Term
| what is the sequence of events in the ubiquitous innate immune response (0-4 hrs)? |
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Definition
| infection->recognition by preformed, nonspecific effectors(complement/mannose pathway)->removal of infectious agent |
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Term
| what is the sequence of events in the induced innate immune response(4-96 hrs)? |
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Definition
| infection->recruitment of effector cells(NK cells)->recognition,activation of effector cells->removal of infection |
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Term
| what is the sequence of events in the adaptive immune response(>96 hrs)? |
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Definition
| infection->transport of antigen to lymphoid organs->recognition by naive B/T cells->clonal expansion/differentiation to effector cells->removal of infectious agent |
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Term
| what is the sequence of events in the protective immune response? |
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Definition
| re-infection->recognition performed by antibody can effector T cells->removal of infectious agent |
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Term
| what is the sequence of events in immunological memory? |
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Definition
| re-infection->recognition by memory B/T cells->rapid expansion/differentiation to effector cells->removal of infectious agent |
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Term
| how do type I interferons play a role in innate immunity? |
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Definition
| type I interferons shift cells into an antiviral state |
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Term
| what is one of the major ways the body prevents re-infection? |
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Definition
| circulating antibody (neutralizes/opsonizes antigen) |
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Term
| how do NK cells "keep a lid on things" during an innate response to herpes virus infection? |
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Definition
| NK cells kill infected cells |
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Term
| how do CD8 CTLs clear herpes virus? |
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Definition
| they lyse all infected cells presenting class I MHC antigen |
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Term
| what are they earliest made interferons? what do they do? what happens to mice lacking their receptor? |
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Definition
| IFN alpha/beta which inhibit viral replication inside the cell. they also activated NK cells and upregulated class I MHC (upregulates CTL activation). mice lacking the IFN alpha/beta receptor are more susceptible to viral infection |
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Term
| who produces IFN gamma? what does it do? what kind of T cell does this circuit favor? |
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Definition
| IFN gamma is made by T (aquired) and NK (innate) cells, it enhances MHC class II expresssion (upregulates CD4 T cell activation) as well as activating macrophages and NK cells. this circuit favors TH1 differentiation. |
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Term
| who makes IL-12? what does it do? |
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Definition
| macrophages make IL-12 which stimulates NK cells to make more IFN gamma (cycle). dendritic cells also make IL-12 upon activation |
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Term
| how soon after infection are NK cells detectable? what cytokines do they respond to? |
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Definition
| NK cells are detectable w/in 2 days after infection. they are incredible responsive to type 1 IFN, IFN gamma, IL-2, IL-15, and IL-12 |
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Term
| how long does it take NK cells to activate? |
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Definition
| as long as it take dendritic cells to make IL-12 |
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Term
| how do NK cells recognize target cells? what do they do to target cells? |
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Definition
| NK cells recognize target cells via KAR/KIR (killer immunoglobulin like receptors) and lyse target cells via perforin/granzymes also ADCC (Antibody-Dependent Cellular Cytotoxicity) kicks in once the aquire immune response starts b/c NK cells can see antibodies via their Fc gamma Rs |
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Term
| what are the 3 levels upon which macrophages act on viruses? |
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Definition
| phagocytosis of virus/virus-infected cells, killing of virally infected cells, and release of IFN alpha, TNF alpha, and NO |
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Term
| how do antibodies mainly control viruses? |
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Definition
| antibodies can contol viruses when they are *extracellular. this is the major mechanism for preventing viral spread between cells and tissues, as well as restricting viremia (IgG), and re-infection at mucosal surfaces (IgA) |
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Term
| what is the mechanism of antibody control of extracellular viruses? |
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Definition
| antibodies neutralize the viruses infectivity by binding/blocking the viral attachment structures as well as activating complement/destruction of enveloped viruses via virolyis (prob not a major viral clearance mechanism, more directed at bacteria) |
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Term
| how does antibody control intracellular virus? |
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Definition
