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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 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.