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63 Cards in this Set
- Front
- Back
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What's the major function of dendritic cells?
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activate T cells by presenting antigen-MHC to them
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How do T cells enter the lymph node?
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1) Afferent lymph and 2) blood (via HEV)
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As T cells enter the lymph node and are rolling along the HEV, what do they bind with to get them to stick there so diapedesis can occur?
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1) <b>L-selectin</b> binds to GLYCAM
2) Cell binds to <b>chemokines</b> which activates LFA L-selectin, chemokines, LFA1 |
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T/F Dendritic cells only use MHC Class II to present antigen
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False, they use both. MHC Class I is used for intracellular pathogens like viruses (they activate both CD8 and CD4 T cells)
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What is a costimulatory molecule that is a critical signal for full T cell activation?
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B7
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What promotes Dendritic cell maturation?
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Interaction with pathogen.
This stimulates the expression of several molecules (CCR7) which directs migration into lymphoid tissue and augments expression of co-stimulatory molecules and MHC |
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What does CCR7 do?
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On the mature DC it directs migration into lymph nodes, augments expression of co-stimulatory molecules (B7) and MHC
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What must a DC express in order to stimulate T cells maximally?
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B7
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What are the 3 APC in lymph nodes?
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B cells; DC, macrophages
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T/F Initial interactions between DC and T cells are low affinity and antigen non-specific.
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T. Mostly just adhesion molecules
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When is CD2 expressed?
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When stem cells enter thymus and get signal from Notch1
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How do T cells initially bind DCs? (what molecules)
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Thru low affinity LFA-ICAM interactions.
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What happens after T cells bind DCs thru ICAM1-LFA1 interactions?
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This event sends signal to LFA1 which causes it to change shape to one with a higher affinity ---> Tighter binding.
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What molecule mediates the signal for enhanced Tcell-DC binding?
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LFA1
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Immediately after activation, do activated T cells remain in the lymph node?
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Initially after they're activated they remain in the lymph node for a bit to allow them to differentiate into effector cells.
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In order to activate T cells, what are the 3 signals given to them by APCs?
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1) MHC-Antigen presentation
2) B7 costimulatory binding 3) Cytokines |
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If T cells only get the 1st (MHC-Antigen presentation) signal, what happens?
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Anergy.
NEEDS other costimulatory signal to work |
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What signal do T cells give that signifies they've been activated?
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Interleukin 2 (IL2). It releases this and stimulates itself which is the signal to activate the T cell and enter the cell cycle
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What are immunoreceptor tyrosine-based activation motifs? (ITAM)
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They're part of the effector portion of the TCR. They can become phosphorylated and transduce downstream signal. They lead to activation of ZAP-70
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How is ZAP70 activated?
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Thru the ITAMs which are activated by antigen/MHC binding TCR.
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What does ZAP 70 do?
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Binds to the phosphorylated ζ chain ITAMs and gets phosphorylated to get activated. This initiates a signal cascade leading to <b>activation of PLCγ)
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How is PLCγ activated?
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Via a signal cascade initiated by ZAP70
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What does PLCγ do?
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Cleaves PIP2 to DAG + IP3 which go to activate other proteins
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What proteins are activated by DAG and IP3 that leads to a change in expression of T cell (indicating activation)
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NFκb, AP1, and NF-AT
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Summary of chain of events thus far:
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APC with MHC/Antigen complex binds Tcell via TCR --> Zap70 gets phosphorylated --> Activates PLCγ --> Cleaves PIP2 to DAG and IP3 --> activates NFκb, AP1, and NF-AT --> changes gene transcription
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Where do the following immunosuppresor drugs work?
A) Cyclosporin - B) Rapamycin |
Where do the following immunosuppresor drugs work?
A) Cyclosporin - works at the IP3 effector level (blocks IP3 from doing its job) B) Rapamycin - prevents cell from receiving its IL2 signal |
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What is the difference in the IL2 receptor the naive vs. activated T cell?
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The naive T cell's IL2 receptor has much less affinity. The mature T cell's IL2 receptor has a higher affinity.
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What comes after T cell maturation?
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Differentiation into different types of T cells
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What changes in surface marker expression do effector T cells exhibit?
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They just get MORE surface markers to become stickier because ligands for these molecules are found in infected tissue
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What's the CD45RA/CD45RO ratio?
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Can tell whether there's an active infection
CD45RA-expressed by resting naive T cells CD45RO expressed by activated cells A high ratio indicates no infection, wherease a low ratio indicates infection |
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T/F activated T cells express a special ligand for binding to the activated endothelium.
