Immunology asked in mrcog part 1
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MRCOG part 1 immunology topics syllabus questions
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MRCOG part 1 immunology topics questions
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Here is a thorough breakdown of all immunology topics tested in MRCOG Part 1, organized by theme, with key facts for each:
Immunology in MRCOG Part 1 - Complete Study Guide
1. Innate Immunity
Key Components
- Physical barriers: skin, mucous membranes, cilia, gastric acid
- Cellular components: neutrophils, macrophages, natural killer (NK) cells, dendritic cells, mast cells, basophils, eosinophils
- Soluble mediators: complement proteins, acute-phase proteins (CRP, fibrinogen), interferons, lysozyme, lactoferrin
Pattern Recognition
- Toll-like receptors (TLRs): recognize pathogen-associated molecular patterns (PAMPs) on bacteria, viruses, fungi
- NOD-like receptors: intracellular sensors for bacterial peptides
- Response is non-specific, immediate (minutes to hours), no memory
Natural Killer (NK) Cells
- Kill cells lacking MHC class I (virus-infected, tumor cells) - "missing self" hypothesis
- Uterine NK cells (uNK/dNK) are the most abundant leukocyte in the decidua in early pregnancy (up to 70% of decidual leukocytes in first trimester)
- uNK cells promote trophoblast invasion and spiral artery remodeling
- uNK cells are CD56brightCD16- (different from peripheral blood NK cells)
- Deficiency of uNK cells is linked to recurrent pregnancy loss and preeclampsia
2. Adaptive Immunity
T Lymphocytes
| Cell Type | CD Marker | MHC Restriction | Function |
|---|---|---|---|
| Helper T cells (Th) | CD4+ | MHC Class II | Activate B cells, macrophages; cytokine secretion |
| Cytotoxic T cells (CTL) | CD8+ | MHC Class I | Kill virus-infected/tumor cells |
| Regulatory T cells (Treg) | CD4+CD25+FoxP3+ | - | Suppress immune responses; critical for fetal tolerance |
Th1 vs Th2 responses:
- Th1: IFN-γ, IL-2, TNF-α → cell-mediated immunity, macrophage activation
- Th2: IL-4, IL-5, IL-13 → humoral immunity, IgE production, allergy
- Th17: IL-17 → neutrophil recruitment, mucosal defence
- Pregnancy shifts immune response from Th1 toward Th2 to protect the fetus (paternal antigens would otherwise be rejected by Th1)
B Lymphocytes & Immunoglobulins
| Immunoglobulin | Structure | Key Properties |
|---|---|---|
| IgG | Monomer | Most abundant in serum; only Ig that crosses placenta (via FcRn receptor); 4 subclasses; activates complement via classical pathway (IgG1,2,3 - not IgG4) |
| IgM | Pentamer | First produced in primary immune response; best complement activator (1 molecule sufficient); does NOT cross placenta; ABO blood group antibodies are IgM |
| IgA | Dimer (secretory) | Predominant in breast milk, saliva, tears, gut; 2 subclasses; does NOT activate complement |
| IgE | Monomer | Lowest serum concentration; binds mast cells/basophils; mediates type I hypersensitivity/allergy; anti-parasitic |
| IgD | Monomer | B cell surface receptor; function largely unknown |
Key exam points:
- IgG is the only immunoglobulin that crosses the placenta → provides passive immunity to neonate for 3-6 months
- IgM is the first immunoglobulin produced in a primary response; its presence indicates acute/recent infection
- ABO antibodies (anti-A, anti-B) are naturally occurring IgM - they do NOT cause haemolytic disease of the newborn (HDN) because IgM cannot cross the placenta
- Anti-D (Rh) antibodies are IgG - they CAN cross the placenta → HDN
3. MHC / HLA System
- MHC (Major Histocompatibility Complex) genes are located on chromosome 6
- Human equivalent = HLA (Human Leukocyte Antigens)
| Class | Molecules | Expression | Presents to |
|---|---|---|---|
| MHC Class I | HLA-A, HLA-B, HLA-C | All nucleated cells | CD8+ T cells |
| MHC Class II | HLA-DR, HLA-DQ, HLA-DP | APCs (dendritic cells, macrophages, B cells) | CD4+ T cells |
| MHC Class III | C4, C2, Factor B, TNF | - | Complement components |
Exam pearls:
