📖 Definitions Bank

The state of protection against disease, particularly infectious disease; more broadly, a reaction to foreign substances (antigens), including microbes and macromolecules such as proteins and polysaccharides. The molecules, cells and organs responsible constitute the immune system, and their collective, coordinated reaction is the immune response.TMU Lecture 1 (Prof. Shan Yu Fung) Slides 9–10→ read the unit

A foreign (non-self) substance that is recognised by the immune system and can induce an immune response, and that binds specifically to the product of that response — antibody or an antigen receptor. (Set as a Section I definition in 2019; developed fully in Unit 2.)Past Paper 2019, Section I Q1 · TMU Lecture 1 (Prof. Shan Yu Fung) Slide 38→ read the unit

The process by which the immune system recognises and removes “non-self” substances — the collective and coordinated reaction of immune organs, cells and molecules to a foreign substance. It comprises two categories: innate (non-adaptive) and adaptive (acquired) responses.TMU Lecture 1 (Prof. Shan Yu Fung) Slides 9, 42→ read the unit

Immunity mediated by mechanisms that exist before infection, are capable of rapid response, and react in essentially the same way to repeated infections — that is, without memory. Recognition is by pattern-recognition receptors. Components: physical and chemical barriers, blood proteins (complement), cytokines, and phagocytes.Janeway's Immunobiology 10e, §1-2 to §1-5 · TMU Lecture 1 (Prof. Shan Yu Fung) Slides 44–49→ read the unit

Immunity stimulated by exposure to an infectious agent, which increases in magnitude and defensive capability with each successive exposure. Mediated mainly by lymphocytes and their products. Its six features are specificity, diversity, memory, specialisation, self-limitation and non-reactivity to self.Janeway's Immunobiology 10e, §1-8 onward · TMU Lecture 1 (Prof. Shan Yu Fung) Slide 50→ read the unit

Burnet's 1957 theory that each lymphocyte bears a single type of receptor of unique specificity, generated before antigen is encountered; that antigen binding activates that lymphocyte; that its daughter cells carry identical specificity; and that self-reactive lymphocytes are deleted before maturity. Janeway's calls it the single most important principle in adaptive immunity.Janeway's Immunobiology 10e, §1-12 · TMU Lecture 1 (Prof. Shan Yu Fung) Slide 54→ read the unit

The immune system's capacity to recognise and remove “non-self” components arising within the body — mutant, transformed and malignant cells. Its failure permits tumours and persistent viral infection. ⚠️ TMU / Chinese-curriculum framing; the term is not used in Janeway's ch.1.TMU Lecture 1 (Prof. Shan Yu Fung) Slides 39–40→ read the unit

Active immunity is induced by exposure to antigen (infection or vaccination) — slow to develop, long lasting, and it establishes memory. Passive immunity is acquired by transferring serum or lymphocytes from an immunised individual (adoptive transfer) — immediate but short-lived, with no memory.TMU Lecture 1 (Prof. Shan Yu Fung) Slide 72→ read the unit

A molecule that can induce the production of antibodies and/or effector T cells and can in turn interact specifically with the antibodies and/or effector lymphocytes produced. It therefore possesses two properties: immunogenicity (the ability to induce a response) and immunoreactivity or antigenicity (the ability to combine specifically with the products of that response).Past Paper 2019, Section I Q1 · TMU Lecture 2 (Lei Zhi) Slides 7, 12→ read the unit

The immunologically active region of an immunogen that binds to antigen-specific membrane receptors on lymphocytes (TCR or BCR) or to secreted antibodies. Usually composed of 5–15 amino acid residues, or of polysaccharide residues or nucleotides. Epitopes may be linear (a sequential fragment) or conformational (non-sequential residues brought together by folding).Past Paper 2020, Section I Q1 · TMU Lecture 2 (Lei Zhi) Slides 23, 26→ read the unit

A small-molecular-weight substance which is antigenic but incapable by itself of inducing a specific immune response — it lacks immunogenicity but reacts with specific antibody. Coupling to a carrier renders the conjugate immunogenic. A hapten is equivalent to a single epitope and is therefore monovalent. Penicillin is the classic example.TMU Lecture 2 (Lei Zhi) Slides 16–17, 25→ read the unit

The total number of epitopes on an antigen molecule that can bind antibody. A hapten, being the equivalent of one epitope, binds only one site on a TCR, BCR or antibody and is monovalent.TMU Lecture 2 (Lei Zhi) Slide 25→ read the unit

The reaction in which antibody induced by one antigen reacts with an unrelated antigen, because the two share an identical epitope or carry epitopes of similar conformation. The shared determinant is the common antigen. Antigenic specificity is therefore not absolute, and cross-reaction can occur between unrelated species.TMU Lecture 2 (Lei Zhi) Slides 31–33→ read the unit

A molecule that polyclonally activates a large fraction of T cells by binding simultaneously to MHC class II molecules and to the T-cell receptor, outside the peptide-binding groove. Features: polyclonal activation, no antigen processing required, and no MHC restriction.TMU Lecture 2 (Lei Zhi) Slide 67→ read the unit

