Antigen recognition Flashcards
what is an antigen
antibody generator - a molecule that can elicit a response from the adaptive immune system
what are antigen recognition molecules
B cell receptor (BCR) and T cell receptor (TCR)
what is an immunoglobulin and what two forms of the molecule exist?
Y shaped molecule with a transmembrane tail anchored in the plasma membrane of B cells - with 2 identical antigen binding sites. 1st form -> BCR (expressed on B cells) and 2nd is the secreted immunoglobulin = lacking the transmembrane tail
what happens upon antigen recognition?
B cells -> differentiate into their active form = plasma cells
T cells -> several functions: active CD8 T cells kill human cells infected with a virus or intracellular bacteria. CD4 T cells mediate an appropriate immune response
what are the different regions of an immunoglobulin and their functions
constant (C) region - transmembrane region with the effectr function because it interact with the effector molecules of the immune system. the variable (V) region is the antigen binding site
what are the different chain of the immunoglobulin molecule
2 heavy chains and 2 light chains
what is the function of the hinge region
it is flexible - ties the heavy chain first domain to heavy chain second domain
what is the structural difference of different subclasses of IgG molecules
4 subclasses - they vary in the length of the hinge region –> the longer the length, the more flexible the antibody is
structure of the IgG molecules
4 polypeptide chains -> 2 heavy chains and 2 light chains. heavy chains are linked by disulphide bonds and each heavy chain is linked to a light chain by diuslphide bonds
what is the 3D structure of each domain (C and V regions of Ig)
the strands of polyppetide chains are beta sheets which run in opposite direction = forming a beta barrel structure (also called the immunoglobulin fold)
what ensures the ability of the Ig to bind an epitope?
the variable domains (both heavy chains and light chains) have 3 areas of hypervariability = HV1, HV2, HV3 (these areas allow the Ag-binding site to be so unique). altogether, 6 hypervariable regions in each arm of the Y shape
CDRs?
complementarity determining regions
FRs? what is their function?
framework regions are the regions in between complementarity determning regions -> they provide the structure of the V domains
what is a paratope?
the unique antibody combining site –> the combination of H + L chain CDRs
where do antigen/epitope bind?
antigen-binding site also called the peptide binding groove
briefly describe what happens after BCRs recognize an antigen
there are multiple BCRs on the B cell which recognize the antigens at once = creating a cluster of BCRs. that activates the BCR complex = Ig-alpha and Ig-beta. They contain ITAMs inside the cell which when brought together are phosphorylated by the Lyn kinase. Now ITAMs are ready to bind the adaptor molecule BLNK which triggers the MAPK pathway
what is the purpose of the MAPK pathway
transduction cascade which allows the transcription factor Ap1 to enter the nucleus and start replication and cell cycle progression. meaning the ativated B cell can now divide and proliferate
wha are the 3 signals that activate the B cell?
- the binding of several BCR to an antigen
- the recognition of the complement opsonizing the pathogen (B cells have complement receptors)
- secreted cytokines from T helper cells (T follicular cells promote class switching to the antibody isotype that is useful for the particular infection)
TCR structure
consists of 2 chains - TCR alpha and TCR beta chain
what are the regions of a TCR
constant (C) region, variable (V) region - conains Ag-binding site, transmembrane region and cytoplasmic tail
ITAM ?
immunoreceptor tyrosine kinase activator motif
what is the function of a TCR
only recognition - because the heterodimer is a part of a large multiprotein complex (6 additional subunits)
how does the antigen recognition differ between BCRs and TCRs
BCRs bind the intact antigen whereas TCRs bind to short amino acid sequences = peptides (that are usually buried within the structure of the protein - that is why they need to be degraded)
structural difference between CD4 and CD8
CD4 has 4 identical domains and a transmembrane area
CD8 consists of an alpha nad beta chain connected with disulphide bonds
what is CD3 and the function?
CD3 is a co-receptor complex which starts the signalling transduction for T cell activation. it contains ITAMs = same singalling role as in B cells
what MHC class I molecules bind to
they are recognized by CD8 cytotoxic T cells -> because MHC class I are on all human cells (except RBCs). the CD8 T cells recognize peptides of virally infected cells and then kill them
what size peptides do MHC class I present
small peptides - around 8 amino acids
structure of MHC I
3 alpha chains + beta-2 microglobulin. the peptide binding groove is made up of alpha 1 and alpha 2 subunits
how big peptides can MHC II present
at least 13 amino acids - because the peptide is anchored into the peptide-binding groove (not contained inside)
MHC class II structure
2 alpha subunit and 2 beta subunits
where is the peptide anchored in MHC II
in specific pockets of the peptide binding groove -> pockets 1, 4, 6, and 9 interact with side chains of the peptide = holding it in place
can B cells act as APCs?
yes, B cells can directly bind a pthogen which activates the B cell - production of cytokines - activation of T helper cells to mediate a bigger production of antibodies
TAP?
transporter associated with antigen processing
what is the role of calnexin?
it hold partially bound MHC class I alpha chains together until beta-2 microglobulin binds
what are chaperone proteins and what is their function?
calreticulin and ERp57 they hold the MHC class I complex together and also bind to tapasin and TAP - to facilitate peptide loading onto the peptide binding groove
what is the function of the invariant chain?
when MHC class II are produced in the ER of cells they contain the invariant chain attached to the Ag-binding site. this ensures that a viral peptide does not get loaded onto MHC class II
function of clip molecule
facilitates the binding of the invariant chain to the MHC II peptide binding groove
3 signals of T cell activation
- TCR direct recognition of the peptide presented by an MHC molecules –> activation of the CD3 complex sends the 1st signal
- the interaction of co-receptors: CD28 and CD80/CD86
- cytokine release from APCs
what is MHC polymorphism
there are regions of hypervariablity in the peptide binding groove (the same principle as a BCR)
CD4 T helper subsets
Th1, Th2, Th17, Tfh, and Tregs
what is the purpose of Tfh cells?
Tfh are always activated with another T helper cell. they mediate antibody class switching in response to the specific pathogen (this ensures the correct antibodies are produced)
what cytokine is characteristic for Th1 cell subset and what does it interact with (function)?
IFN-gamma, enahnces macrophage activity
in response to what pathogens is the Th1 cell subset activated
intracellular microbes -> certain viruses, protozoa, and bacteria (sometimes bacteria gets engulfed by macrophages and then can avoid the macrophage bactericidal activity)
what cytokines are characteristic for Th2 cell subset
IL-4, IL-5, and IL-13. they act on eosinophils, mast cells, mucus-producing cells = epithelial cells
in response to what pathogens is the Th2 cell subset activated
multicellular microbes -> helminths or intestinal parasites
what cytokines are characteristic for the Th17 cell subset
IL-17A and IL-17F -> they amplify neutrophilic and monocytic responses + the production of antimicrobial peptides from epithelial cells
in response to what pathogens is the Th17 cell subset activated
extracellular bacteria and fungi
what is the antibody isotype characteristic for Th1 response
IgG3
what is the antibody isotype characteristic for Th2 response
IgE
what is the antibody isotype characteristic for Th17 response
IgG3
