What are TH1 CD4 cells involved in
Killing intracellular pathogens
How do we present intracellular pathogens antigens to the naive T cells?
Extracellular is easier to present as they can be phagocytosed by the dendritic cells. The only way we can present antigens for intracellular pathogens is by the help of cross presentation.
These antigens have to be presented in both MHC 1 and 2 by APCs
What other properties are important in cross presentation
He briefly mentioned in the slide that intracellular pathogens have an extracellular phase to their life. This helps in phagocytosis and presentation on MHC class 1.
Also remember that MHC class 1 presentation of intracellular antigens ALWAYS needs cross presentation
What is the takeaway from this slide
1. Dendritic cells are large cells, their cytoplasmic extensions allows them to connect with multiple T cells at a time
2. DC secrete IL-12. This causes the T cells to secrete IFNgamma and CD40L. This leads to denritic cells to secrete more IL-12 and then this will cause increase IFNgamma and CD40L.
It is important to know that this mechanism happens through autocrine and paracrine loop.
Basically what are Th1, 2 and 17 cells
They are differentiated T cells or effector T cells that are now cytotoxic T cells
What happens after T cell activation and what chemicals are responsible for that specifically
T cell has to migrate from the site of infection to the lymph node. This happens by the help of chemokines. Most notably CCR7 is a chemokine that is downregulated so the T cell can move from the lymph node to the site of infection
What is the role of endothelial cells and what signals do they respond to
IL-1 and TNFa induces vasodialtion and increased vascular permeability
If you cut your finger and your toe at the same time and different pathogens infilterate the 2 areas how does T cells know where to go
The T cells after activation go through the blood stream and then to the site of infection by crossing endothelial layer via diapedesis (exact same process through which neutrophils crossed the endothelial lining). If the activated T cell is at the right site of infection for that pathogen it is activated again and involves itself in immune response. If the right pathogen is not there it moves along.
Important point here to remember is that it is not the antigens but the chemokines that direct the effector T cells to the site of infection and these chemokines are the same for all pathogens
How are Th1 t cells presented with antigen
By macrophages via MHC class 2 for CD4 cells and MHC class 1 by any infected cell
What are the 2 branches of Th1 mediated T cell response
1. CD4 Th1 cells lead to the activation of phagocytes. When CD4 T cells get activated they express CD40L (aka CD154). This interacts with CD40 on phagoctyes and activates them. Cytokines such as IFNg also further activates phagocytes
2. CTL T cells kill cell harboring intracellular pathogen
What are the functions of a macrophage and what do we mean by an activated macrophage?
Macrophages function by:
1. Phagocytosing the microbes or infected cell, lysosome destroys the microbe.
2. Produce ROS and NO
4. Make TNFa, chemokines, IL1 and IL12
An activated macrophage by a CD4 Effector cell just does these function in greater quantities
What is the function of IL12 made by macrophages
It drives the differentiation of naive CD4 cells into Th1 cells
What is bidrectional communication
How do CTLs function
1. They express antigen receptors.
2. Recognize antigen receptors
3. Leads to the formation of a conjugate
4. All the receptors and granules are focussed on the target cells
5. Granules are released that contain perforin and granzymes. Perforin pokes holes for granzymes to enter which then activate caspases.
6. Apoptosis of target cell is induced
Whats another way CTLs function
They have FASL in their surface. FAS ligand interacts with FAS and this also leads to caspase activation and induction of apoptosis
Summary of CTL mechanism of action
1. MHC 1 has to be recognized first.
2. This is the same mechanism of killing by the NK cells and also by NKT cells
What is another function of CTL in immune response
They make a ton of IFNg which is necessary of amplification loop which has a function of developing inflammation which allows more WBCs to be recruited at the site of infection.
Main function of Th17 CD4 cells
They secrete chemokines to attract neutrophils and macrophages.
What is presented to NKT cells
Does NKT cells express TCR? YES!
Explain delayed type hypersensitivity response (DTH)
When a pathogen infilterates into the skin the macrophages are stimulate instantaneously and they start the process of phagocytosis and start secreting chemokines and cytokines.
The dendritic cells evetually phagocytose and go to the lymph node to stimulate T cells when then go to the site of infection as part of the adapative immune response. Hence there is a time delay of 24 to 48 hours for adaptive immune response to kick in and this is termed DTH response
Expalin the phenomenon observed in TB
1. Macrophages line the alveoli of the lungs and are involved in destroying air-borne pathogens.
2. When a macrophage engulf a pathogen, macrophages of the lungs or dust cells can actually move to the lymph nodes and activate naive T cells (unlike other macrophages in the body).
3. In the case of mycobacterium tuberculosis a Th1 response is mediated
4. Mycobacterium TB is a facultative intracellular pathogen
5. MTB can be contained by the dust cells but it cannot be eliminated. This containment leads to the formation of granulomas.
6. Granulomas develop central necrosis (caseous necrosis in this case).
What is it that is absolutely necessary for granuloma formation
What are the function sof TNFa
Drugs that inhibit TNFa