5. B-cells and Antibodies Flashcards
What is an antibody?
Antigen receptor of B-lymphocytes. 4 glycoprotein molecule, 2 heavy (identical) and 2 light (identical) chains. Each chain has a variable and constant region.
Differentiate between variable and constant regions on the chains of an antibody molecule.
How many antigen binding sites are on one antibody molecule, and what are they made by?
What are the 2 main ways antibodies differ from each other?
Variable regions on each chain comprise 1 domain only. Constant regions on heavy chains comprise 3 or 4 domains, on light chains: 1 domain.
2 identical antigen binding sites, each made by variable regions of one heavy and one light chain. (Both variable regions will differ)
In variable and constant regions.
Are the heavy chain and light chain variable regions the same on any one B-cell?
How are B-cells with different specificies created?
What happens if B-cells with autoreactive antibodies are generated?
Yes, thus on any one B-cell all the antigen-binding sites are identical.
In different B-cells the variable regions of the antibodies will be different, giving different specificities, which are initially created by random genetic events. Vast numbers of diff specificities over the B-cell population as a whole.
Self tolerance maintained by clonal deletion.
How many different versions are there of heavy chain constant regions?
What portion of the Ab does the heavy chain constant region form?
What determines the class of the Ab? List the classes.
9. On any 1 Ab molecule, the heavy chains are both the same.
Fc portion
The heavy chain constant region: IgM, IgE, IgA (2 subclasses), IgD and IgG (4 subclasses)
What do the following Ab classes do:
a) IgM
b) IgE
c) IgA
d) IdD
e) IgG
a) can block pathogen binding, activate complement
b) activates mast cells
c) can block pathogen binding, present in many secretions (tears, digestive juices etc.)
d) not secreted, function unknown
e) can block pathogen binding, activate complement and opsonise antigen for phagocytes. Specially transported across placenta
What are the different versions of light chain constant regions?
Describe how B-cells form.
How can a B-cell become activated without seeking T-cell help?
Kappa and lamda. No functional significance.
From pluriopotent bone marrow stem cell -> lymphoid lineage -> B-cell - first expresses IgM (still in bone marrow, sensitive to clonal deletion if fits antigen with its Ab). If avoids deletion, leaves marrow: expresses IgM and IgD simultaneously.
Encounters antigen that its Ab fits. If determinant is repeated over and over again: crosslinking of Ab molecules: B-cells can become activated without seeking T-cell help = T-independant antigen
If the determinant is not repeated, the B-cell must seek T-cell help to become activated (the T-dependant antigen). Describe how this happens.
What 3 things can the first class of Ab produced from an activated B-cell do?
Endocytosis, processing, presentation to CD4 T-cell. If the B-cell can’t find a T-cell with a receptor specific for presented antigen, the B-cell will die. Once activated, B-cell forms a clone. First class of Ab produced = IgM.
Class switch, slightly alter specificity, differentiate to plasma cell to secrete Ab. (T-cell help needed for first 2)
What are 5 features of the B-cell memory response?
Describe complement.
What are the 2 entries and 4 results?
Faster, higher levels of specific Ab, lasts longer, more specific, IgG rather than IgM
Series of glycoproteins in blood and lymph which can sequentially activate each other. Made by hepatocytes, epithelial cells and macrophages.
Entries: classical and alternative pathways
Results: opsonisation (making tasty for phagocytes: C3b receptor), lysis, activation of mast cells, chemotaxis of neutrophils etc. Mostly activated by cleavage.
Distinguish between the classical and alternative complement pathways.
Classical: antigen-Ab complexes involving IgG or IgM. CRP + antigen. MBL + antigen. Results in cleavage of C3. C3b sticky - adheres to nearest membrane.
Alturnative: doesn’t need Ab, activated by non-self substances, cell walls lack DAF and MCP. This path is a positive feedback loop resulting in splitting of more C3, kept in check by DAF and MCP on cell surface, factors H and I in serum.
Describe how the complement system causes the following:
a) opsonisation
b) lytic sequence
c) chemotaxis
What are neutrophilic polymorphonuclear leukocytes?
What kind of receptors do they have? What is induced by interaction with a receptor?
a) C3b opsonises antigen for phagocytosis
b) C5 split by C3b into C5b and C5a. C5b sticks to nearest membrane, initiates lytic sequence, which inserts pores into membrane
c) C3a and C5a activate mast cells and are chemotactic
(neutrophils, polymorphs) - short lived phagocytic motile chemotactic cells. From pluripotent bone marrow stem cells - GEMM lineage -> G-M lineage (myeloid linage).
TOLL-like, lectins, Fe and C3b receptors (cooperation with Ab and complement). Phagocytosis induced by receptor interaction.
How do neutrophilic polymorrphonuclear leukocytes kill?
What are the first cells to appear in acute inflammation, and what do they secrete?
Enzymes (proteases etc.), free radicals (superoxide etc.), witholding of iron etc. from bacteria.
Neutrophils. Respond to inflammatory mediators, which they also secrete: leukotrienes, chemokines
