Genetic basis of antibodies + t cell receptors Flashcards
what are the 2 theories of immunity
Instructive
selective
what does instructive theory entail
antigen instructs the immune system how to produce antibodies specific for it
what does selective theory entail
antigen selects pre made antibody specific for it
is the side chain theory selective or instructiv? and who found it
selective
Paul Ehrlich
* figureed out antibodies must be produced by cells
what’s the gist of the side chain theory
When an antigen comes, it binds to
a matching side chain. Then the cell stops synthesis of other side chains + makes only the one that has reacted. It accumulates and is secreted as a soluble antibody.
why was the side chain theory abandoned
. New data emerged showing unlimited ability of the immune system to produce diverse antibodies. (so 1 cell doesnt secrete side chains)
This ability was demonstrated e.g., by Landsteiner’s experiments
What was the suggested template theory
suggetsed that all antibodies had the same primary structure + When an antigen
comes, the precursor polypeptide chain bends around it and becomes a functional antibody.
- thought antigen was the template for structure of antibody. (not mRNA)
What is the clonal selection theory
David Talmage
. antibody diversity is generated before any
antigen is met;
. antibodies are exposed on the surface of
cells producing them;
. after that, antigens select matching
antibodies
** every cell produces only 1 type of antibody
*****Immunoglobin genes are rearranged in B cells. what are the parts on the AB light chain
V and C parts
. Germline DNA contains dozens of gene frafments for the V region. In every differentiating B lymphocyte, one
of them is (randomly) selected.
- What is VJ recombination of light chain
. one of the V fragments and one of several
smaller fragments called J (from “joining”). This of
course increases the diversity of the variable region.
what is VDJ recombination for heavy chain
heavy chain has additional diversity
between the V and the J segments, there is a group of short D (“diversity”) segments.
So, the “gene” for the variable region is obtained by VDJ
recombination at two stages.
what are V D J segements flanked by
Recombinaiton signal seq (RSS)
what does RSS consist of
heptamer and nonomer separated by 12/23 base pairs
what are RSS recognized by
VDJ recombinases
Important = RAG ( recombination activating gene)
what does VDJ recombination create
Combinatorial diversity
what do differnetiating lymphocytes contain.
Enzyme: terminal deoxynucleotidyl transferase Tdt
what do Tdt do?
Adds random nucleotides to an exposed 3’ end of DNA.
how is junctional diversity introduced
During V(D)J recombination, before coding ends are joined together, Tdt may insert one or several
nucleotides between V and J for light chain + between V and D / D and J for the heavy chain.
what is somatic hypermutation (additional diversity)
When a mature B cell binds Ag and is activated to produce a clone,
genes for variable domains tend to have point
mutations, especially in the hypervariable regions (CDR). what does these increase
increases the variability and gives
chances to create new B cell clones that synthesize
antibodies with improved affinity for antigen.
summarize: combinatorial diversity, Junctional diversity, somatic hypermutation
C- produced by random
combination of germline V, D and J segments
J - produced by random addition of
nucleotides at the joints between these segments
S - involves entire variable region during T - dependant humoral immune responses
How does TCR diversity arise
.From genetic recombination of the
gene segments in individual somatic T cells
by V(D)J recombination and by junctional
diversity created by TdT
which diversity is not used by t cells
Somatic hypermutation - could genertae autoreactive TCRs
what happens if therre is a mutation in VDJ recombinases.
- severe combined immunodeficiency (SCID)
- theres no immunocompetant lymphocytes (B + T cells)
Treatment for SCID
bone marrow transplant
- until then they hv to be kept in sterile enviroment (bubble)
