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cell mediated immunity
cmbm exam III
35
Chemistry
Graduate
01/17/2010

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Term
both TH1 and CTLs secrete cytokines, but which secretes more? what cytokines are secreted?
Definition
TH1. cytokines are IL-1, IFN gamma, and TNF alpha
Term
what do activated CTLs do?
Definition
directly kill microbes
Term
how do TH1 cells induce macrophage activation?
Definition
macrophages have receptors, (toll-like and mannose) that bind to bacteria and other pathogens facilitating macrophage mediated phagocytosis, destruction, and intracellular degradation, (via antigen processing)
Term
what happens when macrophages process and present antigen via class II MHC to CD4 T cells, (in the presence of IL-12 and IFN-gamma)?
Definition
CD4+ cells are activated and differentiated to TH1 cells
Term
what is the effect of APCs activating CD4+ cells into TH1 via class II MHC?
Definition
the TH1 cells in turn, induce macrophage activation, causing the phagosomes that contain captured microorganism to more efficiently fuse with lysosomes, as well as cause synthesis of highly reactive and microbicidal molecules including oxygen radicals, NO, and proteases
Term
other than making the macrophage more cytotoxic when the TH1 CD4+ T cell activates the macrophage, what else does it induce in terms of the macrophage's surface expression?
Definition
more class II MHC, B7 (upregulate costimulation), CD40 (better response to CD40L), and TNF-R, (responds better to TNFalpha)
Term
what are the 2 signals that the activated macrophage recieves from the activated TH1 CD4+ T cell? is there a specific sequence of signals
Definition
IFN gamma and CD40L. IFN gamma is the primary signal made by TH1, (also NKs) and CD40L is the secondary signal, (makes the cell responsive to IFN gamma)
Term
once activated and macrophage surface expression is increased, what does the macrophage secrete?
Definition
cytokines, TNF, IL-1, and IL-12, (which is important b/c it promotes differentiation of naïve CD4+ T cells to Th1 cells)
Term
what is the circular interaction between TH1 CD4 cells and macrophages in terms of cytokine secretion?
Definition
IL-12 secereted by macrophages promotes differentiation of naïve CD4+ T cells to Th1 cells. IFN gamma, secreted by TH1 CD4+ cells activates macrophages, allowing them to better kill microbes
Term
what is delayed type hypersensitivity?
Definition
a clinical physical manifestation of the TH1 driven CD4+ T cell-macrophage/dentritic cell interaction. seen with a raised red bump with TB test, mosquito bites
Term
similar to delayed-type hypersensitivity, what can cause contact hypersensitivity?
Definition
haptens, (poison ivy), small metal ions, (nickel, chromate)
Term
what is the morphology of delayed type hypersensitivity?
Definition
perivascular mononuclear cell infiltrates, (lymphocytes+macrophages) and endothelial cell activation
Term
what is granulomatous hypersensitivity? when does it occur? is there a particular pathogen this is seen with?
Definition
occurs when antigen in delayed type hypersensitivity is not cleared, resulting in persistent T cell activation and release of cytokines. macrophages are promoted to differentiate into epithelioid cells, which secrete TNF alpha and some fuse to form multinucleate giant cells. this is often seen in mycobacterium infections.
Term
if granulomas, (caused by granulomatous hypersensitivity), is caused by TB, what kind of necrosis is often seen in the center? what kind of necrosis is seen with sarcoidosis?
Definition
TB: caseating necrosis
sarcoidosis: noncaseating necrosis
Term
if pts have defective TH1 or are TH2 dominant, how does this affect their ability to respond to mycobacterium leprae or leishmania major that cause granulomas?
Definition
TH1 activates macrophages which will clear the infection via cell-mediated immunity, and TH2 inactivates macrophages, causing the infection to spread
Term
how are CD8+ cells activated? where does the antigen usually come from?
Definition
the CD8+ TCR engages the MHC class I peptide complex in a similar fashion to how CD4+ cells do, however the antigen peptide is usually of endogenous, viral origin.
