📋 Comparison Tables

The instruction is explicit about the answer format — single words, not sentences. Write “no / quick / no / no” and “yes / slow / yes / yes” and the six marks are banked in under a minute. Padding it with prose gains nothing and costs time you need for Section V's later questions.

Note that immune defence has two failure modes in opposite directions — too little gives immunodeficiency, too much gives hypersensitivity. Stating both is what separates a full answer from a partial one.

If there is room, add the clinical pay-off: because TI antigens give no memory and work poorly in infants, the pneumococcal polysaccharide is conjugated to a carrier protein to convert it into a TD antigen.

1 · Properties of the antigen — foreignness (the dominant factor); chemical nature (proteins and glycoproteins strongest); molecular weight (>100 kD strong, <10 kD poor); structural complexity; epitope conformation and accessibility; physical form (polymer > monomer, cyclic > linear, particulate > soluble).

2 · The host — genetic background, especially MHC type; age, sex and state of health; infection or immunosuppressive drugs.

3 · Method of administration — dose (a moderate dose is best; extremes induce tolerance); timing of injections; route (intracutaneous > subcutaneous > intravenous > oral); use of an adjuvant.

If there is room, add the clinical point: tetanus antitoxin is pepsin-digested so that the immunogenic Fc is removed while the bivalent F(ab′)₂ still neutralises the toxin.

1 · Mediated by the V region — antigen recognition. Binding is highly specific, one epitope per site, two sites per monomer. The direct consequence is neutralisation of viruses, of Gram-negative bacteria and of toxins — which requires neither complement nor cells.

2 · Mediated by the Fc portion:

① Activation of complement — C1q binds C_H2 of IgG or C_H3 of IgM, triggering the classical pathway; aggregated Ig can trigger the alternative pathway.
② Opsonisation — phagocytes bearing FcγR ingest IgG-coated microbes far more efficiently.
③ ADCC — NK cells and leucocytes bearing FcγR bind IgG on a target cell and lyse it.
④ Mediating type I hypersensitivity — IgE on mast cells and basophils, cross-linked by allergen, causes degranulation.
⑤ Crossing the placenta or mucosa — IgG via placental Fc receptors; sIgA into external secretions.

① Opsonisation — C3b (and iC3b) coats the microbe and is bound by CR1 (CD35) on phagocytes, greatly increasing ingestion. Quantitatively the most important function.

② Inflammation — the anaphylatoxins C3a, C4a and C5a trigger mast-cell degranulation and increase vascular permeability.

③ Chemotaxis — C5a is the most potent chemoattractant for neutrophils and monocytes, and activates them so that CR1-bound microbes are actually ingested.

④ Cell lysis — the MAC (C5b–C9) forms a membrane pore; particularly important against Neisseria.

⑤ Clearance of immune complexes — C3b-tagged complexes bind CR1 on erythrocytes and are carried to liver and spleen.

⑥ Linking innate to adaptive immunity — C3d bound to antigen engages CR2 (CD21) on the B-cell co-receptor, lowering the activation threshold.

Two clinical points earn the final marks. In hereditary angioedema the swelling is complement-mediated, not histamine-mediated, so antihistamines and adrenaline are ineffective. In PNH, DAF and CD59 are both GPI-anchored, so a single anchor defect removes both at once and the patient's own alternative pathway lyses their red cells.

Secretion. A brief, self-limited event — cytokines are not stored preformed but synthesised and immediately secreted.

Synthesis. Different cell types make the same cytokine (IL-6 from macrophages, endothelium and T cells); one cell type makes many cytokines.

Action. Through high-affinity receptors on target cells, in three modes: autocrine (same cell), paracrine (nearby cell) and endocrine (at a distance).

Cytokines do not possess specificity — stating this explicitly is worth a mark, and it is what MCQ Q15 tests.

Worth adding: each lineage's cytokines inhibit the other lineage (IFN-γ suppresses Th2; IL-4 and IL-10 suppress Th1), so the commitment is self-reinforcing.

