L6 - cellular responses

Question 1

difference between CD4 and CD8 cells in terms of recognition

Answer 1

CD4:
MHC class 2
- recognise antigens presented on Antigen Presenting Cells and help activate others

CD8:
MHC class 1
- recognise antigens presented on surface of all cells
- only cells with certain antigens cause activation

Question 2

decsribe the T-Cell receptor (TCR)

Answer 2

resembles a bound Fab region of an antibody

heterodimer with 2 chains = 1 antigen binding site (BCR has 2)

each chain contains:
- 1 Ig-V-like domain (binding)
-1 Ig-C-like domain

6 other polypetide chains to complete the TCR as cytoplasmic tail of chains is too short for signalling

Question 3

describe the structure of the chains in TCR (alpha + beta)

Answer 3

2 transmembrane glycoproteins form heterodimer - alpha and beta

= core of TCR

Question 4

what is the name of the 6 signalling polypetide chains that complete the TCR

Answer 4

CD3s

ITAMs (immunoreceptor tyrosine-based activation motifs) on chains

phosphorylated at key tyrosine residues for intracellular signalling

Question 5

compare the mechanisms between generating diversity of BCR and TCR

Answer 5

both:
V(D)J recombination
12/23 rule
junctional diversity

= all by the same enzymes

different:
no samatic hypermutation in TCR
In thymus not bone marrow

Question 6

MHC class 1 molecule structure

Answer 6

2 polypetide chains; alpha and B2-microglobulin

a chain has 3 domains: a1,a2 , a3

a1 and a2 form petide-binding cleft (U-shaped thing that presents antigen)

Question 7

advantage of TCRs over BCRs

Answer 7

can bind to and be activated by antigens buried within cells

proscessed and presneted by MHC molecules on surface

Question 8

MHc class 2 structure

Answer 8

2 polypetide chains - alpha and beta

each have 2 domains

a1 and b1 form petide-binding cleft

Question 9

which MHC is present on all nucleated cells

Answer 9

MHC class 1

Question 10

what is polymorphism and how does it describe MHC molecules petide-binding cleft

Answer 10

allelic variations of genes determine which petides will bind

a1 + a2 in MHC-1

a1 + b1 in MHC-2

Question 11

differences in the peptides bound by MHC molecules

Answer 11

MHC 1:
bind shorter peptides

binds at the terminal ends of the petide

endogenous - viral,tumour

MHC 2:
longer peptides

binds all along the peptide

exogneous - bacteria

Question 12

what are CD4 and CD8

Answer 12

Co-receptors on T cells

acsocaite witrh the TCR on surface of T cells

bind to regions of the MHC molecule AWAY from the peptide

Question 13

summarise peptide loading onto MHC class 1 of intracellular antigens

Answer 13

1. Ubiquitinated proteins are continously degraded by proteosomes in the cytoplasm
2. newly syntheised MHC 1 molecules held in ER form peptide-loading complex (PLC)
3. bind a petide and migrate to surface to be presented

= both self and non-self antigens presented by MHC-1
= self-reactive T cells removed during development

Question 14

whereare MHC 2 molecules found

Answer 14

professional antigen presenting cells

• dendritic cells
• macrophages
• B cells

Question 15

summarise peptide loading onto MHC 2 of extracellular antigens - 5 steps

Answer 15

1. antigen is engulfed and degraded inside acidic endosomes by proteases
2. vesicles containg MHC 2 fuse with vesicles with peptides
3. CLIP protein blocks binding of peptide to MHC 2
4. binding of HLA-DM removes CLIP allowing peptide to bind
5. MHC with peptide transported to surface

Question 16

how many signals are needed to activate T cells and how many for B cells

Answer 16

2 = B-cell

3 = T-cell

Question 17

what 3 signals are needed for T cell activation

Answer 17

1. Antigen
   MHC molecule on APC presenting antigen to TCR
2. CD28 - co stimulation
   CD28 binds to B7 on APC
3. cytokines
   cytokines produced by APC provide growth signals

Question 18

effector CD8 T cells can bypass 1/3 of the activating signals. which one and how

Answer 18

No need for costimulation of CD28 to B7

effector cells can therfore kill of infected cells rapidly

release granules:
perforin,graneznymes

Question 19

name the cytokine produced by T follicular helper cell that causes class siwtching of antibodies and affinity maturation

Answer 19

Il-21