The Immune Response
Assembling the whole picture ★★
Every unit so far has described a component — an antigen, an antibody, a cell, a molecule. This unit puts them in motion. It is the point where the parts become a process, so almost nothing here is genuinely new; what is new is the order.
The process in which the immune system recognises and removes antigens.
| Form | Mediated by | Divided into |
|---|---|---|
| Innate immune response | Innate cells and molecules | — |
| Adaptive: cellular immunity (CI) | Primarily T cells | CD4⁺ T-mediated and CD8⁺ T-mediated immunity |
| Adaptive: humoral immunity (HI) | Primarily B cells | — |
One point of geography matters and is easily forgotten: most events of the adaptive immune response take place in the secondary (peripheral) lymphoid organs — spleen, lymph node and MALT. The infection may be in your foot, but the response is organised in a lymph node, because that is where antigen is delivered and where naïve lymphocytes circulate. That is why Unit 1 called the peripheral organs the site where responses are initiated.
- Define the immune response. → The process in which the immune system recognises and removes antigens
- What are the two arms of adaptive immunity? → Cellular (T cells) and humoral (B cells)
- Where do most adaptive events occur? → Secondary lymphoid organs — spleen, lymph node, MALT
The three phases ★★★
| Phase | Cell-mediated immunity | Humoral immunity |
|---|---|---|
| 1 · Antigen recognition | APCs ingest, process and present antigen to naïve T cells; T cells recognise the peptide–MHC complex via TCR/CD3 | B cells recognise antigen directly via the BCR |
| 2 · Activation, proliferation and differentiation | Naïve T cells are activated, proliferate and differentiate into effector T cells and memory cells | Naïve B cells are activated, proliferate and differentiate into plasma cells and memory cells |
| 3 · Effector | Effector T cells (CD4⁺ and CD8⁺) remove the antigen by various mechanisms | Antibodies secreted by plasma cells remove the antigen |
Look at row one. The T cell needs an intermediary; the B cell does not. That single asymmetry, from Unit 11, propagates through the whole response.
Because the T cell can only read peptide–MHC, it is restricted — it sees only what an APC chooses to show it, and only in the context of self-MHC. Because the B cell reads native antigen directly, it can respond to shapes, sugars and surfaces the T cell will never see. Neither is better; they are complementary sensors, and phase 1 is where they diverge.
Phases 2 and 3 then look almost identical for both, because both are running clonal selection: find the right cell, expand it, arm it, and keep a memory copy.
- Name the three phases. → Antigen recognition; activation/proliferation/differentiation; effector
- How does phase 1 differ for T and B cells? → T cells need an APC to present peptide–MHC; B cells bind native antigen directly
- What does each arm produce in phase 2? → T → effector T cells and memory cells; B → plasma cells and memory cells
Cell-mediated immunity ★★
The cellular arm was covered mechanistically in Unit 7; what matters here is the sequence and the two conditions that must be met.
T cells only recognise and respond to antigens associated with self MHC molecules, not non-self ones. MHC class II restriction operates between APCs and CD4⁺ T cells; MHC class I restriction operates between target cells and CD8⁺ CTLs.
| Requirement | Detail |
|---|---|
| Signals for full T-cell activation | Signal 1 — antigen recognition signal Signal 2 — co-stimulatory signal Cytokines — IL-1, IL-2, IL-12 and others |
| Signals for full B-cell activation | Signal 1 — antigen recognition, via the BCR/Igα/Igβ complex Signal 2 — co-stimulation, via CD40 with CD40L on activated Th cells |
- Which MHC class restricts APC–CD4⁺ interaction? → Class II
- Which restricts target cell–CD8⁺ interaction? → Class I
- Name the three requirements for full T-cell activation. → Signal 1, signal 2, and cytokines (IL-1, IL-2, IL-12)
- What provides signal 2 for B cells? → CD40 binding CD40L on activated Th cells
Humoral immunity ★★★
The humoral response to a protein (TD) antigen is a two-cell collaboration, and the lecture sets out the requirement plainly: a humoral response against a TD antigen needs T-cell help. That help takes two forms — a contact signal and a set of cytokines.
