Hypersensitivity II — Type II
Antibody against a cell ★★★
Type I was antibody sitting on a mast cell, waiting for antigen to arrive. Type II is the reverse: antibody binding an antigen that is already on a cell surface — and the cell carrying that antigen is then destroyed. The defining feature, and the one the exam asks about, is that there is a specific target cell.
| Component | Detail |
|---|---|
| Antibodies | IgG and IgM |
| Antigen | Present on the cell surface |
| Effectors | Complement, macrophages and NK cells |
| Cells affected | Blood cells and self tissue cells |
⚠️ The original paper misprints this question: two options are both labelled “B”. It is reproduced here with corrected lettering.
- Which antibodies mediate type II? → IgG and IgM
- Where is the antigen? → On the cell surface
- Which effectors are involved? → Complement, macrophages and NK cells
- What is the defining feature? → Damage to a specific target cell
Where the surface antigen comes from ★★
- Constitutive components of the cell membrane — ABO blood group antigens, Rh blood group antigens, HLA antigens
- Common antigens shared by host cells with exogenous antigens — for example the cell wall of streptococcus and the cardiac valve
- Modified self antigens — altered by chemicals, infections or drugs
- Antigens or haptens adsorbed to the cell surface
Category 2 should look familiar — it is Unit 2's cross-reaction and molecular mimicry, reappearing as a disease mechanism. Antibody raised legitimately against a streptococcus binds a cardiac valve because the two share an epitope. Category 4 is Unit 2's hapten: a drug adsorbed onto a red cell can make that cell a target, which is how drug-induced haemolytic anaemia happens.
- Name the four sources of type II antigen. → Constitutive membrane components; shared/cross-reactive antigens; modified self antigens; adsorbed antigens or haptens
- Give an example of a constitutive one. → ABO, Rh or HLA antigens
- Which category explains drug-induced haemolytic anaemia? → Haptens adsorbed to the cell surface
Three ways to destroy the target ★★★
| Mechanism | How it works |
|---|---|
| 1 · Complement-mediated lysis | IgG or IgM on the cell surface activates the classical pathway; the MAC (C5b–C9) lyses the target cell |
| 2 · Opsonised phagocytosis | The coated cell is phagocytosed — via FcγR binding the antibody, and via C3b binding complement receptors on macrophages and neutrophils |
| 3 · ADCC | NK cells bind the IgG coating the target through FcγRIII (CD16) and kill it |
Look at the three mechanisms and notice that every one is a normal antibody effector function from Unit 3, working perfectly. Complement lysis is what antibody does to bacteria. Opsonisation is how phagocytes clear infection. ADCC is how NK cells kill virus-infected cells.
The pathology is entirely in the target. The machinery is not malfunctioning — it has simply been aimed at a host cell. That is why type II diseases are so destructive and so hard to switch off: there is nothing broken to repair.
- Name the three mechanisms of type II damage. → Complement-mediated lysis, opsonised phagocytosis, ADCC
- Which complement product lyses the cell? → The MAC, C5b–C9
- Which two opsonins drive phagocytosis? → Antibody via FcγR, and C3b via complement receptors
- Which cell performs ADCC, and via which receptor? → The NK cell, via FcγRIII (CD16)
Transfusion reactions ★★
| Detail | |
|---|---|
| Scenario | A type A individual transfused with blood from a type B individual |
| Mechanism | Red cells + IgM → complement activation |
| Symptoms | Haemolysis, fever, chills, nausea, clotting within blood vessels, pain in the lower back, haemoglobin in the urine |
| Therapy | Terminate the transfusion; maintain urine flow with diuretics |
Note that the antibody here is IgM. Anti-A and anti-B are the natural antibodies mentioned in Unit 3 — present without prior transfusion, and IgM because they arise against carbohydrate (TI) antigens with no class switching. Being IgM, they are outstanding complement activators, which is why ABO incompatibility causes immediate intravascular haemolysis rather than a slow process.
- Which antibody causes an ABO transfusion reaction? → IgM
- What is the mechanism? → IgM on red cells activates complement, causing lysis
- Name the key symptoms. → Haemolysis, fever, chills, nausea, intravascular clotting, lower back pain, haemoglobinuria
- What is the therapy? → Stop the transfusion and maintain urine flow with diuretics
- Why is ABO haemolysis so rapid? → Anti-A/anti-B are IgM, the most efficient complement activator
Haemolytic disease of the newborn ★★★
HDN is the most instructive disease in the whole course, because solving it requires almost everything taught so far — primary versus secondary responses, memory cells, class switching, and which immunoglobulin crosses the placenta.
