors.
• Subsequent exposure triggers mast cell degranulation, releasing histamine and other mediators.
• This response produces inflammation and anaphylaxis.
• Causes of anaphylaxis commonly involve ingested food, medications or insect stings.
• Systemic reactions can be life-threatening.

Type II Hypersensitivity (Cytotoxic)

• Antigens are frequently cell surface antigens (e.g., Rh and ABO antigens on RBCs).
• Initial exposure recognized as foreign leads to IgG or IgM generation by plasma cells.
• Subsequent exposure causes IgG/IgM binding to cell surface antigens, triggering complement activation.
• This can lead to antibody-dependent cellular cytotoxicity and inflammation.
• Common examples include acute hemolytic transfusion reactions and hemolytic disease of the newborn.

Type III Hypersensitivity (Immune Complex)

• Antigens are typically soluble (e.g., anti-venom, self-DNA).
• Initial exposure recognized as foreign, leading to IgG generation in plasma cells.
• Subsequent exposure causes IgG binding to soluble antigens, forming immune complexes.
• These complexes deposit in tissues, activating complement and inflammatory responses.
• Examples include serum sickness and Systemic Lupus Erythematosus (SLE).

Type IV Hypersensitivity (Delayed-Type)

• Antigens can be soluble (e.g., poison ivy, metals, dyes, tuberculin) or cell surface antigens (e.g., granulomatous hypersensitivity).
• Initial exposure leads to activation of cellular immunity.
• The subsequent exposure causes memory T cells to recognize antigen.
• This involves activation of the Th1 pathway, cytokines (IFN-γ, TNF-α) and CD8+ and macrophage activation, leading to inflammation.
• Common examples include contact dermatitis and the tuberculin skin test (PPD).

Hypersensitivity Management

• Management depends on the specific hypersensitivity condition.
• Treatments include antihistamines, corticosteroids, mast cell stabilizers, and epinephrine.
• Allergen immunotherapy, also known as desensitization, is an option in some cases (e.g., subcutaneous or sublingual).

Summary & Review

• A summary of different hypersensitivities, including the immune components, antigens, mechanisms, timeframes and associated disorders is provided.

Explore the types and mechanisms of hypersensitivity reactions as part of your immunology studies. This quiz covers the pathophysiology, immune components, and correlation of disorders with hypersensitivity reaction types. Test your understanding of how the immune system can misidentify antigens and lead to an overreaction.