Lecture 8- T cell responses II

Lecture 8- T cell responses II - TH1 cells activate...

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T H 1 cells activate macrophages that have ingest bacteria to induce increased killing They release IFN g , and also provide contact-dependent signals through CD40-CD40L. This confers cell specificity, along with TCR-MHC interactions This process represents the intersection of the adaptive and innate immune responses, as lymph node primed/activated T cells have re-entered the infected tissue
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Activated macrophages induce increased fusion of lysososmes with phagosomes, release proteases, oxygen radicals and NO within and outside the cell that kill pathogens (and host tissues) Upon activation, antigen presentation increases and cells release TNF a to augment the immune response
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In addition to increasing the killing capacity of infected macrophages, T H 1 cells attack granulomas, induce macrophage differentiation and migration to infection site, and increase proliferation of more T cells to continue pathogen killing
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A naïve CD4 + T cell can differentiate into several lineages, that are defined by the cytokines they secrete (and surface molecules) Each T helper cell subset antagonizes the development of other subsets
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A Novel Transcription Factor, T-bet, Directs Th1 Lineage Commitment Szabo et al., Cell , 2000 What the authors knew: T-helper cells are can be distinguished as either Th1 or Th2, based on the production of IFN g and IL-4, respectively Each subset activates itself, and represses the other Though the transcription factors for Th2 cells were characterized (c-maf, NFAT and GATA-3), those for Th1 lineage commitment were not (those involved in Th1 cell fate were not exclusive to these cells) Though several transcription factors induced IL-2, none were specific to Th1 cells Question: Is there a lineage specific transcription factor for Th1 commitment In this paper: Screened a yeast-one-hybrid target containing the IL-2 promoter with a cDNA library from Th1 cells
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A. Northern blot analysis showed T-bet transcript in Th1 T cell clones, (PL17, OF6, AE7) but not in Th2 clones (CDC35 or D10). B. Western blot and FC with monoclonal antibodies illustrated T-bet expression in Th1 clones (both resting and activated), but not in Th2 cells. Cell activation increased protein levels only in Th1 clones
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