Disease caused by Rh or ABO blood-group incompatibility between mother and fetus. It develops when maternal IgG against fetal blood-group antigen crosses the placenta and destroys fetal red blood cells. Consequences: fetal anaemia, jaundice and bilirubin deposition.
- 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.
- The mother mounts a primary response: IgM, which cannot cross the placenta. The first baby is therefore unharmed. But memory cells are formed.
- In a subsequent pregnancy with an Rh⁺ fetus, those memory cells mount a secondary response: IgG, at high titre.
- IgG crosses the placenta, binds fetal red cells, and lyses them → haemolytic disease of the newborn.
Every step is Unit 12's primary-versus-secondary table and Unit 3's placental-transfer rule, applied to a real disease.
Trace the logic and notice how neatly it explains the clinical facts.
Why is the first baby spared? Because a primary response makes IgM, and IgM is a 900 kD pentamer that cannot cross the placenta. The sensitising event usually happens at delivery, when the baby is already out.
Why is the second baby affected? Because memory cells produce IgG — and IgG is the one class that crosses the placenta. The mechanism that normally gives a newborn passive immunity is the same one that destroys its red cells.
So the target is the mother's memory. If you prevent memory forming, there is never a secondary response — which is exactly what the prevention does.
| Consequence | Mechanism |
|---|---|
| Anaemia | Mild, severe or fatal — from red cell destruction |
| Jaundice | From released haemoglobin |
| Brain damage | Haemoglobin → lipid-soluble bilirubin → accumulates in the brain |
The 72-hour window matters: it must be given before sensitisation is established. This is passive immunisation used not to protect the recipient but to prevent an immune response — the only place in the course where antibody is given for that purpose.
| Therapy | Purpose |
|---|---|
| Intrauterine blood-exchange transfusion | Replace fetal Rh⁺ red cells with Rh⁻ cells |
| Blood-exchange transfusion | Primarily to remove bilirubin |
| Low-level UV light (phototherapy) | Break down bilirubin and prevent cerebral damage |
| Plasmapheresis | Discard the maternal plasma containing anti-Rh antibody |
- What causes HDN? → Maternal IgG against fetal blood-group antigen crossing the placenta and destroying fetal red cells
- Why is the first baby usually unaffected? → The primary response makes IgM, which cannot cross the placenta
- How does the mother become sensitized? → Fetal Rh⁺ cells entering her at delivery, or by transfusion or abortion
- How does Rhogam work? → It binds fetal Rh antigen and clears the cells before B-cell activation and memory formation
- Within what time must Rhogam be given? → 72 hours after the first delivery
- Why does bilirubin damage the brain? → It is lipid-soluble and accumulates in brain tissue
Revision layer
The exam map for this unit
| Section | Item | From |
|---|---|---|
| III. MCQ Q19 | Haemolytic disease shows target-cell damage | §1 |
| IV. True/False Q7 | Rhogam within 72 h prevents HDN — T | §5 |
| IV. True/False Q10 | NK cells, macrophages and complement act in type II — T | §3 |
The whole unit on one screen
| Question | Answer |
|---|---|
| Antibodies? | IgG and IgM |
| Antigen location? | On the cell surface |
| Effectors? | Complement · macrophages · NK cells |
| Three mechanisms? | Complement lysis (MAC) · opsonised phagocytosis · ADCC |
| Four antigen sources? | Constitutive membrane · shared/cross-reactive · modified self · adsorbed haptens |
| Transfusion reaction antibody? | IgM, activating complement |
| Transfusion therapy? | Stop the transfusion; maintain urine flow with diuretics |
| Why is the first baby spared in HDN? | Primary response is IgM — cannot cross the placenta |
| Why is the second affected? | Memory → secondary response → IgG — crosses the placenta |
| Rhogam mechanism and timing? | Clears fetal Rh⁺ cells before B-cell activation, preventing memory; within 72 h |
| Diseases? | Transfusion reaction · HDN · haemolytic anaemia · hyperthyroidism |
- Define type II hypersensitivity. → IgG or IgM binding antigen on a cell surface, causing that target cell's destruction
- Name the three destruction mechanisms. → Complement-mediated lysis, opsonised phagocytosis, ADCC
- Which cell performs ADCC here, and why not in type I? → The NK cell via CD16 — ADCC needs IgG on a target cell, which type I lacks
- Trace HDN from first to second pregnancy. → Fetal Rh⁺ cells sensitize mother → IgM (no placental transfer, first baby safe) → memory → second pregnancy → IgG crosses → fetal red cells lysed
- How is HDN prevented, and why does it work? → Rhogam within 72 h clears the fetal cells before memory can form
- Which disease is the answer to 'target cell damage'? → Haemolytic disease