Antigen Recognition by T-Lymphocytes

Question 1

what is an antigen

Answer 1

a toxin or other foreign substance which induces an immune response in the body, especially the production of antibodies.
is the entire molecule

Question 2

what is an epitope

Answer 2

specific portion of the antigen that the Ig interacts with

Question 3

how do Bcells recognise antigens

Answer 3

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

Question 4

how does a tcell recognise antigens

Answer 4

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

Question 5

what type of cells is MHC1 expressed in

Answer 5

all nucleated cells

Question 6

what type of cell is MHC2 expressed in

Answer 6

APC

Question 7

what type of cell recognises MHC1

Answer 7

CD8+ tcells

Question 8

what type of cell recognises MHC2

Answer 8

CD4+ Th cells

Question 9

what are the 4 main APC that can express MHC and induce tcell response

Answer 9

• Monocytes
• Macrophages
• Dendritic Cells
• B-cells

Question 10

what are monocytes

Answer 10

largest type of wbc. can differentiate into macrophages and dendritic cells

Question 11

what are macrophages and dendritic cells

Answer 11

highly phagocytic. able to induce strong T-cell responses and inflammation.
rarely in blood but densely populated in mucosal tissues.

Question 12

bcells are not phagocytic so how can they become APC

Answer 12

they contain surface Ig .’.internalise antigens into endosomes by receptor-mediated internalisation.
then present these antigens to tcells

Question 13

how are exogenous antigens (eg bacteria) processed and presented on the APC

Answer 13

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

Question 14

why does MHC2 contain self-peptide

Answer 14

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

Question 15

how are endogenous/cytosolic antigens (eg virsus) processed and presented on the APC

Answer 15

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

Question 16

what happens when CD8+ recognises foreign MHC2 complex

Answer 16

becomes CTL and kills infected cells

Question 17

what is the TCr

Answer 17

on Tcell membrane that interacts with peptide-MHC complex

each TCR that is specific towards a single antigen.

Question 18

similarities between TCr and BCr

Answer 18

• Both have a very huge diversity, each with a single specificity
• In essence the TCR is like the Fab fragment of an Ig

Question 19

differences between TCr and BCr

Answer 19

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)

Question 20

how does affinity maturation of b cell occur

Answer 20

after bcell is activated, dna undergoes hypermutation to try and improve efficiency. mutations that produce better Ig are conserved/selected

Question 21

how is Bcell receptor (Ig) diversity generated

Answer 21

by somatic recombination of DNA (VDJ) while bcells are developing in BM. then once activated undergo affinity maturation

Question 22

how is TCr diversity achieved

Answer 22

somatic DNA rearrangement whilst in thymus .’. express specific TCr. Activate after being exposed to APC with their antigen.
DO NOT hypermutate

Question 23

what is required for CD4+ tcell to be activated

Answer 23

3 signals

1. peptide-MHC II complex
2. Co-stimulation through co-stimulatory molecules (e.g. CD80/CD86 on APC)
3. Cytokines (released from APC)

Question 24

importance of cytokines in tcell activation

Answer 24

needed to determine Tcell phenotype
IL-12 =promote Th1 cells
IL-4 = promote Th2 cells
IL-23 = promote Th17 cells

Question 25

role of CD8+ tcells

Answer 25

see MHC1 and if holding nonself peptide = infected cell .’. becomes CTL and kills the cell

Question 26

role of CD4+ TH1 cells

Answer 26

when activated produce cytokines that activate macrophages that help then digest and kill ingested pathogens .’. macrophage more efficient

Question 27

role of CD4+ Th2 cells

Answer 27

stimulate and secrete cytokines that allow plasma cells to secrete antibodies

Question 28

how do we regulate and limit tcell activity

Answer 28

are negative regulators of antigen presentation that provide immune checkpoints

Question 29

two important negative regulatory molecules of tcell activity

Answer 29

CTLA4 (Cytotoxic T-lymphocyte Associated Protein 4)

PD-L1(Programmed Death Ligand 1)

Question 30

how does PD-L1 regulation of tcell activity work

Answer 30

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.

Question 31

how does CTLA4 regulation of tcell activity work

Answer 31

competes with CD28 for APC stimulation

when CTLA4 is stimulated it will try to blunt the CD28 signalling pathway