Flashcards in MCB Lecture 47 T cells Deck (44)
How is diversity of BCRs generated?
Outline the steps
Immunoglobulin gene rearrangement
1. Somatic recombination: one of the many V, D and J genes are selected
2. Gene transcription of the recombinant gene
3. mRNA is spliced
Which gene locus is responsible for diversity of BCRs?
Describe the structure
Immunoglobulin gene locus
There are three loci, each on different chromosomes:
The heavy loci contains many V, D and J genes
The lambda and kappa loci contain many J and V genes
Which genes code for the variably portion of the heavy chain?
V, D and J
Which genes code for the variable portion of the light chain?
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
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)?
Which enzymes mediate gene rearrangement of BRC?
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?
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?
Removal of attractive BCR
Where do lymphocytes reside in the body?
50% mucosal associated lymphoid tissue
40-50% Lymph nodes
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
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
Describe the specificity of MHC
Ie which MHC bind to which antigens and TCR
For a peptide to be presented in an MHC molecule, it most contain the correct residues, so that it can bind to residues of the MHC cleft
Also, for the T cell receptor to bind to the peptide being presented, it must have the correct binding site
Also, the MHC and TCR must agree
Describe how peptides come to be presented on MHC II
Pathogen in engulfed by a APC
Pathogen is broken down in a lysosome into peptides
Peptides bind to the cleft of the MHC
MHC inserted into membrane, with the peptide facing the outside
What is the medical importance of MHC? (5)
The structure of an individual's MHC determines many things:
- Disease susceptibility
- Allergic response
- Infection potential
Describe how T cells become activated
T cells each have a unique TCR on their surfaces
A TCR recognises and binds to its complimentary antigen, which is being presented by an MHC
The T cell now divides and proliferates
When does isotype switching occur?
After a B cell has found its antigen, ie after it has been clonally selected
How many segments does each locus have?
Kappa: v: 40 j: 5
Lambda: v: 30 j: 4
Heavy: v: 40 d: 25 j: 6
Which chain rearranges first?
First the heavy chain, then the light chain
What is a pre-B cell?
It has, as of yet, only rearranged the heavy chain locus
Surrogate light chain bind whilst the light chains are still being produced
Which process makes the largest contribution to overall diversity of BCRs?
Once in circulation, B cells express which isotypes bound to their surface?
IgM and IgD (passed the autoreactive test)
What do TCRs resemble?
The Fab region of a BCR
Can TCR and BCR be found unbound in plasma or tissue fluid?
Only BCRs can
TCR must be membrane bound
Describe the structure of a TCR
How many types of C-alpha and C-beta are there respectively?
There is only one C-alpha, but there are two C-betas
How is PRR diversity generated?
We inherit our Pattern Recognition Receptors
What is HLA?
The name for MHC found inhumans
What is beta-2 micro globin?
It is one of the subunits making up MHC I (HLA) in humans
What are the MHC genes in humans?
For MHC I:
For MHC II:
Compare the length of the peptide presented in MHC I and MHC II
MHC I: 8-11 amino acids long
MHC II: 10-30 amino acids long