Immune Evasion and Suppression Flashcards
1
Q
what features does E.coli have that can manipulate the host?
A
- PAI of genes
- type 3 secretion system (T3SS)
- E.coli immodulatory expression: shiga toxin
2
Q
what is the PAI?
A
- extra pathogenecity island DNA in pathogenic strain
- encodes toxins, adhesins, sidenophores, immunoe modulatory factors
3
Q
what is the T3SS?
A
- pathogen delivery system and its effector molecules to modulate host cell properties
- about 20 proteins encoded by the PAI
- like a syringe that injects proteins into the host cell (complex molecular syringe)
0 can alter host in different ways depending on specific effector proteins
4
Q
what is the shiga toxin?
A
- extracellular toxin
- targets ribosomes
- inhibits ribosomes and induces the apoptotic pathway
- bacteria are also competiting with each other
- HUS - kidney damage
5
Q
what is helicobacter pylori?
A
- causes gastric ulcers, can block transcription of T cell growth factor IL-2
6
Q
what does HIV do?
A
directly attacks the innate immune system, prevents phosphorylation of T cell receptor cascade and prevents formation of immunolgical synapse
7
Q
how does the HIV affect the immune system?
A
- presentation of antigens with signalling, viruses can disrupt the formation of this synapse
- leaves patients with a weakened immune system so they die of secondary infection
8
Q
what does HIV target?
A
- mainly targets T cells and macrophages (HIV replication)
- destroys their function and reduces their numbers
- HIV attaches to CD4 on the surface of T cells
9
Q
how does HIV infect macrophages?
A
interaction between viral gp120 with CD4 and CCR5 (co-receptor)
10
Q
how does HIV effect T cells?
A
interaction between viral gp120 with CD4 and CXCR4
11
Q
how does T. cruzi prevent T cell activation?
A
- prevents activation of T-cells by re-sialiation, transfers SA from host cells to parasite surface
12
Q
how do large extracellular helminths interact?
A
- surface molecules
2. secreted molecules
13
Q
how do helminths not be targeted?
A
give off an elaborate system of chemicals
14
Q
why does helminth infection correlate with inflammatory disease?
A
- helminth infection ubiquitous throughout human evolution
- our immune system has evolved in the presence of worms
- helminth infection is now rare
- allergy and autoimmunity
15
Q
what is the hygeine hypothesis?
A
- western inflammatory is the direct result of reduced pathogen exposure (including helminths)
16
Q
how can helminths modify the host with secretory models?
A
- ‘Excretory/Secretory (ES) molecules
- produce parasite and modulatory molecules
- suppress macrophages, B and T cells and dendritic cells
- in combination with commensal bacteria can bias the host cells and influence inflammations
- allows worms to prevent/limit immune attack
17
Q
does worm infection prevent inflammatory disease?
A
- asthma = allergic lung inflammation
- induce inflammation in mice, cause acute inflammation
- infect the mice with worms it completely goes down
- suggest that intestinal helminth infection prevents lung allergic reaction
- worm induces regulatory T cells (limit inflammation)
18
Q
what are the immunosuppressive molecules in helminths?
A
- want to isolate the molecules the worms are releasing
- eg TGFB
- promotes worm survival but prevents western diseases
19
Q
how do viruses avoid the immune system?
A
devised immunoevasins to block their proteins being present to CD8+ T cells
20
Q
what is the TAP complex?
A
- peptide delivery system from the cytosol ER, proteasome delivers peptides which are taken in by the TAP complex to be processed and loaded onto MHC I
- viruses use molecules to inhibit or block the uptake of peptides so they can’t make it into the ER lumen and can’t be loaded onto MHC I
21
Q
how does herpes simplex avoid the immune system?
A
- stops peptide binding to TAP
- blocks tapasin
22
Q
how does the bovine herpes virus avoid the immune system?
A
- inhibits the peptide transport itself, blocks TAP1 and TAP2 from importing
23
Q
what happens if viruses block their own recognition from the immune system?
A
cant be presented by MHC I
24
Q
what are the 2 forms of leishmania taken up by immune cells?
A
- promastigote
2. amastigote
25
what is the promastigote?
- immune cells only encounter cell
- come from the sand fly
- ones that are human infective won't divide
- have to be taken up into the lysosomal environment
- lysosomal environment has a lower pH and higher temperature which triggers them to become amastigotes
26
what is the amstigote?
divide and cause disease
27
how is leishmania infective?
