Host Response to Viral Infection Flashcards
Physical barriers are part of which type of immunity?
innate
Which cells produce the mucociliary blanket and what does it do?
goblet cells; innate physical defense that traps larger particles so they can be swallowed or coughed out
What 2 things do cytoplasmic granules of NK cells contain?
perforin: produce pores in plasma membranes
granzymes: initiate apoptosis
What activates NK cells?
in virus infected cells, MHC I expression reduced so inhibitory receptors aren’t engaged and ligands for activating receptors are expressed
PAMPs
macromolecules present in viruses and other microbes but not host cells -> recognized by PRRs
PRR
expressed on a variety of cells including macs, DC, neutrophils, NK cells, endothelial cells, mucosal epithelial cells
Binding of PAMP to a TLR on a macrophage results in what?
phagocytosis
chemotaxis
inflammatory mediators
IFN
Which important interleukins are relased when PRRs are ligated by PAMPs?
IL1 and IL12
Do interferons show virus specificity?
NAH
T/F RNA viruses are stronger inducers of IFN than DNAviruses
troooo
How should interferons be administered to a patient?
parenteral route (injection) since they are orally inactive
Type 1 IFN
IFN a
IFN B
IFN a
leukocyte interferon
- produced in large quantities by plasmacytoid DC
- produced in smaller amounts by macs, monocytes and lymphocytes
- not host specific
IFN B
- fibroblast interferon secreted by virus-infected fibroblast
- generally host species specific
roles of type 1 IFNs
- inhibit virus replication
- activate NK cells
- increase MHC I expression
- stimulate differentiation of monocytes into DC
- maturation of DC
- stimulates memory T cell proliferation
How do Type I IFNs inhibit virus replication?
- activate RNAse L -> degrades viral RNA
- induce synthesis of MX proteins that bind and trap viral nucleocapsid and inhibit virus assembly
- induce synthesis of PKR which prevents initiation of translation of viral RNA
Type II IFN
- IFN gamma
- mostly immunoregulatory
- produced by antigen-stimulated T cells and NK cells
- labile at pH 2
- host specific
functions of IFN gamma
- increased MHC expression
- mac activation
- TH1 effector cells
- isotype switching to opsonizing and complement-fixing antibodies
Type III IFN
- IFN lambda1, IFN lambda2, IFN lambda3
- expressed in response to viral infections and activation of TLR
- mainly immunoregulator
- recently discovered
gene silencing
RNAi-endonuclease complex binds to mRNA complementary to RNAi and chops off viral mRNA into small pieces
*can disrupt viral replication
granulocytosis
presence in peripheral blood of an increased # of granulocytes (neutrophils, eosinophils, basophils, mast cells)
*usually not provoked by viral infections
T/F antibodies may be directed against viral proteins on free virions (capsid or envelope) or against viral proteins expressed on surface of infected cells
T
virus neutralization
neutralizing antibodies prevent virus attachment and entry into host cells; bind to viral capsid or host envelope
opsonization
coating of virions with antibodies so its more easily recognized and phagocytosed by macs and sometimes neutrophils
IC formation
clumping of viruses; reduced # of viral particles available for cell invasion
chemotaxis
attracting macs and neutrophils
lysis
rupturing membranes of foreign cells/pathogens
agglutination
clustering and binding of pathogens together
ADCC
- antibodies bind antigens on target cells
- NK cell CD16 Fc receptors recognize cell-bound antibodies
- cross-linking of CD16 triggers degranulation into lytic synapse
- infected cells die by apoptosis
antigenic plasticity
rapid changes in structure of viral antigen that may be the result of mutation, reassortment or recombination -> virus may become resistant to immunity generated by previous infection
antigenic multiplicity
antigenic variants with little or no cross-reactivity -> immunity against one serotype may not work against other variants
negative cytokine regulation
- blocking IFN receptor signal
- virokines
- viroreceptors
virokines
some viruses synthesize proteins which are homologs of cytokines
e.g. E-B has vIL10 which suppresses cytokine production by TH1 CD4 cells
viroreceptors
some viruses encode proteins that are homologous to receptors for cytokines; secreted cytokine receptor homologs bind to cytokines and serve as competitive agonist (poxviruses)
down-regulation of MHC I pathway
interfere with expression of MHC I molecules and inhibit antigen presentation
*form of evasion
inhibition of complement activation
- vaccinia virus has VAP which binds C4b to inhibit classical complement pathway
- glycoprotein of herpes simplex virus binds C3b inhibiting both classical and alternative complement pathways
evasion of neutralizing antibodies
- soluble proteinsthat soak up antibody
- variation in viral antigens
- antibodies incapable of neutralization (caprine arthritis-encephalitis of goats)
- slow production of antibodies compared to fast infection of cells by virus
latency
- transcription of viral genes that encode antigenic proteins are blocked
- integration of viral genome in host cell genome (retroviruses)
cell-to-cell spread
not exposed to host immune mediators
inhibition of apoptosis
poxvirus and herpesvirus produce caspase inhibitors that protect infected cells against death and allow completion of viral replication
