Imm Resp To Viral Infect

Question 1

Order of imm resp

Answer 1

Once barriers have been broke
Initial d is IFN macro and NK cells operating within first few hrs incr in intensity over 2-3 d. to hold the virus, checking dissem before adaptive im. Resp med by Ab and T cells kicks in cytotox T cells first around 4d in lymphoid tissues and migrate to infection sites, Ab appears around day 7 and remains elevated for months pr yrs dep on virus

Question 2

IFN

Answer 2

Produced by infected cells
Released and react with inifevted cells to render them res to viral infection
All have antiviral activity but also have antitumour act, able to act macro and NK cells and upreg MHC c1&2 and induce apoptosis
There is alpha beta and gamma.

Question 3

Ifn gamma

Answer 3

Gamma not strictly prod by viralninfection but by lymphocytes after act by antig so its really a lymphokine reg prod by NK cells and T cells, mainly immunoreg but also has an antiviral activity
1 gene

Question 4

Ifn alpha

Answer 4

Prod by leukocytes esp macro and epi cells during viral infection
At least 12 genes

Question 5

Ifn beta

Answer 5

Prod by virally infect fibroblasts and epi cells

1 gene

Question 6

Ifn induction

Answer 6

Alpha and beta not constitutively prod but induced by most viruses when they repl. RNA virus esp good IFn inducers, most dna are poor. Exhibit host spec but jot viral spec
dsRNA is pamp recog by TLRs
Gamma induction doesnt involve dsRNA
Pamp-prr - signal transduction cascade involving NF-kB - IFN B gene expre

Question 7

IFn mech of action

Answer 7

Secr from cells and bind spec cell surf rec on adjacent cells triggering cascade of events resulting in induction of many cellular genes
Induction of spec anti-viral molecules, and other imm resp to virus important genes eg MHC c1
Anti viral properties of alpha and beta med by induction of 3 enz: 2-5 An synthetase, RNase L and PKR

Question 8

2-5 An synthetase

Answer 8

Catalyse ATP conversion into polyribonucleic acid comp only of A (2-5 oligomers)
Induced by IFN and act only in dsRNA presence
Oligomers activates endonuclease RNase L
2-5A synthetase bind viral dsRNA repl complexes causing localised pro of 2-5oligomers which are metabolically unstable

Question 9

RNase L

Answer 9

Cleaves RNA
Act in localised manner by metabollically unstable oligomers made of viral RNA
So viral RNA preferentially cleaved

Question 10

PKR

Answer 10

Pro only act in dsRNA presence
Preferentialky phosphorylates itself and the alpha subunit of pro synth initiation factor inactivating the subunit so inhibiting pro synth
Similar localised act to RNase. Cause localised act of eIF-2alpha in pref inhib of viral pro synth

Question 11

IFN effectiveness dep on

Answer 11

Types and mix of IFN differ at diff infection stages. kinetics of prod very by cell type
Diff IFN can act as synergists and spec antiviral Ab can help by red viral load

Question 12

Interference with IFn

Answer 12

Viruses can prod pros that inhib IFn induced enz eg reovirus has pro tgat binds dsRNA so it cant act enz and vaccinia virus PKR homologues disrupt PKR fx
Or can inhib IFN - IFN rec interaction eg vaccinia virus prod soluble IFN rec thag competes

Question 13

IFN med defence process

Answer 13

Pamp recog by prr
Signal transduction
IFN B prod
Autocrine and paracrine fx
Stim IFN responsive genes to prod IFn alpha that binds IfN B rec and amplify antipathogen effectors in infected and non infected cells which down reg viral repl

Question 14

Macro fx

Answer 14

Active in restrict virus infection
Major prod of IFN alpha, TNF alpha (cytokine active in triggering apoptosis), IL 12 (NK activator) and restrict virus spread by phagocytosis and IC killing or killing via ADCC

Question 15

NK cell act and fx

Answer 15

Act within hrs of infect and peak at 2-3d
Act by IL2 and 12 and IFN alpha and beta
Prod IFN gamma so can connect innate d as alpha and beta trigger NK which prod gamma that act macros
Recog cells with red MHCc1 expr as this inhibits Nk act. Also recog IgG Ab via IgGFc rec and kill via Ab dep cell cytotoxicity
Particularly active against herpes

Question 16

T cell response

Answer 16

After appropriate antig prssentation to CD4 and CD8 t cells in lymphoid tissue

Question 17

CD4 T cells

Answer 17

Promote b cell expansion and gen antiviral Ab resp

Question 18

CD8 t cells

Answer 18

Undergo clonal expansion and migrate to infected tissues they recog virus infect cells by MhC c1 and kill by direct cell killing or release of antiviral cytokines eg IfN gamma

Question 19

Viral methods of t cell evasion

Answer 19

Failure of proteosome proteolysis of some virus pros
Block peptide transport from cytosol to endoplasmic reticulum
Block MHC c1 migration to cell surf

Question 20

Ab methods of blocking or neutralising infectivity

Answer 20

Block attachment to cell rec
Block fusion and entry
Block viral uncoating
Some methods augmented by complement act - can bind virions or infect cells directly causing lysis of virion envelope

Question 21

Complement methods of viral destruction

Answer 21

Ab dep complement med lysis (req large amount of viral antigen to be effective)
Ab dep cell mes cytotoxicity (ADCC) - v efficient req little bound Ab to cause lysis

Question 22

Viral interference with Ab and complement

Answer 22

Herpes and pox interfere with complement induction

Some RNA virus evade Ab by antigen variation