T-Cell Effector Flashcards
What do Th1 cells secrete and activate?
Secrete IFN gamma and TNF alpha
activate Macrophages and CD8 T cells
What do Th2 cells secrete and who do they activate?
Secrete IL-4, IL-5, IL-13
activate B cells
What do Th17 cells secrete and who do they activate?
Secrete IL-17 and activate neutophils
What type of pathogen is presented by MHC I and who responds to it?
MHC I presents intracellular antigens and CD4 cells respond
What type of pathogen does MHC II present and who responds to it?
MHC II presents extracelllular antigens and CD8 T cells respond
Describe the steps of cross presentation
A virus infected cell (extracellular) is engulfed by a DC (so now the virus is intracellular). Then the DC presents the antigen as MHC I
-so a normally extracellular antigen is engulfed, becomes intracellular and is therefore expressed with MHC I to CD4 cells
What do CD4+ T cells differentiate into? What about CD8+ T cells?
CD4+ turn into Th1, Th2, or Th17
CD8+ turn into Cytotoxic T lymphocytes (CTLs)
How does a effector T cell go from the LN to the site of infection?
It stiwtches the expression of its adhesion and molecules and chemokine receptors
-responding to the chemokines produced at the site of infection by the macrophages
What do macrophages secrete at the site of infection
- produce chemokines to attract effector cells
- produce inflammatory cytokine that act on endothelial cells like IL-1 and TNF alpha
What does endothelial cells have to do with effecctor T cells?
Endothelial cells are induced by IL-1 and TNF alpha secreted by the macrophages. This makes the endothelial cells express ligands for adhesion molecules expressed on effector T cells. Allowing the T cells to be localized to the site of the infection. The T cell will then look to recognize the antigen presented by Macrophages and decide if it should stay or not.
What are the two branches of Th1 mediated immunity?
- CD4+ Th1 cells lead to actiavtion of phagocytes
- CTLs kill cells haboring intracellular pathogens
How does a Th1 cell activate a macrophage?
Direct connection with CD40-CD40L (upon activation a naive CD4 T cell will express CD40L)
and by cytokines (IFN gamma)
-side note: CD40 is also known as CD154
What is an activated macrophage?
An activated macrophage is doing what it normall does just at a higher rate because it was activated by CD40 from Th1
- it will capture the pathogen in a phagolysosome
- lyosomal proteases will destory the pathogen
- produce ROS and NO
IFN gamma and CD40L will induce expression of proteases and ROS/NO producing enzymes (hence upregulating the activity of the macrophage)
Give an example of Bi-directional communication?
Professional APC (DC or macphage) is secreting IL-12 activate CD4 cells and CD4 (Th1) cell is secreting IFN-gamma to actiavte the macrophage to kill the microbes
What is the granule way CTLs kill
CTL has antigen recognition and conjugate formation, then it becomes activated and lines up its granules towards the target cell (CTL cytoplasmic reaarangment) then it spits the granules at the target killing it (CTL granule cytosis)
What are the granules released by CTLs and how do they work?
CTL secrete ganules that are known as Granzyme B and perforin that poke holes in the membrane and activate caspases within the infected cell causing it to undergo apoptosis
Describe the ligand death pathway of CTLs
CTLs express FasL which binds with Fas on the target cell and activates caspases and the cell undergoes apoptosis
What are the amplification loops of the immune response?
- macrophages secrete IL-12 to Th1 cells which secrete IFN- gamma back to macrophages making them secrete more Il-12
- Th1 cell produce TNF alpha which acts on the endothelial cells to increase adhesion molecules and thus recruit more T cells (TNF alpha causes vasodilation and permeability)
- CTLs produce IFN gamma which also further activates the macrophages
- Th17 cells secrete chemoines to attract more neutrophils and monocytes
What are the 3 lymphocytes with cytotoxic activity?
CD8+ T cells
NK cells
NKT cell
Describe NK cells
- Not T cells
- kill rapidly without proliferation
- kill by perofrin/granzyme, fas/fas ligand
- recognize lack of MHC class I, thus MHC I is inhibitory for NK cells (KIR)
- produce cytokine line IFN gamma
- side note: NK cells kills with lack of MHC I, while CD8 cells need MHC I to kill
- many virus inhibit TAP1 thus down regulate MHC 1 in order to avoid CD8 cells, but therfore will be caught by NK cells
Describe NKT cells?
Natural Killer T cells
- express some NK cell markers
- express a TCR with limited variability
- specific for glycolipids + CD1 (Liparabinomannan of mycobacterium tuberculosis)
CD1 is an MHC class I like molecule with a beta 2 microglobulin associated
-kills by perforin/granzyme, and fas/fas ligand mechanisms
What is delayed type hypersensitivity?
It is the classical Th1 response and takes 24-48 hours for the Th1 cells to home to the infection, respond to the antigen, and induce a detectable response.
- This is due to the 2nd exposure with a memory cell, 1st exposure illicits no immune response
- example is the TB skin test
- after 24-48 hours there is T cell and monocyte infiltration, thus increased vascular permeability (edema) and fibrin deposition
Describe mycobacterium tuberculosis
it is a facultative intracellular bacteria that causes respiratory infection, contained in the alveolar macrophages, but it cannot be eliminated
- leads to activation of CD4 and CD8 and macrophages that leads to formation of granulomas
- the granulomas develop central necrosis (caseous necrosis)
What are the 6 things TNF alpha does?
- DC maturation
- Granuloma formation
- Fibrosis
- Vascular permeability/dilation
- Phagocyte activation (ROI/RNI)
- apoptosis
What is TNF alpha blockers used to treat and what must we do before treating the patient.
used to treat autoimmunity
must test them for TB
What are some methods of resistance to Th1 mediated immunity?
- preventing fusion of phagolysosome
- Escape to the cytoplasm
- inhibit MHC class I
- decoy receptors (such as soluble IFN gamma receptor)
