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73 Cards in this Set
- Front
- Back
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What are the reasons for increased mortality to a pathogen?
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-Urban growth and exploitation of the world
-Destruction of natural habitat or carrier species -Ecological changes -Population growth -Moving and mixing of ppl's -Speed of transportation of disease carriers -Excessive use of antibiotics -Overuse of insecticides -Stress in the workplace -Lack of vaccination -Reliance on unproved remedies -False sense of security -Iatrogenic factors |
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How does Urban growth and exploitation increase mortality to a pathogen?
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Causes increased contact of susceptible hosts with rural reservoirs (virus/vectors)
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How does destruction of the natural habitat of carrier species increase mortality to a pathogen?
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Causes migration to or contact with urban areas
ex: Peromyscys (mouse) carries Hanta virus into homes and cottages |
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How do ecological changes increase mortality to a pathogen?
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Ecological changes in env't due to irrigation, deforestation and global warming may favor the survival of vectors and encourage the spread of pathogens into urban env't
ex: Japanese tiger mosquito can carry yellow fever and live in cooler climates |
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How does population growth/change to high density urban demographics increase mortality to a pathogen?
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Increases the need for a wider range of food sources to feed the susceptible host population and increased risk of exposure
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How does the moving and mixing of ppl increase mortality to a pathogen?
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Promotes disease spread from one gp to another during holidays, conferences....
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How does the speed of transportation of disease carriers increase mortality to a pathogen?
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Introduces pathogens to susceptible populations outside of endemic areas where herd immunity may commonly protect indigenous ppls vs acute diseases
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How does excessive use of antibiotics increase mortality to a pathogen?
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Selects more resistant and maybe more virulent variants of existing pathogens
Antibiotic resistant commensal organisms may allow susceptible pathogens to persist MDR plasmids (multi drug resistant) |
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How does the overuse of insecticides increase mortality to a pathogen?
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Get resistant disease vector species and the extermination of protective and beneficial species of insects
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How does stress in the workplace increase mortality to a pathogen?
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Ppl go to work even though they're sick
Stress can also reduce resistance |
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How does lack of vaccination increase mortality to a pathogen?
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Increased risk of disease for younger populations
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How does reliance on unproved remedies increase mortality to a pathogen?
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Not necessarily more effective
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How does a false sense of security increase mortality to a pathogen?
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Epidemic disease and prematur death from disease relatively rare in Western countries
--> ppl always think a vaccine can help them after they get a disease |
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What is an iatrogenic factor?
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Physician caused disease
->Can be due to inappropriate treatment, counteractive treatments or harmful treatments |
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What are some of the meds that do this and how?
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Anti-acid: reduce antibacterial action of stomach acidity (H+ pump inhibitors: inc C. difficile)
Antibiotics: reduce pop'l of commensals and pathogens can colonize instead. Also commensals that make nutritious factors are removed Analgesics:reduce IL-1 mediated fever .: inc microbial growth and inhibit blood clotting Immunosuppressive drugs: reduce effectivenes of host resistance Super bugs in hospitals can cause life threatening disease |
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Describe the immediate response to a viral pathogen.
(0-4 hours) |
Nonspecific
Innate No memory No specific T cells |
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For an immediate response, what are:
-the barrier fcts -response to virus-infected cells |
Barrier: skin, epithelial
Response to virus: NK cells |
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Describe the early response to a viral pathogen.
(4-96 hours) |
Nonspecific
Inducible No memory No specific T cells |
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For an early response, what are:
-the barrier fcts -response to virus-infected cells |
Barrier: Local inflammation and TNF-a
Response to virus infected cells: IFN-a/B, IL-12 activated NK cells |
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Describe the late response to a viral pathogen.
(after 96 hours) |
Specific
Inducible Memory Specific T cells |
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For a late response, what are:
-the barrier fcts -response to virus-infected |
Barrier: IgA Ab in luminal spaces, IgE Ab on mast cells, local inflammation
Response to virus infected cells: Tcyt, IFN-y |
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What are produced after infection (cytokines/cells involved)?
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1) Production on IFN-a/b, TNF-a. IL-12
2) NK-cell mediated killing of infected cells 3) T cell mediated killing of infected cells |
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What is the cell that kills virally infected cells?
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NK cells (not MHC restricted)
-->Kills cells if they don't express the right MHC I |
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What do cytolytic T cells require to kill infected cells?
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1) Ag presentation
2) MHC recognition 3) Co-stimulation 4) Cytokine production 5) Killing is Ag:MHC restricted *Viruses can block any step |
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What protects newborns in their first year from viremia?
