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5: Immunity to Viruses
yes it is the second number five
62
Veterinary Medicine
Professional
02/05/2016

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Term
What is the most difficult barrier in the body to penetrate? Why?
Definition
-skin
-cells on the surface are dead and thus do not allow for viral replication
Term
The majority of viral infections occur through contact with what?
Definition
-mucosal surfaces
Term
How do respiratory epithelial cells fight viral infection?
Definition
-covered in a blanket of mucus for trapping pathogens and moving it towards opening
Term
How does the digestive tract fight pathogens?
Definition
-digestive enzymes, acidic pH of stomach, and emulsifying properties of bile all delp
Term
What are the 2 most important components of the innate immune system to fight infections?
Definition
-interfeons: IFN-alpha and IFN-beta
-natural killer cells
Term
Unlike the adaptive immune response, the innate immune response is (non-specific/specific) in that it recognizes (all/some) viruses.
Definition
-non-specifc
-all
Term
What is the most important arm of the inante resistance to viruses?
Definition
-IFNs
Term
What produces IFN-alpha and IFN-beta?
Definition
-viral infected cells
Term
What produces IFN-gamma?
Definition
-activated NK cells and Th cells
Term
IFN-alpha and IFN-beta are produced in what two situations?
Definition
-infected cells which detect components of viral infection within them
-cells of the innate immune system which detect presence of the virus via tool-like receptors
Term
What do macrophages and dendritic cells recognize as PAMP molecues in the IFN system?
Definition
-dsRNA and ssRNA
Term
Where are TLRs situated?
Definition
-internally on endosomes and bind to PAMP molecules after phagocytosis
Term
What happens after TLRs are activated?
Definition
-they phosphorylate Nuclear Factors that initiate the transcription of mRNAs that thranslate IFN-alpha, IFN-beta, TNF-alpha, IL-12, and IFN-gamma
Term
dsRNA also causes macrophages, dendritic cells, and lymphocytes to maufacture ______ that are multiprotein oligomers which includes Caspase 1. What do they do?
Definition
-inflammasomes
-promote inflammation by promoting the maturation of inflammatory cytokines
Term
True or FAlse: IFN-alpha and IFN-beta are active in the induced cell.
Definition
-FALSE, they are not anctive in the induced cell, the are transported out
Term
What happens to IFN-alpha and IFN-beta after they leave the induced cell? What is the purpose of this?
Definition
-they bind to surface receptors of non-infected host cells and induce the production on antiviral proteins
-it is these antiviral proteins that cause the cells to resist a viral infection
Term
The antiviral proteins induced by IFNs consist of three enzymes. What are they?
Definition
-2-5(A) synthetase
-protein kinase (PK-1)
-RNase L enzyme
Term
The antiviral protein enzymes are present in the cytoplasm in an (active/inactive) form. How are they activated?
Definition
-inactive
-they are activated only when viral dsRNA is detected if the cell is infected by a virus
Term
What does 2-5(A) synthetase do? What does that do?
Definition
-sytnesizes 2-5(A)
-activates RNaseL which chews up viral mRNAs
Term
What does protein kinasee (PK-1) do? What does this do?
Definition
-phosphorylates the translation initiating factors (eIF-2) which binds to viral mRNA
-prevents viral protein translation
Term
Are IFN-alpha and IFN-beta directly or indirectly antiviral?
Definition
-indirectly
Term
Are IFNs broad or narrow spectrum? Potent or no?
Definition
-narrow
-potent
Term
In general, how do IFNs work?
Definition
-induce cellular antiviral enzymes in non-infected cells that become activated ONLY BY VIRAL dsRNA
-destroys the virus through activated enzymes that digest viral RNA and prevent viral protein synthesis
Term
NK cells are large granular __(type of cell)__ that exhibit spontaneous ______ against ______. They make up ___% of the circulating leukocytes.
Definition
-lymphocytes
-vytotoxicity
-viral infected cells
-10%
Term
Do NK cells need to be sensitized to a particular virus before they attack and kill the viral-infected cell?
Definition
-NO, they have the potential to recognize and kill all viral infected cells
Term
What are the three important NK cell receptors that play a role in viral immune response? What do they do?
Definition
1)m Natural Cytotoxic Receptors (NCR): recognize and bind to peplomers on viral infected cells
2) Inhibitory MHC-I receptors: recognize MHC-1 naturally present on all host cells
3) Fc receptors: bind to Fc portion of Ab that have attached to peplomers on viral infected cells
Term
Which of the 3 receptors on NK cells is the dominant receptor? How is it activated and what does it do?
Definition
-MHC-1 Rc
-activated by the presence of normal MHC-1 molecules on cells
-prevent the NRC from activating the NK cell
Term
How do MHC-I and NCRs work together?
Definition
-if NCRs are activated by viral infected cells that do not display MHC-I, the NK cell will kill the cell
-if the NCR binds to a cell that does display MHC-I, it will stop the activation of NK cell thus sparing the cell
Term
How do NK cells kill viral infected cells?
