Activation and differentiation of CD4+ T cells Flashcards
What are the basic components needed for CD+ T cell activation?
- CD4+ T cell
- Antigen
- Antigen presenting cell= dendritic cell
Where does T cell activation occur?
Lymphoid tissue- lymph node
What is signal 1?
T cell recognising antigen
Why is T cell recognition of antigen not enough to activate them?
Some antigens presented may be self or harmless antigens so a reaction to them would cause autoimmune disease or allergy.
What is signal 2?
Interaction between co-stimulatory molecules (between dendritic cell and T cell)
Examples of co-stimulatory molecules
CD28 on T cell
CD80/CD86 on dendritic cell
What happens to co-stimulatory molecules when a pathogen is present?
They are up-regulated. DCs recognise pathogen associated molecules via PRRs which activates MHCII and the antigen which causes the up-reguation of CD80 or CD86.
What happens if a T cell recognises an antigen but doesn’t get co-stimulated?
The T cell becomes anergic= unresponsive to antigen
What is an example of an inhibitory pathway to prevent T cell activation?
CTLA-4 inhibits the CD28-CD80/86 interaction which limits T cell activation.
What is a positive and negative of CTLA-4 function?
- It limits T cell activation against self antigens
- Can limit T cell responses during chronic infection and against tumours.
Example of important adhesion molecules for T cell:DC interaction.
LFA-1:ICAM-1 interactions allow loose adhesion between the two cells. If the T-cell recognises the antigen then signalling events make the molecules bind with higher affinity so more TCR/MHCII interactions can occur.
What happens if the T cell does not recognise the antigen?
The loose LFA-1:ICAM-1 interactions are not strengthened so the T cell moves on to look for another DC.
What are clusters of molecules at the T-cell/DC interface called?
Supramolecular activation clusters (SMACs)
How does antigen binding and co-stimulation cause T cell activation?
Signal 1 and 2 trigger signals inside the T cell which alter gene transcription and drive T cell activation and differentiation.
What happens when a CD4+ T cell is activated?
T cell are first stimulated to proliferate to increase the number of antigen-specific T cells. This is called clonal expansion.
How does clonal expansion work?
Activated T cells express the receptor for IL-2 on their membranes. This acts in an autocrine and paracrine manner to drive T cell proliferation.
What is the definition of cytokines?
Small protein released by cells that have specific effects on interactions between cells, on communications between cells or on the behaviour of cells.
Types of cytokines
- Intreleukins
- Interferons
- Colony stimulating factors
What are the two sub-classes of CD4+ T cells and what do they respond to?
Th1 cells- responses to intracellular pathogens
Th2 cells-responses to extracellular responses
How are Th1 cells characterised and what do they do?
Characterised by production of: IL-2, interferon gamma and lymphotoxin.
- Activates macrophages
- Stimulates CD8+ T cells (killer cell)
- Stimulates B-cells to produce opsonising antibodies.
How are Th2 cells characterised and what do they do?
Characterised by production of: IL-4, IL-5, IL-9 and IL-13.
- Stimulates B-cells to produce neutralising antibodies
- Attract and activates eosinophils and basophils.
How are different Th cells made?
Need signal 3= cytokine signal to the T cell
What is signal 3 for Th1 cells?
-IL-12
-IFN-gamma
Positive feedback means you always make more
What is signal 3 for Th2 cells?
- a number of cytokines from epithelial cells
- IL-4
How are Th cells regulated?
Th1 and Th2 cross-regulate each other
- Th1 cells down regulate the production of Th2 by the secretion of IFN-gamma
- Th2 cells down regulate the production of Th1 by the secretion of IL-4.
What are some of the harmful properties of Th1 and Th2?
Th1: autoimmunity and transplantation rejection
Th2: allergy and autoimmunity
What do Th cells acquire during differentiation which enables them to migrate?
Homing molecules
What are some newly discovered CD4+ T cell subsets?
Novel effector CD4+ T cell subsets- help fight infection:
- Th17
- T follicular helper cells
Regulatory T-cells (Tregs)- help suppress responses
What is the function of T follicular helper cell?
They are helper cells specialised to of to the B cell follicles (germinal centres) of lymph nodes to help B cells make antibodies.
What do Tregs do?
Suppress the activity of T cells which bind to self-antigens to prevent autoimmunity.
What are the two ways in which Tregs are made?
Made in the thymus as part of normal T cell development
Made in peripheral tissues/organs by naive CD4+ T cells via IL-2 and TGF beta to produce induced of peripheral Tregs.
How do Tregs inhibit harmful T cells?
- anti-inflammatory cytokines
- outcompete effector T cells for resources
- kill self-reactive T cells