A substance which, when injected before or together with an antigen, non-specifically enhances the immune response or changes its type. It acts by altering the antigen's physicochemical form, improving processing and presentation by macrophages, and non-specifically stimulating lymphocyte proliferation. Examples: Al(OH)₃, BCG, poly I:C, Freund's adjuvants.TMU Lecture 2 (Lei Zhi) Slides 70–71→ read the unit

Thymus-dependent (TD) antigens cannot induce antibody without T-cell help; they are mainly proteins, carry a few copies of many different epitopes, elicit both humoral and cellular immunity, produce multiple antibody classes and generate memory. Thymus-independent (TI) antigens stimulate B cells directly; they are mainly polysaccharides with one epitope repeated many times, give IgM only, and generate no memory.TMU Lecture 2 (Lei Zhi) Slides 47–49→ read the unit

The globulins with antibody activity, or with a structure similar to the antibody molecule. Immunoglobulins exist in two forms: secreted Ig (sIg), soluble molecules released by plasma cells into serum and tissue fluids, and membrane Ig (mIg), the cell-surface receptor form (BCR). Relationship to antibody: all antibodies are immunoglobulins, but immunoglobulins are not always antibodies.Past Paper 2019, Section I Q2 · TMU Lecture 3 (Lei Zhi) Slides 5, 8→ read the unit

The immune functional protein produced by B cells after activation by antigen. Antibodies are immunoglobulins that bind specifically to the antigen that induced their production, and they mediate humoral immunity.Past Paper 2020, Section I Q2 · TMU Lecture 3 (Lei Zhi) Slide 5→ read the unit

A three-dimensional globular structural motif of about 110 amino acids, stabilised by an internal disulfide bond and built from two layers of β-pleated sheet (3–5 antiparallel strands per layer). This is the Ig fold; molecules containing it form the Ig superfamily — TCR, MHC, CD4, CD8, B7, FcR, ICAM.TMU Lecture 3 (Lei Zhi) Slides 13, 15→ read the unit

Three regions of extreme amino acid variability within each V region — CDR1, CDR2, CDR3, each about 9–12 amino acids — which together form the surface complementary to the antigenic determinant, hence complementarity-determining regions. The rest of the V region is the framework region (FR1–FR4). Six CDRs (three from V_H, three from V_L) form one antigen-binding site.TMU Lecture 3 (Lei Zhi) Slides 21, 25→ read the unit

A short flexible segment between C_H1 and C_H2, present in γ, α and δ chains (IgG, IgA, IgD) but absent from IgM and IgE. Rich in proline, which makes it flexible — allowing the arms to move and exposing the complement-binding site once antigen is bound — and protease-susceptible, which is what papain and pepsin exploit.TMU Lecture 3 (Lei Zhi) Slides 32–33→ read the unit

The J (joining) chain is a cysteine-rich polypeptide made by plasma cells that links Ig monomers into polymers — 2 IgA into a dimer, 5 IgM into a pentamer. The secretory piece (SP) is a polypeptide made by mucosal epithelial cells, involved in the secretion of sIgA and protecting it from hydrolysis by proteases.TMU Lecture 3 (Lei Zhi) Slides 35, 37→ read the unit

Isotype — constant-region determinants that define the class, subclass, type and subtype, and are the same in all healthy members of a species. Allotype — constant-region determinants arising from allelic forms of the same gene, so they differ between individuals of one species. Idiotype — the unique determinants of the V_H and V_L domains of a given antibody, i.e. of one clone.TMU Lecture 3 (Lei Zhi) Slides 49, 53–54→ read the unit

Antibody produced by a single clone of B lymphocytes and specific for a single epitope. Made by cell fusion of an antibody-producing B cell with a myeloma cell (the hybridoma method), which combines the B cell's specificity with the tumour cell's immortality. Contrast polyclonal antibody: the mixture produced by many B-cell clones when an animal is immunised.TMU Lecture 3 (Lei Zhi) Slides 91, 93→ read the unit

A collective name for a group of plasma proteins that become proteolytic enzymes after activation, and which opsonise and destroy pathogens. They exist in blood serum, tissue fluid and on cell membranes, circulate as inactive zymogens, and are activated by proteolytic cleavage in a cascade. Complement is a major effector mechanism of both humoral and innate immunity.TMU Lecture 4 (Juan Li) Slides 7–8→ read the unit

The antibody-dependent route of complement activation. Initiated by an immune complex (antigen bound to IgM or IgG1–IgG3); C1q binds the Fc (C_H2 of IgG, C_H3 of IgM), activating C1r then C1s, which cleave C4 and C2 to form the C3 convertase C4b2a and then the C5 convertase C4b2a3b. Requires Ca²⁺ and Mg²⁺.TMU Lecture 4 (Juan Li) Slides 16–38→ read the unit

The antibody-independent route, initiated by spontaneous hydrolysis of C3 whose product C3b is sustained on microbial surfaces (LPS, peptidoglycan, zymosan). C3b binds factor B, factor D cleaves it, and the resulting C3bBb C3 convertase — stabilised by properdin — generates more C3b in an amplification loop, then forms the C5 convertase C3bBb3b. Requires Mg²⁺ only.TMU Lecture 4 (Juan Li) Slides 39–52→ read the unit