General activities: innate antibacterial — IL-1, TNF, IL-12; innate antiviral — IFN-α, IFN-β; adaptive — IL-2, IL-4, IL-5, IL-6, IFN-γ; haematopoiesis — CSF, IL-7, EPO, IL-6, IL-11, TPO.

Definition. CD stands for cluster of differentiation — a series of membrane molecules or markers determined by monoclonal antibodies. They are so named because these molecules appear or disappear at different stages of cell differentiation and maturation.

Scale. Numbered CD1–CD247, organised into 13 groups (T cell, B cell, NK cell, platelet, adhesion molecules, and others).

Uses. ① Identifying cell lineage and developmental stage — the basis of immunophenotyping in leukaemia and lymphoma. ② Many CD molecules have defined functions: CD3 transduces the TCR signal; CD4 and CD8 are co-receptors; CD28 receives B7; CD40 receives the B-cell second signal; CD21 is the C3d and EBV receptor; CD16 mediates ADCC.

Worth adding: selectin–carbohydrate binding is deliberately weak and rapidly reversible, producing rolling; integrin binding is strong and stable, producing arrest. The two-stage design exists because a firm bond formed at full flow velocity would tear.

① Co-receptors and co-stimulators in the immune response. Some CAMs act as co-receptors — CD4 and CD8, which grip MHC and stabilise the contact while the TCR reads peptide. Others act as co-stimulators — CD28, CD80 and CD86 — supplying the second signal for T-cell activation.

② Leukocyte migration and inflammation. Extravasation proceeds in four steps: rolling (selectins binding mucin-like carbohydrate) → activation of integrins by chemokines displayed on the endothelium → firm adhesion (integrins binding ICAM-1 and VCAM-1) → transmigration. Endothelium is licensed for this by TNF-α, which externalises preformed P-selectin.

③ Lymphocyte homing. Mediated by lymphocyte homing receptors (LHR) on the lymphocyte and addressins on the tissue. Naïve T cells home to secondary lymphoid tissue; effector T cells home to mucosal or skin sites according to where they were activated.

① TCR–CD3 complex. TCR binds antigen (αβ 95–99%, γδ 1–5%) and is a lineage marker; CD3 transduces the signal through ITAM motifs.

② Co-receptors. CD4 (monomer, 60–65% of αβ T cells) binds the β2 domain of MHC class II and is the HIV gp120 receptor; CD8 (heterodimer, 30–35%) binds the α3 domain of MHC class I. Both increase antigen sensitivity and participate in activation signalling.

③ Co-stimulatory molecules. Positive: CD28 (ligand B7.1/B7.2 — signal 2), ICOS (ligand ICOSL). Negative: CTLA-4 (same B7 ligands, ITIM, inhibitory), PD-1 (ligands PD-L1/PD-L2). Also CD40L (ligand CD40 on B cells/APC), CD2 (ligand LFA-3), LFA-1 (ligand ICAM-1).

④ Mitogen receptors. PHA, Con A, PWM — polyclonal, non-specific activators used in the T-cell transformation test.

Characteristics. CTLs are CD8⁺, kill with antigen specificity and MHC class I restriction, and are not injured in the process — so one CTL can kill repeatedly.

① Perforin / granzyme pathway. Perforin, a pore-forming monomer stored in CTL granules, is released and polymerises to form an aqueous channel in the target membrane; the target may die by osmotic swelling. Granzymes enter through these channels, activate caspases and induce apoptosis.

② Fas–FasL pathway. The CTL expresses FasL, which binds Fas on the target cell; this activates caspases and causes apoptosis.

Both pathways converge on apoptosis rather than lysis — which destroys the viral genome and packages the remains for phagocytosis instead of spilling infectious virions into the tissue.

The examiner supplies the six rows, so the marks are for filling each one — not for an essay. Anchor every row to a mechanism (antibody, presentation, ADCC) rather than a general statement.

