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54 Cards in this Set
- Front
- Back
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How does protective immunity take care of pathogens in extracellular (interstitial spaces, blood, lymph)?
Extracellular (epithelial surfaces)? Intracellular (cytoplasmic)? Intracellular (vesicular? |
- Abs, complement, phagocytosis, neutralization
- Ab (esp IgA), antimicrobial peptides - Cytotoxic T cells, NK cells - T-cell and NK-cell dependent macrophage activation |
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Do viruses infect organisms intracellularly or extracellularly?
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- intracellular: Obligatory intracellular parasites
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Do intracellular bacteria infect organisms intracellularly or extracellularly?
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- intracellular: Obligatory or facultative intracellular parasites
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Do extracellular bacteria infect organisms intracellularly or extracellularly?
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- extracellular
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Do fungi infect organisms intracellularly or extracellularly?
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- Intra and extracellular
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Do protozoa infect organisms intracellularly or extracellularly?
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- Intra and extracellular
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Do helminths infect organisms intracellularly or extracellularly?
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- extracellular
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MOA of viral infection?
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- Infect nucleated cells -> redirect macromolecular synthesis -> disrupt normal cellular functions -> some viruses are “lytic”
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How does the immune system respond to viruses (2)?
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- Block/prevent infection
- Eliminate infected cells |
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How does innate immunity inhibition of infection by viruses?
How does innate immunity kill virus infected cells? |
- by type I interferons
- by NK cells |
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What are the type I interferons?
What are type I interferons produced by? When are type I interferons produced? |
- IFN alpha and beta
- virus-infected cells - when double-stranded RNA (PAMP) binds to a pattern recognition receptor (TLR3) |
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What is another name for IFN-a?
What is another name for IFN-b? |
– mononuclear phagocytes “leukocyte interferon”
– “fibroblast interferon” |
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What are the three actions done by type I interferons?
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- induction of enzymes that block viral replication
- increased expression of class I MHC on infected cells, killing by CTLs - activate NK cells to kill virus-infected cells |
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MOA of interaction of NK cell with virus-infected cells?
How do NK cells know if a cell is healthy? |
-virus infected cell loses MHC class I -> activating receptor on NK cell binds to ligand on infected cell -> kills cell
- Inhibitory receptor on NK cell recognize MHC class I on healthy cell |
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What products secreted by NK cells kill virus-infected cells?
MOA? |
- perforin and granzymes
- granzymes enter through perforin holes -> activation of caspases |
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MOA of viral protein presentation to CD8+ T cells by MHC class I?
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- virus infects cell -> viral ptns synthesized in cytosol -> peptide fragments of viral ptns bound by MHC class I in ER -> bound peptides transported by MHC class I to cell surface
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What are the two signals involved in CTL development when bound to virus-infected cell?
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- Signal 1: MHC class I/peptide (on cell) → TCR
- Signal 2: B7 (on cell) → CD28 |
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MOA of CTL development when bound to virus infected cell?
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- stimulation of naïve T cell -> proliferation of T cell by IL-2 -> active effector T cells kill virus-infected target cells
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How does CD4+ T cell help for CTL development?
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- IL-2 produced by CD4+ T cells stimulates proliferation and differentiation of CTLs -> CD40 – CD40L interactions increase expression of costimulators on APC
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How do FasL play a role in killing of virus-infected cells by CTLs?
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- FasL on CTL interacts with Fas on target cell -> apoptosis
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MOA of killing of virus-infected cells by CTLs?
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- CTL recognizes and binds virus-infected cell -> CTL programs target for death, inducing DNA fragmentation -> CTL migrates to new target -> target cell dies by apoptosis
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MOA of inhibition of viral infection by B cells and neutralizing antibodies?
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- virus binds to receptor on cell surface -> receptor-mediated endocytosis of virus -> acidfication of endosome -> triggers fusion of virus with cell and entry of viral DNA -> Ab blocks binding to virus receptor
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What types of Ab are used to neutralize antibodies block virus binding and entry into host cells?
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- IgG and IgA mostly
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What is the order in which the immune response responds to viruses?
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- production of IFN-alpha, IFN-beta, TNF-alpha and IL-12 -> NK cell mediated killing of infected cells -> T cell mediated killing of infected
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Which viruses evade the immune system by inhibition of proteasomal activity?
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- EBV, CMV
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Which viruses evade the immune system by blocking in MHC synthesis and/or ER retention?
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- adenovirus, CMV
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Which viruses evade the immune system by blocking TAP transport (entry into ER)?
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- HSV
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Which viruses evade the immune system by removal of class I from ER?
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- CMV
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Which viruses evade the immune system by interference with CTL recognition by decoy viral class I-like molecules?
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- CMV
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Principle mechanism of elimination of intracellular bacteria?
Effector functions principally performed by? |
- engulfment and destruction by phagocytes
- cells of the innate and adaptive immune system |
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MOA of phagocytosis of intracellular bacteria?
