Hypersensitivity Reactions Overview

Hypersensitivity Reactions (HPS)

• Hypersensitivity (HPS) are excessive immune responses causing damage in reaction to specific antigens.
• Three types of antigens trigger HPS reactions: infectious agents, environmental substances, and self-antigens.
• Influenza virus and chronic hepatitis are examples of infectious agents that can cause HPS.
• Allergies and atopy, such as asthma or rhinitis, result from environmental substances. Dust can trigger IgE production.
• Autoimmune diseases exemplify self-antigens causing HPS.

Types of Hypersensitivity Reactions

• Four major types of HPS reactions are clinically recognized, classified by Coomb's and Gell.
• Type I (Immediate): IgE-mediated.
• Type II (Antibody-Mediated): IgG-mediated (cytotoxic; bound antigen).
• Type III (Immune Complex): IgG-mediated.
• Type IV (Delayed): T cell-mediated.

Immediate Hypersensitivity (Type I): Allergy

• Atopy is an immediate HPS reaction to environmental antigens, mediated by IgE.
• Atopy is inherited and often associated with high IgE levels, synonymous with allergy.
• Common diseases associated with atopy include anaphylaxis, angioedema, urticaria, rhinitis, asthma, and dermatitis/eczema.
• Allergic reactions have two phases: Early and Late-phases.

Allergens

• Allergens are triggering antigens of allergies.
• Some allergens are low molecular weight and prevalent in the environment.
• Allergens can be inhaled (e.g., pollens, fungal spores, house dust mite feces, grass), ingested (e.g., peanuts, fish, eggs, milk), or administered as drugs (e.g., penicillin, cephalosporins) or venoms.

Degranulating Cells

• Mast cells are the primary cells involved in allergic reactions.
• Mast cells are resident in tissues and express IgE receptors (FcER1).
• Cross-linking of IgE by allergens triggers mast cell degranulation, releasing allergy mediators, particularly in the early phase.
• Eosinophils are circulating cells migrating to areas with type I reactions.
• Basophils are circulating cells that can differentiate into mast cells in tissues. Their functions are still being investigated.

Non-Allergic Reactions

• Non-allergic reactions include complement activation during infections and nervous system signals, such as temperature changes.
• These mechanisms can also activate the previously mentioned cells in the body.

Antibody (IgE)

• B cells, co-stimulated by IL-4 secreted by TH2 cells, switch to IgE production.
• IgE binds to FcER1 on mast cells and eosinophils.
• High IgE levels can occur during parasitic infections (e.g., schistosomiasis) and atopy.
• Allergic reactions are often tested for with prick tests and ELISA.

Mediators of Early Phase

• Mast cells, responding to allergen activation release prostaglandins (cyclooxygenase pathway) and leukotrienes (lipoxygenase pathway).
• These mediators cause vasodilation, increased vascular permeability, and a drop in blood pressure (BP).
• Leukotrienes contribute to nasal secretions (in rhinitis/asthma) and smooth muscle contraction in the lungs.
• Histamine, released from skin mast cells, causes swelling and fluid shift.

Mediators of Late Phase

• Eosinophils release peroxidase, major basic protein, and cationic protein, which damage bronchial tissue, leading to chronic inflammation, smooth muscle hypertrophy, and increased mucus secretion.
• TH2 cells release IL-4 and chemokines, promoting chronic allergic inflammation.

Treatment

• Treatment for hypersensitivity reactions is tailored to severity.
• Identify and avoid allergens when possible.
• Medications, including drugs like beta2-adrenergic agonists (e.g., salbutamol), epinephrine, antihistamines, leukotriene receptor antagonists (e.g., montelukast), and corticosteroids, are used.

Desensitization (Immunotherapy)

• Desensitization is most effective for single allergens.
• A single-allergen desensitization involves subcutaneous injections of increasing doses of the allergen, often successful up to 90% of cases.
• Desensitization may involve TH1 stimulation to block allergen attachment to IgE, or T regulatory (Treg) cells inhibiting TH2 responses.

Predisposing Factors

• Allergy prevalence is high in developed countries, with peanut allergies increasing.
• Factors influencing susceptibility to allergy include:
  • Atopy trait (a genetic tendency to an exaggerated IgE response that runs in families).
  • Several genes influencing allergy susceptibility (polymorphisms, with variations in genes such as IL-4 and FcER1 genes, significantly contributing, with genes from the mother often influencing allergy more so than those from the father).

Hygiene Hypothesis

• The hygiene hypothesis suggests that allergies are influenced by.
• cleaner living conditions or lack of exposure to certain microbes in the environment.
• exposure to mycobacteria, such as those causing tuberculosis (TB), may prevent a TH2-polarized immune response by eliciting a TH1 response that downregulates TH2 responses in individuals living where TB is common.

Latex Allergy

• Latex allergy is detectable by a skin prick test.

Peanut Allergy

• Peanut allergy can result in complications like angioedema.