Anti-viral Immunity

Distinct features of viruses Viruses are intracellular pathogens

Viruses cause changes in infected cells. Infected cells bear stress signals. These

changes and signals render these cells targets for the immune effector cells.

Viruses may infect spme mononüclear phagocytes and/or lymphocytes and replicate within these cells.

Viruses possess cytopathic effects and may lead lysis of infected cells

Viruses interfere with the cellular fuctions and protein synthesis machinary

Components of host defense Natural barriers Innate immunity Acquired immunity

The first two components are usually not fully effective in eliminating of viral agents. Their main functions are:- To constrain the replication and the spread of the viruses at the entry-site- To stimulate the activation and maturation of the the effector cells of specific (acquired) immune response- To warn the non-infected cells against the invading viral agent

Doğal bariyerler

Fever: IL-1, TNF and IFN’s elevate the body temperature and hinder viral replication

Age of the host: Maternal antibodies The maturity of the target host-

cells Senescence of the immune

system Severe infections in advanced age

Nutritional status: Malnutrition is ascociated more severe infections Measles

Hormonal status: Corticosteroids execerbate certain viral infections; severe infections during the pregnancy

Genetic factors: MHC, CCR5 del32, IL-28B polymorphism

Resistance at species level: Presence of the appropriate receptors

Most of KIRs recognise HLA-C

Modulators on the virion surface

Various host-derived proteins may be embedded in the envelope of the viruses. These may be immunoregulators, CD-family receptors, complement inhibitors, signaling ligands, adhesion molecules

Viral modulators secreted at the infected cell surface

Superantigenes Immune cell ligands, receptor

mimicks, CD homologs, Complement inhibitors Herpes viruses encode altered G

protein coupled chemokine receptors

Antigenic variation

> ın RNA viruses; due to error prone RNA polymerases

Also DNA viruses shpw antigenic variations

Subversion of the phagocytosis Blocking type 1 interferons accompanied

be the repression of inducible nitric asit synthase.

In contrast some viruses induce the iNOS augmentation of the inflammation spread

Somer viruses (HSV) express surface proteins mimickin CD200, which delivers inhibitory activities on the macrophages.

Subversion of the TLRs TLR Activation of NFkappaB, IRF3 TLR2 and 4 recognise virion particles TLR 3, 7, 8, 9 detect viral nucleic acids

(intracellular) The roles of TLRs differ accroding to:

entry route, tropims and replication properties of the virus

Some viruses (hepatitis A,C, poxviruses) interrupt these pathways.

Inhibiton of the Complement Complement inhibitors may be virus or host derived Assembling of C3 convertase is critical in all of three

pathways Some viruses (HCMV) induce the expression of

cellular Complement inhibitors like DAF, MCP Some viruses incorporate complement inhibitors into

the viruses (HIV, HTLV). Glycoprotein C-1 of HSV (binding to heperan sulfate)

inhibits C3 b GP1-anchored vCD59 homolog of HSV blocks MAC

formation Kaposica protein of KSHV inhibits both classical and

alternative patways

Inhibition of the cytokines and chemokines

The main targets IFN, TNF and IL-1 Numerous anti-cytokine activity: Virus derived chemokie mimics can interact

with the host chemokine receptors There two grops: Type1: Low affinity to

glycoseminoglyca binding domain of chemokine receptors; Type 2: High affinity

Inhibition of the atraction of the immune cells to the infection site

Blocking cellular immunity Anti-NK strategies: expressions of MHC

homologs, modulation of MHC expression, blocking NK-activationg cytokines (type I IFN), antagonism of NK-receptors, inhibition of effector pathways of NK cells

In contrast for the modulation of cell mediated immunity: inhibition of MHC-1 restricted ag presentation; CD4 cells?

Viruses alter the differentiation and signall,ng pathways of DCs ; Virus derived proteins modulate directly the effector functions of DCs.

Manipulation of the cell death

Cross presentation of viral antigens through the phagocytosis of virus infected apoptotic cells is critical

Viruses developed different strategies based on their biological properties.