Immunopathology for NEET PG Pathology: Hypersensitivity Types, HLA, Transplant Rejection, SLE, Complement, HIV/AIDS

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🎯 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.

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

• Type I

  IgE, mast cells; < 1 h; atopy, anaphylaxis.

• Confirm anaphylaxis

  Serum tryptase within 2 h.

• Type II

  Antibody on cells: hyperacute rejection, Coombs+ haemolysis, Hashimoto, anti-GBM.

• Type III

  Immune complexes: serum sickness, SLE, RA, vasculitis.

• Type IV

  T cells: contact dermatitis, TB, SJS/TEN, DRESS, acute/chronic rejection.

• Autoimmunity never uses

  Type I.

• Molecular mimicry

  Streptococcal M protein vs heart.

• Sequestered antigen

  Sympathetic ophthalmia.

• HLA genes

  Chromosome 6p; β2m on 15.

• Class I vs II

  All nucleated cells/CD8 vs APCs/CD4.

• Class III region

  C2, C4, factor B, TNF-α.

• Matching priority

  DR > B > A.

• HLA-B27

  Ankylosing spondylitis, reactive arthritis.

• HLA-DQ2/DQ8

  Coeliac, type 1 diabetes.

• HLA-DR4

  Rheumatoid arthritis.

• Hyperacute rejection

  Minutes–hours; HLA antibody; graft lost.

• SLE antibodies

  ANA sensitive; anti-dsDNA specific.

• Drug-induced lupus

  Hydralazine, procainamide, TNF inhibitors.

• Anti-Ro mother

  Congenital heart block.

• C5–C9 deficiency

  Neisseria.

• Hereditary angioedema

  C1-INH; AD; no urticaria; larynx.

• HIV entry

  gp120–CD4 + CCR5/CXCR4; gp41 fusion.

• CD4 thresholds

  < 200 PCP, toxo, crypto; < 50 CMV, MAC.

• NACO

  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)

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

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

Q4. Anti-glomerular basement membrane disease is classified by MSD as

• (a) type III

• (b) type I

• (c) type IV

• (d) type II hypersensitivity

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

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)

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

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)

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

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

Q11. Which hypersensitivity type is NOT involved in autoimmune disease?

• (a) type I

• (b) type III

• (c) type IV

• (d) type II

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)

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)

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

Q15. The light chain of HLA class I (β2-microglobulin) is coded on chromosome

• (a) 17

• (b) 15

• (c) 11

• (d) 6

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

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

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

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

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

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

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

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

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

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

Q26. The commonest cardiac complication of SLE is

• (a) pericarditis

• (b) Libman-Sacks endocarditis

• (c) aortic stenosis

• (d) coronary vasculitis

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)

Q28. Defects in early classical-pathway components (C1, C4) predispose to

• (a) hereditary angioedema

• (b) systemic lupus erythematosus

• (c) asthma

• (d) Neisseria infection only

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

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

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

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

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

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.