An antibody-independent route initiated when mannose-binding lectin (MBL) — structurally similar to C1q — binds mannose or other carbohydrate residues on a microbial surface. MASP-2 then acts like C1s, cleaving C4 and C2 to give the same convertases as the classical pathway, C4b2a and C4b2a3b. MASP-1 can cleave C3 directly. Requires Ca²⁺.TMU Lecture 4 (Juan Li) Slides 55–58→ read the unit

The complex of complement components C5b, C6, C7, C8 and C9 (C5b–C9), formed in the terminal steps of all three pathways, which mediates cell lysis by creating a pore in the target cell membrane. Assembly requires no further enzymes; several C9 molecules polymerise to form the channel.TMU Lecture 4 (Juan Li) Slide 59→ read the unit

The small fragments C3a, C4a and C5a, released into the fluid phase during complement activation, which act as peptide mediators of inflammation — triggering mast-cell degranulation and increasing vascular permeability. C5a is the most potent and is also a powerful chemoattractant and activator of neutrophils and monocytes.Janeway's Immunobiology 10e, §2-14→ read the unit

Coating of a microbe with C3b (and its cleavage product iC3b), which is then bound by CR1 (CD35) on phagocytes, greatly increasing ingestion. It is quantitatively the most important function of the complement system. CR1 binding alone is insufficient — the phagocyte must also be activated by C5a.Janeway's Immunobiology 10e, §2-12, §2-13→ read the unit

Any of numerous secreted, low-molecular-weight proteins that regulate the intensity and duration of the immune response by exerting a variety of effects on lymphocytes and other immune cells that express the appropriate receptor. Cytokines act locally (autocrine or paracrine) rather than at a distance, are not stored preformed, and play a role in both innate and adaptive immunity. ⭐ Set as a Section I definition in BOTH the 2019 and 2020 papers.Past Paper 2019, Section I Q3 and Past Paper 2020, Section I Q3 · TMU Lecture 5 (Juan Li) Slide 7→ read the unit

Pleiotropism — one cytokine mediates diverse effects on different target cells. Redundancy — several cytokines mediate the same effect. Synergy — two cytokines together produce a greater effect than either alone. Antagonism — two cytokines oppose each other. Cascade induction — one cytokine induces others, which then mediate its biological effect. Cytokines notably do NOT possess specificity.TMU Lecture 5 (Juan Li) Slides 14, 16→ read the unit

Autocrine — the cytokine acts on the same cell that secreted it. Paracrine — it acts on a nearby cell; this is the usual mode. Endocrine — it enters the circulation and acts at a distance from the site of production.TMU Lecture 5 (Juan Li) Slide 12→ read the unit

A class of cytokine that interferes with viral infection and replication. Type I comprises IFN-α and IFN-β, produced by dendritic cells and infected cells, and is the antiviral arm. Type II is IFN-γ, produced by activated T cells and NK cells, and acts principally to activate macrophages.TMU Lecture 5 (Juan Li) Slide 20→ read the unit

A large family of structurally homologous cytokines that stimulate leukocyte movement and regulate the migration of leukocytes from the blood into tissues. Classified by primary structure into CXC, CC, C and CX3C families, where C is cysteine and X is any amino acid — the letters describe the spacing of the first two cysteines.TMU Lecture 5 (Juan Li) Slides 24, 26→ read the unit

The two effector lineages of CD4⁺ helper T cells, arising from Th0. Th1 produces IL-2, IFN-γ and TNF (not IL-4), promotes cellular immunity by activating macrophages, NK cells and CTL, and participates in type IV hypersensitivity. Th2 secretes IL-4, IL-5, IL-6, IL-10, IL-13 (not IL-2 or IFN-γ), promotes humoral immunity and class switching to IgG1 and IgE, and participates in type I hypersensitivity and defence against parasites. IL-12 + IFN-γ drive Th1; IL-4 drives Th2.TMU Lecture 7 — Immune Cells Slides 139–144→ read the unit

A cytokine receptor that has detached from the cell membrane to circulate in solution, where it competitively antagonises the effect of its cytokine by binding it before it can reach a cell-bound receptor. The drug etanercept — a soluble TNF receptor fused to an Fc fragment — is a therapeutic application of this principle.TMU Lecture 5 (Juan Li) Slide 32→ read the unit

The pathological secretion of extremely high levels of cytokines, induced by massive infection with particular pathogens. Typical features include increased capillary permeability with resultant loss of blood pressure and shock, sometimes leading to death; also clotting, renal failure, lung injury, cell death and immune paralysis.TMU Lecture 5 (Juan Li) Slides 33–34→ read the unit

A series of membrane molecules or markers determined by monoclonal antibodies. They are called clusters of differentiation because these molecules appear or disappear at different stages of cell differentiation and maturation. Numbering currently runs from CD1 to CD247, organised into 13 groups — CD molecules of T cells, B cells, NK cells, platelets, adhesion molecules and others.TMU Lecture 6 — CDs and CAMs Slides 4–5→ read the unit