Definition
-secrete perforin and inject granzymes to activate the apoptosis cascade
Term
What is Antibody Dependent Cell Cytotoxicity (ADCC)?
Definition
-when an NK cell bind to Fc receptors of any Ab that is bound to viral infected cells thus inducing the perforin/gransyme pathway
Term
Other than cell binding, what else can activate NK cells?
Definition
-IFN-alpha, IFN-beta, TNF-alpha, IL-12, macrophages, dendritic cells
Term
What other function do activated NK cells serve in addition to killing viral infected cells?
Definition
-secrete IFN-gamma to help recruit immune cells to the area of infection
Term
The level of IFN increases and peaks at __-__ days post-infection when viral replication is at its peak.
Definition
3-5
Term
The NK cell activity is detected early during infection and peaks at about __ days.
Definition
3
Term
The adaptive immune response is not usually detected before __-__ days after virus inofulation in an acute viral infection. Its appearance coincides with what?
Definition
-7-10
-decrease in virus excretionor replication
Term
Which immunoglobulin is important in primary response to viral infection but quickly drops off? What does it do?
Definition
-IgM
-activates complement and is important in opsonization, neutralization, and agglutination of virus particles
Term
What does the presence of serum IgM indicate?
Definition
-that the animal is undergoing an acute active infection with a virus
Term
Describe the functions of IgG. How long does it persist in the body?
Definition
-enters tissue spaces during inflammation and escapes into damaged mucosal surfaces
-opsonize, agglutinate, and neutralize
-last for a very long time in the body
Term
What is the function of IgA? What makes it well-suited to its job?
Definition
-secretory Ab that protects mucosal sufaces
-trypsin resistant
Term
Describe the structure of IgA.
Definition
-dimers with J-chain and secretory piece
Term
What does IgA do to viruses?
Definition
-agglutinates and neutralizes them, preventing viral adherence
-important in lactogenic immunity
Term
Definition: Seronegative
Definition
-the animal has no circulating antibodies to a particular virus
Term
Definition: Seropositive
Definition
-the animal has circulating Abs to a particular virus
Term
What is the term used to describe when an animal changes form seronegative to seropositive?
Definition
-seroconverted
Term
What are the 4 methods by which antibodies prevent viral infection?
Definition
-neutralization
-lysis of virus
-aid in phagocytosis
-caus lysis of host cells
Term
Definition: Neutralization
Definition
-Ab binds to epitopes on the virion surface and prvents viral attachment ot the cells
-also cause conformatioal changes in capsid and agglutination of virus particles
Term
What happens during Ab lysis of viruses?
Definition
-Ab bound to virus particle (enveloped virus) activates the complement cascade, whch results in viral lysis
Term
How do Abs aid in phagocytosis?
Definition
-Abs arm macrophages or opsonize viral particles or viral-infected cells
-the Fc receptors on the macrophages bin to the Abs and initiate phagocytosis
-can also activate the complement system
Term
How do Ab's cause lysis of the host cell?
Definition
-Abs bind to virrus infected cells and cell becomes lysed bo complement or ADCC involving lymphocytes (NK cells and CTLs), neutrophils, or macrophages
Term
Why does lysis of host cell work to stop viral infections? Doesn't it just release the virus to infect another cell?
Definition
-cells are lysed before virus particles are released by the infected cell (before they have actually made anything) thus preventing virus spread
Term
How is Cell mediated immunity (CMI) regulated?
Definition
-through T-cells via secretion of cytokines
Term
True or False: Severe malnutrition can affect CMI response and enhances severity of diseases
Definition
-TRUE
Term
Cytotoxic T lymphocytes (CTL) are detcted __-__ days following viral infection.
Definition
4-10
Term
CTLs respond to (endogenous/exogenous) antigens.
Definition
-endogenous
Term
What do CTLs recognize on viral infected cells and how does it get there?
Definition
-recognize cognate peptide:MHC molecule
-during virus replication, small biral peptides are formed which bind to the groove on the MHC_I molecules and are transported to the cell surface to flag down said CTL
Term
What do CTLs do once they are activated?
Definition
-lyse any viral infected cell
Term
T-helper cells produce ______ that activate ______. What does this cause?
Definition
-cytokines
-B-cells and T-cells
-causes proliferation of said cells those receptors have recognized and bound to specific viral antigens
Term
What are Th1 cells primarily responsible for? What about Th2?
Definition
-stimulating cell-mediated immune responses
-stimulating a humoral immune response to viruses
Term
What must happen for memory T-cells to be stimulated?
Definition
-virus must replicate so that the Ag can be presented to the MHC-I and MHC-II molecules
Term
-True or False: In a sensitized animal, antibodies are important in diminishing the virus load thereby reducing the number of cells the virus can infect.
Definition
-true
Term
What do T-cells do in an effort to minize virus relase and ease the load on the antibodies?
Definition
-recognize and eradicate the infected cells before the virus has a chance to mature
Term
Is cell-mediated or humoral immune response important in eliminating virus during viral infection? What about in preventing viral infection?
Definition
-cell-mediated = elimination during infection
-humoral = prevention of infection
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