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61 Cards in this Set
- Front
- Back
activation of T cells requires what kind of cell?
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APC- antigen presenting cells ( express MHC)
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T cell response are directed towards what kind of invader
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intracellular pathogens
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2 types of T cells
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cytotoxic
Th1 |
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cytotoxic
effector T cell antigen recognition action |
Cytotoxic CD8 T cell
peptide-MHC Class I complex on infected cell kill infected cells |
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Th1
effector T cell antigen recognition action |
Th1 cell
peptide-MHC Class II complex on macrophages activate infected macrophages |
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humoral immnity
effector T cell antigen recognition action |
TH1 and Th2
peptide-MHC Class II complex on antigen specific B cell activation of specific B cell to make antibody |
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What cytokine drives T cell production?
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IL-2
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2 interactions that stimulate decline of T cells
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Fas- FasL
TNFalpha- TNF receptor |
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What downregulates the decline of T cells?
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FLIP
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purpose of dendritic cells
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transport antigens from periphery to lymphoid organs where T cells become activated following antigen presentation
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APC in lymph nodes
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dendritic cells
macrophages B cells |
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where dendritic cells are found in lymph node
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cortex
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here macrophages are found in the lymph node
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marginal sinus
meduallary cords |
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where B cells are found in the lymph nodes
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follicles
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purpose of immature dendritic cells
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facilitates phagocytosis of antigens in peripheral tissues
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purpose of mature dendritic cells
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stimulate T cells
DC-SIGN |
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how do pathogens induce expression of important APC molecules?
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most APCs express little MHC and costim molec
after phagocytosis, they are degraded and relase molec that lead to an innate reponse. innate response is necessary for an adaptive response binding of microbrial degradatin productions leads to an increase in MHC and costim molec |
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two fates for T cells in lymph nodes
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1. don't encounter antigen. They are returned to the blood stream
2. if encounter antigen, are retained in the lymph node. proliferate and differentiate into effector cells |
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purpose of leukocyte adhesion molecules
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act to direct migration of leukocytes to specific areas of the body
act as costimulatory molecules that are directly involved in the activation of specific leukocyte cell types |
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L-selectin
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a leukocyte adhesion molecule in naive T cells that binds to either GlyCam-1 or CD34 expressed on the HEV that allows them to leave blood and enter peripheral lymphoid tissues
--non specific, non activated situation |
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HEV
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HEVs enable naïve lymphocytes to move in and out of the lymph nodes from the circulatory system.
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diapedesis
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leaving the vessel
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MadCam-1
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on mucosal endothelium
can bind to L selectin that is bound to T cell and allows them to leave blood and enter mucosal lymphoid tissue of gut |
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process to cross HEV
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1. L-selectin binds to Glycam-1 and CD34 which enables rolling interaction
2. LFA-1 is activated by chemokines 3. activated LFA-1 binds tightly to ICAM-1 4. diapedesis ICAM and LFA-1 stabilize |
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LFA-1 is an
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integrin that is expressed on all leukocytes and binds to ICAM-1 on APC
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LPAM-1 is an adhesion
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that is on a subset of naive cells and minds to MAdCAM-1 on the mucosal endothelium
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VLA-4 is an
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integrin that is on activated effector T cells that binds to VCAM-1 on endothelium
VCAM is upregulated at the site of inflammation. VLA4 on the T cells will bind to it and let it know where the T cell can be found |
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steps in antigen presentation
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1. T cell binds APC through LFA1-ICAM-1 (slows down T cell rolling so it can pay attention to what is going on with dendritic cells- sampling peptide bound to MHC)
2. this allows for other T cell receptors to be bound 3. conformational change in LFA-1 increases affinity and prolongs cell-cell contact |
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T cell activation
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2 signals needed
1. MHC ClassII w/ antigen -- TCR along with CD4/ CD8 2. CD28 (T)- CD80(APC) |
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How does the T cell signal get transduced?
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release of Ca after receptor engagement
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ex of how the innate immune response potentiates the later adaptive immune respons
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the phagocytosis and breakdown of bacteria by macrophage induces expression of MHC ClassII and CD80
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adjuvants
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microbial products known to increase T cell responses
if on APC next to bacteria, will co-stim T cells |
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Is costim signal (Cd28-CD80) needed for both naive and effector T cells?
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No, only for naive
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B cells as APCs
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antigen derived presented on surface of B cell
need 2 signals CD40-CD40L CD28-CD80 |
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CTLA-4
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on T cell, binds to CD80 to shut down proliferation of t cell
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VLA-4
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controls migration of effector T cells
expressed on activated T cells interacts with VCAM-1 which is expressed on endothelium of blood vessels in inflamed tissue |
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naive vs activated T cells and IL-2
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naive have low affinity IL-2 R
activated have high affinity IL-2R and they also secrete IL-2 which stimulates proliferation of T cells |
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function of Th1 cells
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macropahge activation
B cell activation production opsonizing antibodies such as Ig1 |
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function of Th2 cells
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general activation of B cells to make antibodies
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where do Th1 and Th2 cells come from?
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CD 4 T cells
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pathway of Th1 and Th2 cell production
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maive CD4 T cell + APC--> proliferating T cell
cytokine IFN gamma induces TF Tbet which activates transcription of TF STAT4. STAT4 is activated by IL-12 --> Th1 cytokine IL4 induces GATA-3 which turns into STAT6 which with IL-4 --> Th2 |
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if equal amt of IL12 and 4 in production of T helper cells, which cell will result?
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Th2
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What cytokines does Th1 produce?
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IFN gamma, IL3
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What cytokines do Th2 produce?
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IL 3, 4, 5, 10, 13
no IFN gamma |
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cytotoxic effecotr molec
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perforin
granzymes granulysin |
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main function of CD8 T cell
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cytotoxic T cell
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main function of CD4 T cell, Th1
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activate macrophage
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main fxn of CD4 T cell Th2
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produce antibodies
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effector function of Th1 cell
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produce IFN gamma which acts on:
activate macrophage to kill intracellular pathogens B cells to stimulate IgG that oposonize microbes for phagocytosis produce LT and TNF to activate nuetrophils and stimulate inflammation |
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how is the activation of macrophages controlled?
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by inhibiting activated macrophages
Th2 cells relase cytokines GF, IL4, IL10, IL13 these cytokines also reduce Th1 production of IFN gamma which reduces Th1 direct effects on macrophages |
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granuloma
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bunch of bacteria surrounded by T cells in order for containment
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effector functions of Th2 cells
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produce IL4 that stimulate B cells to produce neutralizing IgG and IgE
produce IL5 that activates eosinophils produce IL10 and IL4 to suppress activated macrophages |
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what chenokines are importnat in regulation of T regulatory cells?
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IL10
TGF-beta (lead to development of T regulatory and effector cells) |
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do effector T cells require costim?- consequence
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nope
can kill any cell that expresses target antigen on MHC molec |
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2 mechanisms of CTL killing
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1. granzymes enter through perforin holes on T cell --> activation of capsases --> apoptosis
2. Fas- FasL |
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specificity of CTL response vs macrophage response
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CTL response is targeted, activated macrophages are not specific- there will bebystander damage
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perforin
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pore spans entire membrane to allow entry of granzymes
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cytokines that CTL cells make
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IFN gamma, TNF gamma, TNF beta
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purposes of IFN gamma
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increase MHC expression and make targets more visible
inhibits viral replication directly activates macrophages |
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function of TNF
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activates macrophages
kills through TNFR-1 |
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cognate interaction
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B and T cell recognize same antigen.
helps with vaccines |