A group of cell-surface molecules that mediate adhesive interactions with other cells or with the extracellular matrix, playing crucial roles in cell migration and cellular activation in immune responses. There are four protein families: selectin, mucin-like, immunoglobulin superfamily and integrin.TMU Lecture 6 — CDs and CAMs Slide 8→ read the unit

Membrane glycoproteins that bind carbohydrate ligands, typically presented by mucin-like CAMs. Their function is to initiate the leukocyte–endothelial interaction — the bonds form and break rapidly, producing rolling rather than arrest. Three types: L-selectin on leukocytes, E-selectin on endothelial cells, P-selectin on platelets.TMU Lecture 6 — CDs and CAMs Slide 9→ read the unit

Heterodimeric proteins consisting of an α and a β chain, which bind CAMs (often of the Ig superfamily) and the extracellular matrix, and provide strong adhesion. They must first be activated — typically by chemokine signalling — to reach their high-affinity state.TMU Lecture 6 — CDs and CAMs Slide 12→ read the unit

Adhesion molecules containing a variable number of immunoglobulin-like domains, including ICAM-1, ICAM-2, ICAM-3 and VCAM-1. They are usually expressed on vascular endothelial cells and bind various integrin molecules.TMU Lecture 6 — CDs and CAMs Slide 11→ read the unit

CAMs that direct lymphocyte homing — the routine circulation of lymphocytes to particular tissues. The lymphocyte homing receptor (LHR) is carried by the lymphocyte; the addressin is the tissue-specific ligand it recognises. Naïve T cells home to secondary lymphoid tissues; effector T cells home to mucosal or skin sites according to where they were activated.TMU Lecture 6 — CDs and CAMs Slides 14, 16→ read the unit

The fact that a given T cell will recognise a peptide antigen only when it is bound to a particular MHC molecule — normally self-MHC. It is acquired during positive selection, so the MHC haplotype of the thymus in which a T cell develops determines its restriction. Recognition by CD8⁺ CTLs is restricted by MHC class I; responses of CD4⁺ helper T cells are restricted by MHC class II.TMU Lecture 7 — Immune Cells Slides 98, 100→ read the unit

Selection occurring in the thymic cortex at the double-positive stage, in which DP thymocytes interact with thymic epithelial cells bearing self-peptide–MHC complexes. Cells recognising with proper affinity survive; those unable to recognise, or recognising with high affinity, die by apoptosis. Result: self-MHC restriction, and commitment to CD4 (class II) or CD8 (class I).TMU Lecture 7 — Immune Cells Slide 90→ read the unit

Selection occurring at the cortico-medullary junction and thymic medulla at the single-positive stage, in which SP cells interact with thymic dendritic cells and macrophages. Cells recognising self-peptide–MHC with high affinity undergo apoptosis; those recognising weakly or not at all survive and mature. Result: self-immune tolerance.TMU Lecture 7 — Immune Cells Slide 91→ read the unit

The T-cell antigen receptor together with CD3. TCR performs antigen binding and is a lineage-specific marker; CD3 performs signal transduction from the TCR and is also lineage-specific. CD3's cytoplasmic tails carry ITAM motifs — two tyrosines about 10 residues apart, phosphorylated on activation. TCRs are αβ (95–99%) or γδ (1–5%).TMU Lecture 7 — Immune Cells Slides 95, 102–103→ read the unit

Signal 1 — the TCR signal: the TCR–CD3 complex recognises the antigen–MHC complex, with CD4 or CD8 as co-receptor. Signal 2 — the co-stimulatory signal: CD28 on the T cell binds B7.1 (CD80) / B7.2 (CD86) on the APC. A third set of signals, from local cytokines, directs differentiation into distinct effector types. Signal 1 without signal 2 causes anergy.TMU Lecture 7 — Immune Cells Slides 108–110→ read the unit

A T-cell surface molecule induced on activation and absent from resting cells. It binds B7.1 and B7.2 — the same ligands as CD28 — but carries an ITIM (immunoreceptor tyrosine-based inhibition motif) and therefore delivers inhibitory signals. It is an important negative regulator of T-cell activation and is critical for maintaining T-cell homeostasis.TMU Lecture 7 — Immune Cells Slide 114→ read the unit

A subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens and prevent autoimmune disease. They express CD4 and CD25, with FoxP3 as the master transcriptional regulator — necessary and sufficient to induce the lineage. They suppress by secreting IL-10 and TGF-β and by killing activated T cells directly. Thymic Treg develop in the thymus; peripheral Treg differentiate in the periphery.TMU Lecture 7 — Immune Cells Slides 147–148→ read the unit

A CD8⁺ effector T cell whose function is to directly kill target cells. Its characteristics are antigen specificity, MHC class I restriction, and that the CTL is not injured while killing. Two mechanisms: the perforin/granzyme pathway and the Fas–FasL pathway, both ending in caspase activation and apoptosis.TMU Lecture 7 — Immune Cells Slides 154–157→ read the unit

The B-cell antigen receptor complex. BCR is membrane-associated immunoglobulin (mIg), which binds specific antigen through V_H + V_L. Igα (CD79a) and Igβ (CD79b) associate with mIg and perform signal transduction into the B cell through ITAM motifs — the same role CD3 plays for the TCR.TMU Lecture 7 — Immune Cells Slide 178→ read the unit

