Hypersensitivity :Autoimmunity, Alloimmunity and Allergy — Quick Reference

Innate immunity: first and second line defenses, acute and chronic inflammation, wound healing.
Adaptive immunity: recognition and response to threats; develops over life from neonate to geriatrics.
This lecture moves from normal defenses to alterations in immune/inflammatory responses.

Altered immune responses: exaggerated, misdirected (autoimmunity), or inadequate.
Hypersensitivity: immune response to an antigen causing host damage.

Exaggerated immune response to environmental antigens (food, plants, chemicals, medications).
Genetic predisposition; typically multiple allergies.
Testing: skin prick tests; serum IgE assays; desensitization possible in some cases.

Breakdown of immune tolerance leading to autoantibodies against self antigens.
Examples: multiple sclerosis, lupus, celiac disease, Graves' disease, myasthenia gravis.
Female predominance; genetic factors; treatment ranges from anti-inflammatories/steroids to immunosuppressants.

Immune response against foreign tissue from another individual (transfusions, transplants, pregnancy).
Can cause transfusion or transplant rejection and issues in pregnancy (fetal-maternal alloimmune interactions).

Sensitization required; immediate reactions upon re-exposure (minutes to hours).
IgE binds mast cells; cross-linking → degranulation → histamine release.
Effects: ↑ gastric acid, bronchoconstriction, ↑ vascular permeability with edema, widespread vasodilation.
Anaphylaxis: systemic or localized; rapid airway management required.
Common triggers: bee stings, peanuts, eggs, shellfish; environmental allergens common.

Antibodies target specific tissues; mechanisms include complement-mediated lysis and ADCC; receptors can be blocked or overstimulated.
Examples:
- Autoimmune thrombocytopenia (platelets targeted)
- Graves' disease (TSH receptor stimulation)
- Goodpasture syndrome ( kidney basement membrane)
- Transfusion reactions (ABO mismatch)
- Heparin-induced thrombocytopenia (HIT)
Key concept: tissue-specific; mechanisms can damage cells or disrupt receptors.

Preformed antigen–antibody complexes circulate and deposit in tissues; activate complement; recruit neutrophils.
Sites: vasculitis, arthritis, glomerulonephritis.
Examples: serum sickness (historical), lupus, post-streptococcal GN, rheumatoid arthritis, Farmer's lung, RA.
Timing: typically within hours; immune complexes cause tissue injury.

T-cell mediated; no antibodies.
Delay of days to weeks after exposure; macrophage activation and cytokine release damage tissue.
Examples: contact dermatitis (poison ivy, metals, latex), drug reactions, Stevens–Johnson syndrome, granulomatous diseases (tuberculosis, sarcoidosis).

Types I–III: immediate, IgE/IgM/IgG mediated; Type IV: delayed, T-cell mediated.
Testing approaches: skin prick tests, serum IgE testing; challenge testing carries risk of systemic reaction.

ABO system: A, B antigens; antibodies to missing antigens are IgM; O type is universal donor; AB is universal recipient.
Rh system: D antigen; Rh-positive vs Rh-negative; Rh-negative mothers can form anti-D antibodies after exposure to Rh-positive fetal erythrocytes.
Hemolytic disease of the newborn (erythroblastosis fetalis): maternal anti-D can attack fetal RBCs; prevention with RhoGAM (Rh immune globulin).
Transfusion reactions: risk with incompatibility; monitor for pruritus, fever; ABO incompatibility can cause hemolysis.

MHC (HLA) are tissue antigens on cell surfaces; codominant inheritance; matching reduces rejection risk.
Rejection types by timing:
- Hyperacute: immediate; rare due to vigilant HLA matching; type II hypersensitivity.
- Acute: days to months; type II (antibody/complement) and/or type IV components.
- Chronic: months to years; type IV component; progressive graft failure.
Immunosuppressants: reduce IL-2 synthesis, deplete T/B cells, or block inflammatory cytokines (e.g., IL-6).

HIT (Heparin-Induced Thrombocytopenia): type II hypersensitivity; stop heparin; switch to non-heparin anticoagulant if needed.
Systemic lupus erythematosus (SLE): autoantibodies to nuclear components; immune complex–driven kidney injury; butterfly rash; ANA often positive; treat with NSAIDs, steroids, hydroxychloroquine; immunosuppressants for severe disease.
Desensitization: controlled exposure to allergens (e.g., penicillin, peanut) to reduce reaction risk in life-threatening allergies.
RhoGAM: prevents maternal sensitization to RhD antigen in Rh-negative mothers.
This concludes the hypersensitivity section. For questions, please reach out to the instructor.