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56 Cards in this Set

  • Front
  • Back
What is the effector function of T cells?
Cell mediated immunity(CMI)
What do T cells defend against?
Microbes that replicate within phagocytes and nonphag cells
What initiates effector phase of CMI?
recognition of antigens by T cells
What is the difference in the pathogens that each of these respond to: Th1, Th2 and CTL's
TH1 respond to microbes in phagocytic cells
TH2 respond to helminthic parasites and various allergens
CTLs respond to microbes in various other cells
What does a defect in CMI cause susceptibility to?
Intracellular parasites
What is DiGeorge syndrome?
Deletion of portion of chromosome 22 that causes absence of thymus and parathyroids, also cardiac and facial abnormalities
What are the Sx of DiGeorge syndrome?
Tetany(hypocalcemia)
Variable T cell counts
Decreased response to skin test antigens
Suscebtable to opportunistic infection
What are the function of Th cells and Tc cells?
Th: activation of B lymphocytes, phagocytic cell activation, inflammation
Tc: lysis of target pathogen
What are the cell surface molecules on T cells that are involved in signal transduction? Functions?
CD3 and ζ
CD4 or CD8= Th or Tc
CD28=Co-stimulation
CTLA-4=inhibitory
What is the cell surface molecules on T cells that is involved in adhesion?
Integrins: LFA1 and VLA-4
Where does T cells activation occur?
Secondary lymphoid tissue
What are the 2 signals needed for T cell activation?
1)Bind of TCR complex to MHC on APC, if TCR bind MHC+antigen the CD8 or 4 will bind MHC

2)Binding of B7 with CD28 on T cell
What is the function of CD28 binding B7 on APC?
initiate intracellular signall transduction pathway
Why are dendritic cell the APC that activates naive T cells?
They don't require cytokines (IFN) to be activated
Where are macrophages most actively stimulating T cells?
At site of infection after effector t cells have been activated in 2ndary lymphoid tissue
What is anergy? Cause?
state of unresponsiveness. Lack of second signal to activate T cells(B7-CD28)
What do activated APCs express that unactivated ones don't that allows them to activate T cells?
costimulator-B7 and IL-2
What are the Transcription factors that are released as a result of the 2 APC activation signals?
NFAT, NF-KB, AP-1
What is the function of the 3 transcription factors activated by the 2 APC activation signals?
expression of the IL-2 gene
Where are each of the activation transcription factors activated in the T cell?
Aggregated signalling motifs activate, NFAT and NF-kB in the cytosol and AP1 is activated in the cytosol
How is T cell proliferation activated?
activation signals cause expression of IL2 and HIGH AFFINITY IL2R. When IL2 binds IL2R is activates Jak\Stat pathway which increases transcription of CYCLINS
How is T cell proliferation regulated?
After several rounds of proliferation the T cells begin to express NTLA-4 which binds to CD28 and inhibits proliferation and limits number of T cells produced
How can IL-2 be used to fight cancer?
T cells from cancer are isolated=TIL(tumor infiltrating lymphycytes), TIL's are given IL-2 exogenously and allowed to proliferate, cells put back into patient to fight cancer
What are 2 drugs that inhibit T cell activation? Action?
Cyclosporin and Tacrolimus, bind calcinerurin and prevent NFAT activation so no IL2 production
Which T cells are responsible for primary immune response and secondary immune response?
Th and Tc are primary IS
Memory T are 2ndary IS
T\F effector T cells circulate for long periods of time?
False short lived
T\F Memory T cells live a long time and generate a hightened sensitivity to antigens?
True
What are the 3 types of T helper cells, their function and specific cytokines expressed
Th1-controll CMI, IFN-γ
Th2-control humoral reactions, IL-4,IL 5, IL 13
Th17-inflamatory disorders and microbial defense, IL17
What are the Types of antigen that each subset of Th cells responds to and the cytokines that cause differentiation to the 3 types? Where do Cytokines come from?
TH1-Bacterial fungal and viral
IL-12, IFN-γ
TH2-Parasites and Allergens
IL4