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Passively transferred maternal IgG
Babies start making their own transient levels of IgG (but low) |
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What is recovery from influenza infection ass't with?
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Production of protective neutralizing Ab to influenza HA receptor
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What do protective Ab do?
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Neutralize viral receptors required for infection
-->The V:Ab complex is phagocytosed by Macs and degraded in the phagolysosome |
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What is the point of vaccination?
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Reduces immediate virus induced pathology and sequelae (delayed pathology)
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What type of immunity is required for recovery from viral diseases?
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Cell mediated immunity
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What are the different types of vaccines?
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Killed vaccines
Live attentuated vaccines |
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What are killed vacines?
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Induce primarily Ab-mediated immunity
-Stable and Safe (no risk) Can prevent viremia but not all infections -Ab alone don't cure latently infected/actively infected patients if the cells are infected -Passive Ab can prevent viremia but not all infections |
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What are live attenuated vaccines?
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Primarily induce cell-mediated immunity
--> They actively infect the cells of the host and activate Tc-cells (some risk of disease) CMI cures infections by killing infected cells -Immune memory prevents future infections -Passive transfer of CMI isn't safe or possible because of the possibility of Graft vs Host disease |
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How can viral pathogenicity be attenuated?
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Create live viral vaccines
Isolate virus from a patient Grow in human cultured cells Grow cultured virus in non-permissive monkey cells Virus mutated so it can grow well in the monkey cells .: Virus can't grow properly in human cells anymore and can be used as a vaccine |
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How do you attenuate specific virulence genes?
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Gene mutation
Gene deletion |
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What is a DNA vaccine?
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Use a plasmid containing viral genes
vDNA is transcribed and expressed as host cell ptns DNA vaccines safely induce host CMI to viral peptides |
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What are the general host determinants of cellular resistance?
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Cell permissiveness
Expression of cellular receptor or ligand for virus Cell prod'n of IFN Non-specific resistance genes Inflammatory response Fever induced by IL-1 Mac response to infection MHC ass't viral presentation B and T cell idiotype repertoire Passive/active immunity to virus Site/route of infection (tssue tropisms) Sex/hormonal differences Nutrition Age Pregnancy and lactaction Stress Dual/multiple infections Lifestyle |
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What are viruses?
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Infectious obligate intracellular parasites
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What kind of immunity is required to get rid of virally infected cells?
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Tc-cytotoxic
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What type of vaccine is more effective at inducing CMI?
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Live vaccines
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What kind of immunity do killed vaccines induce?
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Ab mediated immunity
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What does Ab-mediated immunity prevent?
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Systemic viral infection
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What is immune memory important for?
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Ensures that those who survive an infection have long term immunity
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What is passive maternal immunity important for?
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Reduces severity of common viral infections during the first year of life
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What are the innate defences?
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Humoral factors: Complement, Acute phase ptns, IFN
Cellular factors: Inflammatory leukocytes, Macs, NK cells |
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What is the principle behind the IFN mechanism?
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The first cell is permissive. It gets infected
Then it releases IFN which boosts NK activity, MHC expression and humoral immunity The second cell will not be permissive to the infection |
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What are the innate defenses and what do they use? (cytokine-wise)
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Complement: alternate path, C3b
Cytokines: IFN a/B Granulocytes: Phagocytosis Macrophages: phagocytocis, prod'n of monokines, IL-1/6/12/18, TNF-a NK cells: cytolysis, cytokines, IFN-y, IL-15, TNF-a Cellular suicide after infection (apoptosis) |
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What are the fcts of macs?
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Phagocytosis
Chemotaxis, migration to the site of infection Ag processing and presentation via MHC Expression of co-stimulatory ptns (B7) Prod'n of monokines, IL1, IL6 Also make IL12, IL18 and cytotoxins TNF-a, NO, O- --> Activation of all these requires IFN-y |
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What do NK cells recognize?
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Loss of MHC-I on cells
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What do normal NK cells express?
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NK-activating receptors (NKAR)
NK-inhibiting receptors (NKIR) that bind to cellular MHC-I Cytotoxic granules |
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What happens when the NKAR and NKIR are both activated?
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No killing
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What happens if there is no/low NKIR binding to MHC-I?
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Early killing of the virally infected cells
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What are some viral activities that promote cell replication and evasion of host innate defences?
