Adaptive Antigen Recognition Flashcards
What are the 3 types of antigen recognition receptors?
- B-cell receptors on B lymphocytes
- T-cell receptors on T lymphocytes
- antibodies (soluble)
What is the process of clonal selection? (4 steps)
- lymphocyte clones with diverse receptors arise in generative lymphoid organs
- clones of mature lymphocytes specific for many antigens enter lymphoid tissues
- antigen-specific clones are activated (“selected”) by antigens
- antigen-specific immune responses occur
*gene rearrangement of receptors and combinatorial association of receptor chains occurring during cell development is independent of exogenous antigen
- the sum of the diversity of BCRs and TCRs clones generated during development in a specific individual
- what an individual can respond to
pre-immune response
- immunological memory repertoire
- changes occur within this after an immune response
- what an individual has responded to
post-immune response
What type of antigens are recognized by B-cell receptors?
- carbohydrates
- DNA
- lipid
- protein 3D conformation
- macromolecule antigens
What type of antigens are recognized by T cell receptors?
predominantly linear protein peptide antigens
What immunoglobulin isotypes exist bound to B cells? (2)
IgM and IgD
What is the purpose of invariant chains, Igα and Igβ within BCR complex?
the heterodimer ensures surface expression of immunoglobulin during development and functions in signal transdunction through ITAM
What is the purpose of invariant proteins CD3 within TCR complex?
CD3 (CDγ, CDδ, CDε (2), and CDζ) ensures the cell surface expression of the TCR and is involved in signal transduction (CD3ζ)
How do lymphocytes mature? (5 steps)
- commitment of progenitor cells
- proliferation of progenitors
- sequential and ordered rearrangement of antigen receptor genes
- selection events
- differentiation of effectors
An individual’s preimmune repertoire is large enough to ensure there will be an antigen-binding site to fit almost any potential antigenic deterimant, with low affinity. After repeated stimulation by antigen, B cells can make antibodies that bind their antigen with much higher affinity. What is this process called?
affinity maturation
- major mechanism for lymphocyte receptor diversity
- somatic recombinations between V-J (light chain) and V-D-J gene segments allow for an insane amout of combinations (aka antigen binding sites)
combinatorial diversification
- major mechanism for lymphocyte receptor diversity
- addition of nucleotides at random during of D-J joining or V to DJ joining
junctional diversity
- major mechanism for lymphocyte receptor diversity
- point mutations occurring in fully assembled V-J and V-D-J regions during immune response
- provides significant source of Ab diversity
- only occurs in B cells (peripheral)
somatic hypermutation
- mechanisms for immune diversity in BCR and TCR are indentical
- heavy chain BCR = __ chain TCR
- light chain BCR = __ chain TCR
However ______ _________ does not occur in TCRs
- β
- α
- somatic hypermutation
Why is IgM the first antibody secreted during an immune response?
Because it is the first constant region on the gene (Cm)
What are IgM and IgD the only 2 antibodies expressed on mature, naive B cell surface?
Becuase the IgM and IgD are the 1st and 2nd isotypes coded for on the constant region of the heavy chain gene
When does isotype class switching occur for the heavy chain of an antibody?
During an immune response
developing lymphocytes make the ____ (__) chain first. Correct expression of this chain is necessary for the initiation of ____ (__) chain
- heavy, β
- light, α
- provide recognition sites for recognition enzymes that cut and rejoin DNA
- ensure gene segments are joined in the correct order (especially important in heavy chain VDJ rearrangement)
recombination signal sequences (RSS)
- enzyme responsible for recombining V, D, and J segments
- these genes are only made by lymphocytes, encode for two necessary components of recombinase
RAG-1 and RAG-2
- between coding segments there is often an insertion of a series of nucleotides which is catalyzed by enzyme TdT (catalyzes random polymerization of nucleo into DNA w/o template)
- N (non-template) nucleotides are added in a non-template manner between coding gaps
- P (palindromic) nucleotides are added to sticky ends in a templated manner
- creates random unique sequence between coding gaps, major source of generation of diversity
- could also lead to frameshifts, junk DNA, stop codons, non-codons
junctional diversity
What is the difference between heavy (β) and light/κ (α) chain production? (2)
- there is a lack of diversity coding segments (D) for light chain
- TdT may not be upregulated for addition of N nucleotides, cell can use remaining enzyme from production of heavy chain for N nucleotide addition
(this is why light/α do not have as much diversity as heavy/β chains, although the rest of their production is the same)
What is the 2nd type of combinatorial diversity? (other than V-J or V-J-D genes coming together in different arrangenents)
2nd type occurs after both receptor chains have been successfully rearranged, transcribed, and translated. Any chain can associate with any other chain, creating more diversity.
(will be checked prior to leaving BM/thymus to ensure no self-reactivity)
