Antigen Recognition by T-Lymphocytes Flashcards
what is an antigen
a toxin or other foreign substance which induces an immune response in the body, especially the production of antibodies.
is the entire molecule
what is an epitope
specific portion of the antigen that the Ig interacts with
how do Bcells recognise antigens
express bcell receptors (surface IgM) specific to an epitope and when come into contact with its epitope bcell is activated and proliferates. resulting bcells are clones, and produces sIg specific to the same epitope
how does a tcell recognise antigens
express TCr but cannot see soluble OR surface antigen/peptides. needs microbe to be broken down by phagolysome -> APC which then combines with MHC and tcell can recognise this
what type of cells is MHC1 expressed in
all nucleated cells
what type of cell is MHC2 expressed in
APC
what type of cell recognises MHC1
CD8+ tcells
what type of cell recognises MHC2
CD4+ Th cells
what are the 4 main APC that can express MHC and induce tcell response
- Monocytes
- Macrophages
- Dendritic Cells
- B-cells
what are monocytes
largest type of wbc. can differentiate into macrophages and dendritic cells
what are macrophages and dendritic cells
highly phagocytic. able to induce strong T-cell responses and inflammation.
rarely in blood but densely populated in mucosal tissues.
bcells are not phagocytic so how can they become APC
they contain surface Ig .’.internalise antigens into endosomes by receptor-mediated internalisation.
then present these antigens to tcells
how are exogenous antigens (eg bacteria) processed and presented on the APC
taken up by APC into phagosome -> fuses with lysosome = phagolysosome.
bacteria broken down .’. bacterial peptides generated
bacterial peptides in vesicle fuse with vesicle containing MHC.
bacterial peptide displaces self-peptide & sits in MHC II
peptide-MHC complex is presented on the surface
why does MHC2 contain self-peptide
MHC II always needs to contain some peptide or the MHC will fall apart. Therefore in the ER it contains a self-peptide called the invariant chain that stabilises it.
if no infection it will just carry on containing self-peptide
how are endogenous/cytosolic antigens (eg virsus) processed and presented on the APC
virus taken up by cell w/ a nucleus.
starts to replicate .’. viral proteins present in cytosol
viral proteins undergo ubiquitination -> degraded by proteosomes .’. viral peptides produced
viral peptides transported to ER where they fit into MHC1
MHC1-viral peptide complex transported to membrane to be recognised by CD8+ cells
what happens when CD8+ recognises foreign MHC2 complex
becomes CTL and kills infected cells
what is the TCr
on Tcell membrane that interacts with peptide-MHC complex
each TCR that is specific towards a single antigen.
similarities between TCr and BCr
- Both have a very huge diversity, each with a single specificity
- In essence the TCR is like the Fab fragment of an Ig
differences between TCr and BCr
TCR = lower affinity to antigen TCR = cannot be secreted TCR = no Fc portion .'. no cellular function TCR = 1 binding site (2 of Ig) TCR only 2 classes (5 of Ig)
how does affinity maturation of b cell occur
after bcell is activated, dna undergoes hypermutation to try and improve efficiency. mutations that produce better Ig are conserved/selected
how is Bcell receptor (Ig) diversity generated
by somatic recombination of DNA (VDJ) while bcells are developing in BM. then once activated undergo affinity maturation
how is TCr diversity achieved
somatic DNA rearrangement whilst in thymus .’. express specific TCr. Activate after being exposed to APC with their antigen.
DO NOT hypermutate
what is required for CD4+ tcell to be activated
3 signals
- peptide-MHC II complex
- Co-stimulation through co-stimulatory molecules (e.g. CD80/CD86 on APC)
- Cytokines (released from APC)
importance of cytokines in tcell activation
needed to determine Tcell phenotype
IL-12 =promote Th1 cells
IL-4 = promote Th2 cells
IL-23 = promote Th17 cells
role of CD8+ tcells
see MHC1 and if holding nonself peptide = infected cell .’. becomes CTL and kills the cell
role of CD4+ TH1 cells
when activated produce cytokines that activate macrophages that help then digest and kill ingested pathogens .’. macrophage more efficient
role of CD4+ Th2 cells
stimulate and secrete cytokines that allow plasma cells to secrete antibodies
how do we regulate and limit tcell activity
are negative regulators of antigen presentation that provide immune checkpoints
two important negative regulatory molecules of tcell activity
CTLA4 (Cytotoxic T-lymphocyte Associated Protein 4)
PD-L1(Programmed Death Ligand 1)
how does PD-L1 regulation of tcell activity work
PD-1 on surface of Tcells. stimulate SHP-2 =inhibit T-cell activation by blocking the signalling pathway, via dephosphorylating signalling molecules, used by the TCR.
how does CTLA4 regulation of tcell activity work
competes with CD28 for APC stimulation
when CTLA4 is stimulated it will try to blunt the CD28 signalling pathway