| antibody, complement and NK ADCC all lead to killing of infected cells. this is not a major clearance mechanism however, it will be done mostly by another cell |
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Term
| what is antiviral antibody production usually dependent on? what does antibody help in the induction of? |
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Definition
| CD4 Th1 cells for class switching and affinity maturation. antibody helps in the induction of CD8 CTLs, &vtheir production of IL-2/IFN-gamma as well as recruitment/activation of macrophages via CD40L and IFN gamma |
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Term
| how do CD8 cells know which cells to kill? how do they kill? |
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Definition
| CD8 kill virally infected cells in a class I MHC restricted, antigen specific manner. they kill using perforin/granzymes, Fas/FasL and cytokine production |
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Term
| what cells are all involved in clearing viral infections? |
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Definition
| CTL, Th1, macrophages, NK, B cells (via antibody) |
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Term
| what is the progression of response with viral immune clearance? |
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Definition
| NK cells plateau the viral titer, CTLs drop the viral titer and antibodies keep that drop low |
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Term
| what immune system mechanisms can viruses disrupt? |
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Definition
| IFN, complement, cytokine, chemokine, MHC production, induction of apoptosis, and NK cell action (via making MHC class 1 homologue) |
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Term
| what are the main ways that extracellular bacteria cause disease? |
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Definition
| invasiveness, inflammatory response, seretion of exotoxins (exotoxin A: pseudomonas aeruginosa/lethal factor bacillus anthracis), gram (-) endoxin (potent TNF alpha stimulator) |
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Term
| what are the 2 goals in fighting bacterial infections? |
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Definition
| clear the bacteria and neutralize toxin |
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Term
| how do diptheria/cholera cause disease/how are they dealt with? |
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Definition
| both create toxin that is neutralized by antibody |
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Term
| how do bacterial meningitis/S. aureus cause disease/how are they dealt with? |
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Definition
| invasion, opsonized and killed |
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Term
| what are the principal mechanisms of innate immunity to extracellular bacteria? |
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Definition
| complement activation, phagocytosis, and inflammation |
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Term
| how is the complement pathway activated by extracellular bacteria? what part of immunity is this? |
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Definition
| the alternative complement cascade can be activated by: direct activation by peptidoglycan (gram+ or gram - LPS), generation of C3b (opsonization/phagocytosis), generation of membrane attack complex (classical/alt pathway). this is part of the innate immune response |
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Term
| what is the mannose pathway? what part of immunity is this? |
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Definition
| a complement pathway that is initiated by the bacterial expression of mannose. this is part of the innate immune response |
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Term
| what do complement byproducts C3a/C5a do? what part of immunity is this? |
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Definition
| participate in inflammation by recruiting/activating leukocytes. this is part of the innate immune response |
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Term
| how do phagocytes participate in natural immunity to extracellular bacteria? |
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Definition
| in innate immunity, phagocytes can indpendently recognize extracellular bateria via mannose or scavenger receptors or they can use Fc receptors/complement receptors to recognize previously opsonized bacteria. TLRs also contribute to activation of phagocytes. |
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Term
| how do phagocytes contribute to inflammation in the innate immune response to bacteria? |
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Definition
| activated phagocytes secrete cytokines, either proinflammatory cytokines (IL-1, TNF, or IL-6) or chemokines |
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Term
| what are the effects of cytokines secreted by extracellular bacteria in innate immunity? |
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Definition
| phagocytically secreted cytokines stimulate inflammation, induce adhesion of neutrophils/monocytes to vascular endothelium and induce migration, local accumuation and activation of inflammatory cells (this will eliminate bacteria, but can also induce tissue injury) |
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Term
| what are cytokine effects in extracellular bacterial infection? |
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Definition
| fever, stimulation of acute phase reactants, and regulation of specific immunity through effects on B+T lymphocytes, and APC |
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Term
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Definition
| a severe, often fatal, pathologic consequence of disseminated infection by gram - and some gram + bacteria. in its early phases, sepsis is caused by: TNF alpha (possibly also IL-1,6, IFN-gamma, and IL-12) |
