Lymphoctye activation: T cell Flashcards
What is the percentage break down of T lymphoctyes that circulate and stay in one place
50% vs 50%
What are the three type of mature T lymphoctes
naive, effector, memory
What is the function of naive lymphocytes, where are they located
antigen recognition, reside in lymph nodes
What is the function of effector T lymphocytes
perform functions required to eliminate microbes in periphery
What is the function of memory T lymphocytes
functionally silent cells but mount rapid responses to antigen challenge (secondary response)
What is a key difference in T cells and B cells
T cells require antigen presentation by other cells vs B cells that recognize whole antigens on their own; antigen peptides vs antigen parts
What is the function of helper T cells, what protein causes activation
Cytokine production that leads to T cell differentiation, B cell growth, macrophage activation, MHC 2 restricted activation
What is the function of cytotoxic T cells, what protein cause activation
Lysis of virus and tumor infected cells, MHC 1 restricted activation
Which cells present MHC 1 protein, MHC 2
all nucleated cells, antigen presenting cells
What is the difference in antigen that would determine MHC class
MHC 1 -> endogenous protein antigen catabolized in the cytoplasm MHC 2-> exogenous protien antigen catabolized in acid compartment
What are the functions of antigen presenting Cells
process and present antigen to T-lymphocytes, provide secondary stimuli to the T cell required for achievement of full T cell response
T/F: APCs can express MHC 1 and MHC 2
True
What is the most key feature of dendritic cells. what are other important features
Most efficient in initiating adaptive immune response, travel from periphery (site of infection) to lymph nodes to activate naive T cells/express high levels of costimulatory and adhesion molecules
What is the most key feature of macrophages, what are other important features
provide continuous stimuli to keep T cells going at the periphery, have low levels of MHC 2 at first but cytokine stimulation will lead to higher levels of MHC 2
Where does a large number of APC interactions with Naive T cells occur
Lymph nodes
What part of the T cell interacts with the APC
TCR
T/F: It is sufficient and necessary to have and interaction between the TCR and MHC 2 of APCs
False: it is necessary but not sufficient to propagate a signal
What are the components needed for full T cell activation
Co-receptor (CD4 or CD8), costimulatory pairs, adhesion molecules
What are costimulatory pairs, are they essential for activation of naive T cells
clustered intracellular signaling molecules around the TCR allowing activation signal to dispatched to the nucleus, yes
What are the two most important costimulatory pairs (for this class) where cell types are they located on
B7 (infected cells)/CD28 (T cells). CD40L (T cells)/CD40 (APCs)
T/F: Effector and memory T cells require less co-stimulation
True
What are processes that occur due to B7/CD28 binding
mobilize kinases and other signaling proteins around TCR, increase half life of cytokine mRNA molecules ( leads to 100x more cytokines produced), increase T-Cell proliferation, prevent apoptosis
What are processes that occur due to CD40/CD40L binding
On APC: promote up regulation of MHC and other costimulatory molecules/increase longevity of dendritic cells by increasing production of IL-12, For B cell: Promotes B cell proliferation/promote Ig class switching
What is the function of adhesion molecules
form an outer ring, stabilizing the T cell-APC contact and assist in migration of T cell to sites of inflammation and infection
What is the most important membrane kinase for T cell activation
Zap-70
What is the enzyme that is the result of the IP3 pathway, what transcription factor does it release
Calcineurin, NFAT
What is the enzyme that is the result of the DAG pathway, what transcription factor does it release
PKC, NF-kB
What is the enzyme that is the result of the Ras pathway, what transciption factor does it release
ERK/JNK, AP-1
What does NFAT lead to, what is the purpose of
Calcineurin, increase synthesis of IL-2 (T cell growth factor)
What are the three signals needed for T cell activation
1) Antigenic signal 2) Co-stimulatory signal 3)Cytokine signal
T/F: Once activated lymphocytes will plofierate to build up clones with the same antigen specificity and after doubling its numbers every 6 hours for 3-4 days differentiation occurs
True
Once activation ends due to disengagement what are changes the T cell will make
Upregulation of chemokine receptors and adhesion molecules in order to migrate to the affected tissue
What is the function of CD8 T cells, CD4 T cells
destroy antigen carry target cell, secrete cytokines
How does CD4 T cells know what cytokines to produce
The presence of cytokines in the environment during activation drives the differentiation
What cytokine leads to T Helper 1 cells, what APC releases what cytokine for this differentiation, what cytokine do Th1 produce,
IL-12, dendritic cells, IFN-gamma and IL-2
What cytokine leads to T Helper 2 cells, what APC release what cytokine for this differentiation, what cytokine to Th2 produce
IL-4, macrophages, IL-4 and IL-5
What type of immunity does T helper 1 cells assist in, where does its actions take place
Cell mediated immunity ( increase phagocytosis, cytotxicity), activated endothelium tissue
What type of immunity does T helper 2 cells assist in, where does its actions take place
Antibody mediated immunity (IgE,IgA eosinophil recuitemnt, mast cell recruitment)
T/F: T helper 2 cells cause macrophage activation
False: T helper 1 cells are involved in macrophage activation
What occurs in Helper T cell independent activation of CD8+ T cells
TCR interacts with MHC 1 leading to activation and proliferation capable of killing cells
What occurs in Helper T cell dependent activation of CD8+ T cells
APC interaction with CD4+ cell leads to release of IL-2 that induces CD8+ activation resulting in destruction of target cells expressing MHC 1 associated antigenic peptides
In T helper cell dependent activation what is needed for the CD8+ T cell to recognize the correct cells to destroy
The same antigenic peptide and the same MHC protein
What are the two major mechasim for cytotoxic kills
cytotoxins (perforin and granzymes) Fas/FasL
What is the mechanism of action for perforin, granzymes
poke holes in the cell membrane induce apoptosis
How does Fas cause cell death
FasL (CD8+) binds Fas (infected cell) causing caspases to be release inducing apoptosis
T/F: CD8+ T cell memory T cells can be activated by dependent and independent T helper cell activation
False: CD8+ T cell memory cells will only be generated via T helper dependent activation
Negative selection can prevent hyper activation of immune response through what mechanism
CTLA4 binds to B7 more than CD28 inhibiting the T cell response