TH17-unknown
IL-6 and TGF-β
Where does IL- 12 come from? what causes secretion
Activated macrophages and dendritic cells
Secreted in response to phag of microb or intracellular microbe infection
Where is IFN-γ secreted from to cause Th cell differentiation? Why do they secrete these?
NK and TH1 cells

NK secretes IFNγ in response to IL-12, TH1 secrete it to increase cell development
What is another function of IFNγ?
augments phagocyte killing mechanisms and antigen presentation
What are the 2 places that IL-4 is secreted to stimulate differentiation of TH to TH2 cells?
Mast cells and TH2 cells(autocrine)
Why do mast cells secrete IL12?
Inresponse to parasites and allergens activation of mast cells
What are the functions of IL-6 and TGF β outside of TH17 differentiation?
IL6= inflamatory cytokine
TGFβ=immunoreglatroy cytokine(often at mucosal surfaces)
What are the 2 things that IL-6 and TGFB do to stimulate TH17 cell differentiation and proliferation?
incudes synthesis of IL-21 which is an autocrine for TH17 differentiation
Where does Th cell differentiation take place?
Secondary lymphoid tissue. Enter circulation after differentiation
The 3 cytokines secreted by Effector Th1 cells?
IL-2, IFNγ, TNF
What are the 3 functions of TH1 effector cells?
cytokine secretion inresponse to intracellular infections and tumor antigens, regulation of CMI responses
What are the CMI regulatory functions of TH1 cells?
Activation of PMNs(neutrophils), macrophages, NK and Tc cells, stimulation of B cell production of opsonizing antibodies
What is the function of IFNγ and CD40L secreted by TH1 cells regarding macrophages?
aupment APC and phagocytic functions of macrophages
What is the function of IFN γ on B cells? Antibody class?
stimulate production of opsonizing antibodies, IgG's
Why would a TH1 cell be required to activate a Tc cell? What activates Tc
Because APC lacks both stimulation signal(B7 and MHC), TH1 secretes IL-2 and IFNγ
What is the function of TNF secreted by THI cells?
increase expression of CAMs and production of chemokines, increases extravasation
What are primary functions of TH2 effector cells?
humoral response to parasites and allergens: stimulate B cells to make non-opsonizing ab's and stimulate mast and basophils during helminthic infections, inhibition of macrophages
What can the balance between TH1 and TH2 cells tell you about the outcome of infection?
B\c TH2 inhibits macrophages it tells you how well u will respond
What is the hypothesized function of Th17 cells?
Help with massive inflammatory responses that overcome TH1 and TH2 cells
What do the 3 cytokines that TH17 cells secrete do?
IL 17, IL 21, IL 22 stimulate inflammatory responses: acute phase protein synthesis, chemokine secretion, stim. production of inflamatory cytokines
What are the functions of Effector Tc(CTL's)?
-recognize infected or tumor cells via TCR-MHC interaction(recog triggers killing)
What is required for a CTL to kill target? What are the 2 mechanisms?
Cell to Cell contact
Degranulation and Fas-FasL interaction
How does the degranulation mechanism of CTL killing work?
Cells release Granzymes(serine esterase, activate apoptosis via caspase act.) and perforin(perforating protein, insert and polymerize)
How does the mechanism of Fas-FasL interaction of CTL killing work?
All nucleated cells express Fas, only CD8 cells express Fas L. When CTL binds MHC is allow enough time for Fas-FasL interaction and caspase activation=apoptosis
How many subsets of memory cells exist for each type of T cell? What are they?
2, central memory(Tcm) and Effector memory(Tem)
What is the function of Tcm cells?
home to 2ndary lymphoid tissue and generate many effector T cells and memory cells
What is the function of Tem cells?
go to peripheral tissues(esp mucosal), secrete cytokines
*not much proliferation just provide initial rapid response
What is required for a prolonged response of Tem cells?
cytokine dependent, IL-7, proliferation is still low