Flashcards in Antigen recognition (7) Deck (76):
What are T lymphocyte receptors not expressed as?
What is T cell immunity important in defence against?
What are T cytotoxic cells also known as?
What are T helped cells also known as?
What do T cytotoxic cells do?
Specifically kill infected host cells
What do T helper cells do?
Augment immune responses
What is B cell immunity particularly important in?
Defence against extracellular pathogens.
What do B cells recognize?
Soluable, free native antigens.
What do T cells regcognize?
Cell associated pathogens.
What MHC class is expressed by all nucleated cells?
What MHC class is expressed by certain leucocytes?
What Leucocytes express MHCII?
Dendritic cells, B cells and macrophages.
What do MHC class 1 do?
Present peptides from endogenous proteins.
What do MHCII do?
Present peptides from exogenous proteins.
What type of cell recognises peptides bound to MHC1?
Cytotoxic T cells.
How do cells present peptides for cytotoxic T cells?
A virally infected cell produces viral proteins. These are broken down in the cytosol and the peptides are transported to the ER. Here they bind to the MHCI and are taken to the cell surface.
What type of cell recognises proteins bound to MHCII?
Helper T cells.
How do cells present peptides for T helper cells?
The antigen presenting cell internalises and breaks down foreign material. The peptide is then bound to MHCII in the endosomes which takes the proteins to the cell surface.
What receptor has a Fab like structure?
What domains of the TCR are homologous to the V and C regions of the immunogloblins?
What two chains make up the TCR?
Alpha and beta.
How big is the TCR?
What percentage of T cells express gamma/delta receptor?
Where are T cells that express gamma/delta found?
T cells that express gamma/delta receptors are less diverse. What is the consequence of this?
They recognise a broader range of antigens.
What complex do TCR's recognise?
Antigen + self MHC.
What region of the alpha and beta chains are most variable?
Crystallographic studies of TCR showed that CDR1 and CDR2 bind what?
Crystallographic studies of TCR showed that CDR3 bind what?
What forms the TCR complex?
TCR receptor, CD3 subunit (x2), signal transduction.
What components are found in the CD3 subunits?
Elipson, delta and gamma.
What component is found in the signal transduction subunit of the TCR complex?
What is the TCR complex required for?
Optimal cell surface expression and signalling.
What subunit of the TCR complex contains ITAMS in their cytoplasmic regions?
How many antibody receptors are in the immune repertoire?
How many T cell receptors are in the immune repertoire?
What are the main determinants of antibody diversity?
The sequence and length of CDRs.
What CDR tends to be most variable in length an sequence?
What chain contributes more to antigen binding as it is more variable?
The antibody repertoire is more than 10^14 in humans, however there are only 30,000 genes in the human genome. What three early hypotheses were there for this?
1. Multiple genes.
2. Somatic mutation.
3. Somatic recombination.
How does antibody diversity actually arise?
Through somatic recombination and mutation of a limited number of inherited gene segments which make up the variable regions of antibodies.
What was the Dreyer and Bennett hypothesis (1965)?
Immunoglobulins are encoded for by separate C region and multiple V region genes.
What did Susumu Tonnegawa (1976) suggest?
Immunoglobulin genes are rearranged during B cell development.
What were the steps of the experiment determining the light chain (k) recombination?
1. A mouse embryo and mouse myeloma cell line were taken.
2. DNA extracted and digested with restriction enzymes.
3. Restriction fragments separated by gel electrophoreses.
4. V and C regions identified by hybridisation with radioactive probes.
5. The germline pattern was found in all cells except those of B linage.
What are the three sets of immunogloblin genes and what chromosomes are these found on?
H cheavy (14)
Kappa chain (2)
Lambda chain (22)
What is found at each immunoglobulin gene locus?
Multiple variable region genes and one/ few constant region genes.
How many exons encode the variable regions?
2 or more.
What two segemens make up the variable region in a light chain?
Vk and Jk. (or L)
What segments encode the variable region in the heavy chain?
VH, DH, JH.
What does the D stand for in the DH segement?
What part of the antibody is always expressed first?
IgM heavy chain.
How many copies of the functional V lamada are there in the genome?
How many copies of the functional V Heavy are there in the genome?
How many copies of the functional D heavy are there in the genome?
When does rearrangement of light and heavy chain genes occur?
During B lymphocyte differentiation.
What happens in somatic recombination during B lymphocyte development?
A v gene is spliced to a J gene with the inverting DNA being excised.
What does somatic recombination result in meaning transcription can take place?
The rearranged V promoter being close to an enhancer.
Does D-J joining or V-D joining occur first?
D-J joining. This is followed by V-D-J joining.
What does recombination of B lymphocytes require?
Lymphocyte specific recombinases and conserved recognition signal sequences (RSSs).
What do RSSs contain?
A conserved heptamer and a conserved nonomer separated by either 12 or 23 random nucleotides.
Where are RSS sequences found?
Directly adjacent to coding sequences V,D or J.
What three types of enzymes are found in the V D J recombinase?
1. Normal DNA cleavage/ repair enzymes.
2. Products of RAG1 and RAG2 genes.
3. Terminal deoxynucletoide transferase (TdT)
What does RAG stand for?
Recombination activation genes.
What are the products of the RAG1 and RAG2 genes?
Specialised endonucleases expressed in developing lymphocytes.
Mutations in the normal DNA cleavage/ repair enzymes and RAG2 genes in the V (D) J recombinases can result in what?
SCID (severe combined immunodeficiency)
What happens to the RSS in recombination?
The RSS flanking the gene segements to be joined are brought together.
What is the 12-23 base pair rule?
A gene segment with a 12bp spacer only joins with a gene segment with a 23bp spacer.
What does the 12-23 base pair rule ensure?
Correct V-D-J joining
What is the relevance of 12 and 23bp in the 12-23 bp rule?
Correspond to either 1 or 2 turns of the DNA helix.
What causes junctional diversity?
The fact that recombination is imprecise meaning nucleotides may be added or lost.
Where does junctional diversity mainly add diversity to?
What factor does junctional diversity diversity by?
3 x 10^7
What four factors are responsible for diversity?
1. Multiple copies of each V region segment genes
2. Heavy and light chain combination
3. Junctional diversity
4.. Somatic mutations of V regions
When will somatic mutations in the V regions take place?
After antigen activation.
What time of mutations happen in the V regions somatically?
Point mutations- normally clustered in the CDRs.