- neutrophil infected by promastigote it presents the antigen to a macrophage and is engulfed
- attacks macrophages and DCs
- phagocytes internalise leishmania and then are destroyed
28
how does leishmania affect sandflies?
- have commensal bacteria in their
- when they transmit their bacteria with the leishmania and saliva it creates an inflammasome activation
- draws out the immune cells which they can then infect
- human infection form can also swim towards macrophages
- when you treat the sand-flys first with antibiotics you dont get the inflammation response and transmission
29
what impact does the surface of parasites of on phagosomes? (leishmania)
- whether the lysosome can fuse with the phagosome
- whether they can cleave the VAMP8 thats necessary for fusion of phagocytic vesicle
- can inhibit their own presentation to MHC I cells
30
what is the surface of parasites like? (lesihmania)
- GP63 is on the surface of the metacyclic stage of the parasite
- once in the parasitic vacuole its theorised that they give off exosomes
- immunomodulatory factors in them and can shut down translation of host macrophages
31
what happens once the parasite is in the parasitic vacuole? (leishmania)
- bud off parasite
- fuse with parasitic vacuole
- go into the cytoplasm of the macrophage
- can the pH of the lysosome for its own survival
- they can also flip the mebrane
32
how can leishmania stop microbididal functions?
NO, TNFa, ROS
33
how does Lesihmania promote an anti-inflammatory response?
- IL-10 leading to Lesihmania persistence
34
what are the two key proteins on influenza?
- hemagglutinin (attach to host receptors)
| - neuraminidase (breaks down sialic acid to allow budding)
35
what are the major serovars in influenza?
15 different Ha and 9 different Na
36
what are the two causes of antigenic variation in influenza?
- antigenic drift (minor mutations)
| - antigenic shift (major re-assortment)
37
what happens in antigenic shift?
- infected by two flus simultaneously, tend to have an animal associated with them
- this is how we get pandemics
38
what is the main source of variation in trypanosomes?
variation surface glycoproteins (VSGs)
39
what role does VSG have?
- can switch
- if an antibody lands on a VSG it moves the antibody to its flagella pocket and ingests it and digests it and switches the VSG back on the surfaces
40
how does VSG create antigenic variation?
- many more than 1000 VSG genes on the genome
- almost all are pseudogenes or gene gragments
- can create new genes by recombining fragemnts
41
what is the role of PfEMP1 proteins?
- insert into RBCs and develops surface knobs
- contains the parasite proteins
- stick to the endothelial lining of blood vessels (dont get cleared by the spleen)
- become sticky and form blood clots and inflammation
42
what is the strutcure of PfEMP1?
- massive protein complex
- DBL domains are variable
- multiple copies of the genes throughout the genome they can recombine
- PfEMP1 can recombine multiple of the DBL and CIDR domains
- variable enough that the host never really clears the RBCs
43
what makes T.cruzi difficult to target?
- every stage of T.cruzi is infective
- infect any nucleated cell
- do this by triggering their own endocytosis via calcium signalling
44
what are some key points of infectivity of T.cruzi?
- have multiple receptors
- trigger their own endocytosis
- once on a parasitic vaciole they have to escape in order to get into the cytoplasm where they differentiate into amastigotes and divide rapidly
45
what is the main surface antigen of T.cruzi?
surface trans-sialidases
46
what is the role of trans-sialidases?
- snip off sialic acid off of your normal cells
- ligate them onto the muscins of the T.cruzi
- basically disguises the T.cruzi trypamastigote
- suppression of T cell recognition and internalisation into any cell
47
how does T.cruzi escape the lysosome?
- post phagocytosis - NADPH oxidase - O2 - H2O2 - can be toxic to a parasite
- T.cruzi peroxidases and superoxide disumtases
- escape the lysosome to the cytosol
- do this via TC-TOX (insert this into the membrane)
- forms multiple pores and rips the parasitic vacuole apart
48
why does T.cruzi need to get to the amastigote stage?
- to divide
- re-differentiate to trypamastigotes and they're much larger
- rip the cell apart
49
what is congenitcal transmission?
- complement can act as a bridge to the trypamastigote
- triggers phagocytosis
- tried to block this
- but this actually promoted uptake of T.cruzi
