# Immunopathology for NEET PG Pathology: Hypersensitivity Types, HLA, Transplant Rejection, SLE, Complement, HIV/AIDS Source: https://tracknation.in/story/immunopathology-for-neet-pg-pathology-hypersensitivity-types-hla-transplant-rejection-sle-complement-hiv-aids (TrackNation — free UPSC notes with PYQs) > NEET PG Pathology: Gell and Coombs hypersensitivity types with examples, autoimmunity mechanisms, HLA classes and disease links, transplant rejection, SLE antibodies, complement deficiencies and hereditary angioedema, and HIV/AIDS with India's NACO testing and Treat All policy, with a diagram, hooks, vignette MCQs and cards. ## Start Here 🎯 **Exam priority: Very high.** *Expect: classify a disease by hypersensitivity type, HLA–disease pairs, rejection by timing, SLE antibodies, complement deficiencies, and HIV entry and CD4 thresholds.* CBME mapping: **PA 8.1–8.6**. *Gell and Coombs hypersensitivity types, HLA classes and kidney transplant rejection. Drawn by TrackNation.* ## The Four Hypersensitivities - **Type I (immediate)**: antigen cross-links IgE on mast cells and basophils, releasing histamine, leukotrienes and other mediators within an hour. All atopic disorders, anaphylaxis, urticaria. Anaphylaxis is confirmed by serum tryptase, ideally within 2 hours. - **Type II (antibody against cells)**: antibody bound to a cell-surface antigen triggers complement or ADCC — hyperacute graft rejection, Coombs-positive haemolytic anaemia, Hashimoto thyroiditis, anti-GBM disease. - **Type III (immune complex)**: circulating antigen–antibody complexes deposit in vessels and tissues — serum sickness, SLE, rheumatoid arthritis, leukocytoclastic vasculitis, cryoglobulinaemia, several glomerulonephritides. - **Type IV (delayed, T cell)**: no antibody — contact dermatitis, SJS/TEN, DRESS, the response to tuberculosis, acute and chronic allograft rejection. ## Autoimmunity and HLA - Autoimmune diseases use types II, III and IV — never type I. Females are affected more often. Mechanisms: altered self-antigens, **molecular mimicry** (streptococcal M-protein antibodies cross-react with heart muscle) and **sequestered antigens** released by injury (sympathetic ophthalmia after eye trauma). HLA variants nearly always contribute. - **HLA** genes sit on the short arm of chromosome 6. Class I (A, B, C) is on all nucleated cells and presents to CD8 T cells; its light chain, β2-microglobulin, is coded on chromosome 15. Class II (DP, DQ, DR) is on antigen-presenting cells, thymic epithelium and activated T cells, and presents to CD4 T cells. Class III region codes C2, C4, factor B and TNF-α. HLA-G in the placenta protects the fetus. - For transplant matching, HLA-DR matters most, then B, then A. | **HLA allele (MSD)** | **Disease** | | HLA-B27 | Ankylosing spondylitis, reactive arthritis | | HLA-DR4 | Rheumatoid arthritis | | HLA-DQ2 and DQ8 | Type 1 diabetes, coeliac disease | | HLA-DR3 | SLE, Graves disease, Sjögren | | HLA-B51 | Behçet syndrome | | HLA-DR2 | Multiple sclerosis, narcolepsy | ## Transplant Rejection - **Hyperacute** (minutes to hours; HLA incompatibility; antibody-mediated, type II): fever, anuria; usually means graft failure. **Accelerated** (days; antibody). **Acute** (days to weeks; T cell or antibody): rising creatinine, graft swelling — usually reversible with pulse steroids. **Chronic** (months to years): proteinuria, hypertension, graft loss. ## SLE and Complement - **SLE** mainly affects young women. ANA is very sensitive but not specific; **anti-dsDNA** is highly specific. Hydralazine, procainamide and TNF inhibitors cause drug-induced lupus. Pericarditis is the commonest cardiac lesion; Libman-Sacks endocarditis is rare. Mothers with anti-Ro (SSA) can have babies with congenital heart block. Antiphospholipid antibodies raise the risk of late miscarriage. - **Complement**: deficiency of C5–C9, factor B, factor D or properdin → recurrent *Neisseria* infection; defects in C1, C4 or C5 → SLE. C3a and C5a are anaphylatoxins. - **Hereditary angioedema** (C1 inhibitor deficiency, autosomal dominant): swelling