MCB Lecture 47 T cells Flashcards
Which gene locus is responsible for diversity of BCRs?
Describe the structure
Immunoglobulin gene locus
There are three loci, each on different chromosomes:
Heavy, H
Lambda
Kappa
The heavy loci contains many V, D and J genes
The lambda and kappa loci contain many J and V genes
How is diversity of BCRs generated?
Outline the steps
Immunoglobulin gene rearrangement
- Somatic recombination: one of the many V, D and J genes are selected
- Gene transcription of the recombinant gene
- mRNA is spliced
- Translation
Which genes code for the variably portion of the heavy chain?
Heavy
V, D and J
Which genes code for the variable portion of the light chain?
Lambda
Gamma
V, J
Why are there both the kappa and lambda locus?
The kappa locus is used first
If this does not produce a viable BCR, lambda is used
Which cells play a vital role in gene rearrangement of BCRs?
Bone marrow stromal cells
What is the requirement for a pre-B cell?
It must have produced viable heavy chains
Describe how further diversity of antibodies is generated
Junctional diversity
When the genes are being rearranged, extra nucleotides are added at the junctions between the V D and J regions
How many unique antibodies does junctional diversity give rise to?
10 to the 13
Which enzyme is required for junctional diversity (hyper variation)?
TdT
Which enzymes mediate gene rearrangement of BRC?
TdT
Exonucleases
RAGs: recombinase activating genes
How do we prevent auto reactive antibodies from causing damage in the body?
The BCR must pass a test to make sure they are not auto reactive before they can move out into the blood
If they fail the test, they are removed
What is the outcome of isotype switching?
Different Fc
The Fab doesn’t change, however
Describe the structure of TCRs
Two chains: alpha and beta
Which genes code for the TCRalpha?
V J D
Which genes code for the TCRbeta?
V D J C
Which processes follow on after gene recombination for BCR and TCRs?
Rapid proliferation
Removal of attractive BCR
Where do lymphocytes reside in the body?
Give percentages
50% mucosal associated lymphoid tissue
40-50% Lymph nodes
2% blood
What are the main differences between PRR and TCR & BCRs?
PRR: bind to common features (PAMPs)
100-300 different types
BCR/TCR: bind to specific antigens
10 to the thirteen - 10 to the 18 receptors
Give a brief description of the cellular adaptive immune response
When pathogens get into cells, BCR can not find them to bind and produce a response
We now need T lymphocytes that recognise protein coming from inside a cell to detect that a cell is infected
When T cells get activated in this way, they launch a response to kill the cell
What are the two types of MHC?
Where are they each found?
Type I: all nucleated cells
Present protein that has been made inside that cell (can include virus protein)
Type II: present on antigen presenting cells
Present protein that originated outside the cell and was endocytosed
What are APC?
List a few
Antigen presenting cells
Macrophages
Dendritic cells
B cells
What is the structure of MHC?
A beta sheet and two alpha helices form a cleft, to which peptides bind
Describe how diversity is generated for MHC
The genes for MHC are highly polymorphic
Diversity is inherited
We inherit one type from mum and one type from dad
The two alleles are codominantly expressed
