Immunology — Core — USMLE Step 1 Notes

The four hypersensitivity reactions

• Type I (immediate, minutes): IgE, mast-cell degranulation — anaphylaxis, atopy
• Type II (antibody vs cell): IgG/IgM against surface antigen — haemolysis, Goodpasture (linear)
• Type III (immune complex): deposition and complement — lupus nephritis, serum sickness (granular)
• Type IV (delayed, days): T-cell mediated — contact dermatitis, TB skin test, transplant rejection

Immunodeficiencies by the missing compartment

• B-cell (Bruton, X-linked): recurrent encapsulated infections after ~6 months; absent B cells
• T-cell (DiGeorge, 22q11): tetany from hypocalcaemia, cardiac defects, absent thymus
• Combined (SCID): failure to thrive, opportunistic infection; adenosine deaminase deficiency
• Phagocyte (chronic granulomatous disease): catalase-positive organisms; abnormal dihydrorhodamine test

MHC and T-cell basics

• MHC I (all nucleated cells) presents to CD8; MHC II (antigen-presenting cells) presents to CD4
• Positive selection in the thymic cortex; negative selection in the medulla
• Superantigens cross-link MHC II to the T-cell receptor → massive cytokine release (toxic shock)

Cells & what they do

• Neutrophils — acute bacterial; macrophages — chronic/granuloma, antigen presentation; eosinophils — parasites and allergy; mast cells/basophils — IgE-mediated histamine release.
• T cells: CD4 helper (Th1 → macrophages/IFN-gamma; Th2 → B cells/IgE; Th17; Treg tolerance); CD8 cytotoxic. B cells → plasma cells (antibody).
• NK cells kill 'missing self' (low MHC I) and antibody-coated cells (ADCC).

Antibodies

• IgG — most abundant, crosses placenta, secondary response, opsonises/fixes complement. IgM — first, pentamer, best complement fixer. IgA — mucosal/secretions. IgE — allergy/parasites. IgD — naive B cells.
• Class switching (T-dependent) needs CD40L; hyper-IgM syndrome from CD40L defect.

Hypersensitivity — the four types

• Type I (IgE) — anaphylaxis, atopy; Type II (antibody) — autoimmune haemolysis, Goodpasture, Graves; Type III (immune complex) — SLE, serum sickness, post-strep GN; Type IV (T-cell/delayed) — contact dermatitis, TB test, transplant rejection.

Immunodeficiencies

• B-cell: Bruton (X-linked agammaglobulinaemia — no B cells), selective IgA, CVID.
• T-cell: DiGeorge (22q11, no thymus, hypocalcaemia). Combined: SCID (recurrent everything). Phagocyte: chronic granulomatous disease (catalase+ infections, DHR test), Chediak-Higashi, LAD (delayed cord separation).
• Complement: C5-C9 → Neisseria; C1 esterase inhibitor → hereditary angioedema.

Transplant & immunosuppression

• Hyperacute (minutes, preformed antibodies), acute (weeks, T-cell), chronic (months-years, vascular), graft-versus-host (donor T cells attack host — skin, gut, liver).
• Immunosuppressants: calcineurin inhibitors (ciclosporin, tacrolimus — nephrotoxic), mTOR (sirolimus), antimetabolites (azathioprine, mycophenolate), steroids, monoclonals (basiliximab, rituximab).