without itching, urticaria or bronchospasm, but laryngeal oedema can kill. ## HIV and AIDS - **Entry**: gp120 binds CD4, then a co-receptor (CCR5 or CXCR4); gp41 fuses the envelope. Reverse transcriptase turns the RNA genome into DNA. - **Advanced disease**: CD4 < 200/µL (or < 14%) or an AIDS-defining infection or cancer. Below 200: Pneumocystis, toxoplasma, Cryptococcus. Below 50: CMV and Mycobacterium avium complex. - **India (NACO)**: Strategy III uses three rapid tests in sequence — negative if the first is non-reactive, positive only if all three are reactive. ART is started for everyone regardless of CD4 count or stage ("Treat All", since 2017). ## Traps the Examiner Sets - Hyperacute rejection = type II; acute and chronic rejection = type IV (MSD). - Hashimoto and anti-GBM = type II; SLE and serum sickness = type III; TB and contact dermatitis = type IV. - ANA = sensitive; anti-dsDNA = specific. - C5–C9 deficiency = Neisseria; HAE = no urticaria. ## Memory Hooks & Shortcuts *Shortcuts to lock in this article's numbers and lists. Each one only re-packages facts proven above.* - 🧠 **ACID: Anaphylactic, Cytotoxic, Immune complex, Delayed** — types I to IV in order - 🧠 **Hyperacute is Hurried antibody (II); later rejection is T-cell (IV)** — rejection types - 🧠 **DR before B before A — 'Doctors Before Assistants'** — HLA matching priority - 🧠 **B27 bends the Back** — HLA-B27, ankylosing spondylitis - 🧠 **ANA = Any lupus? dsDNA = Definitely SLE** — sensitive vs specific - 🧠 **Terminal complement gone, Neisseria comes** — C5–C9 deficiency - 🧠 **Two hundred: Pneumocystis; fifty: CMV and MAC** — CD4 thresholds ## Rapid-Revision Cards - IgE, mast cells; < 1 h; atopy, anaphylaxis. - Serum tryptase within 2 h. - Antibody on cells: hyperacute rejection, Coombs+ haemolysis, Hashimoto, anti-GBM. - Immune complexes: serum sickness, SLE, RA, vasculitis. - T cells: contact dermatitis, TB, SJS/TEN, DRESS, acute/chronic rejection. - Type I. - Streptococcal M protein vs heart. - Sympathetic ophthalmia. - Chromosome 6p; β2m on 15. - All nucleated cells/CD8 vs APCs/CD4. - C2, C4, factor B, TNF-α. - DR > B > A. - Ankylosing spondylitis, reactive arthritis. - Coeliac, type 1 diabetes. - Rheumatoid arthritis. - Minutes–hours; HLA antibody; graft lost. - ANA sensitive; anti-dsDNA specific. - Hydralazine, procainamide, TNF inhibitors. - Congenital heart block. - Neisseria. - C1-INH; AD; no urticaria; larynx. - gp120–CD4 + CCR5/CXCR4; gp41 fusion. - < 200 PCP, toxo, crypto; < 50 CMV, MAC. - Strategy III: 3 tests all reactive; Treat All since 2017. ## Sources *Facts in this article were checked against these documents.* - MSD Manual Professional: Overview of Allergic and Atopic Disorders; Anaphylaxis; Autoimmune Disorders; HLA System; Complement System; C1 Inhibitor Deficiency — Merck & Co. (MSD Manuals), reviewed 2025–26 (link) - MSD Manual Professional: Kidney Transplantation; Systemic Lupus Erythematosus; HIV Infection — Merck & Co. (MSD Manuals), reviewed 2025–26 (link) - National Guidelines for HIV Counselling and Testing Services — National AIDS Control Organisation, MoHFW, 2024 (link) - National Guidelines for HIV Care and Treatment — National AIDS Control Organisation, MoHFW, 2021 (link) - Competency Based Undergraduate Curriculum, Pathology (PA 8) — National Medical Commission, 2024 ## Test Yourself: Practice Questions Thirty-three questions in NEET PG style, most of them clinical vignettes. ## Practice Questions (NEET PG pattern) *Original questions written in the style of the exam: +4 for a correct answer, −1 for a wrong one. Every answer was checked against the sources listed above. NEET PG papers are not published by NBEMS, so these are not past-paper questions.* **Q1.** Within minutes of a bee sting, a man develops hives, wheeze and hypotension. The mechanism is - (a) immune complexes (type III) - (b) IgE on mast cells and basophils (type I) - (c) antibody against red cells (type II) - (d) T cells (type IV) **Answer: (b)** — Type I reactions develop within an hour. **Q2.