HRR: antigen recognition in the adaptive immune system Flashcards
Describe the difference between B-cell antigen receptors and T-cell antigen receptors
B-cell antigen receptors are membrane bound and can recognize whole proteins, peptides, polysaccharides, lipids, nucleic acids, and small chemicals. T-cell antigen receptors are T-cell receptors and can only recognize short peptide antigens displayed by major histocompatibility complex (MHC)
What is a complementarity determining region
They’re found at the tip of the variable region on antibodies. They interact with the antigen and make it so different antibodies bind to different things
What does papain do to antibodies?
Cuts them into Fab and Fc. The Fab region takes part in monovalent antigen binding and is very similar to T cell receptors structurally!
What does pepsin do to antibodies?
Cuts them into F(ab’)2 small fragments, which take part in bivalent binding to antigens. It can bind two of the same things at the same time!
All B cell receptors are encoded by which 3 genes
Heavy chain, kappa light chain, and lambda light chain
All T cell receptors are encoded by which 2 genes
Alpha chain and beta chain
Describe what VDJ recombination is, and the multiple ways that it generates
diversity of antigen receptors on lymphocytes.
Each gene associated with B and T cell receptors have many exons for variable regions, meaning there are many choices to make the actual antigen receptor. The heavy and beta chains have VDJ, while the alpha and light chains have VJ. In the final antigen there will only be one each of V, D, and J. the presence of many options allows for diversity of antigen receptors
Describe the role of VDJ recombinase
An enzyme that cleaves DNA at recognition sequences at the ends of V, D, and J segments and repairs the breaks with ligases.
How does VDJ recombinase decide which segments to join together?
The segments that get joined by ligase are random, and the alleles used in the final receptor are also random. This allows for combinatorial diversity
What is junctional diversity?
Ligases add random numbers of nucleotides to the join sites during VDJ recombination. This provides a large amount of variability
What does VDJ recombinase require to work? What happens if someone does not have them?
RAG-1 and RAG-2. If someone doesn’t have these, they cannot properly make functional B and T cells and will be immunodeficient
What are the 3 steps for lymphocyte maturation
-Proliferation of immature cells
-Expression of antigen receptor genes
-Selection of lymphocytes that have useful receptors
Describe the progression from pro-, pre-, immature and mature lymphocytes in terms of order, antigen receptor expression, and positive and negative selection
-A pro T/B cell proliferates in response to IL7
-Pre-B/T cell expresses one chain of an antigen receptor. If it fails to express the receptor the cell will die
-The pre-T/B cells proliferate in response to IL7
-Immature B/T cells express their complete antigen receptor
-Positive or negative selection occurs (able to function vs being eliminated)
- mature B/T cell is formed!
True or false: all receptor molecules on a given B or T cell are identical
True! There is variation among B and T cells, but the individual cells must have identical receptor molecules
How many constant region genes are present for light chains? Heavy chains?
Light chains have 1, heavy chains have 9
What is special about mature naïve b cells?
They have IgM and IgD on their cell surfaces at the same time. They are the only cell that has this. This is because IgM and IgD have the same antigen binding specificity
Which antibody classes exist as monomers?
IgD, IgE, IgG
which antibody classes exist as dimers?
IgA
which antibody classes exist as pentamers?
IgM
what is the purpose of allelic exclusion?
It exists in order to ensure only one heavy, and one light chain gene get expressed in each mature B or T cell; once one gives a signal, the other gets silenced to avoid its rearrangement and expression
Describe allelic exclusion in B cell receptors
-First heavy chain undergoes VDJ rearrangement
-If this rearrangement is non-productive, a 2nd heavy chain undergoes VDJ rearrangement. If it is productive, the first kappa light chain undergoes rearrangement
-Subsequent kappa light chain followed by lambda light chains (4 total) will undergo rearrangement.
-If the 1st and 2nd heavy chain rearrangements both prove to be non-productive and the light chains fail, the cell will die.
What is the last test for mature B cells to prevent autoimmune disease
They interact with self-proteins on stromal cells. If there is weak binding, the cell is positively selected and IgD and IgM are expressed. If there is strong binding, the cell will be deleted via apoptosis
Describe allelic exclusion in T cell receptors
-Pro-T cells recombine one beta chain gene.
-If the beta chain gene recombination is productive, the alpha chain gene will undergo recombination
-If both alpha and beta are productive, CD4 and CD8 are induced
Describe allelic exclusion in T cell receptors
-Pro-T cells recombine one beta chain gene.
-If the beta chain gene recombination is productive, the other is silenced and the alpha chain gene will undergo recombination
-If both alpha and beta are productive, CD4 and CD8 are induced
how is a T cell’s fate determined?
Recognition of MHC and peptides is tested. Positive selection occurs first in the cortex, then negative selection occurs in the medulla of the thymus.
describe determination of the 4 T cell fates
-Weak binding between class II MHC and a peptide will lead to CD4 expression.
-Weak binding between class I MHC and a peptide will lead to CD8 expression
-No recognition of MHC and peptide will lead to death of the cell
-If there is a strong recognition of either, the cell dies.
Explain what a double positive T-cell is and where and when they appear in T-
cell maturation
A double positive T cell expressed both CD8 and CD4. It occurs while the T cell is immature in the thymus
Explain the relationship of BCR and TCR to continuous and discontinuous/
conformational epitopes
BCR: can see continuous/discontinuous epitopes
TCR: can only see continuous epitopes
describe B1 cells
derived from fetal liver; only have IgM and contain CD5. They’re thought to protect us from bacteria moving across our gut wall and into the bloodstream
describe marginal B cells
they have CD21 instead of IgM/IgD. They’re primarily in the spleen and protect us from things in the blood
where are B2 cells derived from?
the bone marrow
