Hypersensitivity Reactions in Immunology

Hypersensitivity Reactions

• Immune reactions triggered by non-pathogen antigens, occurring on subsequent exposures to a sensitized individual.
• Allergies and immune conditions cause excessive side effects destroying host tissues (inflammation).
• Drives allergic or atopic responses, not autoimmune.

Type I Hypersensitivities

• IgE on FceRI receptors bind soluble antigens (allergens), causing degranulation of mast cells, basophils, and eosinophils.
• Histamine leads to inflammation.

Hypersensitivity Differences

• Type II: IgG binds to cell-associated antigens or receptors, activating complement or altering signalling.
• Type III: IgG binds to soluble foreign proteins forming immune complexes, which deposit in tissues.
• Type IV: CD4 Th1 cells and CD8 cytotoxic T cells respond to foreign/modified self-proteins.

Autoimmunity

• Adaptive immune responses directed at healthy host cells and tissues (types II, III, and IV).
• Immune system mistakenly targets the body's own cells.

Allergens

• Antigens that elicit allergic/atopic responses (type I).
• Small, soluble, dried proteins that rehydrate on contact with mucus, releasing antigens.

Mast Cells

• Primary responders in allergic reactions.
• Release histamine and TNF-α to induce allergic inflammation.
• When IgE binds to FceRI, histamine and TNF-α release causes leaky capillaries, recruiting immune cells.

Eosinophils

• Granulocytes in mucosal and epithelial tissues.
• Long-lived, retain memory for antigens.
• Secondary responders in late effector phase.
• Release toxic granules.
• Found in respiratory, GI, and GU tracts.

Basophils

• Secondary responders; recruited to inflamed tissues.
• Activated via TLRs.
• Secrete IL-4 and IL-13, which influence T cell differentiation and IgE switching.

FceRI

• Receptor with high affinity for IgE on mast cells and basophils.
• Cross-linking results in degranulation.

Phases of Type I Hypersensitivity

• Sensitization Phase: Initial allergen exposure triggers T cell differentiation into Th2 cells, stimulating IgE production against the specific allergen.
• Immediate Effector Phase: Re-exposure leads to cross-linking of IgE on mast cells, causing immediate degranulation and release of pre-formed mediators like histamine and TNF-α.
• Late Effector Phase: Mast cells release lipid factors (PAF), leukotrienes, and prostaglandins causing more potent effects. Th2 cells are further activated.

Allergic Reaction Effects

• Gastrointestinal tract: Increased fluid secretion, diarrhea, vomiting.
• Airways: Constriction, mucus production, coughing, sneezing.
• Blood vessels: Increased permeability, edema, inflammation.

Allergy vs Intolerance

• Allergy: IgE-mediated response (anaphylaxis, urticaria).
• Intolerance: Not IgE-mediated (asthma).

Type I Diagnoses

• Allergic Rhinitis
• Atopic/Allergic Asthma
• Urticaria
• Angioedema
• Atopic Dermatitis (eczema)
• Systemic Anaphylaxis

Predisposing Factors

• A combination of genes and environmental factors.
• Exposure to various environmental factors can influence susceptibility to certain conditions.

Purpose of IgE-mediated Responses

• Protect against helminths/parasites too large to be phagocytosed.

Hygiene Hypothesis

• Developed countries have increased incidence of atopic disorders.
• Limited exposure to pathogens during childhood might contribute to immune system development, potentially influencing susceptibility to conditions like allergies.

Treatments for Atopic Disorders

• Avoiding allergens is a common treatment approach.
• Managing symptoms with medications.
• In some cases, allergen immunotherapy (desensitization) is employed.

Pharmacological Treatments

• Immunological: Desensitization with allergen-specific immunotherapy (SIT).
• Helminthic therapy aims to induce parasite-specific IgE response, potentially influencing allergic responses.
• Antihistamines block histamine binding to H1 receptors, mitigating effects.
• Monoclonal anti-IgE blocks IgE from binding to Fc receptors.
• Lipoxygenase antagonists prevent leukotriene generation.
• Corticosteroids and epinephrine manage inflammation and allergic reactions, respectively.

Skin Conditions

• Urticaria, hives.
• Angioedema, swelling.