Topic 11: Immunity
11.1 The immune system
Students should be able to:
1) describe the mode of action of phagocytes (macrophages and neutrophils)
2) explain what is meant by an antigen and state the difference between self-antigens and non-self antigens
3) describe the sequence of events that occurs during a primary immune response with reference to the roles of: • macrophages
• B-lymphocytes, including plasma cells
• T-lymphocytes, limited to T-helper cells and T-killer cells
4) explain the role of memory cells in the secondary immune response and in long-term immunity
1 — Mode of action of phagocytes (macrophages and neutrophils)
Phagocytes such as neutrophils and macrophages recognise, ingest and destroy pathogens as part of the innate immune response by a coordinated sequence of events: first, chemotaxis and receptor-mediated recognition direct phagocytes to sites of infection where pathogen surfaces or opsonins (antibody or complement fragments) bind to phagocyte surface receptors; next, the phagocyte membrane engulfs the target to form an internal membrane-bound vesicle called a phagosome, which fuses with lysosomes to form a phagolysosome where acid hydrolases and reactive oxygen species (the “respiratory burst”) degrade microbial components; macrophages additionally process fragments of the degraded pathogen and present antigenic peptides on their surface bound to MHC class II molecules to activate helper T cells and so link innate and adaptive responses, whereas neutrophils are short-lived, highly phagocytic cells that rapidly accumulate and may form pus as they die after intense antimicrobial activity.
2 — Antigen: definition and difference between self and non-self antigens
An antigen is any molecule — typically a protein or polysaccharide — that is specifically recognised by components of the adaptive immune system and that can stimulate an immune response; antigens present discrete recognition sites or epitopes that are bound by antigen receptors on B and T lymphocytes or by antibodies. Self antigens are molecular structures that are normally expressed by an organism’s own cells (including peptides presented by MHC molecules) and are usually tolerated by the immune system through central and peripheral tolerance mechanisms, whereas non-self antigens are foreign molecules derived from pathogens, transplanted tissue or environmental substances that are recognised as foreign and elicit an immune response; failure to discriminate self from non-self underlies autoimmune disease.
3 — Sequence of events in a primary immune response (macrophages, B-lymphocytes/plasma cells, T-helper and T-killer cells)
A primary immune response begins when a pathogen breaches innate barriers and is captured by antigen-presenting cells such as macrophages, which phagocytose the pathogen, degrade it and display peptide fragments on MHC class II molecules at the cell surface; helper T cells (T-helper, CD4⁺) with complementary T-cell receptors bind these MHC–peptide complexes and, after becoming activated, secrete cytokines that stimulate the proliferation and differentiation of antigen-specific B lymphocytes and of other T cells. B lymphocytes that bind the same antigen via their surface immunoglobulin receptors internalise, process and present antigen and receive T-helper cell signals, causing clonal expansion and differentiation into plasma cells that secrete large quantities of specific antibody; these antibodies neutralise pathogens, agglutinate or opsonise them for phagocytosis and activate complement. Meanwhile, cytotoxic or T-killer cells (CD8⁺) become activated (directly or with help from other cells) to recognise and kill host cells presenting foreign antigen with MHC class I, using mechanisms such as perforin and granzymes to induce apoptosis of infected cells; the combined actions of macrophages, B cells/plasma cells, T-helper and T-killer cells clear the pathogen over days to weeks and establish immunological memory.
4 — Role of memory cells in the secondary immune response and long-term immunity
Memory B and T cells are long-lived, antigen-specific lymphocytes generated during the primary immune response that persist in the body at higher frequency and with altered functional properties compared with naïve cells; upon re-exposure to the same antigen these memory cells are rapidly reactivated, proliferate and differentiate to produce a faster, stronger and often higher-affinity response — the secondary immune response yields more antibody more quickly (often of different isotypes) and increased numbers of effector T cells, providing effective long-term immunity and usually preventing symptomatic reinfection.