① BCR complex. Membrane Ig (mIg) binds antigen via V_H+V_L; Igα (CD79a) / Igβ (CD79b) transduce the signal through ITAM motifs.

② Co-receptor. CD19 / CD21 / CD81 — enhances naïve B-cell responsiveness and helps transduce signal 1. CD21 is CR2, the C3d and EBV receptor.

③ Co-stimulatory molecules. CD40 (ligand CD40L on activated Th cells) delivers the most important second signal; B7-1/B7-2 (CD80/CD86) give signal 2 to T cells via CD28; adhesion molecules ICAM-1 and LFA-1 stabilise the contact.

④ Other molecules. CD19 — B-cell marker and CAR-T target; CD20 — B-cell marker and monoclonal-antibody target; CD22 — ITIM, negatively regulates the co-receptor; CD32 — negatively regulates activation and antibody secretion; mitogen receptors PWM-R, LPS-R, SPA-R.

Note the parallel with γδ T cells and TI antigens: the same innate-lymphocyte signature — narrow repertoire, no help needed, IgM only, no memory — recurs three times across this course.

NK cells carry two opposing receptor systems:

On a normal cell, class I HLA is expressed normally, so the inhibitory receptors are engaged and their signal outweighs the activating signal — killing is suppressed.

On an abnormal cell — many tumours, and cells infected by viruses that down-regulate MHC I — class I expression is lost or reduced. The inhibitory signal disappears, the activating receptors (NKG2D and the NCRs) predominate, and the target is killed. This is “missing self” recognition.

NK cells can additionally kill by ADCC: FcγRIII (CD16) binds IgG already coating a target cell.

Significance: a virus that switches off MHC I to escape CD8⁺ CTLs thereby exposes itself to NK cells — the two killers are complementary.

Origin and distribution. HSC → myeloid progenitor → pre-monocyte → blood monocyte → tissue macrophage. Tissue names: Kupffer cells (liver), mesangial cells (kidney glomerulus), microglia (brain), alveolar macrophages (lung), histiocytes (connective tissue).

Recognition receptors. Non-opsonic (PRR) — mannose receptor, scavenger receptor, Toll-like receptor. Opsonic — FcγR and C3bR/C4bR.

Killing mechanisms. Oxygen-dependent — reactive oxygen intermediates (O₂⁻, OH⁻, H₂O₂, ¹O₂) and reactive nitrogen intermediates (NO). Oxygen-independent — low pH (3.5–4), lysozyme, defensins.

Functions. ① Kill and remove pathogens. ② Kill intracellular bacteria and target cells (tumour cells, virus-infected cells). ③ Participate in and stimulate inflammation. ④ Process and present antigen. ⑤ Immunological regulation.

PRR — pattern recognition receptors: the receptors expressed by innate immune cells which recognise certain molecular structures owned by pathogens. Families: Toll-like receptors (TLR1–9; LPS, peptidoglycan, viral nucleic acids), C-type lectin receptors (mannose receptor; fungal and mycobacterial carbohydrate), scavenger receptors (CD36), pentraxins (C-reactive protein).

PAMP — pathogen-associated molecular patterns: highly conserved structures expressed by pathogens or their products, absolutely distinct from normal host substances. DAMPs are the equivalent signals released from damaged and dying host cells.

Why it works. PAMPs are conserved because they are essential to the microbe — a bacterium cannot discard its cell wall to evade detection. So a small, germline-encoded set of receptors covers whole classes of pathogen, is available immediately without any prior exposure, and cannot be escaped by mutation as an antigenic epitope can.

Link to adaptive immunity. PRR engagement induces B7 expression on APCs, supplying signal 2 for T-cell activation — Janeway's prediction that innate immunity controls adaptive immunity.

Memory aid: class I × CD8 = 8 and class II × CD4 = 8.

① Polygeny — several different MHC genes exist (A, B, C; DP, DQ, DR), so each person expresses several different class I and class II molecules.