Term
how might class I MHC also present antigen from extracellular microbes that have been phagocytized by dendritic cells?
Definition
if leaky phagosomes spill some peptide out in the cytosol, (calledcross-priming/presentation)
Term
how do CD8+ T cells "see" antigen?
Definition
CD8 interacts with the invariant region of MHC class I
Term
when do CD8+ cells not need help from CD4+ cells?
Definition
if professional APCs are directly infected, this increases the probability that cross-priming has occured and co-stimulation/APC provided cytokines will be enough to fully activate the CD8+ cells
Term
can CD4+ cells help activate naive CD8+ cells with a "second signal"? when might this be necessary?
Definition
in the case of a weak innate immune response, (latent viral infection, organ transplant, tumor).
Term
how do CD4+ cells help with CD8+ cell differentiation?
Definition
CD4+ cells can provide secretion of necessary cytokines,(IL-2 and TNFα -these are TH1), production of CD40L - which binds to CD40 on APCs, making them better at promoting CD8+ T cell activation/differentiation. or CD4+ helper T cells can directly give its own cytokines to activate CD8+ T cells
Term
what are the most prominent cytokines in clonal expansion of activated T cells?
Definition
IL-2, which is made by TH1 CD4+/CD8+ T cells (and promoted by TNF, IL-1, and IL 12). IL-15 is the other, (and it and it's receptor) which is very similar to IL-2
Term
what does an activated CTL need to be able to do? does it need any more costimulators?
Definition
it must be able to recognize antigens on non-professional APCs, (virally infected and tumor cells). it doesnt need costimulators anymore.
Term
how do active CTL cells adhere to target cells? is it specific?
Definition
non-specific interaction, via the CTL's integrin and target cell's CAM
Term
how do CTLs induce apoptosis via lytic granules?
Definition
lytic granules contains perforin and granzymes. perforin is analogous to C9, where it creates a transmembrane channel, allowing granzymes to enter. granzymes are a family of serine proteases that cleave cellular proteins and activate endonuclease, (an effector capsase) to induce apoptosis.
Term
what is another way that CTLs can induce apoptosis not by lytic granules?
Definition
Fas-FasL interactions, which induces apoptosis like all members of the TNFR superfamily
Term
can one CTL can kill multiple target cells?
Definition
yes
Term
what are most NK cells? do they have TCRs or surface Ig? what do they express? what do they do?
Definition
most NK cells are large granular lymphocytes, & they represent 10-15% of peripheral blood mononuclear cells. they do not have a TCR or any surface antigen, (do not recognize any antigen). they do express IL-R and IL-2R, which allow responsiveness to IL-2 and thus can provide immunity against infections
Term
how to NK cells know where to go?
Definition
they respond to IL-2 via their IL-R and migrate through blood to tissue in response
Term
what kind of immunity do NK cells mediate? what do people who lack NK cells suffer from?
Definition
NK cells mediate innate immunity against intracellular infections. persistent infections and herpes common, however they should be able to eventually clear the infection via aquire immune response
Term
how does the NK decide to kill a cell? if the target cell expresses MHC, what does the NK cell do?
Definition
these only recognize "killing activator receptors" which are positive signals for apoptosis if they bind to cell stress proteins, but the NK only kills when the inhibitory receptor fails to bind to the target MHC class I. if the host still expresses MHC, it is still pretty normal.
Term
how can NK cells kill indirectly? do any cells stimulate the NK cells?
Definition
NKs can secrete of IFN-gamma which activates macrophages to kill microbes. then the macrophages secrete IL-12 which activates more NK cells. and the cycle continues
Term
how do NK cells kill targets?
Definition
perforin and granzymes
Term
how do NK cells recognize target cells?
Definition
NK activating receptors recognize host cell surface molecules that are expressed during intracellular pathogen infection, (cell stress protein). inhibitory receptors are specific for class I MHC and HLA-E, (many viruses block MHC expression)
Term
are there any other ways the NK cells recongnize cells to be killed beyond KIR/MHC?
Definition
NK cells can bind Fc regoin of antibodies that have opsonized target cells
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