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Term
| what is virchow's classic triad in sepsis? what do they lead to? |
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Definition
| changes in coagulation (DIC - disseminated intravascular coagulation), endothelial cell injury, and abnormal blood flow. these lead to reduced blood flow to vital organs, (hypoglycemic) shock, and death |
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Term
| what is the primary agent active in adaptive immunity against extracellular bacteria? what does it function to do? |
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Definition
| humoral immunity which functions to block infection, eliminate microbes and neutralize toxins |
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Term
| what may be all that is needed in protection from extracellular bacteria pathogenic only due to a single toxin or adhesion molecule in the aquire immune response? what else can be activated by this? |
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Definition
| neutralizing IgA or IgG which can activate classical complement to lyse, or be opsonized for phagocytosis (how most extracellular bacteria are disposed of) |
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Term
| what are ways that extracellular bacteria can evade the immune response? |
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Definition
| antigenic variation (gonorrhea, e coli, salmonella), complement inhibition, (many), phagocytosis resistance, (Strep. pneumoniae), scavenging ROS intermediates, (cat-positive staph) |
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Term
| what are ways that intracellular bacteria can evade the immune response? |
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Definition
| inhibition of phagolysosome formation, (TB, legionella), inactivation of ROS/NOS, (leprosy), disruption of phagolysosome membrane/escape->cytoplasm, (listeria) |
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Term
| what is the innate immune response to intracellular bacteria mediated by? |
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Definition
|
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Term
| what are intracellular bacteria resistant to? |
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Definition
| degradation within phagocytes |
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Term
| what is a key player in the innate immune response to intracellular bacteria? |
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Definition
| NK cells that are activated by ligands induced by cells infected by intracellular bacteria or by stimulation of IL-12 by macrophages/dendritic cells (*this will really tip the scales back in favor of the host). this is b/c intracellular bacteria are resistant to phagolysosomes |
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Term
| what cyokine is produced by NK cells when they are stimulated by IL-12? what does it do? |
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Definition
| NK cells make IFN gamma which activates macrophages and promotes killing of phagocytized bacteria. |
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Term
| how was the importance of IL-12/IFN gamma demonstrated in the innate defense against intracellular bacteria? |
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Definition
| IFN-gamma and IL-12 knock out mice were very susceptible to mycobacteria infection |
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Term
| what is the pathological manifestation of an intracellular bacterial infection? |
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Definition
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Term
| what is the major adaptive/protective immune response to intracellular bacteria? what do they effect? |
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Definition
| Th1 CD4 T cells (help form protective granulomas) who produce cytokines (IFN gamma/TNF) driving differentiation into giant cell macrophages, (caseating necrosis is seen as a result). (NK cells/cytokines only transiently protect from an infection) |
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Term
| what do T cells do in adaptive immunity to intracellular bacteria? |
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Definition
| CD4 Th1 T cells under the influence of IL-12 active macrophages to kill phagocytized bacteria via IFN gamma/CD40L. the macrophages then produce ROS/NO/lysosomal enzymes |
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Term
| how do CD8 CTLs become involved with intracellular bacterial infection? what does this depend on? |
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Definition
| phagocytized bacteria "leak" into cytosol or bacteria escape from phagosomes and enter cytosol, they are then no longer accessibly to phagocytes and the killing has to be accomplised by CTLs. this depends on IFN-gamma activating the CD4s from NK cells (which are activated by the CD4s by IL-12) |
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Term
| what can CD4 T cells do in the instance of an intracellular bacterial infection? in terms of CD8s/macrophages? |
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Definition
| they can stimulate phagocytic killing by the phagocyte or killing of the infected phagocytic cell by CTLs |
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Term
| what kind of tissue injury is caused by intracellular bacteria? |
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Definition
| most tissue injury is caused by macrophage activation. intracellular bacteria have evolved to resist phagocytic killing so they often persist for long periods, causing chronic antigenic stimulation, and prolonged T cell/macrophage activation. granulomas eventually form, which are the hallmark of intracellular infection |
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Term
| what is clearance of intracellular bacteria dependent on? |
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Definition
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