A complex of CD19, CD21 and CD81 which enhances the ability of naïve B cells to respond to antigen and transduces the first signal together with Igα/Igβ. CD21 is CR2, the receptor for complement C3d and for Epstein–Barr virus. CD20 is NOT part of this complex.TMU Lecture 7 — Immune Cells Slide 180→ read the unit

Signal 1 — the BCR signal: the BCR complex binds antigen, with CD19/CD21/CD81 as co-receptor. Signal 2 — the co-stimulatory signal: CD40 on the B cell binds CD40L on the activated Th cell. CD40–CD40L delivers the most important second signal of B-cell activation.TMU Lecture 7 — Immune Cells Slides 182, 184→ read the unit

Three mechanisms operating on self-reactive immature B cells in the bone marrow: clonal deletion (apoptosis), receptor editing (re-rearrangement of the light-chain gene to give a new specificity) and anergy (survival and migration to the periphery in a functionally unresponsive state).TMU Lecture 7 — Immune Cells Slides 168–171→ read the unit

Innate B lymphocytes, 5–10% of all B cells, derived from fetal liver and capable of self-renewal. They reside in the peritoneal cavity, pleural cavity and intestinal mucosal lamina propria, recognise a narrow spectrum (mainly TI antigens and autoantigens), require no T-cell help, show no class switching and no memory, and produce low-affinity multi-reactive IgM including natural antibody against microbial LPS.TMU Lecture 7 — Immune Cells Slides 194–195→ read the unit

The effector cell into which activated B cells differentiate. Plasma cells lose surface immunoglobulin and become highly specialised for antibody secretion. They do not divide; some travel to the bone marrow and live for years, others die within one or two weeks. The secreted antibody has the same antigen specificity as the original BCR.TMU Lecture 7 — Immune Cells Slides 174, 193→ read the unit

① Production of antibody — neutralisation of toxins and pathogens, complement activation, Fc-receptor-mediated opsonisation, ADCC and type I hypersensitivity, and transport across placenta and mucosa. ② Antigen presentation to T cells — B cells are professional APCs, concentrating antigen via the BCR and presenting it as peptide–MHC class II to Th cells; especially important for soluble antigen. ③ Immune regulation — secretion of IL-6, IL-10 and TNF-α, and suppression by regulatory B cells (Breg).TMU Lecture 7 — Immune Cells Slides 199–210→ read the unit

The receptors expressed by innate immune cells, which can recognise certain molecular structures owned by pathogens. Families include Toll-like receptors (TLR1–9, recognising LPS, peptidoglycan and viral nucleic acids), C-type lectin receptors (e.g. mannose receptor), scavenger receptors (e.g. CD36) and pentraxins (e.g. C-reactive protein).TMU Lecture 7 — Immune Cells Slides 26, 28→ read the unit

Highly conserved specific molecular structures expressed by pathogens or their products, which are absolutely distinct from normal host substances and are recognised by the PRRs of innate immune cells. Because PAMPs are essential to the microbe, they cannot be discarded to evade detection — which is why a small germline-encoded receptor set suffices.TMU Lecture 7 — Immune Cells Slide 27→ read the unit

Substances produced by or released from damaged and dying cells, recognised by the same PRRs that read PAMPs. The innate system therefore reports tissue injury as well as infection.TMU Lecture 7 — Immune Cells Slide 27→ read the unit

An innate lymphoid cell distributed in peripheral blood, liver, lymph node and spleen, carrying no antigen-specific receptors. Human surface markers: CD3⁻ CD19⁻ CD56⁺ CD16⁺. NK cells directly kill tumour cells and virus-infected cells without antigen stimulation and can mediate ADCC through FcγRIII (CD16).TMU Lecture 7 — Immune Cells Slide 43→ read the unit

The mechanism by which NK cells discriminate targets. NK cells carry both killer activating receptors (binding non-class-I-HLA molecules) and killer inhibitory receptors (binding class I HLA). On a normal cell, class I is expressed normally and the inhibitory signal outweighs activation, so killing is suppressed. On an abnormal cell with reduced class I, inhibition is lost and the activating receptors (NKG2D, NCRs) drive killing.TMU Lecture 7 — Immune Cells Slides 45–47→ read the unit

Monocytes that leave the blood and mature into tissue macrophages, taking the name of their tissue: Kupffer cells (liver), mesangial cells (kidney glomerulus), microglia (brain), alveolar macrophages (lung), histiocytes (connective tissue). Functions: kill and remove pathogens; kill intracellular bacteria and target cells; participate in and stimulate inflammation; process and present antigen; immunological regulation.TMU Lecture 7 — Immune Cells Slides 36–40→ read the unit

A cluster of genes encoding membrane glycoproteins that display peptide antigen to T cells. In humans it is the HLA complex on chromosome 6; in mice, H-2 on chromosome 17. Class I genes (HLA-A, B, C) encode the α chain of class I molecules; class II genes (HLA-DP, DQ, DR) encode the α and β chains of class II molecules; class III encodes complement C4, C2 and Bf, plus TNF and HSP70.Past Paper 2020, Section I Q4 · TMU Lecture 10 — MHC Slides 3, 5, 7→ read the unit

