Hypersensitivity Overview and Type I Quiz

Hypersensitivity Overview

• Hypersensitivity is an exaggerated immune response to antigens, potentially causing pathological reactions, either to foreign antigens or self-tissue.
• Four categories classify hypersensitivity reactions. Some reactions involving antibody-antigen complexes are further categorized.

Type I Hypersensitivity (Immediate/Anaphylactic Hypersensitivity)

• Characterized by a rapid immune response (15-30 minutes).
• Late-phase reaction (10-12 hours) also possible.
• Affects various systems: skin (urticaria, eczema), eyes (conjunctivitis), nasopharynx (rhinorrhea, rhinitis), bronchopulmonary (asthma), and gastrointestinal tract (gastroenteritis).
• Range of effects: from mild discomfort to death.
• Mast cells/basophils are the primary immune cells. Platelets, neutrophils, and eosinophils also affect the process.
• Triggered by IgE binding to allergens on mast cells and basophils.
• Subsequent allergen exposure cross-links IgE, releasing pharmacologically active substances.
• Mast cell degranulation depends on intracellular calcium flux.

Type II Hypersensitivity (Antibody-Dependent)

• Antibodies target self-cell surfaces.
• Antigens can be intrinsic (part of the patient's cells) or extrinsic (absorbed onto cells).
• Macrophages/dendritic cells process the antigen, triggering B-cell response.
• Antibodies (IgG, IgM) form complexes.
• Complement system activation occurs, causing cell lysis/death.
• Antibody-dependent cell-mediated cytotoxicity (ADCC) involves NK cells and macrophages targeting antibody-tagged cells for phagocytosis.
• Reaction time: hours to a day.
• Examples include hemolytic anemia, rheumatic fever, and systemic lupus erythematosus (SLE).

Type III Hypersensitivity (Immune Complex)

• Soluble immune complexes (antigen-antibody aggregates) form and deposit in tissues (skin, kidney, joints), eliciting an immune response through the complement system.
• Reaction time: hours to days.
• Two types:
  • Arthus reaction (localized): Inflammation at specific sites (e.g., hemorrhagic vasculitis and edema).
  • Serum sickness (systemic): Inflammation spreads throughout blood and tissues (fever, splenomegaly, lymphadenopathy, arthralgia, urticaria).
• Examples: Immune complex glomerulonephritis, rheumatoid arthritis (post-GABHS infection), subacute bacterial endocarditis, malaria symptoms, hydralazine-induced SLE.

Type IV Hypersensitivity (Cell-Mediated/Delayed-Type Hypersensitivity)

• A cell-mediated, not antibody-mediated, response.
• Reaction develops over two to three days.
• CD8+ cytotoxic T cells and CD4+ helper T cells recognize antigen-MHC complexes.
• Antigen-presenting cells (APCs) are macrophages which produce IL-1. IL-1 stimulates further CD4+ T cell proliferation.
• CD4+ T cells produce IL-2 and interferon-gamma (IFN-γ), promoting the release of Type 1 cytokines.
• Activated CD8+ T cells directly destroy target cells.
• Activated macrophages produce hydrolytic enzymes and can form multinucleated giant cells.
• Examples: Contact dermatitis (e.g., poison ivy), temporal arteritis, leprosy symptoms, tuberculosis symptoms, transplant rejection, celiac disease.

Rheumatoid Arthritis (RA)

• A chronic inflammatory, systemic disease affecting multiple body systems.
• Significant work disability in 60% of patients within ten years of disease onset.
• Characterized by polyarthritis (symmetrical joint inflammation), morning stiffness lasting over an hour, and improvement in pain with use of the joints.
• Extra-articular manifestations distinguish RA from osteoarthritis, including anemia (possibly from GI bleeding), hepatosplenomegaly with leukopenia (Felty's syndrome), and lymphocytic infiltration of salivary/lacrimal glands (Sjögren's syndrome).
• Other features: Pericarditis, pleurisy, alveolitis, scleritis, subcutaneous nodules.
• Etiology is unknown, but likely involves autoimmune response (immune system mistakenly targeting self-proteins).

Asthma

• Characterized by paroxysmal narrowing of bronchial airways due to inflammation of bronchi and smooth muscle contraction.
• Inflammation is central to symptoms (dyspnea, cough, wheezing).
• Antigen-antibody interactions (e.g., allergen exposure) initiate a cascade: membrane phospholipase activation leads to arachidonic acid production.
  • Arachidonic acid metabolism produces vasoactive prostaglandins and leukotrienes (potent smooth muscle constrictors triggering airway hyperresponsiveness and inflammation).
• Causes include viral infections, allergens, smoke, cold/dry air, and potentially menstrual cycle fluctuations in women.

Rheumatic Fever (RF)

• A serious complication of group A streptococcal infections (usually upper respiratory tract).
• Marked inflammatory response affecting multiple systems (heart, joints, CNS, skin).
• Occurs primarily in school-aged children during periods of high streptococcal infection prevalence (e.g., colder months).
• Two patterns of presentation:
  • Sudden onset: polyarthritis, fever, toxicity, 2-6 weeks after infection.
  • Insidious or subclinical: mild carditis develops gradually.
• Diagnosed using Jones criteria (major criteria: carditis, migratory polyarthritis, subcutaneous nodules, erythema marginatum, Sydenham chorea; minor criteria: arthralgia, fever, elevated acute-phase reactants, positive streptococcal tests, prolonged PR interval.

Treatment & Prognosis:

• RF: Treatment focuses on treating streptococcal infection with antibiotics (benzathine penicillin G, penicillin V, or erythromycin), pain/inflammation management with steroids/salicylates, and heart failure management with digitalis, plus long-term prophylaxis for recurrent streptococcal infections.
• RF: Prognosis depends on the severity of acute heart involvement. Complications include carditis, mitral stenosis, and congestive heart failure.