23- Evasion of the Immune Response by Pathogens Flashcards
Explain how bacteria can interfere with TLR signaling pathways through unrecognized molecules (Modified PAMPs)
The bacteria modifies the PAMPs to not be recognized. This can be a small change and cause a poor binding to the TLR and cause a weak signal. This can lead to no signal transduction occurring.
Explain how bacteria can interfere with the TLR signaling pathways through accelerated destruction of intermediates.
Many bacteria can interfere with intracellular signaling pathways. For example, Brucella synthesizes a protein called TcpB that closely resembles the mammalian Toll/IL-1 receptor. As a result, it causes accelerated degradation of an adaptor protein and blocks the TLR signaling pathway
How do bacteria avoid being killed by phagocytic cells through protein A?
Bacteria inhibits phagocytosis by expressing protein A, which binds to Fc portion of IgG, so it prevents Abs to bind Fc receptor on phagocytic cells or activating the classical complement pathway
Discuss how bacteria avoid being killed by phagocytic cells using the hydrophilic capsule
Encapsulated bacteria such as pneumococci possess a thick hydrophilic capsule that is difficult for phagocytes to bind to
Discuss how bacteria avoid being killed by phagocytic cells using complement
Bacteria produce M protein which bind fibrinogen and masks C3b binding sites
Discuss how bacteria avoid being killed by phagocytic cells using fibrinogen
M protein binds factor H, inactivating bound C3b
Discuss how bacteria avoid being killed by phagocytic cells using leukotoxins
Several gram negative bacteria secrete leukotoxins that kill leukocytes, especially granulocytes. The most important leukotoxins are the RTX proteins. RTX toxin kills ruminant neutrophils, alveolar macrophages, and lymphocytes
Discuss how bacteria avoid being killed by phagocytic cells using type III secretion systems
Some bacteria use methods to inject toxins into their targets. Some gram-negative bacteria have developed an elaborate needle complex- a type III secretion system, to convey effector molecules directly into the cytosol of effector cells. Once the needle complex enters the cytosol and detects its neutral pH, injection of effector molecules occurs. These molecules activate guanosine triphosphates and disrupt intracellular signaling pathways. At high concentrations, they produce transmembrane pores and cell necrosis
Explain how some bacteria bind to complement regulatory protein factor H and resist killing by alternative pathway of complement system.
Some bacteria use M protein to bind Factor H on bacteria to stop the bacteria from dying. Normally factor H binds to stop the alternative complement pathway from destroying normal non-pathogenic cells
What are some strategies employed by intracellular bacteria to survive within cells.
- prevention of lysosome-phagolysosome fusion. This is needed to kill the microorganisms
- changes the way IL are secreted- switch to M2 response
- inhibition of autophagy- stopping of self induced apoptosis
- Bacteria escaped from phagolysosome and is free-floating in the cytoplasm
- resistance to lysosomal enzymes
How do viruses evade the immune system using cytokine targeting
Some viruses block the effect of IFN-gamma by making soluble receptors of IFn or blocking the activities of IL-12 and IL-18, both of which are required for IFN-gamma production. These interfere with the normal functioning of host cytokines
How do viruses evade the immune system by using inhibition of antigen presentation
Reducing the transcription of MHC genes, blocking TAP function and the transport of peptides into the ER, inhibiting protesomal degradation of viral proteins, inhibiting intracellular transport of MHC I alpha chains, and preventing delivery of a loaded MHC to the cell surface
How do viruses evade the immune system using modulation of MHC I response
Viruses down regulate MHC I expression to escape detection by T cells, but they can still be detected by NK cells. To evade killing by NK cells, some viruses decrease expression of the stress-related protein MICB and in doing so inhibit NK cell mediated cytotoxicity
What is the difference between antigenic drift and shift
Drift: a gradual change in the antigenicity of a virus as a result of mutations and selection
Shift: A sudden, major genetic change in which a new strain develops as a result of recombination between two virus strains