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T. All T cells express LFA-1 that binds to antigen presenting cell adhesion molecule ICAM-1.
However, only activated effector T cells express VLA4 which binds to VCAM-1 in the activated endothelium. |
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What do Th1 cells activate?
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Macrophages
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What do Th2 cells activate?
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antigen-specific B cell
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What do Th17 cells activate?
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neutrophils
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What are the pathogens eliminated by CD4 T helper cell effector subset Th1?
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microbes persisting in macrophage vesicles; extracellular bacteria
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What are the pathogens eliminated by CD4 T helper cell effector subset Th2?
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Helminth worms
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What are the pathogens eliminated by CD4 T helper cell effector subset Th17
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extracellular bacteria
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What are the pathogens eliminated by CD8 T killer cell?
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They're specialized for viral infections.
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T/F CD4+ T cells can be important for activation of CD8+ T cells
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T. CD4 cells can be activated by APCs, which can in turn be further activated by CD4 cells, and then the APCs can release several molecules that costimulate the CD8 cell.
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What is the granule exocytosis pathway of cytotoxicity?
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Pathway used by CD8 t cell to kill. they form lytic granules containing cytotoxins that become active once they leave the cell. These can induce apoptosis via caspases.
Polymers form in cell membrane via perforin; granzyme B activates caspases which activate DNAses which essentially kill the cell. |
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What is the receptor-mediated pathway of cytotoxicity?
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Trimeric Fas ligand binds to and trimerizes Fas --> DD clutersting --> recruitment of caspases --> etc. --> apoptosis
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What causes differentiation of CD4+ effector subsets?
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APC-derived factors. The number 3 in the 1)activation 2) survival and 3) differentiation path. It depends on the pathogen, each will induce unique pattern of cytokines.
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The Th1 effector T cell subset produces what cytokine?
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IFNγ
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What cells also produce IFNγ?
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CD8 T cells
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What is a granuloma?
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An isolation chamber formed in response to intracellular infection. Associated with Th1. If we can't clear infection we wall it off.
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How does a granuloma form?
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If we can't clear an infection this localized lesion develops to wall it off.
results from partial activation of macrophages. |
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what is the delayed-type hypersensitivity reaction?
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Through Th1 cell effector, recognizes antigen and releases cytokines which recruit other cells, fluid, etc. to form a visible lesion. takes 24-72 hours
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The Th2 effector T cell subset produces what cytokines?
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IL-4, IL-5, IL-10
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T/F Th1 and Th2 both activate macrophages.
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False. The cytokines the Th2 cell secretes are inhibitory to macrophages.
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What is the immediate hypersensitivity reaction?
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Antigen recognition induces expression of CD40 ligand by Th2 cell which activates the B cell --> Antigen Specific IgE +Mast cell --> immediate reaction
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What is difference in tuberculoid and lepromatous leprosy? What is this an illustration of?
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Illustrates how the type of response you make determines whether you get infection.
Tuberculoid leprosy is mediated by Th1 and is much less severe infection. Lepromatous leprosy is mediated by Th2 cells and is much more severe. Th1 activation is needed to eliminate. |
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What is difference between a cytokine and chemokine?
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Chemokine is a type of cytokine that has a chemoattractant.
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What is an interleukin?
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generic term that means a lymphokine, a cytokine produced by a lymphocyte
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What is the primary method of cytokine effects?
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Binding to receptor (structure can be varied but are usually heterodimers), activation of Jak-STAT pathway
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what are cytokine receptors like?
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Typically dimers or trimers.
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What's the importance of the common γ chain?
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they're involve in development and survival of lymphocytes. Without them, cells can't respond and SCID develops.
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What is the Jak-STAT pathway?
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1) Cytokine binds to receptor
2) Jak dimerizes 3) Activation of Jak by phosphorylation of receptor 4) STAT (signal transducers and activators or transcription) proteins are recruited 5) STATs get phosphorylated and go to nucleus to change gene transcription |
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What are the pro-inflammatory cytokines?
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IL-12: IFNα/β; IFNγ ; TNF
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What can mutations in IFNγ receptor lead to?
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Increased susceptibility to infections
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What are the anti-inflammatory cytokines?
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Transforming growth factor β (TGFβ), IL-10
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What are the effects of IL-10 and IL-12?
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They're opposites. IL-10 suppresses IL-12
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What are chemokine receptors like?
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They're 7 transmembrane domain G-protein coupled receptors
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Compare cytokine vs. chemokine receptors.
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Cytokine - use jak-stat pathway with heterodimeric receptor
Chemokine- use GPCR, 7 transmembrane domain |
