6 T-Cell mediated immunity Flashcards
Compare the recognition of antigens between T cells and B cells (receptors, etc)
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
Compare B-cell and T-cell receptors
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)
Describe the structure of the T cell receptor (TCR)
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
State the key populations of T cells
T cells
- CD4 Helper T-cells
- CD8 Cytotoxic T-cells
Describe CD4 Helper T-cells
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
Describe CD8 Cytotoxic T-cells
CD8 Cytotoxic T-cells
- Function: to KILL infected cells
They express TCR and CD8 co-receptor
What is the significance of the CD4 and CD8 co-receptors?
The CD4 and CD8 co-receptors are very important
- They ensure that the correct type of T-cell is activated
Describe why T cells are not instantly activated?
why there is no recognition of antigen in native form
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)
How is MHC class determined?
Class I or II
when presenting antigen
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
Describe the Structure of MHC Class I
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
Describe the structure of MHC Class II
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
Describe how the Antigen is presented by MHC Class I to the TCR
and which/how the co-receptor binds
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
Describe how the Antigen is presented by MHC Class II to the TCR
and which/how the co-receptor binds
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)
Describe the processing of antigen for MHC Class I
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)
Describe the processing of antigen for MHC Class II
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
Describe what must happen for a T-cell to be activated
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)
Describe the other pathway that is in place to ensure that T-Cells are only activated when they are needed\
(second interaction)
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
