L8 + L9: Immunoengineering & translational considerations Flashcards
What do T helper cells do?
They travel to the infection where they secrete cytokines for inflammation and phagocytosis.
They activate: B-cells and cytotoxic T-cells
- CD8 > cytoxic T cells
- CD4 > T helper cell
Activated when their receptor interacts with a MHC class II molecule.
What do dendritic cells do?
They are named because of their many, long processes that resemble neuronal dendrites which makes them very efficient in making contact with foreign materials.
Dendritic cells are expert messenger cells (for the adaptive system). They bind to antigens and activate T cells.
What is the difference between MHC class I and II?
MHC I: on all cells, present endogenous protein (‘I am one of us, don’t kill me’).
MHC II: APCs only, present non-self antigen (to kill).
Dendritic cells can mature into 2 types. What are those and what are their characteristics?
Mature dendritic cell (mDC)
- high MHC II
- secretion of inflammatory cytokines; IL-12, IFN-y
Tolerogenic dendritic cell (tDC)
- low MHC II
- Secretion of anti-inflammatory cytokines; IL-10, TGF-b1
- Effective induction of regulatory T cell types
–> it inhibits inflammation in every way possible.
T-cell activation occurs from 3 signals?
How is this called?
- Antigen presentation
- Co-stimulation
- Cytokines
This is called the immunological synapse.
Explain Signal 1: antigen presentation.
T cells are generated in the thymus and are programmed to be specific for one particular antigen. Once they leave the thymus, they circulate throughout the body until they recognize their antigen on the surface of antigen-presenting cells (APCs). Both CD4 helper T cells and CD8 cytotoxic T cells bind to the antigen (held in a structure called the MHC complex). This triggers the activation of the T cells.
Dendritic cell has eaten anything and presents this to the T cell.
Explain Signal 2: co-stimulation.
This is a signal to activate the T cells and respond to the threat. This leads to the production of many T cells that recognize the antigen.
Explain Signal 3: Cytokines.
Once the T cell has received a specific antigen signal (1) and a general signal (2), it receives more instructions in the form of cytokines. They are secreted by cytokines. These determine which type of responder the cell will become:
T helper cell → TH1 (when exposed to IL-12), TH2 (IL-4), or TH17 (IL-6, IL-23). Each of these cells performs a specific task in the tissue and in developing further immune responses. (Cytokines → TH cell polarization)
Licensing=
? Not sure?
If dentritic cells comes along a antigen and becomes activated, there are co-stimulatory signals CD40-CD40L. They show it to T helper cells via MHC class II. It can also show DC-CD8+ to cytotoxic T cells via the MHC class I receptor.
Antigenicity=
The ability of foreign material (antigen) to bind to an antibody or an activated T cell (having signal 1).
Immunogeneicity=
The ability to elicit an immune response (first triggering the innate immune response and later the adaptive immune response).
What is the purpose of peripheral tolerance by DCs?
The main purpose of peripheral tolerance is to ensure that self-reactive T and B cells which escaped central tolerance do not cause autoimmune disease. It presents immune response to harmless antigens and allergens (e.g. food).
What are the 4 ways of peripheral tolerance by DCs?
- Ignorance; is has the antigen, but it doesn’t show it. The mechanism of ignorance is when the affinity to antigen is too low to elicit T cell activation.
- Anergy; the antigen is shown, but there is no pro-inflammatory signal. There is an ‘are you sure?’-button. This is used as an checkpoint. So, signal 1 is present, but signal 2 isn’t. Also, without pro-inflammatory cytokines, co-stimulatory molecules will not be expressed on the surface of the APC.
- Phenotypic skewing; cytokines are anti-inflammatory (il-10).
- Apoptosis; self-destruct switch.
What does cancer immunotherapy aims to do? And what are the 4 approaches?
Boost/ improve the natural anti-tumor immune response.
1. Blocking inhibitory signaling pathways on T cells.
2. Increasing the number of effector T cells.
3. Vaccination with tumor antigens.
4. Cytokine therapy.
Explain blocking inhibitory signaling pathways on cells (cancer immunotherapy)
Immune checkpoint= are regulators of the immune system. These pathways are crucial for self-toleance, which prevents the immune system from attacking random cells. Some cancers can protect themselves from attack by stimulating or blocking receptors for immune checkpoint targets (on T cells).
