Antibody Genes Flashcards
toxoid
bacterial toxin (usually an exotoxin) whose toxicity has been weakened or suppressed either by chemical (formalin) or heat treatment
DNA recombination
changing the relative positions of 2 pieces of DNA
primary RNA transcript
RNA splicing
somatic mutation
affinity maturation
Define cross-reactivity
Cross-reactivity: refers the tendency of one antibody to react with more than one antigen. Other antigenic determinants might also fit into the complementary-determining region (CDR) and if they did so detectably, we would say that the antibody cross reacted with those determinants.
give an example of a non-self antigen which cross-reacts with a self antigen
if you immunize a person with cow pox, the antigenic determinants of small pox will also be recognized and the person will be immunized.
Discuss the Clonal Selection Theory in terms of: the number of different receptor specificities it postulates per cell; the role antigen plays in the initial expression of receptors; the role of antigen in clonal selection;
each cell of the immune system is programed to make only one antibody, the choice of which antibody the cell makes is random, NOT dependent on outside information and that the entire population PREEXISTS in a normal individual BEFORE contact with the antigens. When a new antigen enters the body, it contacts many lymphocytes. When it encounters a lymphocyte whose receptors bind it with a high affinity, the lymphocyte is activated and makes closes and antibodies. The best fitting clones are SELECTED by the antigen. Clonal selection is Darwinian because it has to do with the survival of the fittest.
Discuss the Clonal Selection Theory in terms of: an experiment which provides strong evidence for the theory
Antigen X linked with radioactive label, such that any cell bound to it would die of radiation. If instructional theory was true, enough antigen would bind all the B cells, because they were “non-specific” until instructed, so no antibody could be made. If selection theory was correct, only pre-existing B cells with randomly expressed receptors for X would bind and die, all other would survive. After receiving radioactive X, animal immunized with nonradioactive X and Y, unrelated antigen. It responded normally to Y, but not to X. Selection theory was proven
Discuss the Clonal Selection Theory in terms of: how it differs from an instructional theory; and whether it is Darwinian or Lamarckian.
instructional theory: old theory, antigen told the immune system in some way to make antibodies of appropriate conformation. Lamarckian theory because they implied that the outside world instructed the cell to change its genetic information. WRONG
Define allotypic exclusion and state the number of chromosomes in a cell which bear H or L genes, including the number that actually contribute to a single B cell’s antibody product.
a. Allotype: minor allelic differences in the sequence of immunoglobulins between individuals, determined by allotypes of your parents, useful in determining relatedness.
b. The lambda, kappa and H chain gene families are all on different chromosomes. Each cell has 2 copies of each gene, but only 1 H chain (maternal or paternal) and 1 L chain (either kappa or lambda) are synthesized in any 1 B cell. All other genes are silenced. Though a person can make 2 allotypes, an individual B cell can only make 1.
- Draw a diagram of the heavy and light chain gene regions of human DNA. Indicate V, D, J and C subregions. Show how a heavy or light chain gene is assembled out of these subregions during the differentiation of a B cell.
a. Many genes encode for the variable domains, only one of each set of constant domain genes (1 gene for the constant part of the delta chain, 1 gene for mu)
b. DNA rearranges in developing B cells, to bring one of the many V’s together with the correct C so that the unit can be made into mRNA. Changing the relative positions of 2 pieces of DNA is called recombination. This is occurring in SOMATIC cells, which is unusual.
c. Assembling a Heavy Chain gene: variable domain is code for by V, D, and J segments. Developing B cell brings one random D segment close to 1 J, the DNA is cut, and intervening DNA is excised and ends are joined. Then, V segment is brought up to the recombined DJ, cutting is repeated, and ends are joined. The entire region from the assembled VDJ unit through to the end of the delta constant region gene is transcribed into nuclear RNA. These primary RNA transcripts are alternatively spliced to make VDJ-C(mu) and later to make both VDJ-C(mu) and VDJ-C(delta). IgM from VDJ-C(mu) is always produced first, hangs out in the bone marrow for 24 hours and if nothing-self binds to IgM it makes IgD and IgM simultaneously, matures, and enters the circulation.