11.2 Antibodies and vaccination
Students should be able to:
1) relate the molecular structure of antibodies to their functions
2) outline the hybridoma method for the production of monoclonal antibodies
3) outline the principles of using monoclonal antibodies in the diagnosis of disease and in the treatment of disease
4) describe the differences between active immunity and passive immunity and between natural immunity and artificial immunity
5) explain that vaccines contain antigens that stimulate immune responses to provide long-term immunity
6) explain how vaccination programmes can help to control the spread of infectious diseases
5 — Molecular structure of antibodies related to function
An antibody molecule (immunoglobulin) is typically composed of two identical heavy polypeptide chains and two identical light chains linked by disulfide bonds to form a Y-shaped structure; each arm of the Y contains a variable region at the amino-terminus (formed from heavy and light chain variable domains) that creates the antigen-binding site complementary to a specific epitope, while the stem and lower parts of the arms contain constant regions that determine effector functions (for example binding to Fc receptors on phagocytes, activating complement or crossing the placenta). The variable regions provide high specificity for antigen recognition and affinity, the bivalent (or multivalent in some isotypes) arrangement allows cross-linking and agglutination of antigens, and the Fc region mediates recruitment of other immune mechanisms (opsonisation, complement activation, antibody-dependent cellular cytotoxicity), so the molecular architecture directly couples antigen binding to pathogen neutralisation and to engagement of downstream immune effector processes.
6 — Hybridoma method for production of monoclonal antibodies (outline)
The hybridoma technique produces monoclonal antibodies by immunising an animal (commonly a mouse) with a chosen antigen to stimulate specific B cells, isolating antibody-secreting B cells from the spleen and fusing them with an immortal myeloma (plasma cell cancer) cell line to create hybridoma cells that combine the antibody specificity of the B cell with the indefinite growth capacity of the myeloma; hybridomas are grown under selective conditions so only fused cells survive, individual clones are screened to identify those producing the desired antibody specificity, and chosen clones are then expanded to produce large quantities of a single-specificity (monoclonal) antibody that can be harvested from culture supernatant or ascites and further purified for diagnostic or therapeutic use.
7 — Principles of using monoclonal antibodies in diagnosis and treatment
Monoclonal antibodies, because they recognise a single defined epitope, provide powerful tools for diagnosis and treatment: in diagnostics they are used to detect specific antigens in assays such as ELISA, lateral flow tests and immunohistochemistry where binding of a labeled monoclonal antibody reveals the presence or quantity of pathogen antigens, hormones or tumour markers; in therapy they can target diseased cells or molecules with high specificity, either by directly neutralising a target, engaging immune effector mechanisms via the antibody Fc region, or acting as vehicles to deliver drugs, toxins or radioisotopes to selected cells, and their specificity reduces off-target effects compared with less selective agents.
8 — Differences between active and passive immunity; natural vs artificial
Active immunity arises when an individual’s own immune system is stimulated to produce an adaptive response including memory cells — this can occur naturally following infection or artificially following vaccination; active immunity typically develops more slowly but is long lasting because of memory. Passive immunity is conferred by transfer of preformed antibodies from one individual to another (for example maternal IgG across the placenta or injection of pooled immunoglobulin), providing immediate but temporary protection without stimulating the recipient’s immune system to form memory. Natural immunity refers to immunity acquired through natural exposure (infection or maternal transfer), while artificial immunity denotes immunity acquired through medical intervention such as vaccination or therapeutic antibody administration.
9 — Vaccines contain antigens that stimulate immune responses to provide long-term immunity
Vaccines introduce antigens — whole organisms that are attenuated or killed, subunit antigens, purified proteins or toxoids, or antigen-encoding material — in a form that safely stimulates the adaptive immune system to generate effector responses and memory B and T cells without causing disease; adjuvants are often included to enhance the immune response and booster doses may be required to achieve long-lasting immunity by promoting affinity maturation and maintaining memory cell populations, so vaccination primes the immune system to respond rapidly and effectively on subsequent exposures to the real pathogen.
10 — How vaccination programmes help control spread of infectious diseases
Vaccination programmes reduce disease spread by directly protecting vaccinated individuals and, when uptake is sufficiently high, by generating herd immunity that lowers the probability of transmission through the population and thereby protects vulnerable individuals who cannot be vaccinated; systematic vaccination can reduce the incidence of a disease, prevent outbreaks, lower morbidity and mortality, and in some cases enable eradication when sustained global coverage eliminates natural reservoirs — effective programmes combine high coverage, cold-chain logistics, surveillance, booster strategies where needed and equitable access to interrupt transmission chains.