② Polymorphism — multiple alleles at each locus within the species: HLA-A 303 alleles, HLA-B 559, HLA-C 150, HLA-DRB 440.

③ Co-dominance — both maternal and paternal gene products are expressed in the same cell; there is no allelic exclusion.

④ Haplotype — the particular combination of MHC alleles on a single chromosome, transmitted as a single unit in most cases.

⑤ Linkage disequilibrium — the difference between the observed frequency of an allele combination and that expected from the individual allele frequencies.

Significance: polymorphism lies between individuals rather than within one, so it defends the species — no pathogen can evade every person's MHC. Co-dominance and polygeny widen the peptide repertoire of each individual.

① Antigen presentation. MHC molecules bind peptides derived from pathogens and display them to T cells. Class I presents endogenous (cytosolic) peptide to CD8⁺ CTLs; class II presents exogenous (vesicular) peptide to CD4⁺ helper T cells. Because a T-cell receptor recognises antigen only as peptide bound to MHC, this is the sole route by which T cells see antigen at all.

② MHC restriction. The interaction between antigen-presenting cell and T cell is MHC-restricted — a given T cell recognises peptide only in the context of a particular MHC molecule.

③ T-cell differentiation in the thymus. MHC molecules on thymic epithelial cells drive positive selection (conferring self-MHC restriction and committing the cell to CD4 or CD8) and, on thymic DCs and macrophages, negative selection (conferring self-tolerance). MHC therefore does not merely impose restriction — it creates it.

Also: MHC class I is the ligand for NK inhibitory receptors, so its loss triggers missing-self killing; and MHC differences between individuals are the basis of graft rejection.

The organising idea worth stating: the compartment the antigen occupies determines the MHC class, which determines the T-cell subset, which determines the outcome. Cytosolic antigen means the cell itself is compromised, so it is killed; external antigen means the APC is a healthy scout, so help is recruited instead.

The reason for the trade is geographical: a DC must be in peripheral tissue to collect antigen and in a lymph node to present it to naïve T cells. Encountering a pathogen triggers the switch from sampling to reporting.

The decisive row is co-stimulation. Only the DC is constitutively equipped with both MHC and B7, so only the DC can supply signal 1 and signal 2 to a naïve T cell — the reason it alone initiates a primary response.

If there is room, give the reason in one sentence: the secondary response is mounted by memory B cells, which are already numerous, already class-switched and already affinity-matured. That single fact accounts for every row.

Add the requirements: full T-cell activation needs signal 1 + signal 2 + cytokines; full B-cell activation needs BCR signal + CD40/CD40L plus IL-2, IL-4, IL-5 and IL-6. Most events occur in the secondary lymphoid organs.

TI antigens subdivide: TI-1 carries a mitogen-like structure and acts as a polyclonal B-cell activator at high concentration; TI-2 carries repeated determinants that cross-link the BCR and activate mature B cells specifically.

The explanatory point worth adding: class switching, affinity maturation and memory all occur in the germinal centre, which requires T-cell help — so a TI antigen, bypassing T cells, can access none of them.

Components. ① Allergens — proteins that selectively activate Th2 and B cells to induce IgE. ② IgE — least abundant serum Ig, does not fix complement, binds FcεRI via C_H2 and C_H3. ③ Cells — mast cells and basophils (both FcεRI⁺), with eosinophils in the late phase. ④ Mediators.

① Sensitization phase. First allergen exposure activates B cells to form IgE-secreting plasma cells; IgE binds FcεRI on mast cells and basophils, producing sensitized target cells. No symptoms.

② Excitation phase. The allergen re-enters and cross-links the bound IgE, changing the target-cell membrane and triggering degranulation.

③ Effector phase. Preformed histamine and newly formed leukotrienes, PGD₂ and PAF cause smooth-muscle contraction, vasodilation with increased vascular permeability, and mucus secretion — giving rhinitis, asthma, urticaria or anaphylaxis according to site.