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-Viral intercellular transmission: fusion ptns link adjacent cells
-Virus specific tissue tropism: infection via cell speciic receptors -Virus loses/changes/represses viral Ag expression: doesn't stimulate an immune response or evade existing IRs -Viral oncogenes transactivate host genes: Activates cell growth, synthesis of growth factors and metabolism, promoting viral replication Viral growth factors activate cell metabolism: activate cell growth and metabolism, make more virus -Virus redirects normal cell metabolism: suppresses normal specific cell fcts to divert all the cellular resources to viral replication -Viral alterations of inflammatory responses: evade innate effectors -Virus alterations of the immune response: evade/regulate the specific acquired host IR to the virus |
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What is the viral strategy to inhibit innate resistance and inflammation?
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Block the host Ab and complement defenses vs viral infection
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What are some specific mechanisms viruses use for this strategy?
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-Virally encoded Fc receptor
-Virally encoded complement receptor -Virally encoded complement ptn |
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What is the result of Virally encoded Fc receptor? ex?
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Blocks effector fcts of Ab bound to infected cells
ex: Herpes simplex Cytomegalovirus |
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What is the result of Virally encoded complement receptor? ex?
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Blocks complement mediated effector pathways
ex: Herpes simplex |
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What is the result of Virally encoded complement ptn? ex?
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Inhibits complement activation of infected cells
ex: Vaccinia |
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What is another viral strategy?
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Block host innate cellular defenses against viral infection
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What are the specific mechanism for this?
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-Virally encoded cytokine homologue (B-chemokine receptor): sensitizes infected cells to effects of B-chemokine
-Virally encoded soluble cytokine receptor (IL-1R homologue, TNF-R homo, IFN-yR homo): blocks effects of cytokines by inhibiting their interaction with host receptors -Viral inhibition of adhesion molecule experssion (LFA-3, ICAM-1): blocks adhesion of lymphocytes to infected cells -PRotection from NFkB activation by short sequences that mimic TLRs: Blocks inflammatory responses elicited by IL-1 or bacterial pathogens |
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What are virokines?
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FActors that activate host cells
Promote viral infection |
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What are viroceptors?
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Factors that bind ligands, activate cells and promote infection
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What are viromitigators?
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Factors that promote cell/viral survival in host cells and promote viral infection
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What do these virokines, viroceptors and viromitigators cause?
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Molecular mimicry/piracy
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What is the virus that is best at molecular mimicry?
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Pox viruses
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How do we know pox viruses are highly specific for their host species?
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Sequence of stolen genes for each poxvirus is the same
They show 60-80% homology to the genes of their respective host species |
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What are the basic ways in which viruses evade elimination?
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Virus hides from the host defense system
Virus may inactivate host defence cells Viruses inactivate cytokine signals Viruses block death of infected cells |
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Why do viruses hide from the host defence system?
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Inactive/latent virus doesn't provide signals/Ag expression to activate the innate or immune system (host is not infectious)
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How does a virus inactivate host defence cells?
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Active virus infects the cells of the host defence system blocking the activation of innate resistance and immunity
Impairs Ag processing, presentation, recognition and host cellular responses |
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Why do viruses inactivate cytokine signals?
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Viruses make inactive homologue competitors of cytokines or cytokine receptors blocking second signals for immunity and greatly reducing the activation and effectiveness of the innate host defences
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Why do viruses block the death of infected cells?
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Block killing of infected cells mediated by innate/immune effectors and their products
Use anti-apoptotic factors prevent apoptosis and promote viral replication |
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When is mac resistance ineffective?
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Virus infection can inactivate mac fct by repressing gene expression
Virus has chemokine binding ptns that block mac chemotaxis Virus expressses IFN-y binding ptns that block the priming of macs Viruses expresses tumournecrosis factor (TNF) binding ptns that block mac activation Virus infection block apoptosis that allow virus survival in macs |
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When are NK cells ineffective vs viruses?
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No NKAR or reduced NKAR (can't rec'z infected cells)
MHC expression not altered by virus infection and NKIR receptors for MHC suppress NK activation) Virus replaces endogenous MHC with viral homologue Virus expresses factors that suppress NK-cell activity/activation Infected cell becomes immortal, can't be killed due to the expression of anti-apoptoic factors |
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Conclusion
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• Innate and immune responses can eliminate
virally infected cells and cure the host. • Pathogenic viruses have evolved of adopted mechanisms of blocking host responses. • While antiviral drugs can treat viral infections viruses often mutate and evade elimination. • A healthy lifestyle that includes effective vaccination programs can prevent infection. |
