Describe the process of phagocytosis.
- Chemotaxis and adherence of pathogen to phagocyte.
- Phagocytosis and phagolysosome formation.
- Phagosome-lysosomes fusion, forming a phagolysosome.
- Pathogen degradation.
- Formation of residual body containing indigestible material and exocytosis.
Describe the processes used in the phagolysosome to destroy a pathogen.
O2 dependent degradation
- Respiratory burst produces reactive oxygen & nitrogen species.
- E.g. Oxidase catalyses reduction of O2 to superoxide anion - very toxic to pathogens. Superoxide anion also generates other powerful oxidising agents, inc. hydroxyl radicals and hydrogen peroxide. Myeloperoxidase produces hyperchlorite from hydrogen peroxide and chloride ions - toxic.
- E.g. Production of nitric oxide.
O2-independent degradation
- Requires release of granules containing proteolytic enzymes such as defensins, lysozyme and cationic proteins.
What is opsonisation?
Pathogen is marked for phagocytosis using opsonins such as antibodies or complement (C3b).
What are the 3 pathways of complement and how are these activated?
- Classical pathway: antigen-antibody complexes bind to pathogen surface
- Lectin pathway: mannose-binding lectin binds mannose of pathogen surface
- Alternative pathway: C3b binds directly to cell surface
At which point do the 3 complement pathways converge?
Proteolysis of C3 into C3a and C3b by C3 convertase.
What are the main immune effects of complement?
- C3a and C5a: inflammation and phagocyte recruitment
- C3b: pathogen opsonisation (binds to complement receptors on phagocytes)
- C5b & other terminal complement components: membrane-attack complex forming pore in pathogen membrane (lysis).
Which cells are the main mediators of the innate immune system?
- Neutrophils = front-line effector cells, mediate phagocytosis.
- Macrophages = mediate phagocytosis and act as APCs.
Which cells are the main mediators of the adaptive immune system?
Lymphocytes:
- B cells - secrete antibodies
- T cells - kill virus-infected cells and cancer cells, and activate other IS cells.
How do T cells mediate infected cell killing?
Killer T cells produce:
- perforins - proteins that form pores in the membrane of target cells
- granzymes - proteases that induce PCD on entry into target cells
How are T cells activated?
- Lymphatic fluid drains through lymph nodes, carrying dendritic cells with it. T cells migrating through the lymph nodes recognise antigen on these antigen-presenting DCs - form germinal centres.
- Interaction mediated by MHC II molecules.
How are B cells activated?
By antigen recognition followed by function of activated T helper cells in germinal centres.