** Hours after a suspected anaphylactic reaction, the test that best confirms it is - (a) ANA - (b) serum IgG - (c) serum tryptase (ideally within 2 hours) - (d) complement C3 **Answer: (c)** — Diagnosis is mainly clinical. **Q3.** All atopic disorders, such as allergic asthma and allergic rhinitis, are - (a) type III - (b) type IV - (c) type II - (d) type I hypersensitivity **Answer: (d)** — Atopy = exaggerated IgE response. **Q4.** Anti-glomerular basement membrane disease is classified by MSD as - (a) type III - (b) type I - (c) type IV - (d) type II hypersensitivity **Answer: (d)** — Antibody against a fixed tissue antigen. **Q5.** A woman has warm autoimmune haemolytic anaemia with a positive direct Coombs test. The hypersensitivity type is - (a) type I - (b) type II - (c) type III - (d) type IV **Answer: (b)** — Antibody on the cell surface. **Q6.** A patient develops serum sickness after receiving a foreign protein. The mechanism is - (a) immune-complex deposition (type III, serum sickness) - (b) antibody against red cells (type II) - (c) IgE (type I) - (d) T cells (type IV) **Answer: (a)** — Type III can develop hours to weeks after exposure. **Q7.** In MSD's classification, SLE and rheumatoid arthritis are - (a) not hypersensitivity disorders - (b) type III (immune complex) disorders - (c) type IV - (d) type I **Answer: (b)** — Also leukocytoclastic vasculitis, cryoglobulinaemia. **Q8.** A gardener develops contact dermatitis from a plant such as poison ivy. The mechanism is - (a) IgE (type I) - (b) T-cell mediated (type IV) - (c) complement deficiency - (d) immune complex (type III) **Answer: (b)** — Contact dermatitis (e.g. poison ivy). **Q9.** A patient develops Stevens-Johnson syndrome after starting a new drug. The hypersensitivity type is - (a) type I - (b) type II - (c) type III - (d) type IV **Answer: (d)** — Also TEN and DRESS. **Q10.** The tuberculin reaction and the granulomatous response to tuberculosis are examples of - (a) type II - (b) type I - (c) type III - (d) type IV hypersensitivity **Answer: (d)** — Delayed, T-cell mediated, no antibody. **Q11.** Which hypersensitivity type is NOT involved in autoimmune disease? - (a) type I - (b) type III - (c) type IV - (d) type II **Answer: (a)** — Autoimmunity uses types II, III and IV. **Q12.** After a streptococcal throat infection, antibodies against streptococcal M protein attack the heart. The mechanism is - (a) sequestered antigen release - (b) complement deficiency - (c) IgE release - (d) molecular mimicry (cross-reaction) **Answer: (d)** — Antibodies to a foreign antigen cross-react with self. **Q13.** After an injury to one eye, a patient develops sympathetic ophthalmia. The mechanism is - (a) complement consumption - (b) molecular mimicry - (c) IgE - (d) release of a sequestered antigen (sympathetic ophthalmia) **Answer: (d)** — Melanin-containing uveal cells released after trauma. **Q14.** HLA class I molecules are found on - (a) only B cells - (b) all nucleated cells, presenting to CD8 T cells - (c) red cells only - (d) only antigen-presenting cells **Answer: (b)** — Class II is on APCs and presents to CD4 T cells. **Q15.** The light chain of HLA class I (β2-microglobulin) is coded on chromosome - (a) 17 - (b) 15 - (c) 11 - (d) 6 **Answer: (b)** — The HLA genes themselves are on 6p. **Q16.** HLA class II (DP, DQ, DR) molecules present antigen to - (a) CD4 helper T cells - (b) red cells - (c) NK cells only - (d) CD8 cytotoxic T cells **Answer: (a)** — On B cells, macrophages, dendritic cells, thymic epithelium, activated T cells. **Q17.** Which genes lie in the HLA class III region? - (a) complement C2, C4, factor B and TNF-α - (b) the T-cell receptor - (c) β2-microglobulin - (d) immunoglobulin heavy chains **Answer: (a)** — MSD. **Q18.** For a kidney transplant, the HLA locus that matters most for matching is - (a) HLA-A - (b) HLA-C - (c) HLA-G - (d) HLA-DR **Answer: (d)** — Then HLA-B, then HLA-A. **Q19.** A young man is diagnosed with ankylosing spondylitis. The HLA allele most associated is - (a) HLA-DQ2 - (b) HLA-B27 - (c) HLA-B51 - (d) HLA-DR4 **Answer: (b)** — Ankylosing spondylitis and reactive arthritis. **Q20.