Medical Microbiology: Microbial Immune Evasion Mechanisms Flashcards
1
Q
What are some of the properties of microbes that drive pathogenic processes of disease?
A
- Adhesin molecules or receptors on surface of viruses
- Toxins
- Capsules (lipopolysaccharides)
2
Q
What are some of the properties of the host that defend against pathogenic processes of disease?
A
- Natural barriers - tight epithelial junctions, mucocillary clearance
- Defensive cells - macrophages, intraepithelial lymphocytes (surveillance property)
- Complement and acute phase proteins (components of innate immunity)
- Adaptive immune response - T cells and B cells
3
Q
Explain the idea of balanced pathogenicity
A
- Idea that a pathogen doesn’t want to kill its host before it can replicate and spread and so pathogens have evolved to reduce their virulence to avoid this
4
Q
What does the severity of a disease within a person depend on?
A
- Depends on the way the balance between the properities of the microbe and the properties of the host tips
5
Q
What are virulence factors?
A
- Components of organisms that drive the pathogenic process
6
Q
What are some of the functions of virulence factrors?
A
- Promote colonisation and adhesion to establish infections e.g. adhesins
- Evade host defences
- Promote tissue damage for growth and transmission of pathogen, e.g. toxins
7
Q
What are some of the roles of complement in the innate (non-adaptive) immune response?
A
- Induces inflammatory response
- Promote chemotaxis by recruiting macrophages/neutrophils to site of infection
- Increases phagocytosis by opsonisation - binds to surface of particles which allows them to be phagocytosed by macrophage
- Increases vascular permeability - releases cytokines which increase permeability of endothelial layers which allows cells recruited to reach site of infection
- Promotes mast cell degranulation
- Lysis of cell membranes - complement pathway eventually forms membrane attack complex (MAC) which assembles on membrane of pathogen and attacks it thus killing it
8
Q
What are some of the mechanisms pathogens use to overcome complement?
A
-
Bacteria can fail to activate complement pathway - Have polysaccharide capsules or lipopolysaccharides (endotoxins) which don’t allow early stages of complement cascade to bind to their surfaces
- Also fails to allow assembly of complement complex as it builds up on surfaces
-
Factor H sequestration - Contain gene that codes for protein present on bacterial surface that binds to factor H
- Factor H is a negative regulator of complement cascade so by having protein that binds factor H you stop complement activating
-
Coat themselves with Non complement-fixing IgA - During complement cascade certain antibodies bind complement which allows for opsonisation of antigen-antibody complement assembly
- IgA antibody unable to bind complement so opsonisation unable to occur
- Polysaccharide capsules block C3b binding/C3b receptor access - C3b released once complement cascade activated and binds to surfaces and allows opsonisation to occur (potent opsonin)
-
Encode C5a proteases which degrade C5a - C5a is released after complement casacde activated
- C5a is a chemoattractant factor which is important in inducing inflammation
- Degradation of C5a blocks activation of complement and minimises inflammation
9
Q
What are intracellular pathogens?
A
- Intracellular pathogens are pathogens that live inside immune system cells which makes them hidden from serum killing, complement and antibodies making it much harder for immune response to kill them
10
Q
Give some examples of intracellular pathogens
A
- Mycobacterium tuberculosis
- Listeria
- Salmonella
11
Q
How do pathogens overcome phagocytosis from macrophages?
A
- Bacteria can contain toxins such as leucocidins - Damage membranes of white cells such as macrophages so prevents phagocytosis by killing macrophages
-
Prevent opsonisation by complement - Contains gene which encodes for protein A which binds antibodies the wrong way around
- Binds IgGs via their Fc receptor so antibody unable to have an effect as it can’t bind to macrophage (opsonise) without Fc receptor
- Have polyasaccharide capsules - Very non-antigenic so can evade phagocytosis
12
Q
How do intracellular pathogens prevent being killed by macrophages?
A
-
Promote own uptake - Enter macrophages via receptors that don’t activate respiratoty burst
- This means reactive oxygen species (ROS) aren’t released and so don’t kill pathogen
- Secrete proteins into macrophages - These proteins act as receptors for pathogen to allow it to be safely internalised into macrophage
-
Blocks phagolysosome fusion - Stops macrophage (phagosome) from fusing with lysosome
- Also prevents acidification of early endosome
- E.g. M. tuberculosis
- Escapes phaolysosome and escapes into cytoplasm - E.g. Listeria
- Produce catalases/peroxidases - These neutralise reactive oxygen intermediates generated via phagolysosome fusion
13
Q
Explain how antibodies are able to cause phagocytosis of pathogens
A
- Antigen-specific antibody binds to specific antigen on microbe via its Fab (fragement-antigen binding) region
- Once bound the Fc region of the antibody binds to the Fc receptor on the macrophage
- This leads to microbe being engulfed by macrophage and being killed (phagocytosis)
14
Q
Explain how the production of Fc receptors by pathogens prevents them from being killed by macrophages
A
- Certain pathogens have genes which encode for proteins on their surface which mimic the Fc receptor
- This means if antigen-specific antibodies are produced their Fc regions have to bind to the pathogen instead of their Fab regions like normal
- This prevents Fc regions from binding to the Fc receptors on macrophages so the pathogen can’t be phagocytosed by the macrophage
15
Q
Give some examples of pathogens that are able to produce Fc-like receptors on their surface
A
- Staphylococci bacteria
- Streptococci bacteria
- Vericella zoster virus (HHV-3)
- Cytomegalovirus (HHV-5)
17
Q
What are some of the diseases that Streptococcus pneumoniae causes?
A
- Pneumonia
- Otitis media
- Meningitis
- Septicemia
18
Q
How does Streptococcus pneumoniae cause infection?
A
-
Streptococcus pneumoniae colonises nasopharynx
- Able to colonise because it has adhesin molecules
- Secrete IgA proteases which prevent IgAs at mucosal surfaces from degrading them
- It gets inhaled into lungs
- Again secretes IgA proteases
- Also switches on pneumolysin genes which produce pneumolysin protein
- Pneumolysin is a toxin which lyses pneumocyte membranes - this allows bacteria to create niche for its own replication in the lung
- Once in the lung Streptococcus pneumoniae results in the following:
- Inflammation due to teichoic acid and pneumolysin production - leads to lung damage
- Damage to endothelial cells due to pneumolysin and inflammation
- Damage to endothelial cells, due to inflammation, leads to pneumonia
- Streptococcus pneumoniae can spread from lobes of lungs into the bloodstream to cause septicaemia and meningitis
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NOTE: Inflammatory response caused by lung damage won’t be very effective against bacteria because it has polysaccharide capsule
- Polysaccharide capsule prevents complement cascade from binding to its surface; prevents antibody binding and is non-antigenic which prevents it from being phagocytosed
21
Q
How does VZV being latent allow it to infect multiple generations of people within a small population?
A
- If VZV caused disease in everybody it infected at the same time then it would create a generation of people who were immune to the virus
- Fact that it remains latent and causes disease in people at different times means immunity isn’t completely built up in subsequent generations allowing virus to infect people who are susceptible
26
Q
Neisseria gonorrhoeae can undergo both antigenic and phase variation. What components of neisseria gonorrhoeae are affected by each type of variation?
A
- Phase variation affcets capsule and opa’s
- Antigenic variation affects the pili
27
Q
What proteins on the surface of the influenza virus are able to undergo variation?
A
- Haemaglutinin (HA) - 15 types
- Neuraminidase (NA) - 9 types