- Trophoblast uniquely expresses HLA-C, HLA-E, HLA-G (not HLA-A or HLA-B) - this prevents maternal NK cell killing while limiting T cell activation
- HLA-G expression by extravillous trophoblast is a key mechanism of maternal tolerance to the fetus
- HLA typing is used for transplant matching
4. Complement System
Three Activation Pathways
| Pathway | Trigger | First Components |
|---|---|---|
| Classical | Antigen-antibody complex (IgM or IgG) | C1q → C1r → C1s → C4 → C2 → C3 |
| Lectin (MBL) | Mannose-binding lectin binds carbohydrates on microbes | MBL → MASP → C4 → C2 → C3 |
| Alternative | Spontaneous C3 hydrolysis on microbial surfaces; activated by properdin | C3 → Factor B → Factor D → Properdin |
All three pathways converge at C3 → C3a + C3b → C5 convertase → Terminal Complement Complex (MAC: C5b-9)
Complement Functions
- C3a, C4a, C5a: anaphylatoxins → mast cell degranulation, vasodilation, increased vascular permeability
- C5a: most potent anaphylatoxin; also chemotactic for neutrophils
- C3b: opsonisation (marks bacteria for phagocytosis)
- MAC (C5b-9): direct lysis of gram-negative bacteria
- C1q: binds apoptotic cells - important for clearance
Complement Deficiencies
- C1q/C2/C4 deficiency: risk of SLE (failure to clear immune complexes)
- C5-C9 deficiency: susceptibility to Neisseria (meningitidis, gonorrhoeae)
- C3 deficiency: severe recurrent pyogenic infections
- DAF (CD55) and CD59 deficiency: PNH (Paroxysmal Nocturnal Haemoglobinuria)
5. Hypersensitivity Reactions (Gell & Coombs)
| Type | Mechanism | Time | Mediator | Examples |
|---|---|---|---|---|
| Type I - Immediate/Anaphylactic | IgE on mast cells → allergen cross-linking → degranulation | Minutes | Histamine, leukotrienes, PGs | Anaphylaxis, asthma, urticaria, hayfever, atopy |
| Type II - Cytotoxic | IgG/IgM bind to cell-surface antigens → complement lysis or ADCC | Hours | IgG/IgM + complement | HDN (anti-D), Graves' disease, myasthenia gravis, autoimmune haemolytic anaemia, Goodpasture's |
| Type III - Immune Complex | Antigen-antibody complexes deposit in tissues → complement activation → neutrophil recruitment | Hours-days | IgG complexes | SLE, serum sickness, post-streptococcal GN, farmer's lung, Arthus reaction |
| Type IV - Delayed (Cell-mediated) | Sensitised T cells (CD4+ Th1) react with antigen | 48-72 hours | T cells, macrophages (NO antibody) | Contact dermatitis, tuberculin test (Mantoux), graft rejection, coeliac disease |
Obstetric relevance:
- HDN = Type II (IgG anti-D crosses placenta)
- Allergic asthma = Type I
- SLE in pregnancy = Type III immune complex disease
6. Autoimmunity
Key Autoimmune Conditions in Obstetrics/Gynaecology
Antiphospholipid Syndrome (APS)
- Autoimmune prothrombotic disorder
- Antibodies: lupus anticoagulant, anticardiolipin antibodies (IgG or IgM), anti-β2-glycoprotein I
- Clinical criteria: venous or arterial thrombosis, recurrent pregnancy loss (≥3 consecutive miscarriages before 10 weeks, or ≥1 after 10 weeks), severe preeclampsia, placental insufficiency
- Treatment in pregnancy: low-molecular-weight heparin + low-dose aspirin
- Despite being called "lupus anticoagulant", it causes thrombosis in vivo (the anticoagulant effect is an in vitro artefact)
SLE in Pregnancy
- Anti-Ro (SSA) and anti-La (SSB) antibodies → neonatal lupus, congenital heart block
- Risk of flares, preeclampsia, fetal growth restriction, preterm birth
Graves' Disease
- TSH receptor-stimulating antibodies (IgG) = Type II hypersensitivity
- Antibodies cross placenta → neonatal thyrotoxicosis
Myasthenia Gravis
- Anti-AChR antibodies (IgG) cross placenta → neonatal myasthenia
7. Immunology of Pregnancy
Fetal Tolerance (Why the fetus is not rejected)
The fetus is a semi-allograft (carries paternal HLA antigens). Several mechanisms prevent maternal rejection:
- Trophoblast lacks classical MHC class I (HLA-A/B) - cannot be recognised by maternal cytotoxic T cells
- HLA-G expression by extravillous trophoblast - inhibits NK cell killing and T cell activation; promotes Treg induction
