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36 Cards in this Set
- Front
- Back
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What are lysozymes? |
Catalyse hydrolysis of 1,4-beta-linkages between NAM and NAG residues in a peptidoglycan Antigen |
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How many Antigen Binding Sitesdoes each Ab have? |
2 Allows Ab to cross-link foreign antigens |
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What part of the antibody differs in the five classes? |
Heavy chain |
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Order the Ab in terms of serum concentration |
GAMDE |
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IgG |
Protection to bloodstream antigens Crosses placenta |
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IgM |
High avidity for complex antigens (10 combining sites)
Produced before IgG |
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IgD |
B cell antigen receptor |
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IgE |
Inflammation Allergy |
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What is the function of antibodies?
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Neutralise bacteria Block microbes adhering to mucosal cell surfaces IgG/IgM - classical arm of complement - lysis/phag - enhances opsonisation Effector cell activation |
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How does antibody neutralise toxins? |
Blocks the binding of toxins which would become endocytoses, dissociate and release active chain - poisoning cell
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How does antibody prevent virus binding? |
Blocks binding to virus receptor Virus would endocytose |
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How does antibody prevent bacterial colonisation? |
Blocks colonisation and uptake Prevents internalisation and propagation in internal vesicles |
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How do antibodies activate complement? |
Pentameric IgM binds to antigens - adopts staple form
C1q binds to one bound IgM molecule/ 2 IgG Activates C1r 4 Cleaves and activates serine protease C1s |
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How do antibodies facilitate immune complex clearance? |
Antigen:Ab complexes Deposition of C3b molecules on immune complex Complement receptor CR1 on erythrocytes bind via C3b Spleen and liver, phagocytic cells remove complexes from RBC surface |
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What is the antibody repertoire? |
Total number of antibody specificities available to an individual |
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How is the antibody repertoire generated? |
Combinational diversity (different gene segments)
Somatic hypermutation (in germinal centres) |
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How many V, J and C segments are there in light chain? |
Up to 40 variable (V) gene segments Five Joining (J) Segments One Constant (C) Segment |
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Steps in light chain remodelling |
1. Somatic recombination - V-J joining, excision of gene series 2. Transcription and Splicing - recombined DNA to pre mRNA, introns spliced- translated |
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How does joining create diversity? |
Imprecise |
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How many V, J and C segments are there in heavy chain? |
Addition D regions |
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Why is IgM made first? |
Gene transcribed first |
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How is this gene rearrangement controlled? |
Conserved DNA heptamer/nonamer sequences flank thecoding regions and form a recombination signal sequence (RSS) Rag1 and Rag2 recombinase enzymes direct the breakage event. DNA ligase repairs the rejoined segments. |
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How is the Ig DNA broken and rejoined? |
RAG1:2 binds to RSS Synapsis of RAG complexes Cleavage of RSSs |
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Name a disorder caused by a missense mutation in RAG1 Describe the symptoms |
Omenn Syndrome Severe rash, liver/spleem/lymph nodes enlargement Low IgG levels |
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When does class switching occur? |
During infection |
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How does class switching occur? |
Replacement of the Cm exon by Cg, and the deletion of the intervening sequence. |
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What is the mechanism for a B cell to produce one specific Ab? |
Allelic exclusion Either maternal/paternal Ab genes expressed |
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How does Ab affinity for antigen increase during immune response? |
Somatic Hypermutation Activated B cells (in germinal centres) make a deaminase. Activation Induced Cytosine Deaminase (AID) converts cytosine to uracil in Ig DNA variable regions. Hypermutation - tries to fix error Ab with high affinity proliferate |
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Which enzymes remove uracil? |
UNG and APE1 |
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Where does somatic hypermutation occur? |
Germinal centre - in lymphoid tissue |
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What are rapidly proliferating B cells in germinal centres called? |
Centroblasts |
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What does flexibility at both hinge joints enable? |
Two arms of an Ab to bind to sites far apart |
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How many complementarity-determining regions are there? |
Three CDRs from each the heavy and light chains |
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What are the four main processes which generaate Ab diversity? |
1. Combinatorial diversity - Multiple copies of each gene segment and different combinations of gene segments 2. Junctional diversity - joints between gene segments, add/sub. nts 3. Combinatorial - diff. combinations of chain V regions for antigen-binding site 4. Somatic hypermutation - point mutations into rearranged V-region genes |
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Explain the mechanism of somatic hypermutation |
Activation-Induced (Cytidine) Deaminase - deaminates C to A. So C:G to U:G mismatch U removed by uracil-DNA glycosylase Error-prone DNAP fills gaps - introduces mutation at deaminated cytosine or neighbouring bp |
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Explain the mechanism of V(D)J recombination |
V(D)J recombinase (through activity of RAG1) binds an RSS flanking a coding gene segment - creates single-strand nick in DNA RSS composed of: heptamer, spacer (12/23 bps) and nonamer. Length of space - one or two turns of DNA helix. Gene segments to be recombined are adjacent to RSSs of different spacer lengths |