What are the two ways phagocytosed microbes are killed? |
- microbes bind to phagocyte receptor (mannose R) -> phagocyte membrane zips up around microbe -> microbe ingested in phagosome -> fusion of phagosome with lysosome
- activation of phagocyte -> killing of microbes by lysosomal enzymes in phagolysosome OR killing of phagocytosed microbes by ROIs and NO |
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When microbes bind to toll-like receptors or mannose receptors, what types of cytokines are produced in innate immunity?
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- inc of IL-12 and dec of IFN-gamma
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What is the source for IFN-gamma?
MOA? |
- NK cells
- macrophage with phagocytosed microbes -> macrophage secretes IL-12 -> IL-12 causes NK cells to secrete IFN-gamma -> killing of phagocytosed microbes |
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What are the two primary functions of NK cells?
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- killing of infected cells and killing of phagocytosed microbes
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Intracellular bacterial peptides are recognized by?
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- CD4+ T cell
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MOA of development of TH1 responses to intracellular bacteria?
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- APC with ingested microbes -> stimulate IL-12 secretion ->bind to naïve CD4+ T cell -> Th1 differentiation -> secrete IFN-gamma (also IL-2 and TNF-beta) -> activate macrophages -> kill microbes
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MOA of inhibition of bacterial infection by neutralizing antibodies?
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- Abs against adhesins block colonization of human cell surfaces and uptake
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Where do extracellular bacteria replicate?
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- outside host cells (Tissue spaces between cells, Alimentary tract, Respiratory tract, Urogenital tract, Cardiovascular system, Skin)
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How does extracellular bacteria activate complement?
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- By binding and fragmenting C3 to C3a and b
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How does complement stimulate inflammatory rxns?
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- binding of C3b to microbe -> release of C3a -> proteolysis of C5 -> release of C5a -> recruitment and activation of leukocytes by C5a and C3a -> destruction of microbes by leukocytes
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How does complement get involved in complement-mediated cytolysis?
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- binding of C3b to microbe -> activation of late components of complement -> formation of MAC -> osmotic lysis of microbe
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How does complement allow opsonization and phagocytosis?
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- binding of C3b (or C4b) to microbe (opsonization) -> recognition of bound C3b by phagocyte C3b R -> phagocytosis of microbe
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What are the receptors on neutrophils that are specific for bacterial LPS and hence phagocytosis?
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- CD14 and CR4
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What are the cytokines ecreted by macrophages?
What is function in liver? hypothalamus? Where is the func same as hypothalamus? bone-marrow endothelium? dendritic cells? |
- IL-1/IL-6/TNF-alpha
- acute-phase ptns (CRP, mannose-binding ptn) -> activation of complement and opsonization in - inc body temp (endogenous pyrogens) -> dec viral and bacterial replication, inc antigen processing, facilitates adaptive immune response - ptn and energy mobilized from muscle and fat - neutrophil mobilization -> phagocytosis - TNF-alpha stimulates migration to lymph nodes and maturation -> initiation of adaptive immune response |
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MOA of the effect of TNF-alpha in local infection with gram neg bacteria?
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- Macrophages activated to secrete TNF-alpha in tissue -> inc release of plasma ptns into tissue -> inc phagocyte and lymphocyte migration into tissue -> inc platelet adhesion to blood vessel wall -> phagocytosis of bacteria -> local vesel occlusion -> containment of infection -> antigens drain or are carried to local lymph node -> survival du to stimulation of adaptive immune response
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MOA of effect of TNF-alpha in systemic infection with gram neg bacteria?
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- Macrophages activated in liver and spleen secrete TNF-alpha in bloodstream -> systemic edema causes dec BV, hypoproteinemia, and neutropenia -> neutrophilia -> dec BV caues collapse of vessels -> DIC -> wasting and multiple organ failure = septic shock -> death
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MOA of Ab-mediated opsonization of extracellular bacteria?
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- opsonization of microbe by IgG -> binding of opsonized microbes to phagocyte Fc R (Fc(gamma)RI) -> Fc receptor signals activate phagocyte -> phagocytosis of microbe -> killing of ingested microbe
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What Abs are most involved in opsonization?
in complement activation? |
- IgG
- IgM and IgG |
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What are the types of adaptive immunity responses to helminths?
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- Th2 response
- ADCC (eosinophils and IgE) |
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What cytokines are secreted by Th2?
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- IL-4, IL-5, IL-10
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MOA of effector functions of TH2 cells?
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- IL-4 -> production of neutralizing IgG antibodies and production of IgE -> mast cell degranulation
- IL-10, IL-4 -> suppression of macrophage activation - IL-5 -> eosinophil activation |
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MOA of Antibody-dependent cellular cytotoxicity (ADCC) on helminths?
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- IgE binds helminth -> eosinophil has high affinity Fc(epsilon)RI that binds to IgE -> secretes granule -> kills helminth
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How is the transformation occuring from resting mast cell to activated mast cell?
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- Resting mast cell contains granules containing histamine and other inflammatory mediators -> multivalent antigen cross-links bound IgE Ab -> release of granule contents
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Effect of mast cell and basophil granules?
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- inc vascular permeability - recruit other cells
- Increase lymph flow to LN - Trigger muscular contractions (gut, respiratory tract) |
