L9 Immunity against infection (viruses and parasites)

what MHC molecule would be present in a processed peptide from extracellular microorganisms

MHC II APCs

define a virus

obligate intracellular parasite, but may also be extracellular at some stage in infection

what are innate defences of viruses

• interferons

• natural killer cells

what is induced in virus infected cells as an early response to infection

synthesis of IFNalpha and IFNgamma (type I)

describe type II interferons in viruses

IFNgamma secreted by activated T cells and by NK cells

• inhibits TH2 response (antibodies) and promotes TH1 (cell killing)

• recruits macrophages

what can rIFNalpha be used to treat

hepatitus B and C

describe therapeutic use of interferons

• some cancers

• side effects can be severe

what are type of lymphoid cell are natural killer cells

innate

what type of lymphocyte are natural killer cells

large granular

what do natural killer cells recognise

structures on viral infected cells

• can recognise stress cells in absence of Igs and MHC

how do natural killer cells kill

by extracellular mechanism-perforin and granzyme

what do NK cell receptors need to distinguish between

infected and uninfected host cells which otherwise would be a disaster

what do activating NK receptors recognise

carbohydrate ligands, triggers killing

what do inhibitory NK receptors recognise

MHC class I molecules

• (no binding, only TCRs can do this)

viruses that reduce MHC expression make cells…

more susceptible to NK killing

describe NK killing occuring

• missing or absent MHC class I cannot stimulate a negative signal

• the NK cell is triggered by signals from activating receptors

• activated NK cell releases granule contents, inducing apoptosis in the target cell

what are cytotoxic T cells (CTL)(CD8+)

recognise viral peptide and MHC class I

give an example of cytokines with anti-viral activity

IFNgamma

• class II helps activate macrophages

what are the 2 mechanisms of killing by cytotoxic T cells

• secretion of cytotoxic granules

• fas ligand on T cell interacts with Fas on target

describe the secretion of toxic granules

• perforin, polymerises in membrane

• granzymes (proteases) enter cell

describe how CTLs (cytotoxic T cells) work

• CTL recognises and binds virus-infected cell

• CTL programs target for death, inducing DNA fragmentation

• CTL migrates to new target

• Target cell dies by apoptosis

no release of virus, no inflammation

what happens wen CTLs secrete IFNgamma

• inhibits viral replication

• upregulates MHC class I and II expression and antigen presentation

• increases macrophage phagocytosis of death cells

• promotes NK cell killing activity