T1 L6 Adaptive immunity 3

Question 1

Why is antigen presentation important?

Answer 1

T-cells can’t recognise native antigen unlike B-cells

Question 2

What are the 2 pathways of dealing with antigens?

Answer 2

Endogenous antigenic pathway

Exogenous antigenic pathway

Question 3

What is antigen processing?

Answer 3

Enzymatic process of degrading proteins through proteases into antigenic peptides

Question 4

What does antigen processing require?

Answer 4

ATP

Movement of endocytic vesicles

Question 5

What T-cells use the endogenous antigenic pathway?

Answer 5

CD8 T-cells

Question 6

What T-cells use the exogenous antigenic pathway?

Answer 6

CD4 T-cells

Question 7

What type of peptides does the endogenous antigenic pathway produce?

Answer 7

Class I MHC peptides

Question 8

Describe the steps of the endogenous antigenic pathway

Answer 8

1) Endogenous antigens broken down in proteasome
2) Complexed with MHC class I molecules in golgi
3) Presentation on cell-surface to T-cells

Question 9

What are TAP proteins?

Answer 9

Transporters associated with antigen processing
TAP 1 & TAP 2 form herterodimer in membrane of ER to facilitate transport of peptides from cytoplasm into lumen or ER

Question 10

Describe the steps of the endogenous pathway from class I heavy chain to the peptide-loading complex being exported from the ER

Answer 10

1) Class I heavy chain is stabilised by calnexin until Beta-2 micro globulin binds
2) Calnexin is released
3) Heterodimer of class I heavy chain & beta-2m form peptide loading complex with calreticulin, tapasin, TAP and ERp57
4) Peptide delivered by TAP binds to class I heavy chain to form mature MHC class I molecule
5) Class I molecule dissociates from peptide loading complex and is exported from ER

Question 11

Why do antigens stimulating CD8 T-cells need to come from the inside of the cell?

Answer 11

They signal an intracellular infection as viruses must replicate inside cell and many bacteria & parasites live inside host cells

Question 12

Describe how HSV interferes with MHC expression

Answer 12

HSV protein ICP47 selectively binds to TAP to inhibit the transfer of peptides into the ER

Question 13

Describe the generation of peptides in the exogenous antigen pathway

Answer 13

Peptides bound to MHC class II molecules are derived from engulfed pathogens and internalised transmembrane proteins
Acidification of endocytic vesicles activates proteases which degrade proteins into fragments
Peptide fragments get loaded on MHC class II molecules

Question 14

Describe the formation of MHC class II molecules

Answer 14

MHC class II alpha & beta chains associate in the ER.
In the trans Golgi network, MHC class II gets sorted into vesicles
Vesicles deliver MHC class II to specialised compartments where peptide loading occurs

Question 15

How is MHC class II prevented from binding to self-peptides in ER?

Answer 15

Invariant chain blocks binding of peptides to MHC class II molecules in ER
In vesicles, invariant chain gets cleaved to leave CLIP fragment bound 
CLIP blocks binding of peptides to MHC class II vesicles
HLA-DM releases CLIP when antigenic peptide is present to allow the antigenic peptide to bind.

Question 16

What is CLIP?

Answer 16

Class II invariant chain peptide

Question 17

What is HLA-DM?

Answer 17

Acts like a chaperone for MHC class II molecules and catalyses release of CLIP once an antigenic peptide is present

Question 18

Where does class II MHC peptide loading occur?

Answer 18

In endoscope where acidic pH is exchanged for protein degradation into peptides
Invariant chain gets degraded and CLIP is exchanged with foreign peptides

Question 19

How does adenovirus inhibit class II MHC?

Answer 19

Interferes with class II upregulation in antigen-presenting cells

Question 20

How does HSV inhibit class II MHC?

Answer 20

Viral envelope protein, glycoprotein B, reduces MHC class II processing and inhibits the production of invariant chain peptide

Question 21

What pathogens prevent phagosome-lysosome fusion?

Answer 21

Leishmania

Mycobacteria (tuberculosis)

Question 22

How are T-cell antigens kept apart?

Answer 22

Location - they load proteins in different cell compartment s
Accessory proteins
- class I requires TAP, tapasin
- class II requires low pH for removal

Question 23

Describe the steps of T-cell dependent B-cell response

Answer 23

1. Antigen binding to B-cell receptor provides ‘signal 1’ to B-cell
2. Antigen gets internalised & processed –> antigen peptides are displaced on MHC for T-cell recognition
3. TH recognises antigen-MHC complex via T-cell antigen receptor –> provides ‘signal 1’ to T-cell
4. CD80 on B-cell binding to CD28 on T-cell provides ‘signal 2’ to T-cell
5. T-cell activation leads to up-regulation of CD40L –> binds to CD40 –> provides ‘signal 2’ to B-cell
6. Cytokine production by activated T-cell helps to activate B-cell
7. B-cell proliferates & differentiates into antibody secreting B-cell (plasma cell)