Immune Evasion 1 (Atu3)

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Evasion mechanisms

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antigenic variation

Immune hiding

Molecular mimicry
Host deletion

Immune skewing/subversion

Resistance to killing

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Antigenic variation

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Alteration of surface antigen

Bacterial serotypes

Phase variation of mycoplasma
Drift and shift in viruses

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HIV has a high mutation rate

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3nt mistakes per 100,000nts and rapid replication of 10^9 viruses per day

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T.brucei

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Trypanosomes constantly vary their surface glycoproteins via gene conversion

Upregulation of immune response leads to down regulation of parasitaemia

Express different epitopes
Cycles of low and high parasiteamia

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Similar cycling of bacteraemia in

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steptococci and gonococci

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Plasmodium falciparium varies antigen

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throughout the complex lifecycle

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Plasmodium exploit lack of MHC expression of

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RBC

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P.falciparium uses pFEMP1 to sequester erthrocytes to post venules capillaries,

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causes RBCs to adhere to the endothelium

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Anaplasma phagocytophilum

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resides in neutrophil intracellular vesicles

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TB resides in

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macrophage phagosomes

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Listeria monocytogenes

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escapes into the cytoplasm

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WASP proteins are involved in cytoskeleton rearrangements

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RickA od rickettsia is a mimic that lacks the same functionality

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Superantigen causes polyclonal T cells to activate and subsequent apoptosis

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staphylococcal enterotoxins

Superantigen cross-links MHC and TCR regardless of what is being presented

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Bacillus anthracis is a

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metalloprotease specific to MAPKK - apoptosis of macrophages and dysfunction of DC maturation

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HIV viral cytotoxicity kills the infected cell, and CD8 antiviral activity

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CD4 loss

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Measles virus-induced immunopathology

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DCs actively inhibit CD4 t cell proliferation via lack of CD40 or kill, TNF-related apoptosis inducing TRAIL

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Mycobacterium leprae skews the immune response to a TH2 type

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Lepromatous leprosy doesn't result in resolution

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Pathigen

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low stringency of pol, multiple offspring, rapid life cycle

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Host

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More complex response, larger genome many pathways and mediators as a population

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Stuggle for Fe2+

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Lactoferrin sequesters iron and IFN-gamma decreases tranferrin receptor- reducing iron for bacterium

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Bacteria have evolved siderophores

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and macrophages lipocalin

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MHC I recognition of virus infection

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alerts the CTLs to infection

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Viruses act to reduce MHC expression

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But NK cells recognise missing self

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MHC class I-like target the inhibitory receptor

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such as the MCMV protein m157

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Viral mimics in eukaryotic systems

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Fv1 mimics viral gag protein
Fv4 is incorporated into virus particles

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Placental development

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syncytins are retrovirus-derived envelope genes coopted for generation of trophoblasts

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Parasitic wasps

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virus-like particles deliver host genes that suppress host-immune responses against the wasp eggs

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Mtb evades phagolysosome maturation

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Phagocytosed by CR3 uptake

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Rab5a effectors (EEA1 and hVPS34) impaired

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no PI3P generation

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LAM cell wall component from Mtb

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inhibit calcium release from the ER by inhibiting sphingosine kinase

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SapM hydrolyses

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PI3P

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Depletion of PI3P

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prevents transition to late stages

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IFN-gamma activated macrophages kill Mtb

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Induces autophagy

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IL-1beta upregulates

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MHC class II expression by macrophages

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Mtb secretes metalloproteases (ZmpA) which results in inhibition of the inflammasome involved in producing

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mature IL-1beta and IL-18

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Mtb induces Arg1 via TLR and MyD88 pathway

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arginase downregulates NO

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Skew towards a TLR2 response

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which leads to MHC II downregulation

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Listeria is taken up via

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C1qR and E-cadherin binding to the bacterial internalin A/B

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Listeria secretes

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cytolysin listeriolysin following phagocytosis

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LLO is activated by low pH

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and the endosomal enzyme GILT

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ActA is similar to host WASP protein

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interacts with Arp2/3

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Listeria proteins induce actin comet tails

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avoid extracellular immunity

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LPS of yersinia pestis is recognised by TLR4

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Yersinia modified LPS but mutant is slow growing

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LPS has

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fewer/longer/branched acyl chains

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Type III secretion system

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is a multiprotein complex that can deliver effector proteins across eukaryotic cell membranes

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YopJ is delivered which

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targets tLR signalling, cleaving ubiquitin residues from proteins and preventing signalling