Ch.4 Antigen Recognition in the Adaptive Immune System Flashcards
Cross linking
- adjacent antigen receptors bind 2 or more antigens
- brings the signal transduction parts closer together into an aggregate
- phosphorylation and signal transduction
Another name for hypervariability region of antigen receptors
complementartity determining regions
Signal transduction component of BCR
BCR = antibody + Igalpha, IgBeta
signal transduction component of TCR
TCR = receptor for MHC + CD3 and zeta
Hv region with most variability?
CDR3 region at junction btw C and V areas
Fab
fragment antigen binding region - where the antigen actually binds
Fc
Fragment crystalline - conserved region responsible for biological activity and effector functions
difference btw kappa and lambda light chain?
they differ in their C(L)region but not in function
types of heavy chains
mu, delta, gamma, epsilon, alpha corresponding to IgM, IgD, IgG, IgE, IgA
- they vary in their C regions (not Fc)
isotypes (or classes) of heavy chains
IgG v. IgA - different C regions
Heavy Chain Class switching
- Naive B-cells (have not been exposed to antigens) express IgM and IgD
- once activated by antigen and T-cells, Some of their progeny B-cells will be of other heavy chain classes
- even though the C-regions change (different classes) the antigen specificity remains the same (same V region)
affinity
- strength of bond btw antibody and epitope of antigen
- represented by Kd - smaller Kd = higher affinity
Affinity Maturation
- increase of affinity of antibodies with increased exposure to the antigen
- so you get the same disease more than once
Avidity
- told strength of multiple Antigen to antibody bonds
- IgA dimer - 4 binding locations
- IgM - pentimer - 10 binding locations
TCR’s
- made up of an alpha and beta chain.
- both have a V and C region like antibodies
- V has 3 hv regions - CDR3 most variable
- always bound to T-cell membrane
- alpha and beta work together to recognize MHC and peptide
gamma-delta TCR
- recognize both protein and non-protein peptides
- abundant in epithelia
TCR signal transducers
CD3 and zeta
- Also TCR’s have either CD4 next to them or CD8 to recognize portions of the MHC
IL-7
- produced in stromal cells of bone marrow and thymus
- required for the proliferation and survival of immature lymphocytes
- creates a large number of them which can later be specified and selected for
Somatic recombination
- in every B and T cell the germ line genes of the variable region are recombined to create diversity of antigen receptors
- there is a V, D, and J region
Combinatorial diversity
- any V region can combine with any D region. Any set of VD regions can combine with any J regions
- can put together any set of three dominos to get many different combination
Junctional diversity
- gives you even more diversity
- When the D region is connected to the J region and the DJ is connected to the V region, nucleotides can be added or subtracted. - this can lead to frame shift and lots of diversity
- Picking different kinds of glue to hold the three dominos together
- Exonucleases cut out nucleotides
- TdT can add in random nucleotides
- When there are overhangs, P-nucleotides can be added in.
- this is the hv region CDR3 (where the VDJ come together)
V(D)J recombinase
- enzyme that recognizes the DNA sequence at the edges of V,D, and J regions
- brings these regions together randomly picking a V,D, and J
- an exonucleas cuts the DNA and then ligase repairs it making the complete straight VDJ DNA region
Pro-B cell
First progenitor from the stem cell - stimulated by IL-7
pre-B-cell
after the pro-B-cell
- the mu heavy chain has been added
Check point 1 for B-cells
- Pre B cell with heavy chain and fake invariant light chains tested for self - recognition
- selects all B cells with a functional H chaing
Allelic exclusion
- after a pre-B-cell passes the heavy chain checkpoint, it shuts of heavy chain recombination on the other parent chromosome/allele
- only expresses one parent allele
TCR maturation steps
Pro-t-cell - double neg. proliferate with IL-7
- Pre-T-cell- somatic recomb. of Beta chain, test with alpha
- if work then stop other B, start alpha recomb etc
- Immature Double + T-cell - express both CD8 and CD4 - exposed to self MHC
- if bind weakly to one or the other - survive - positive selection and become single + mature T-cell
- if bind strongly - apoptosis - negative selection