Immunology 4 Flashcards
How does an ideal T cell receptor behave?
Bind to pathogens with high affinity, but not to self-cells and tissues.
Define immune tolerance.
Immune tolerance = the processes by which immune cells prevent attack of self-tissues.
How is T cell development part of immune tolerance?
During thymic development, T cells which have receptors specific for pathogens are selected, and those with receptors binding to self-antigens are deleted.
What is the structure of the T cell receptor?
In the immunoglobin family.
Have an alpha and a beta chain.
Variable receptor binding region and a constant backbone.
What are the three signals for T cell activation?
- Binding of TCR to epitopes of antigen present on Major Histocompatibility Complex (MHC) molecules on surface of antigen-presenting cells.
- Co-stimulation through CD80/86 and CD28.
- Cytokines which tell T cell about flavour of the immune response.
How do antigens bind to the T cell receptor?
Epitopes recognised by T cell receptors are often buried.
Antigen must first be broken down into peptide fragments.
Epitope peptide binds to a self MHC molecule.
T cell receptor binds to complex of MHC molecule and epitope peptide.
Define Major Histocompatibility Complex (MHC) molecule.
MHC = glycoprotein that is expressed on surface of cells and which display peptide antigens.
How is an antigen presented on an MHC molecule?
Antigen presented on MCH-I from inside the cell - sticks in the endoplasmic reticulum and then is taken to the surface.
Antigen presented on MGC-II from outside the cell - stick in endocytic vesicle and is taken to surface.
What kind of cells are MHC class II found on?
Antigen-presenting cells - dendritic cells, macrophages, B cells.
How are CD4 cells activated?
DCs pick up antigen from pathogens and infected/dead cells.
DCs present antigen to naive CD4+ T cells which cause activation in lymph node (first antigen encounter).
Activated CD4 T cells go to spleen where they meet antigen again, this time on B cells (second antigen encounter) and produce B cell help.
How are CD8 cells activated?
DCs pick up antigen from pathogens and infected/dead cells.
DCs present antigen to naive CD8+ T cells which causes activation in lymph node (first antigen encounter).
Activated CD8+ T cells go to tissues where they meet antigen again, this time on infected self cells (second antigen encounter) and they kill infected self.
Describe the process of Signal 2 (CD80/86).
When DCs present antigen to T cells, T cell needs to be sure antigen is definitely dangerous.
PAMPs and DAMPS in environment cause activation of DCs - upregulate CD80/86.
CD28 on T cells bind to these CD80/86 and tells T cell that there is a genuine threat and it should be activated.
Activation without CD80/86 will not ligate CD28, causing T cells to switch off and become tolerant (immune tolerance).
Define peripheral tolerance.
Peripheral tolerance = immune tolerance that develops outside the thymus.
Describe the process of Signal 3 (cytokines).
Antigen-presenting cells produce cytokines during T cell activation.
IL-2 is a very important cytokine which is required for the T cell to start dividing and making a clone that can respond to the threat.
Other cytokines tell the T cell which kind of pathogen it is responding to.
What is the difference between activation and tolerance?
Activation:
Strong signal 1 - presence of pathogen antigen.
Strong signal 2/3 - good DC activation because self tissue is damaged/infected.
Therefore, pathogen antigen and damage leads to activated DCs and in turn, activated T cells which are effectors.
Tolerance:
Weak signal 1 - self-antigens.
Weak signal 2/3 - lack of DC activation because self tissue not damaged/infected.
Therefore, self-antigen without damage or infection leads to tolerant T cells which switch off.
