6 T-Cell mediated immunity

Question 1

Compare the recognition of antigens between T cells and B cells (receptors, etc)

Answer 1

T-cells

• do not recognise pathogen in native form
• ‘indirect recognition’
• Pathogen must be processed and presented on MHC class I or II

B-cells

• recognise pathogens in the native form
• ‘direct recognition’
• Have B-cell receptors or cell surface - allowing binding to antigen

Question 2

Compare B-cell and T-cell receptors

Answer 2

T-cells

• Two chains - a + ß
• Constant and variable chains

B-cells

• express Immunoglobulin molecules on surface membrane - act as B-cell receptors for antigens
• 2x heavy and 2x light chains
• Constant and Variable regions
• 2 identical antigens - variable domain - V(h) + V(L)

Question 3

Describe the structure of the T cell receptor (TCR)

Answer 3

The receptor sits slightly into the transmembrane region
- Hinge region provides a bit of flexibility

2 chains

• a and ß chain
• which both have a variable and constant region
• a disulfide bond joins the two chains together

All T cells have a TCR

Question 4

State the key populations of T cells

Answer 4

T cells

• CD4 Helper T-cells
• CD8 Cytotoxic T-cells

Question 5

Describe CD4 Helper T-cells

Answer 5

CD4 Helper T-cells
- Function: help other cells of the immune system

They express TCR and CD4 co-receptor

They provide help by producing cytokines:

• Enhance the digestive activity of macrophages
• Cause B-cells to class switch

Question 6

Describe CD8 Cytotoxic T-cells

Answer 6

CD8 Cytotoxic T-cells
- Function: to KILL infected cells

They express TCR and CD8 co-receptor

Question 7

What is the significance of the CD4 and CD8 co-receptors?

Answer 7

The CD4 and CD8 co-receptors are very important

- They ensure that the correct type of T-cell is activated

Question 8

Describe why T cells are not instantly activated?

why there is no recognition of antigen in native form

Answer 8

T cell

• there is no recognition of antigen in its native form
• the Pathogen must be processed + presented on MHC Class I/II for T-cell activation

To make sure only infected cells are killed
(which will only be the presented antigens, hence no other normal antigen recognition)

Question 9

How is MHC class determined?

Class I or II
when presenting antigen

Answer 9

The MHC Class I or II is determined:

• by where the pathogen is (cytosol or vesicle)
• to make sure that the right type of T cell is activated

Cytosolic Pathogen:
- MHC Class I

In vesicles or extracellular pathogens/toxins:
- MHC Class II

Question 10

Describe the Structure of MHC Class I

Answer 10

The MHC Class I molecule is made up of:

• An alpha chain (3 domains)
• and a ß2 micro-globulin

The a-1 and a-2 domains are where the peptide is presented to the T-cell receptor
- i.e. a-1 and a-2 form the Peptide Binding Groove

NOTE: MHC I can be expressed in any cell

Question 11

Describe the structure of MHC Class II

Answer 11

The MHC Class II molecule is made up of:

• An alpha chain
• And a ß chain

a-1 and ß-1 form the peptide binding groove

NOTE: MHC II can only be expressed on certain cells of immune system
- Dendritic cells, Macrophages and B-cells

Question 12

Describe how the Antigen is presented by MHC Class I to the TCR

and which/how the co-receptor binds

Answer 12

Virus infects the cytosol of cell

Virus is degraded + presented on MHC I

Peptide is recognised by the TCR
- and CD8 co-receptor is expressed

CD8 molecule binds directly to the a-3 domain of MHC Class I

CD8 cytotoxic T-cell is activated
- it kills the virally infected cell

Question 13

Describe how the Antigen is presented by MHC Class II to the TCR

and which/how the co-receptor binds

Answer 13

Vesicular pathogen
- taken into cell by endocytosis

Virus is degraded + presented on MHC Class II

Peptide is recognised by the TCR
- and CD4 is expressed as the co-receptor

CD4 molecule binds directly to the ß-2 domain of the MHC Class II

CD4 Helper T-cell is activated
- and produces cytokines to antigen presenting cell (kill the ingested pathogen)

Question 14

Describe the processing of antigen for MHC Class I

Answer 14

Where the pathogen is in within the cell, determines which MHC molecules it is loaded onto

• Cytosolic infection arises
• Proteosomes cleave the endogenous antigen
• The antigen fragments are transported from the cytosol into the Endoplasmic Reticulum (ER)
• The fragments are loaded onto MHC Class I in the ER
• Which is moved out of ER, and presented to the TCR, and the CD8 co-receptor
• CD8 Cytotoxic T-cell (kills infected cell)

Question 15

Describe the processing of antigen for MHC Class II

Answer 15

Pathogen is in a vesicle (+ taken into cell)
- exogenous antigen

The vesicle (with antigen) merges with lysosomes to form endosome

The pathogen is then cleaved in the endosome

MHC class II is synthesised in the ER
- BUT there is an Invariant Chain covering the binding site

MHC Class II leaves the ER in a vesicle

The vesicle (with MHC II) merges with the pathogen-containing vesicle
- and the pathogen (fragments) is loaded onto the MHC Class II

MHC Class II is presented to TCR + CD4 co-receptor

CD4 Helper T-cell

• helps by increasing digestion by macrophages
• and by making B-cells switch class

Question 16

Describe what must happen for a T-cell to be activated

Answer 16

For a T-cell to be activated
- Peptide must be processed + presented on MHC I/II

MHC Class I: CD8 co-receptor ensures CD8 is only activated in a virally infected cell (cytosol infection)

MHC Class II: CD4 co-receptor ensures CD4 is only activated if the cell needs help (extracellular, vesicles)

Question 17

Describe the other pathway that is in place to ensure that T-Cells are only activated when they are needed\

(second interaction)

Answer 17

Due to direct recognition of pathogen by APC

There is an upregulation of B7 molecules

B7 molecule binds to CD28 (T-cell surface)

This is a second interaction
- that must take place before there is T cell activation

Then, there is T-cell proliferation, differentiation, and effector function