- Regulatory T cells (Tregs) are expanded in decidua during early pregnancy and suppress anti-paternal immunity
- Th2 shift - progesterone promotes Th2 cytokine environment (IL-4, IL-10) which tolerates the fetus
- Decidual NK cells (CD56bright) promote trophoblast invasion rather than killing trophoblast
- IDO (Indoleamine 2,3-dioxygenase) - expressed by trophoblast; degrades tryptophan → inhibits T cell proliferation
- FasL expression on trophoblast - induces apoptosis of activated T cells
Decidual Immune Cells
- uNK cells: ~70% of decidual leukocytes in first trimester; promote spiral artery remodeling
- Macrophages: ~20-25% of decidual leukocytes; M1 phase during implantation, switch to M2 for tolerance
- Tregs: ~5-10%; suppress anti-paternal T cell response
- T cells: ~10-20%
8. Rhesus (Rh) Alloimmunisation
- Anti-D antibodies are IgG → cross placenta → haemolytic disease of the newborn (HDN)
- ABO antibodies are IgM → cannot cross placenta (clinically mild HDN if ABO incompatibility)
- Sensitisation occurs when Rh-negative mother is exposed to Rh-positive fetal blood (at delivery, miscarriage, amniocentesis, CVS, antepartum haemorrhage)
- Anti-D prophylaxis: given to Rh-negative women at 28 weeks, after sensitising events, and postnatally (if baby is Rh+)
- The Kleihauer-Betke test estimates fetal-maternal haemorrhage to guide anti-D dosing
9. Immunodeficiency
Primary Immunodeficiencies
| Type | Defect | Examples |
|---|---|---|
| B cell/antibody | Humoral | X-linked agammaglobulinaemia (XLA), common variable immunodeficiency (CVID), selective IgA deficiency |
| T cell | Cell-mediated | DiGeorge syndrome (thymic aplasia - 22q11 deletion) |
| Combined | B + T cells | SCID (X-linked or ADA deficiency) |
| Phagocyte | Neutrophil killing | Chronic granulomatous disease (CGD - NADPH oxidase defect) |
| Complement | Complement | C1q → SLE; C5-C9 → Neisseria infections |
Secondary Immunodeficiencies
- HIV/AIDS (CD4+ T cell depletion)
- Malnutrition, malignancy, diabetes, immunosuppressive drugs
- Pregnancy itself causes physiological immunosuppression (Th2 skewing)
10. Transplant Immunology
- Rejection mechanisms: HLA mismatch activates T cells via direct (donor APCs) or indirect (self APCs present donor peptides) pathway
- Hyperacute rejection: minutes, pre-formed antibodies (Type II hypersensitivity)
- Acute rejection: days-weeks, T cell mediated (Type IV)
- Chronic rejection: months-years, gradual fibrosis and vessel damage
High-Yield MRCOG Exam Summary
| Topic | Key Fact |
|---|---|
| First immunoglobulin in primary response | IgM |
| Only Ig crossing the placenta | IgG (via FcRn) |
| Most efficient complement activator | IgM (1 molecule sufficient) |
| HDN mechanism | Type II hypersensitivity (IgG anti-D) |
| ABO antibodies type | IgM - cannot cross placenta |
| Antiphospholipid syndrome treatment | LMWH + low-dose aspirin |
| Fetal tolerance - key molecule | HLA-G on trophoblast |
| Th shift in pregnancy | Th1 → Th2 |
| Most abundant decidual leukocyte (1st trimester) | uNK cells |
| Delayed hypersensitivity | Type IV - T cell mediated, 48-72 hours |
| Complement deficiency + Neisseria | C5-C9 deficiency |
| Complement deficiency + SLE | C1q, C2, C4 deficiency |
| HLA genes location | Chromosome 6 (MHC region) |
| CD8+ T cell restriction | MHC Class I |
| CD4+ T cell restriction | MHC Class II |
| IgE function | Mast cell binding → Type I hypersensitivity |
| Anti-Ro antibodies in SLE | Neonatal lupus, congenital heart block |
| Kleihauer-Betke test | Estimate fetal-maternal haemorrhage; guide anti-D dose |
This covers the full immunology syllabus for MRCOG Part 1. Topics that come up most frequently in past papers include: immunoglobulin structure/function, hypersensitivity classification, complement pathways, fetal tolerance mechanisms (HLA-G, Tregs, Th2 shift), antiphospholipid syndrome, and Rh alloimmunisation. Let me know if you want deeper coverage of any specific area or practice questions on any topic.
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