Microbial Immune Evasion Mechanisms Flashcards
Balance between the microbe and the host depends on what?
properties of the microbe (e.g. capsule – complex polysaccharide coat, helps drive pathogenic process. toxins)
and properties of the host (e.g. B-cell clonal expansion gives rise to antibodies)
Virulence Factors
the degree to which a pathogen causes disease
- evade host defences
- promote tissue damage, colonisation and adhesion
explain what happens in innate immunity, specifically with complement
induces an inflammatory response
phagocytosis by opsonisation
vascular permeability, promotes chemotaxis
mast cell degranulation
cell membrane lysis
how can BACTERIA overcome complement?
- capsules and LPS’s don’t allow the early stages of the complement cascade to bind to their surfaces, so it blocks the triggering of the cascade.
- some bacteria have a protein encoded in their genome that binds to and negatively regulates Factor H (in the cascade), undermining complement cascade.
- some bacteria can coat themselves with non-complement fixing Ig – antibodies that cannot bind to complement – example is IgA.
once the complement cascade is activated, C3b is released – a potent opsonin that binds to surfaces and allows opsonisation into macrophages
- capsule prevents C3b binding
C5a is released after the component cascade is activated, a chemoattractant factor
- some bacteria have genes for proteases that degrade C5a, C3b and other protein products of the complement cascade - blocking C5a it will minimise inflammation at site of infection, tipping the balance in favour of the pathogen.
how would a pathogen living inside a cell be advantageous?
difficult for immune system to find it
eg. mycobacterium TB hiding inside macrophage
explain what happens in innate immunity, specifically with macrophages - how can BACTERIA over come this?
some bacteria contain extracellular toxins, leucocidins, that damage the membrane of macrophages
protein A - flips the antibody so the wrong part binds to the pathogen and it has no effect, so the pathogen overcomes opsonisation
bacteria have worked out ways to enter macrophages, or inject proteins into the macrophages that causes receptors to form on the macrophage that the bacteria can then bind to
Mycobacterium blocks phagolysosome fusion and stops acidification of the early endosome
some bacteria produce catalses that neutralise ROS intermediates that would kill them in the macrophage.
Production of Fc receptors by microbes
Antibodies are antigen specific and high affinity
Fc component of the antibody binds to antigen on the pathogen – killed via fc receptor mediated phagocytosis
BUT, some viruses have proteins that encode mimicks of the fc receptors, and bind the antibody the wrong way round so it cannot be opsonised, evading antibody neutralisation.
Staphs, Streps, Herpes, VZV, CMV
Adaptive immunity
(T cell mediated responses, antigen specific)
how do VIRUSES overcome this?
- Latency (VZV, herpes simplex) or reactivation
- Hiding inside cells (HIV)
- Moving to immunoprivileged sites
- Blocking antigen presentation on MHC, for example blocking TAP protein, inhibiting the transfer of a small peptide to the surface of the MHC molecule which will be presented (Herpes simplex)
- Immunosuppresion, which includes decreased MCH expression (cytomegalovirus) and decreased interferon gamma receptor expression
- Antigenic variation/mutation
- B cells - neutralisation escape
- T cells - CD8+ escape mutants of HIV or HCV
HIV generates different mutated forms of the virus in 1 indivdual, which can evade immunity - Neutralising secretory IgA (key defence at our mucosal surfaces, we need it)
- Interfering with cell apoptotic pathways and cytokine balance
Streptococcus pneumoniae
-how does it cause infection?
inhalation into the lung
colonises by the nasopharynx due to adhesion molecules, produces secretory IgA proteases during colonisation so they can invade further after post-viral damage - viral infection will damage structure of epithelial cells.
switches on genes for pneumolysin, a toxin that damages pneumocyte membranes - destroys defensive barriers allowing bacteria to replicate there
escapes phagocytosis via capsules
Inflammatory process driven by teichoic acids
pneumonia
Varicella-zoster virus is known as a persistent microbe - what does this mean?
in a small community:
it infects susceptibles, then remains latent
-reactivates and infects next gen of susceptibles
Herpes simplex virus I - where does it go in the body?
Nerves
this is because these are an immunologically privileged site, and poor protective immunity for reactivation
(individuals have creeping lesions and scars from previous episodes)
Antigenic Variation
this is a mechanism for immune evasion and it refers to the successive expression of alternative forms of an antigen
it includes phenotype changes (colony morphology, virulence, serotype, loose flagella, changing surface sugars)
phase variation is ON/OFF switch of an antigen at low frequency, changing antigenic nature to escape immune recognition and spread through a community
Antigenic Diversity/ polymorphisms
genetically stable and alternative forms of antigens in a population of microbes
e.g. serotypes of Strep.pneumoniae
Gonorrhoea (STD) - what is it?
an inflammatory infection of the anterior urethra
- infects mucosal surfaces with columnar epithelium (urethra, cervix, rectum, pharynx, conjunctiva)
- leads to dysuria, redness, swelling, pain on urination, destruction of mucosa, prostatitis, ovaritis, fistulas, sterility
- disseminated infections - arthritis, endocarditis, meningitis
gonorrhoea - what adaptations does it have?
the surface components, which interact with host cells, vary in terms of their frequency in a population of bacteria
these components include capsule, outer membrane, pilus, spa, inner membrane
they can undergo phase and antigenic variation to avoid immune response