A molecule composed of one MHC-encoded α chain (domains α1, α2, α3) together with β2-microglobulin, which is not MHC-encoded. Its peptide-binding cleft is formed by α1 and α2, is closed, and binds peptides of 8–10 amino acids anchored at both ends. CD8 binds the α3 domain. Expressed on all nucleated cells.TMU Lecture 10 — MHC Slides 11, 15, 26, 32→ read the unit

A molecule composed of an α chain and a β chain, both MHC-encoded. Its peptide-binding cleft is formed by α1 and β1, is open, and binds peptides of 13–18 amino acids with anchor residues distributed along their length. CD4 binds the β2 domain. Expressed only on dendritic cells, macrophages, B cells and thymic stromal cells.TMU Lecture 10 — MHC Slides 12, 15, 26, 32→ read the unit

The presence of multiple alleles at a genetic locus within the species — HLA-A has 303 alleles, HLA-B 559, HLA-C 150, HLA-DRB 440. Unlike antibody diversity, which is generated within each individual, MHC variation lies between individuals, so it protects the species rather than the person: no pathogen can evade every human's MHC at once.TMU Lecture 10 — MHC Slide 16→ read the unit

A haplotype is the particular combination of MHC alleles found on a single chromosome, transmitted as a single unit in most cases. Linkage disequilibrium is the difference between the frequency observed for a particular combination of alleles and that expected from the frequencies of the individual alleles.TMU Lecture 10 — MHC Slides 20–21→ read the unit

Structurally related residues by which a peptide binds into the MHC groove. Anchor residues differ between different alleles of MHC but are similar for all peptides that bind the same MHC molecule — so each allele has a characteristic binding motif, and a single MHC molecule can present thousands of different peptides sharing that motif.TMU Lecture 10 — MHC Slide 29→ read the unit

Cell populations that can capture and process antigens, and present them to T lymphocytes. Professional APCs — dendritic cells, macrophages and B cells — express MHC class II constitutively. Non-professional APCs include fibroblasts, thymic and thyroid epithelial cells, glial cells, pancreatic β cells and vascular endothelial cells.Past Paper 2019, Section I Q4 · TMU Lecture 8 — Antigen Presenting Cells Slides 4–5→ read the unit

The most powerful APC and the only one that can activate naïve T cells — hence the initiator of the immune response. Discovered by Steinman in 1973 (Nobel Prize 2011). Classified by derivation into myeloid DC (DC1) and lymphoid DC (DC2), and by function into immature and mature. DCs express MHC and co-stimulatory molecules constitutively.TMU Lecture 8 — Antigen Presenting Cells Slides 8–11, 14→ read the unit

Immature DC: antigen uptake ++++, processing ++++, presentation +, low co-stimulatory molecules, resident in peripheral tissue. Mature DC: uptake +, processing +, presentation ++++, high MHC and co-stimulatory molecules, secretes IL-12, IL-18, IFN-γ and chemokines, resident in secondary lymphoid organs. Maturation is a one-way trade of collecting for reporting.TMU Lecture 8 — Antigen Presenting Cells Slide 11→ read the unit

Endogenous antigen comes from inside the cell — viral proteins, tumour proteins — and is processed by the class I pathway. Exogenous antigen comes from outside the cell — bacteria, cells, protein — is taken up by endocytosis and processed by the class II pathway.TMU Lecture 8 — Antigen Presenting Cells Slide 17→ read the unit

① Antigen protein is synthesised by the target cell. ② It is cleaved into peptides by proteasomes. ③ Peptides are transported from the cytosol to the rough ER (by TAP). ④ They assemble with class I MHC. ⑤ The peptide–class I complex is expressed on the cell surface and presented to CD8⁺ T cells. Available to all nucleated cells.TMU Lecture 8 — Antigen Presenting Cells Slides 18, 22→ read the unit

① Exogenous antigen is taken up by endocytosis into an APC. ② It is degraded into peptide fragments in the endosome/lysosome. ③ Peptides combine with class II MHC molecules. ④ The peptide–class II complex is displayed on the surface and presented to CD4⁺ helper T cells. Restricted to professional APCs.TMU Lecture 8 — Antigen Presenting Cells Slide 23→ read the unit

The process in which the immune system recognises and removes antigens. It comprises innate and adaptive responses; adaptive immunity divides into cellular immunity (primarily T-cell mediated, itself divided into CD4⁺- and CD8⁺-mediated) and humoral immunity (primarily B-cell mediated). Most events take place in the secondary (peripheral) lymphoid organs — spleen, lymph node and MALT.TMU Lecture 9 — Immune Response Slides 6–8→ read the unit

① Antigen recognition — APCs ingest, process and present antigen to naïve T cells, which recognise peptide–MHC via TCR/CD3; B cells recognise antigen directly via the BCR. ② Activation, proliferation and differentiation — naïve T cells become effector and memory T cells; naïve B cells become plasma cells and memory cells. ③ Effector — effector T cells and secreted antibodies remove the antigen.TMU Lecture 9 — Immune Response Slide 9→ read the unit

