antibodies Flashcards
All cells of the immune system share a common progenitor…
the hematopoietic stem cell which is multipotent.
rounds of differentiation and specialisation produce the vast array of what type of cells?
white blood cells, which make up our immune system.
All life starts in the bone marrow, receiving signals from the stromal cells.
T-cells; mature in thymus, regulatory and cytotoxic.
B-cells; mature in bone marrow, produce antibodies.
NK-cells; mature in bone marrow, but also secondary lymphoid tissues, cytotoxic.
B-cell development is dependant on transcription factor pax5. Explain this.
In pax5 mice, these progenitor B-cells can be transformed into T-cells & myeloid cells, suggesting that pax5 is important for commitment to the B0cell development pathway.
The development of B-cells, and thus the B-cell acceptors involves …
…a complex series of gene recombination to produce the vast array of antibodies we need.
Explain the ‘instructive theory’ (1940) in antibody development.
The antigen acts as a template that directs the folding of the unfolded antibody chain. Basically the antigen decides the folding. Thus, a specific AA chain has the propensity to form a variety of antibodies, depending on the antigen present at the time.
Explain the ‘selective theory’ (1950s) in antibody development.
The binding site of the antibody is already predetermined before antigen is even encountered. The presence of the antigen only affects how much of that specific antibody you get.
Classes of antibody; IgA, IgD, IgE, IgG, IgM.
IgA - found in mucous, saliva, tears, breast milk, protects against pathogens.
IgD- part of the B cell receptor. activates basophils and mast cells.
IgE- protects against parasitic worms. responsible for allergic reactions.
IgG- secreted by plasma cells in the blood. able to cross the placenta into the foetus.
IgM- may be attached to the surface of a B cell or secreted into the blood. responsible for early stages of immunity.
what does FAB stand for?
Antigen binding fragment.
what does Fc stand for?
Crystallisable region fragment.
explain Antibody structure in terms of heavy ad light chains.
2 polypeptide chains, light chain & heavy chain. H2L2. Held together by disulphide bridge. Both chains consist of a variable region and a constant region. (variable = 1-108 amino acids, constant = 109-c-terminus.
Explain antibody structure in terms of immunoglobulin folding.
There are broad sheets of anti-parallel b-sheets. Hydrophobic side chains are tightly packed between the sheets and held together with disulphide bridges. Constant domains- 3 beta sheets in 1 strand & 4 on the other.
Variable domains- 2 additional beta-sheets, 3 loops that compose the part of the binding site.
v gene stops encoding the polypeptide chain at …
AA 95, 13 residues too short.
B-cells begin life producing only igM, Class switching recombination is needed to produce the other types of antibodies.
The constant regions of the heavy chains vary, different classes of heavy chains depending on the antibody type; G-y M-u A-a D-δ
Explain the germinal centre reaction.
somatic hypermutation=mutations introduced into the v region of heavy & light chains, altering the affinity of the immunoglobulin for its antigen. Class switch recombination = the initial heavy chain c regions are replaced by another isotope, modifying the effector activity of the immunoglobulin but not its specificity.
