6581865
Description
Flashcards by Florence Edwards, updated more than 1 year ago
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Created by Florence Edwards
over 8 years ago
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| Question | Answer |
| Define complement | A series of plasma proteins which, when activated, interact sequentially to form a self-assembling enzymatic cascade generating biologically active molecules which mediate a range of end processes. |
| Approximately how many plasma proteins form the complement system? | Approximately 30 |
| What is an enzymatic cascade? | Pro-enzyme converted to enzyme This enzyme activates another pro-enzyme Creates an amplification effect |
| How are enzymatic cascades controlled? | Regulatory factors act at specific points in the cascade |
| What are the 3 different initiation pathways in the complement system? | Classical Lectin Alternative |
| What is the end point molecule of all 3 initiation pathways? | C3b |
| Which pathway is activated by the end point molecule of the initiation pathways? | Terminal pathway |
| Give 4 end effects of the terminal pathway | Cell lysis Inflammation Opsonisation Interact with other pathways |
| What activates the classical pathway of the complement system? | Antigens that trigger complement molecules, for example on the cell membrane of a pathogen |
| What is the function of complement molecules? | Damage membranes of cells which they bind to |
| What is the first step of the classical pathway? | Antibody binds to antigen epitope |
| What is the second step of the classical pathway? | C1 protein binds to antibody |
| What is the structure of the C1 protein? | 3 subunits C1q, C1r and C1s All subunits act as enzyme |
| How does the C1q subunit attach to the antibody? | Through CH2 domain |
| W | Activation of C1 subunits q then r then s |
| What is the fourth step in the classical pathway? | Activated C1s subunit acts on the complement molecule C4, activating it by splitting into C4a and C4b subunits |
| What is the fifth step in the classical pathway? | C4b subunit binds to antigen (but not C4a) |
| What is the sixth step in the classical pathway? | C2 complement protein associates with C4b subunit |
| What is the seventh step in the classical pathway? | C1s acts on C2 complement protein, activating it by splitting into C2a and C2b subunit |
| What is the eighth step in the classical pathway? | C2b subunit remains bound to C4b subunit (but not C2a) |
| What is the name for the C4b + C2b complex? | C3 convertase |
| What is the ninth step in the classical pathway? | C3 convertase activates C3 by splitting into C3a and C3b subunit |
| What is the tenth step in the classical pathway? | C3b subunit forms a complex with C2b and C4b |
| What is the name for the C4b + C2b + C3b complex? | C5 convertase |
| What is different about the lectin pathway in comparison with the classical pathway? | Mannan binding lectin directly activates C4 and C2 to form C3 convertase, independent of antibody and C1 |
| Why is the control of complement molecules important? | Can be toxic |
| Give a regulatory mechanism of complement molecules that does not involve enzymes | Short half life of complement molecules Spontaneously degrade after a short time |
| Give a regulatory mechanism of the C1 complement molecule | C1 inhibitor dissociates the r and s subunits |
| Give 2 regulatory mechanisms of the C3 convertase complex | C4 binding protein displaces C2b Factor I converts C4b into the inactive fragments C4c/d |
| Give a regulatory mechanism of the C5 convertase complex | Factor I converts C3b into inactive C3c/d fragments |
| What is the function of membrane regulatory proteins? | Prevent complement pathways being activated on the surface of normal cells |
| How do regulatory proteins work? | Disrupt C3 convertase formation |
| Give 3 examples of membrane regulatory proteins in the complement system | DAF CR1 MCP |
| What is meant by the 'tick over' phase of the alternative pathway? | Continually active at low levels in normal individuals |
| Where does the 'tick over' phase of the alternative pathway occur? | Extracellular fluid |
| Where does the active phase of the alternative pathway occur? | Surfaces of cells in the presence of trigger factors |
| What is the main difference between the alternative pathway and the classical pathway? | Alternative pathway does not require antibodies |
| What is the first step in the 'tick over' phase of the alternative pathway? | C3 undergoes spontaneous proteolysis to form C3i |
| What is the second step in the 'tick over' phase of the alternative pathway? | Factor B interacts with C3i to form a complex |
| What is the third step in the 'tick over' phase of the alternative pathway? | Factor D targets Factor D and activates it by splitting into Ba and Bb subunit |
| What is the fourth step in the 'tick over' phase of the alternative pathway? | Bb subunit remains bound with C3i |
| What is the name for the Bb + C3i complex? | C3 convertase |
| What is the fifth step in the 'tick over' phase of the alternative pathway? | C3 convertase activates C3 by splitting into C3b and C3a subunit |
| What is the final step in the 'tick over' phase of the alternative pathway? | Factors H and I break down C3b into inactive C3c/d fragments and the pathway ends |
| What is the function of the 3 membrane regulatory proteins in the 'tick over' phase of the alternative pathway? | Inactivates any C3b landing on the cell |
| What initiates the active phase of the alternative pathway? | C3b from 'tick over' phase can bind to trigger surface |
| What is the second step in the active phase of the alternative pathway? | Factor D activates Factor B on cell surface, forming Bb (remains bound to C3b) and Ba |
| What is the third step in the active phase of the alternative pathway? | Properdin stabilises C3b and Ba complex, forming C3 convertase |
| What is meant by the amplification loop of the alternative pathway? | C3 convertase activates more C3 into C3a and C3b |
| What is the final step in the active phase of the alternative pathway? | Additional C3b molecule added to C3 convertase, forming C5 convertase |
| What is the initial molecule in the terminal pathway? | C5 convertase from classical/alternative/lectin pathway |
| What is the first step in the terminal pathway? | C5 convertase activates C5 by splitting into C5a and C5b subunit |
| What is the second step in the terminal pathway? | C5b combines with C6, C7, C8 and multiple C9 molecules forming a Membrane Attack Complex |
| What does the abbreviation MAC stand for? | Membrane attack complex |
| Give 2 effects of the C5a subunit | Chemotactic Anaphylactic |
| What is the function of the C59 molecule? | Membrane Attack Complex inhibitor Breaks down Membrane Attack Complex if not required as it can be toxic |
| What is meant by cytolysis? | Cell breakdown |
| How do complement molecules cause cell lysis? | Membrane Attack Complex inserts through lipid bilayer of cells, forming pores Creates osmotic imbalance so sodium and chloride ions pass into cell Water drawn into cell by osmosis Osmotic lysis |
| Which cells are more likely to be affected by osmotic lysis? | Occurs in bacteria more than viruses Lysis of cells also occurs in Type II hypersensitivity |
| What is the function of C3a, C2a and C5a? | Generate biologically active molecules for inflammatory process Especially C3a and C5a |
| How do C3a and C5a affect the action of immune cells? | Form chemotactic gradient for immune cells, as these subunits are generated at the site of bacteria Degranulation of mast cells, which contributes to inflammation |
| What is the effect of C3a and C5a on muscle? | Smooth muscle contraction (especially in airways) |
| What is the effect of C3a and C5a on capillaries? | Vasodilation - increases space between endothelial cells Causes oedema which dilutes bacterial toxins Immune cell extravasation Local influx antibody and complement |
| What is meant by phagocytosis by non-specific adherence? | Antibodies can agglutinate particulate antigens to form a larger target for macrophages |
| How can complement molecules aid opsonisation? | Antigen can be coated with antibody - recognised by macrophage Fc receptor C3b can also opsonise antigen - also recognised by C3b macrophage receptor |
| What is the function of macrophages in the liver and spleen? | Remove antigens from the blood |
| What is meant by immune adherence? | Erythrocytes have C3b receptors so can transport antigen (which has been opsonised by C3b complement) to macrophages in the liver and spleen |
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