The antibody response occurring on first exposure to an antigen, showing four phases: lag, log, plateau and decline. It is characterised by a high immunogen threshold, a long lag phase, a low antibody titre, predominance of IgM, and low affinity and avidity.TMU Lecture 9 — Immune Response Slide 64→ read the unit

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. It is mounted by memory B cells and dominated by IgG.TMU Lecture 9 — Immune Response Slide 66→ read the unit

T cells recognise and respond to antigens only in association with self MHC molecules. MHC class II restriction governs the interaction between APCs and CD4⁺ T cells; MHC class I restriction governs that between target cells and CD8⁺ CTLs.TMU Lecture 9 — Immune Response Slide 74→ read the unit

Two subclasses of thymus-independent antigen. TI-1 antigens contain a B-cell determinant plus a mitogen-like structure, so at high concentration they act as polyclonal activators of B cells. TI-2 antigens carry many repeated determinants which cross-link the BCR and activate mature B cells specifically.TMU Lecture 9 — Immune Response Slides 69–70→ read the unit

When the immune system is re-exposed to the same antigen, the immune response is enhanced. Under some circumstances this enhanced response has deleterious effects, resulting in functional disorder, tissue damage or even death. This inappropriate or pathological immune response is termed hypersensitivity or allergy, and it is specific. Gell and Coombs classified it into four types by mechanism.Past Papers 2019 AND 2020, Section I · TMU Lecture 11 — Hypersensitivity Slides 20–21→ read the unit

An antigen that selectively activates CD4⁺ Th2 cells and B cells and induces an IgE antibody response. Allergens are proteins — only proteins can be presented to T cells — and generally reach mucosal surfaces at very low doses: pollens, dust mites, spores, animal dander, foods.TMU Lecture 11 — Hypersensitivity Slide 29→ read the unit

Anaphylactic or immediate hypersensitivity, mediated by IgE. Components: allergen · IgE · mast cells and basophils (with eosinophils in the late phase) · mediators. Three phases: sensitization (IgE binds FcεRI), excitation (allergen cross-links FcεR → degranulation) and effector (mediators act). Diseases: asthma, allergic rhinitis, urticaria, anaphylaxis.TMU Lecture 11 — Hypersensitivity Slides 22, 41–46→ read the unit

Preformed — made before degranulation and stored in granules: histamine. Newly formed — synthesised after activation: leukotrienes (LTs), prostaglandin D₂ and PAF. All produce three tissue effects: smooth-muscle contraction, vasodilation with increased vascular permeability, and mucus secretion.TMU Lecture 11 — Hypersensitivity Slides 39, 45→ read the unit

Desensitization — repeated injection of small amounts of allergen at short intervals (20–30 min), which gradually exhausts the active mediators; used to give antitoxin to a sensitized patient. Hyposensitization — repeated small doses at long intervals (5–7 days), which shifts antibody production from IgE to IgG.TMU Lecture 11 — Hypersensitivity Slide 59→ read the unit

Antibody-mediated cytotoxic or cytolytic hypersensitivity. IgG and IgM bind antigen present on a cell surface; complement, macrophages and NK cells then destroy the target — typically a blood cell or self tissue cell. Its defining feature is damage to a specific target cell.TMU Type II Hypersensitivity deck (Yu Chunyan) Slides 7–8→ read the unit

① Complement-mediated lysis — IgG/IgM activates the classical pathway and the MAC (C5b–C9) lyses the cell. ② Opsonised phagocytosis — via FcγR binding antibody and C3b binding complement receptors on macrophages and neutrophils. ③ ADCC — NK cells bind the coating IgG via FcγRIII (CD16) and kill the target.TMU Type II Hypersensitivity deck (Yu Chunyan) Slides 11, 14→ read the unit

Disease caused by Rh or ABO blood-group incompatibility between mother and fetus, developing when maternal IgG against fetal blood-group antigen crosses the placenta and destroys fetal red blood cells. Consequences: fetal anaemia, jaundice and bilirubin deposition, with brain damage from lipid-soluble bilirubin. Prevented by anti-Rh antibody (Rhogam) within 72 hours of the first delivery.TMU Type II Hypersensitivity deck (Yu Chunyan) Slides 18, 22→ read the unit

① Constitutive components of the cell membrane — ABO, Rh and HLA antigens. ② Common antigens shared by host cells with exogenous antigens — e.g. streptococcal cell wall and cardiac valve. ③ Modified self antigens — altered by chemicals, infections or drugs. ④ Antigens or haptens adsorbed to the cell surface.TMU Type II Hypersensitivity deck (Yu Chunyan) Slides 8–10→ read the unit

Immune-complex hypersensitivity. Soluble antigen and antibody form complexes; medium-sized complexes (≈19S), formed at an appropriate antigen:antibody ratio, are too small to be phagocytosed and too large to be filtered by the glomerulus, so they deposit in local sites — joint synovium, glomerular basement membrane, choroid plexus — and activate complement strongly, recruiting neutrophils that release lytic enzymes.TMU Type III & IV Hypersensitivity deck Slides 3–8→ read the unit

