101 · IMM-L2 Lecture 9 · Innate & Adaptive Immunity

Master Logic

• This is the execution layer of immunology: who recognises (PAMP/PRR), who enforces (leukocytes), who remembers (B/T cells), who amplifies (complement), who presents (MHC).
• Two systems, one handover: innate immunity reads fixed patterns and reacts in minutes; adaptive immunity rearranges receptors and remembers for years. Antibodies, complement and MHC are the three places they meet.
• Exam focus: the five PAMPs and their PRRs, the blood-cell differential, the five isotypes, C3/C5 convertases, MHC I vs II peptide length and co-receptors, and the two antigen-processing routes.

A · PAMP: molecules that only the pathogen has

Pathogen-associated molecular patterns (PAMPs) are conserved structures shared by whole classes of microbes but absent from host cells — which is exactly why a fixed set of receptors can recognise them.

A · PRR: three families of pattern receptors

A · DAMP: the alarm raised by your own damaged cells

Damage-associated molecular patterns are host molecules released when cells die badly — ATP, uric acid crystals, HMGB1, mitochondrial DNA. They bind the same PRRs, so sterile injury can produce inflammation without any pathogen.

B · Haematopoiesis: every immune cell starts in the marrow

Haematopoietic stem cells give two lineages: myeloid (neutrophils, monocytes/macrophages, dendritic cells, eosinophils, basophils, mast cells, red cells, platelets) and lymphoid (B, T, NK). B cells mature in marrow; T cells mature in the thymus.

B · Red cells and granulocytes: the innate workforce

B · Dendritic cell vs macrophage: the phagocytosis ⇄ presentation seesaw

A macrophage is a killer and cleaner: it phagocytoses, destroys, and presents mainly to T cells already in the tissue. A dendritic cell is a courier: it takes up antigen in the periphery, matures while migrating to the lymph node, and presents to naive T cells. Same uptake machinery, opposite priority.

B · NK cells: killing without antigen recognition

NK cells read MHC I: if a cell has lost MHC I (a common viral evasion), the inhibitory signal disappears and the NK cell kills. This is the "missing-self" rule — the opposite logic to T cells, which require MHC.

C · Adaptive immunity: B cells and antibodies

B cells recognise antigen through the BCR (membrane immunoglobulin). Activation is either T-independent (repetitive polysaccharide cross-links the BCR → IgM only, no memory) or T-dependent (protein antigen presented on MHC II to Tfh → class switching, affinity maturation, memory).

C · The four T-cell subsets

D · Antibody: structure and Fc functions

Two heavy chains + two light chains. Fab = antigen binding (variable); Fc = effector (constant). Four Fc jobs: opsonisation, complement activation (C1q), ADCC (FcγRIIIa/CD16 on NK), and FcRn recycling (long half-life).

D · The five isotypes

E · Complement: three routes, two convertases

All three make C3 convertase, which deposits C3b and builds C5 convertase; C5 convertase starts the lytic arm.

E · The MAC: from C5 to a hole

C5b → C6 → C7 → C8 → 10–16 × C9 polymerise into a pore. C9 polymerisation is the decisive step; regulators such as CD59 exist only to stop it.

E · Three functions of complement

• Opsonisation (C3b → CR1): phagocytosis.
• Inflammation and chemotaxis (C3a/C5a): vascular leak, neutrophil recruitment.
• Lysis (C5b–C9): direct membrane damage.

F · MHC: a mouse in 1948

Snell's transplantation experiments showed that rejection follows a genetic locus — the major histocompatibility complex. Same-strain grafts survive; different-strain grafts are rejected. The locus turned out to be the peptide-display system.

F · MHC I vs MHC II

F · MHC I structure

α1 and α2 form the peptide-binding groove, closed at both ends — hence the short peptide. α3 binds CD8; β2-microglobulin stabilises the whole molecule.

F · MHC II structure

α1 and β1 form an open groove, so longer peptides overhang. β2 binds CD4. Expression is restricted to APCs and is induced by IFN-γ.

F · Antigen processing: two routes

F · MHC I and the CD8 "MHC check"

The CD8 co-receptor binds the α3 domain of MHC I. Only when the TCR sees MHC I plus peptide does CD8-positive T cells get signal 1; without MHC, nothing happens — which is why viruses down-regulate MHC I, and why NK cells watch for that loss.

F · MHC II and the CD4 "MHC check"

CD4 binds the β2 domain of MHC II. This is the physical basis of the "CD4 helper" rule: helper T cells can only be activated by an APC displaying MHC II.

Key Terms