The Adaptive Immune System 1 Flashcards
B cell receptor is bound to which coreceptor?
CD19, igalpha and beta
Light chains are selective 2 types, which chromosomes?
Lambda
Kappa
Chromosome 2 and 22
How many variable segments in heavy and light chain?
H-65
L-70
How many diversity segments in heavy chain?
27
What do light chains not possess?
Diversity segments
How many possible combinations can be made in B cell?
100 trillion
What do alpha chains in T cells not possess?
Diversity segments, similar to light chain in B cell
How many possible combinations in T cell sequences?
Million trillion
Why are there more T cell sequences at VDJ than B cells?
T cells don’t undergo further hypersomatic mutation hence more are required
T cell pool fixed from puberty
Rearrangement of VDJ occurs at which sites?
Recombination signal sequences (RSS)
Contain: conserved segments of DNA composed of a hapatemer, spacer and a nonomer, 3’ of V segments and 5’ of J and both side of D segments
Rearrangements is catalysed by which 2 enzymes?
Recombination activating genes RAG 1 and 2
Steps in VDJ joining?
Cleavage
Repair/ diversity
Joining
Skid mice lack which enzyme?
DNA dependent protein kinases
Somatic hypermutation occurs where?
In a lymph organ
B cell encounters antigen, causing proliferation.
How does somatic hypermutation occur?
In the hyper variable region of light and heavy chains, point mutations that are adjusting the receptor
Are all affinities good?
After somatic hypermaturation, some have worse, better or same
What is mutation rate?
1 base per 1000, which is 1 million times higher mutation rate than observed in normal cell division
The billions of sequences that are not useful are where?
In introns
Which enzyme drives somatic hypermutation?
Activation induced cytosine deaminase AID
How does activation induced cytidine deaminase work?
Introduces uracil in the genetic code, which is spliced out and then replaced, usually a cytidine replacing
What is affinity maturation?
Follicular dendritic cells present antigen to B cells than have undergone SHM.
Only those with high affinity
In affinity maturation those B cells with low affinity will …?
Die, apoptosis
What happens in class switch recombination?
Same receptor but different constant region
IgA is adapted to penetrate?
Mucous membranes
Why is class switch recombination needed?
Constant region can recruit different cell type to site
How do you get igM and igD immunoglobulin?
In igD, the Mu segment is spliced off,
In igM, delta segment spliced off
In CSR, which is the first targeted switch region?
S mu
For CSR which enzyme is needed?
AID
Which CSR occurs in B cells is determined by?
Follicular T helper cells
For neutralisation and diffusion in extra vascular sites which immunoglobulin is needed?
IgG
What is igD good at?
Sensitisation of basophils
What is igE good at?
Sensitisation of mast cells
What is igA good at?
Neutralisation and Transport across epithelium
What is igM good at?
Activation of complement system
Average life of B cells?
5 days
Negative selection?
When receptors bind to self antigen too strongly then are deleted
Examples of thymus dependent and independent antigens?
Dependent- requires T cells to induce antibody production e.g proteins
Independent e.g polysaccharides and lipids
T cell independent responses only require which antibody?
IgM to detect simple repetitive antigens, modest affinity
No memory
B cells are activated by direct BCR crosslinking
What is the signalling complex in the membrane for b and T cells?
Ig alpha and beta
T cells- CD3
B and T cell interaction
MHC to TCR
CD80/CD86 to CD28 on T cells
T cell activation leads to up regulation of CD 40 L which bind to CD 40
Cytokine production from T cells 3rd signal
B cell proliferates and differentiates into antibody secreting B cell or becomes memory
What does somatic hypermutation do?
Add point mutations
The first switch region is always?
Su
The second cut is determined by cytokines released by?
Follicular t helper cells