Delayed-type hypersensitivity, with three defining properties: ① delay of 24–72 hours after the second antigen contact; ② recruitment of macrophages; ③ no antibody and no complement involved. Mediated by effector CD4⁺ Th1 (secreting IFN-γ to activate macrophages, and TNF-α/β causing local tissue injury) and effector CD8⁺ CTL (killing target cells directly).TMU Type III & IV Hypersensitivity deck Slides 20–24→ read the unit

An experimental local immune-complex disease (1903) occurring at a small blood vessel wall. An animal repeatedly immunised subcutaneously with horse serum develops oedema, erythema and even necrosis. The human equivalent is the Arthus-like reaction at the site of repeated insulin injection in a type 1 diabetic.TMU Type III & IV Hypersensitivity deck Slide 9→ read the unit

A systemic immune-complex disease. When large amounts of antiserum — anti-tetanus or anti-diphtheria — enter an individual, 1–2 weeks later they develop fever, weakness and vasculitis. Antigen and antibody meet in the circulation at the mid-range ratio, forming exactly the medium-sized complexes that deposit.TMU Type III & IV Hypersensitivity deck Slide 11→ read the unit

The auto-antibody of rheumatoid arthritis: an IgM anti-IgG antibody directed against degenerated IgG. The resulting immune complexes deposit in the synovium of small joints, producing symmetric, progressive, destructive lesions and eventual deformity.TMU Type III & IV Hypersensitivity deck Slide 14→ read the unit

The interaction of insoluble particulate antigens — intact bacteria or cells — with specific antibodies, resulting in visible agglutinates after a certain time and under a certain electrolyte concentration. Direct agglutination detects antigen (ABO blood typing); indirect agglutination detects antibody (rheumatoid factor, pregnancy test).TMU Lecture 12 — Immunoassay (Yu Chunyan) Slides 18–19→ read the unit

Enzyme-Linked ImmunoSorbent Assay — a labelled immunoassay in which an enzyme conjugated to antibody converts a substrate to a coloured product, so the amount of antigen or antibody present can be measured. Quantitative, sensitive and suitable for many samples at once; used clinically for allergen-specific IgE, hormone assay and infectious serology.TMU Lecture 12 — Immunoassay (Yu Chunyan) — ELISA practical→ read the unit

All immunoassay rests on the specific binding of antigen and antibody. Methods may be qualitative (detecting the existence of antigen or antibody) or quantitative (detecting concentration), and visible or invisible (requiring a label). Immunodetection covers both antigen/antibody and lymphocytes. The final goal is clinical diagnosis, therapy assessment, prognosis and scientific research.TMU Lecture 12 — Immunoassay (Yu Chunyan) Slides 14–17→ read the unit

The treatment of a disease with therapeutic agents that potentiate or inhibit the immune response. Classified three ways: immunopotentiation vs immunosuppression; specific vs non-specific; and active immunotherapy (giving antigen) vs passive/adoptive immunotherapy (giving immune response products).Past Papers 2019 AND 2020, Section I · TMU Lecture 13 — Immunotherapy (Yu Chunyan) Slide 4→ read the unit

A bacterial exotoxin which has been treated, usually with formaldehyde, so that it loses its toxic properties but retains its ability to stimulate an immune response against the toxin. Chemical modification destroys the toxin moiety while preserving the antigenic determinants — the basis of the tetanus and diphtheria vaccines.Past Papers 2019 & 2020, Section IV Q8 · TMU Lecture 13 — Immunotherapy (Yu Chunyan) Slides 11–12→ read the unit

Safe — the vaccine must not itself cause disease. Protective — it must protect against the real pathogen. Sustained protection — protection must last, which requires immunological memory. Practical considerations — cost, stability, storage and ease of administration.Past Papers 2019 & 2020, Section IV Q9→ read the unit

A vaccine in which the gene encoding an immunogenic antigen is inserted into a plasmid under a promoter and delivered — for example on gold particles by 'gene gun' — so that the host's own cells synthesise the antigen. Because the antigen is made endogenously it enters the MHC class I pathway as well as class II, and so elicits both humoral and cellular immunity. Also heat-stable (no cold chain), cheap, and usable in neonates. Risk: integration of foreign DNA, and anti-DNA antibodies.TMU Lecture 13 — Immunotherapy (Yu Chunyan) Slides 13–16→ read the unit

Monoclonal antibodies prepared by recombinant DNA technology to reduce their mouse content, which would otherwise act as a xenogeneic antigen: chimeric (mouse V domain + human C domain), humanized, single-chain (V_H–linker–V_L) and bi-specific.TMU Lecture 13 — Immunotherapy (Yu Chunyan) Slide 22→ read the unit

Therapy using monoclonal antibodies against inhibitory checkpoint molecules — CTLA-4, PD-1 and PD-L1 (also BTLA, VISTA, TIM3, LAG3) — to release the brake on T-cell activity against tumours. Many tumours over-express PD-L1 to inactivate infiltrating T cells; blocking that interaction restores the response. Characteristic toxicity is autoimmune.TMU Lecture 13 — Immunotherapy (Yu Chunyan) Slides 23–24→ read the unit