Detection. ① Skin test — small amounts of allergen by intradermal injection or superficial scratching of forearm skin; a wheal and flare >5 × 5 mm at 30 minutes is positive, showing specific IgE on skin mast cells. Advantages: inexpensive, screens many allergens at once. Disadvantage: rarely may induce systemic anaphylactic shock. ② ELISA for serum IgE specific to a given allergen.

Treatment principles. ① Avoid known allergens. ② Inhibit IgE production. ③ Stabilise mast cells to inhibit degranulation. ④ Antagonise active mediators. ⑤ Medication, including:

Systemic anaphylaxis — a shock-like, often fatal state with onset within minutes, caused by systemic vasodilation and increased permeability. Causes: drugs (penicillin, insulin), animal antiserum antitoxins, and venom from bee, wasp or hornet.

Respiratory. Allergic rhinitis (hay fever) — airborne allergens meet sensitized mast cells in conjunctivae and nasal mucosa; watery exudation, sneezing, coughing. Asthma — the same reaction in the lower respiratory tract; bronchial smooth-muscle contraction and mucus secretion cause airway obstruction and dyspnoea.

Skin. Atopic urticaria (hives) — allergen binds sensitized mast cells in skin, causing swollen red eruptions; also eczema.

Digestive. IgE cross-linking on GI mast cells causes localised smooth-muscle contraction and vasodilation — vomiting, diarrhoea, bellyache.

All share one mechanism; the site of the degranulating mast cells determines the disease. 20–30% of the population is affected by some form.

Components. Antibodies IgG and IgM; antigen present on the cell surface; effectors complement, macrophages and NK cells. Blood cells and self tissue cells are the targets.

Sources of the surface antigen. ① Constitutive membrane components (ABO, Rh, HLA). ② Common antigens shared with exogenous antigens (e.g. streptococcal cell wall and cardiac valve). ③ Modified self antigens (chemicals, infections, drugs). ④ Antigens or haptens adsorbed to the cell surface.

Three mechanisms of destruction.

Worth stating: every one of these is a normal antibody effector function working correctly — the pathology lies entirely in the target.

Sensitisation. An Rh⁻ mother carries an Rh⁺ fetus. Fetal Rh⁺ red cells enter the mother — at delivery of the first baby, or through transfusion or abortion.

Primary response. The mother makes IgM, which cannot cross the placenta, so the first baby is unharmed. But memory cells are formed.

Secondary response. In a subsequent pregnancy with an Rh⁺ fetus, memory cells produce IgG at high titre. IgG crosses the placenta, binds fetal red cells and lyses them.

Consequences. Anaemia (mild to fatal); jaundice; brain damage, because haemoglobin is converted to lipid-soluble bilirubin which accumulates in the brain.

Prevention. Anti-Rh antibody (Rhogam) given to the mother within 72 hours of the first delivery. It binds Rh antigen on fetal red cells and clears them before the mother responds, thereby preventing B-cell activation and memory-cell generation.

Therapy. Intrauterine blood-exchange transfusion (replacing fetal Rh⁺ cells with Rh⁻); blood-exchange transfusion (to remove bilirubin); phototherapy (to break down bilirubin); plasmapheresis (to discard maternal anti-Rh antibody).

The single most useful contrast: in type I the antibody sits on the effector cell waiting for antigen; in type II it sits on the target cell marking it for destruction.

Formation and size. Soluble antigen stimulates antibody; immune complexes form. Their fate depends on size:

Deposition sites. Joint synovium, glomerular basement membrane, choroid plexus — all filter blood under pressure through small vessels.

Injury. Deposited complexes activate complement. C3a, C4a, C5a (anaphylatoxins) degranulate mast cells and increase vascular permeability; C3a, C5a, C5b67 (chemotactic) recruit neutrophils, which release lytic enzymes; C3b activates platelets, giving aggregation and microthrombi. The result is oedema, haemorrhage and tissue damage.

Properties. ① Delay of 24–72 hours after the second antigen contact. ② Recruitment of macrophages. ③ No antibody and no complement involved.

