T-Cell Mediated Immunity Flashcards
T cell circulation
The follicles are going to be present in the cortex.
The follicles in the cortex will contain B cells, while the T cells will be on located on the outside of the follicles.
Also, there will be dendritic cells that will present the antigen to the cells.
If the T cells are activated by the antigen, then they will immediately will undergo clonal expansion, which will occur at the level of the lymph node, meaning that the T cell will lose the ability to leave the lymph node after activation.
The clonal expansion will result in the activation of effector T cells and memory cells of identical antigen specificity.
Once the T cell differentiates, then it will be able to leave the lymph nodes again.
Lymphocyte and T cell movement
Lymphocyte entry into a lymph node from the blood is mediated by adhesion molecules and occurs in stages. It happens by the same mechanism as of the adhesion molecules through selectins, chemokines, and integrins.
The T cells will go to the lymph nodes, but also to the mucosal tissue.
The interaction and activation of the T cells occurs through the ICAMs.
T cell exit from LN involves
sphingosine 1-phosphate (SIP)
Activated T cells by antigen in the lymphoid organs downregulate the surface expression of the SIP receptor for several days.
FTY720 immunosuppressive drug, chronic activation of SIP receptors leading to inactivation and downregulation of the receptor.
Causes rapid lymphopenia.
Dendritic cells in different stages of maturation
Antigen presenting cells that express co-stimulatory molecules found in lymph nodes
The dendritic cells in the tissue need to be activated in order to present the antigen to the T cell. They are immature when they are in tissues. Once we have activation of the dendritic cells, they will have more expression of the lysosome, so they are processing antigen and acquire the shape of a veil. And they will be in the lymphatic circulation, and will be able to engage multiple T cells at a time for activation.
Dendritic cell activation:
Via TLRs
Tissue damage
Cytokines
Onset of inflamation by innate immunity at the site of infection increases the rate of entry of blood plasma into the infected tissues and thus increases the drainage of extracellular fluid into the lymph carrying free antigen.
The macrophages can also be found in the lymph nodes.
Conventional dendritic cells are found under most surface epihitelia and organs (heart and kidney)
INFs can promote the development of conventional dendritic cells from blood monocytes
The dendritic cells can present and process the antigen to the cells by a few pathways:
- receptor-mediated phagocytosis;
- macro-pinocytosis;
- viral infection;
- cross-presentation after phagocytic or macropinocytic uptake;
- Transfer from incoming dendritic cell to resident dendritic cell.
A Langerhans cell can be activated by innate immunity receptors, tissue damage, inflammation in that site of infection. This kind of activation of the dendritic cell is called licensing.
Then those cells migrate to the lymph node, and they can do antigen transfer to a present T cell.
Antigen presentation by different cells
Dendritic cells present the antigen to the T cells and the B cells, so it will induce clonal expansion of the cells, and will produce effector and memory cells.
Macrophages present the antigen to the T cells because it will activate the macrophage to kill the pathogen.
The B cell engages and activates more B cells.
T cell path
The very first presentation of the antigen to the T cells happens through the ICAMs and the LFAs.
Naive T cells bind transiently to APC as they migrate through the cortical region of the lymph node.
When this happens, we are going to have three phases as a result: activation, survival and differentiation.
When a T cell is activated it will express high affinity for IL2. After IL2, we have the T cel proliferation, which will stop because the CTLA-4 that can interact with the B7 in a better way than CD28. and that will stop the clonal expansion in addition to apoptosis.
If there is going to be a co-stimulatory signal alone from the APC to the T cell, the T cell will be inactivated, so the signals have to be together: activation, survival, differentiation.
T cells differentiate into effector cells after 4-5 days of proliferation.
A differentiated T cell does not require co-stimulation.
Now it becomes an effector cell that is able to kill the antigen.
CD molecules
In the majority of viral infections, CD8 T-cell activation requires help from CD4 effector T cells.
The CD4 and CD8 can have specificity for the same antigen, because they are double positives, and therefore they can both interact with the same antigen.
If CD4 is activated, it will release a cytokine that will help the CD8 T cell.
There are different types of CD8 T helper cells, and they have different functions.
Some cytokines are not particular to a cell type, so one cytokine will not give you the outcome, but a mixture of them.
Differentiated effector T cells migrate to sites of infection guided by adhesion molecules expressed on the endothelium of local blood vessels and by local chemokines.
T cell receptor and associated co-receptors cluster at the site of contact with peptide:MHC molecule forming a supramolecular activation complex. This SMACs are important for immunological synapse, meaning that they have the non-specific molecules on top, and specific molecules inside, and they can recognise each other, and there will be the delivery of them to the target cell.
So the target cell can attach to a cytotoxic T cell and the content of the granules in the cytotoxic cell will be delivered to the target infected cell. This is important because the cell will die after the targeting of the infected cell together.
One apoptosis T cell can go multiple rounds of apoptosis induction.
The content of the granules in the cytotoxic T cells are granzymes, granulysin and perforin.
The whole process takes about 40 minutes.
Activated T-helper cells
- Activates a macrophage, but the macrophage will not be able to kill the infected cell, so the helper cell can kill the activated macrophages.
- Kills chronically infected cells, bacteria to be destroyed by fresh macrophages through Fas ligand or LT-beta.
- Induces T cell proliferation, increasing numbers of effector cells by IL-2.
- Induces macrophage differentiation in the bone marrow by IL-3 +GM-CSF.
- Activates endothelium to induce macrophage binding and exit from blood vessel at site of infection by TNF-alpha.
- Causes macrophage to accumulate at site of infection through cytokines.
