MHC recognition and immune tolerance Flashcards
What are the 2 classes of T helper cells?
Th1 cells - aid effector functions of antibodies
Th2 cells - aid B cell differentiation and antibody production
How do B cells stop making self reactive antibodies?
They have to agree with T cells that the antigen needs clearing. T cells will only recognise proteins presented to them on MHC molecules.
What is the role of HLA/MHC proteins in the cell?
A conveyor belt which takes antigens from inside to outside, and then presents antigens to the T cell receptor.
Where are MHC II found?
Made by antigen presenting cells eg. macrophages
Where are MHC-I proteins found?
All cell membranes except neurones
Are MHC genes found on single or multiple chromosomes?
A single chromosome. The genes can be rearranged in a particular order, they order of genes can be called DP, DQ or DR
How does our immune system distinguish self from non self?
Our MHC proteins vary greatly between us, and these are what our immune system recognises as self.
The MHC is a cluster of genes which are highly polymorphic.
List some examples of MHC locations which relate to specific diseases
HLA-B27 - Ankylosing spondylitis
HLA-DR4 - Rheumatoid arthritis
HLA-DR3 - Diabetes
(DP, DQ, DR refer to locations of MHC-II, and BCEAHGF refer to locations on MHC-I)
Do T cells recognise proteins or cells as self/non-self?
T cells will only recognise a cell, they do not recognise individual proteins
What 2 factors can activate a T cell receptor?
- Having the wrong MHC (Ie. in transplant, it wont be recognised as self)
- Having the wrong peptide/antigen (Ie. a pathogen peptide is being displayed)
Describe the mechanism of T cell activation
When a TCR binds to MHC + Peptide on an APC, it causes intracellular signalling, which results in the switching on of genes which activate the T cell. This triggers cell division, and synthesis of cytokines
What is the role of lymph nodes?
They concentrate B and T cells and antigens, and allow them to come into contact with each other. The lymph node is like a sieve which drains all the circulating lymph from the body. Lymph exits from the blood supply, so is closely related to the circulatory system.
Where do dendritic cells go to present antigen in their MHC-II for T cells to find?
Into the lymph nodes. The lymphatics allow APCs to travel from any part of the body to come into close contact with T cells
Where in the lymph nodes are T cells found?
In the middle layer (paracortex). The dendritic cells move into this area first when they enter the lymph node, so they can present their antigen to the T cells, to see if any recognise the antigen they are carrying. If they do, this activates them.
Where are B cells found in a lymph node?
In the outer layer, known as the cortex. Activated T cells from the centre of the node, move into the B cell area. Here they can provide T cell help to activate any appropriate B cells to produce antibodies.
After a B cell has been activated by a T cell in the outer part of the lymph node, where does it go?
Memory B cells move into the germinal centre within the lymph node, where they divide.
Plasma B cells move to lymph and blood to deliver antibody.
Where does VDJ rearrangement of T cells take place?
In the thymus
What is central tolerance?
Any self reactive T cells are removed before they leave the Thymus. This occurs because they thymus medulla epithelium presents self peptides on MHC-II, so the new T cells can see if they are self reactive.
Positive selection of T cells is
A T cell that binds to MHC-II + self peptide weakly. We know its TCR works, but only weakly recognises self.
Negative selection of T cells is:
When a T cell has a strong affinity for an MHC-II + self peptide. The T cell is killed by apoptosis as it is self reactive.
