Lymphocyte interactions - Shaw Flashcards
Why do T cells only recognize antigen bound on self-MHC?
Their development in the thymus requires a weak affinity to self-MHC
What is an endogenous vs exogenous antigen?
Endogenous - foreign particles which are SYNTHESIZED in the cell, including tumor antigens
Exogenous - foreign particles derived from outside the cell (can include viral proteins
What are dendritic cells called in the skin, liver, and brain?
Skin: Langerhaans cells
Liver: Kupffer cells
Brain: Microglial cells
What is the function of DC’s?
First guard against pathogens that break through innate immune system, most potent APC. Highly motile, and express TLR that interact with bacterial and viral moeities
What is the function of macrophages, and how do they differ in number from DC’s?
phagocytose large particles, and present antigens less potently than DCs
Far more numerous than DC’s (make up 5-15% of leucocytes in lymph nodes and spleen)
What stimulates macrophages to upregulate MHC Class 2 to high levels?
Interferon gamma
What type of antigens do B cells bind? Present?
Only SOLUBLE antigens which match their BCR. Whether they can present antigens which do not match their BCR is hotly debated.
What is a TAP protein?
Transporter which removes proteins from the proteasome degradation across the rough ER membrane for attachment to MHC Class 1
TAP = transporter associated with antigen processing
How do degraded proteins get on MHC Class 1?
There are chaperones for MHC 1 folding which relate closely to TAP in order to bring them directly onto MHC
What mediates the antigen moving to MHC 2 in the endocytic pathway?
In the ER, Invariant chain sits in the MHC 2 cleft and stabilizes it. In the lysosome, the remnant CLIP stablizes it.
HLA-DM mediates the exchange of peptides of CLIP for antigen, and MHC Class 2 will be brough to surface to express the peptide.
What is CD40L? What upregulates it and what does it do?
It is expressed on T cell, binds the CD40 of antigen presenting cell for costimulation
It is upregulated by the CD40 of APC, then proceeds to upregulate the B7 on the APC for further interactions with CD28 and CTLA4
How long do a T cell and APC remain bound?
About 8 hours
What is ICOS?
Receptor on T cell which interacts with ICOSL on the B cell.
CD40 Ligand will be on T cell.
Why is the interaction between CD40 on B cell and CD40L on T cell so important?
Important for class switching, as well as memory B cell formation
What cytokine causes massive clonal expansion of T cells, and what type of feedback is it?
IL-2
Positive feedback T cell growth factor
What is the direct effect of B7-CD28 costimulation?
Increases the transcription and halflife of mRNA for IL-2
Also activates the kinase PI3
How does CTLA4 function?
Binds B7 with high affinity and sends inhibitory signal to cell, which reduces IL-2
How does PD1 work? Why might this be important clinically?
PD1 = programmed death, receptor on T cells.
PD1 inhibitors are being used in cancer patients to enhance immunity by allowing T cells to stay active and fight cancer
Where does clonal expansion occur?
In lymph nodes
What are two fates of T cells once activated?
- Differentiation into effector cells or memory cells
2. Migration to sites of inflammation via expression of adhesion molecules and chemokine receptors
What is the mechanism of how superantigens work?
React with constant region of beta chain on T cell receptor, can activate up to 20% of T cells. Can either cause death of T cells or massive cytokine storm leading to toxic shock syndrome
What is one clinical application of plant proteins Con A and PHA?
They activate all T cells, so they can be used to test for immune function post bone-marrow transplant
Where exactly do superantigens bind? How is this different than a mitogen like LPS?
The invariant part of the TCR beta chain
Mitogens like LPS bind a cell surface receptor and trigger polyclonal expansion which is adaptive
What is the function of TH1 cells?
Produce IFN-gamma and IL-2 in response to virus or bacteria