- The CD40–CD40L interaction provides signal 2 for B-cell activation. CD40L is expressed on the activated Th cell.
- IL-2, IL-4, IL-5 and IL-6, secreted by activated Th cells, are the cytokines necessary for further B-cell activation, proliferation and differentiation into plasma cells.
The four effector mechanisms of antibody
| Mechanism | What it achieves |
|---|---|
| Neutralisation | Blocks microbes and microbial toxins — the only mechanism needing neither complement nor cells |
| Opsonisation and phagocytosis | Antibody-coated microbes are ingested far more efficiently |
| ADCC | NK cells and others kill antibody-coated target cells |
| Complement activation | The classical pathway (Unit 4) |
And the two roles of humoral immunity in the individual are worth stating as a pair, because they are the same capability seen from two sides: infection defence — neutralising and eliminating extracellular microbes and toxins accessible to antibody — and hypersensitivity mediation, since humoral immunity mediates types I, II and III. The next three units are that second role going wrong.
- What two forms of T help does a B cell need? → CD40–CD40L contact (signal 2), and cytokines IL-2, IL-4, IL-5, IL-6
- Name the four antibody effector mechanisms. → Neutralisation, opsonisation, ADCC, complement activation
- Which needs neither complement nor cells? → Neutralisation
- Name the two roles of humoral immunity. → Infection defence, and mediation of types I–III hypersensitivity
Primary and secondary antibody responses ★★★
This is Section V question 4 — 6 marks, set identically in both papers. It is also the mechanism behind every vaccine booster you have ever had, so it is worth understanding rather than memorising.
The antibody response occurring when a host is first exposed to an antigen. It shows four phases: lag phase, log phase, plateau phase and decline phase.
The enhanced response when a previously immunised individual is re-exposed to the same antigen, characterised by: (1) a lower threshold dose of immunogen; (2) a shorter lag phase; (3) a higher rate and longer persistence of antibody synthesis; (4) a higher titre of antibody; and (5) increasing affinity and avidity — maturation of the immune response.
| Primary response | Secondary response | |
|---|---|---|
| Immunogen threshold | High — a large dose is needed | Low |
| Lag phase | Long — days before antibody appears | Short |
| Antibody level (titre) | Low peak | High peak, produced faster and persisting longer |
| IgM | Predominant | Present but minor |
| IgG | Little | Predominant |
| Affinity and avidity | Low | High — affinity maturation |
| Responding cell | Naïve B cell | Memory B cell |
If there is room, name the reason — the secondary response is mounted by memory B cells, which already exist in large numbers, have already class-switched, and carry receptors already refined by affinity maturation.
Do not learn six independent rows. Learn one fact — the second time, the response is mounted by memory cells rather than naïve cells — and derive the rest.
Memory cells are far more numerous than the original naïve clone, so less antigen is needed to find enough of them (threshold ↓) and expansion starts sooner (lag ↓) and reaches further (titre ↑). They have already class-switched, so they make IgG immediately instead of starting again at IgM. And their receptors have already been through affinity maturation in the germinal centre, so the antibody binds better from the outset (affinity ↑).
One cause, six consequences. If you can state the cause you can reconstruct the table under exam pressure without having memorised a single row.
The primary dose does something almost useless on its own: it produces a slow, weak, low-affinity IgM response that fades. What it really does is lay down memory cells. The booster then exploits them — and it is the booster that generates the fast, high-titre, high-affinity IgG that actually protects.
The same logic explains a diagnostic rule you met in Unit 3: specific IgM means recent or current infection (a primary response is under way), while specific IgG means past exposure or vaccination. And it explains why hepatitis B vaccination is three doses rather than one — you are not topping up antibody, you are recruiting memory.
