Lecture 6 Flashcards
(32 cards)
clonal expansion
Response of APC-T cell interaction causes activation of T cell and starts to rapidly proliferate
Which cytokine plays an important role in T cell proliferation?
IL-2
What are the effector functions of CD4+ T helper cells?
- assist macrophage activation
- enhance inflammation
- assist B cells with antibody production
What are the effector functions of CD8+ cytotoxic T cells?
-kill infected cells that display MHC I-associated microbial peptides
What are the main roles of DCs?
- surveillance
- capture
- processing of microbial antigens for MHC presentation
Which other cells can perform the same functions as DCs?
B cells and macrophages but DCs are best APC cells for T cell activation
What are the two DC classes?
- classical and plasmacytoid
- classical DCs present antigens to and activate T cells
- plasmacytoid DCs are primary source of Type I interferons
What stimulates DCs to begin maturation process?
-lipopolysaccharide of Gram negative bacteria or viral PAMPs bind to Toll-like receptors and other PRR in DC
While traveling to the draining lymph nodes, the maturing DCs upregulate expression of which molecules?
- MHC molecules
- B7 co-stimulatory molecules
- interaction of integrin ligand ICAM-1
How do DCs know where to migrate during maturation process?
- lose adhesiveness for EC surface and begin to expression chemokine receptor CCR7
- chemokine receptor recognize chemotactic gradient directing DCs to exit infection site and migrate through lymphatic vessels
What are the two signals needed for T cell activation?
- Signal 1: Antigen recognition-T cell receptor recognize specific antigen presented in MHC context by APC
- Signal 2: Co-stimulation- co-stimulatory molecules from both T cell and APC engage
- need both to max signaling response and differentiate T cell populations appropriately
Which signaling molecules are involved in TCR complex?
-CD3 and zeta chains
Which cells increase binding avidity between TCR and peptide-MHC complex?
-interaction of co-receptor CD4 or CD8 with MHC molecule engaged by TCR
Binding of which cells is required for second signal for T cell activation?
-binding of CD28 on T cell to B7 on DC
How are signal 1 and 2 important checks on T cell activation?
- signal 1 provides specificity
- signal 2 helps guard against autoimmunity
Which cells further stabilize the T cell-APC interaction?
-adhesion molecules: integrin LFA-1 on T cell binds to integrin ligand ICAM-1 on APC
Which cytokine is a potent T cell growth factor?
-IL-2
What factors are involved in the immunological synapse?
-engaged TCR complex, co-receptor and CD28 molecules cluster together, pushing engaged LFA-1 molecules to peripheral ring
TCR is clustered with which chains?
-CD3 and zeta chains
CD4 or CD8 co-receptors facilitate signaling through which protein?
-Lck (tyrosine kinase)
What steps are involved in T cell signaling?
- TCR clustered with CD3 and zeta chains
- CD4 or CD8 co-receptors facilitate signaling through Lck
- CD3 and zeta chains contain Immunoreceptor Tyrosine-based Activation Motifs (ITAMs) become involved
- Lck phosphorylates ITAMs to stimulate signaling along phospholipase C-gamma, Ras/Rac, and PI3 kinase pathways
- transcription factors NFAT, NFkB, and AP-1 are generated
What role does T cell signaling events play in organ transplant medicine?
-suppression of the immune system of recipient (immunosupression) permits organ transplantation
How does cyclosporine and rapamycin aid in the organ translant process?
- Rapamycin-block IL-2 response and prevent Akt and mTOR activation in PI3 kinase pathway
- Cyclosporine-inhibit calcineurin and prevent activation of NFAt transcription factor from PLC-gamma pathway
What is an example of a treatment strategy for autoimmune diseases with T cell involvement?
- soluble CTLA4 molecule bind to B7 on APC and prevent interactions with CD28 on T cells and suppressing T cell activation
- blocking PD-1 receptor on T cells (immune enhancement) releasing brakes on T cells so they are able to detect and kill cancer cells