Mechanism. Intracellular bacteria, viruses, parasites or chemicals are taken up by APCs; T cells differentiate into effector CD4⁺ Th1 and CD8⁺ CTL plus memory cells. On re-exposure, Th1 cells secrete chemokines (recruiting macrophages), IFN-γ (activating macrophages) and TNF-α/TNF-β (local tissue injury, increased endothelial adhesion molecules); CTLs lyse target cells directly.

Diseases. ① Infectious DTH — tuberculosis: first infection may give miliary TB, second gives a localised reaction, repeated occurrence gives chronic granuloma. The OT (tuberculin) test shows red induration ~5 mm at 24–48 h; a negative result may mean no exposure or immunodeficiency. ② Contact dermatitis — a hapten (nickel, dye, cosmetics, leather) binds keratin of the cuticle to form the antigen; effector T cells produce local red swelling and blistering.

Note: DTH is an important effector form of cell-mediated immunity — essentially inflammation — and is how intracellular organisms are contained.

Two questions place any disease: is it antibody or T cell? (T cell, macrophages, granuloma or days of delay → type IV); then where is the antigen? (on a mast cell via IgE → I; fixed on a target cell → II; soluble and forming deposits → III).

Principle. All rest on the specific binding of antigen and antibody. Methods may be qualitative (existence) or quantitative (concentration), and visible or invisible (needing a label).

The organising question for any assay: if you supply known antibody you are hunting antigen; if you supply known antigen you are hunting antibody.

Immune cells are assessed along two axes: number (normal range, higher, lower) and function (normal, stronger, deficient). Both are needed, because a normal count can conceal defective function.

The clinical importance of the function axis is shown by the tuberculin test: a negative result may mean no exposure — or that the patient is immunodeficient and cannot mount the response at all.

Definition. The treatment of a disease with therapeutic agents that potentiate or inhibit the immune response.

Antigen-based (active): purified antigen, synthetic peptide–carrier conjugate, recombinant antigen (HBsAg in yeast), DNA vaccine, recombinant virus vector.
Antibody-based (passive): antitoxin, gamma globulin, anti-viral serum, anti-lymphocyte serum; monoclonal antibodies including engineered (chimeric, humanized, single-chain, bi-specific) and checkpoint blockade (CTLA-4, PD-1, PD-L1).
Cytokine-related: supplementation (IFN-α, IFN-β, IL-2, CSF, EPO) and antagonism (anti-TNF mAb, IL-1ra).

The organising point: the compartment in which the antigen appears determines the presentation pathway, which determines the kind of immunity you get. That is why DNA vaccines are pursued for viruses and tumours, where CTLs are needed.

1 · Immune serum (antiserum). Antitoxins for exotoxin-induced disease (tetanus, diphtheria); serum or placental gamma globulin to prevent viral infection (measles, hepatitis) and treat hypogammaglobulinaemia; anti-viral serum for measles and rabies; anti-lymphocyte serum to inhibit graft rejection and treat autoimmune disease.

2 · Monoclonal antibodies. Anti-CD3 and anti-CD4 to prevent graft rejection and GVHD; anti-IL-1 and anti-TNF for rheumatoid arthritis and chronic inflammation; antibody-guided therapy — radioimmunotherapy (¹³¹I, ¹²⁵I), chemotherapy conjugates, and immunotoxins (ricin, diphtheria toxin).

3 · Engineered monoclonal antibodies. Chimeric (mouse V + human C), humanized, single-chain (V_H–linker–V_L) and bi-specific — each step reducing the mouse content that would otherwise act as a xenogeneic antigen.

4 · Immune checkpoint blockade. Monoclonal antibodies against CTLA-4, PD-1 and PD-L1 (also BTLA, VISTA, TIM3, LAG3), used in tumour immunotherapy to release the brake on T cells. Characteristic toxicity is autoimmune, because checkpoints normally prevent autoimmunity.