- Name the four phases of the primary response. → Lag, log, plateau, decline
- List the five features of the secondary response. → Lower threshold · shorter lag · higher rate and longer persistence · higher titre · increased affinity and avidity
- Which antibody class predominates in each? → Primary IgM; secondary IgG
- Which cell mounts the secondary response? → Memory B cells
- Why is the secondary response faster and stronger? → Memory cells are numerous, already class-switched, and already affinity-matured
TD and TI antigens in the humoral response ★★
Unit 2 introduced the TD/TI distinction; here it returns with the mechanism filled in, and with TI antigens split into two kinds.
| TI-1 antigen | TI-2 antigen | |
|---|---|---|
| Structure | Two parts: a B-cell determinant and a mitogen-like structure | Many repeated determinants on the surface |
| How it activates | At high concentration it acts as a polyclonal activator — a B-cell mitogen | The repeated structures cross-link the BCR and activate the mature B cell specifically |
| TD antigen | TI antigen | |
|---|---|---|
| Chemical nature | Protein | Polysaccharide |
| Th help | Needed | Not needed |
| Classes of antibody | IgG (and IgM) | IgM |
| Class switching | + | − |
| Anamnestic response | + | − |
| Memory cells | + | − |
Notice that the last three rows of that table are all consequences of the second row. Class switching, affinity maturation and memory formation all happen in the germinal centre, and the germinal centre reaction requires T-cell help — specifically the Tfh cells from Unit 7.
So a TI antigen, which bypasses T cells entirely, cannot access any of it. It gets a fast IgM response and nothing else: no switch, no maturation, no memory, no booster effect. That is exactly why §5's whole secondary-response story does not apply to polysaccharide antigens — and why conjugating a pneumococcal polysaccharide to a carrier protein, converting it into a TD antigen, transforms an ineffective vaccine into an effective one.
- How does a TI-1 antigen activate B cells? → Polyclonally, as a B-cell mitogen, at high concentration
- How does a TI-2 antigen activate them? → Specifically, by cross-linking the BCR with repeated determinants
- TD vs TI — antibody class? → TD gives IgG (and IgM); TI gives IgM only
- Which shows an anamnestic response? → TD only
- Why does TI give no memory? → Class switching, affinity maturation and memory all need the germinal centre, which needs T help
Revision layer
The exam map for this unit
| Section | Item | From |
|---|---|---|
| V. Brief answer Q4 | ⭐ Primary vs secondary humoral response — 6 marks | §5 |
| — | Supports the MHC restriction and two-signal items in Units 7, 8 and 10 | §3 |
The whole unit on one screen
| Question | Answer |
|---|---|
| Define immune response | The process by which the immune system recognises and removes antigens |
| Where does it happen? | Secondary lymphoid organs — spleen, lymph node, MALT |
| Three phases? | Antigen recognition → activation/proliferation/differentiation → effector |
| Phase 1 difference? | T cells need peptide–MHC on an APC; B cells bind native antigen |
| T-cell activation needs? | Signal 1 + signal 2 + cytokines (IL-1, IL-2, IL-12) |
| B-cell activation needs? | BCR signal + CD40/CD40L + IL-2, IL-4, IL-5, IL-6 |
| Four antibody effector mechanisms? | Neutralisation · opsonisation · ADCC · complement activation |
| Primary response phases? | Lag · log · plateau · decline |
| Secondary response — five features? | Lower threshold · shorter lag · higher rate and persistence · higher titre · higher affinity |
| Primary vs secondary antibody class? | IgM → IgG |
| Why is secondary better? | Memory cells: numerous, class-switched, affinity-matured |
| TD vs TI? | Protein/polysaccharide · help needed or not · IgG/IgM · memory or none |
- Name the three phases of the adaptive response. → Recognition, activation/proliferation/differentiation, effector
- Which MHC class restricts each T-cell type? → Class II for CD4⁺; class I for CD8⁺
- What are the two signals for B-cell activation? → BCR–antigen, and CD40 with CD40L
- Which cytokines drive B-cell proliferation? → IL-2, IL-4, IL-5, IL-6 from activated Th cells
- Give the six rows of the primary vs secondary table. → Threshold, lag, antibody level, IgM, IgG, affinity
- State the single reason the secondary response is better. → It is mounted by memory cells, not naïve cells
- Why do polysaccharide vaccines give no booster effect? → TI antigens produce no memory, because there is no T help and no germinal centre