** Coeliac disease and type 1 diabetes are both associated with - (a) HLA-B27 - (b) HLA-B51 - (c) HLA-DR2 - (d) HLA-DQ2 and DQ8 **Answer: (d)** — RA: DR4; Behçet: B51. **Q21.** Minutes after a kidney transplant is connected, the patient becomes febrile and anuric. This is - (a) chronic rejection - (b) hyperacute rejection from HLA incompatibility - (c) calcineurin toxicity - (d) acute T-cell rejection **Answer: (b)** — Usually means graft failure; MSD classes it as type II. **Q22.** Years after a kidney transplant, a patient has slowly rising proteinuria and hypertension. This is - (a) chronic rejection (T cell or antibody) - (b) type I hypersensitivity - (c) hyperacute rejection - (d) accelerated rejection **Answer: (a)** — May end in graft loss. **Q23.** A young woman has arthritis, a facial rash and a positive ANA. The test that is highly specific for SLE is - (a) ESR - (b) rheumatoid factor - (c) anti-dsDNA - (d) ANA titre **Answer: (c)** — ANA is very sensitive but not specific. **Q24.** A man on long-term hydralazine develops arthralgia and a positive ANA. This is - (a) rheumatoid arthritis - (b) serum sickness - (c) drug-induced lupus (resolves when the drug is stopped) - (d) primary SLE needing lifelong steroids **Answer: (c)** — Also procainamide and TNF inhibitors. **Q25.** A newborn has congenital complete heart block. The mother's blood should be tested for - (a) anti-CCP - (b) anti-GBM - (c) anti-dsDNA - (d) anti-Ro (SSA) antibodies **Answer: (d)** — Neonatal lupus. **Q26.** The commonest cardiac complication of SLE is - (a) pericarditis - (b) Libman-Sacks endocarditis - (c) aortic stenosis - (d) coronary vasculitis **Answer: (a)** — Libman-Sacks is rare. **Q27.** A young adult has a second episode of meningococcal meningitis. A defect to look for is deficiency of - (a) IgE - (b) C1 inhibitor - (c) CD4 cells - (d) a terminal complement component (C5–C9) **Answer: (d)** — Also factor B, factor D, properdin. **Q28.** Defects in early classical-pathway components (C1, C4) predispose to - (a) hereditary angioedema - (b) systemic lupus erythematosus - (c) asthma - (d) Neisseria infection only **Answer: (b)** — MSD complement table. **Q29.** A teenager has recurrent episodes of painful swelling and abdominal colic, never with itching or hives; her father has the same. The defect is - (a) mast cell disease - (b) C1 inhibitor deficiency (hereditary angioedema, autosomal dominant) - (c) IgE-mediated food allergy - (d) C5 deficiency **Answer: (b)** — Laryngeal oedema can be fatal. **Q30.** HIV enters a CD4 T cell when gp120 binds CD4 and then a co-receptor, which is - (a) CCR5 or CXCR4 - (b) CD8 - (c) HLA class I - (d) the IgE receptor **Answer: (a)** — gp41 then mediates fusion. **Q31.** A person with HIV has a CD4 count of 150/µL and develops pneumonia. The infection that becomes likely below 200 cells/µL is - (a) CMV retinitis only - (b) Mycobacterium avium complex only - (c) Pneumocystis jirovecii pneumonia - (d) influenza only **Answer: (c)** — Below 50: CMV and MAC. **Q32.** Under NACO Strategy III for the general population, a person is reported HIV-positive when - (a) any two tests are reactive - (b) all three rapid tests are reactive - (c) a single ELISA is reactive - (d) the first test is reactive **Answer: (b)** — Negative if the first test is non-reactive. **Q33.** Under India's national programme, a newly diagnosed adult with HIV and a CD4 count of 700/µL should - (a) wait until CD4 < 200 - (b) start ART now — Treat All, regardless of CD4 or stage - (c) wait until CD4 < 350 - (d) start only if symptomatic **Answer: (b)** — Treat All since 2017; same-day start offered. ### Active Recall From memory: give the mechanism and two examples of each hypersensitivity type; explain molecular mimicry and sequestered antigens; compare HLA class I and II and name four HLA–disease links; describe the rejection categories; list SLE antibodies and complement deficiencies; and outline HIV entry, CD4 thresholds and NACO testing and treatment policy.