Microbial immune evasion mechanism Flashcards
Balance between microbe and host
State the properties involved in the balance of pathogenecity between the microbe and the host?
- Pathogenecity = Capacity of pathogen to infect + cause disease
- Microbe + host properties balance - clinical course of disease
- Microbe (pathogenic) -> adhesions, toxins + capsule
- Host (defensive) -> Natural barriers, defensive cells, antibacterial peptides, I + A immunity
Virulence factors
State the 3 purposes of virulence factors?
- Virulence factors are the molecules that assist the bacterium to colonize the host at the cellular level
- Increase colonisation + adhesion (infection establishment via adhesins)
- Evade host defences
- Increase tissue damage (growth via toxins)
Elements of the immune system evaded by pathogens
What aspect of immunity have pathogens evolved to overcome or avoid?
- Natural defences (mucosal layers, skin)
- Innate immunity (complement system, macrophages)
- Adaptive Immunity (antigen specific and memory AB T cells -> CD4 H + CD8 CT -> via pathogen diversity + multiple immune evasion strategies
- Pathogen diversity: Multiple immune evasion strategies
Innate immunity- Complement system
Very nice summary of the complement system (DNL)
VD
State ways in which negative binding failed to be triggered in the complement system?
LPS OR capsules, coating with non-fixing IgA -> Capsule blocks C3b binding -> Capsule prevents C3b receptor access
State ways in which disrupted regulation/ block MAC occurs in the complement system?
Factor H sequestration, C5a proteases, blebbing
State the 6 roles of the complement system?
- Induces IF response
- Increase chemotaxis
- Increase phagocytosis by opsonisation
- Increase vascular permeability
- Mast cell degranulation
- Lysis of cell membranes
State 3 examples of intracellular pathogens?
- Mycobacterium tuberculosis
- Listeria
- Salmonella
- Hidden from serum killing, complement + AB
How do bacteria prevent phagocytosis from occuring with examples?
- Kill cells (via leucocidins - staphs), prevent opsonisation + block contact
How do bacteria survive inside macrophages + polymorphonuclear?
Protein A (binds Fc portion of IgG - staphs), capsules (meningococcus, Hib)
State 5 ways with examples of bacteria which aid intracellular pathogens?
- Increase own safe uptake (CR3, mannose lectin receptors)
- Preps cell for invasion (shigella)
- Inhibit phagosome-lysosome fusion (M.tuberculosis)
- Escape P-L to cytoplasm (listeria)
- Resist oxidative killing (via catalases/peroxidases)
State 7 mechanisms which enable life inside macrophages?
- Directs phagocytosis via CR3 - no ROI - Reactive O2 Species
- Actin rearrangement - +ve engulfmant
- Type 3 secretion systems - prepares cell
- Resists digestion and ROls in PLs - SOD, catalase
- Escape into cytoplasm e.g. Listeria - Before lysosome fusion so doesn’t get acidified
- Inhibits PL fusion maintains early endosome -> Blocks acidification e.g. mycobacteria
- Controls antigen presentation Stops CTLs or P Lactivation -> presents decoy
Adaptive immunity
Describe how microbes can evade from adaptive immunity?
- Concealment of antigen
- Immunosuppression
- Antigenic variation
- Establishment of persistance/latency/reactivation
Describe the concealment of antigens
- COA: Hide inside cells
- Privileged sites
- Block MHC antigen presentation (herpes interfes TAP protein)
- Surface uptake of host molecules (CMV + beta-2 microglobulin)
Describe immunosuppression
Immunosuppression
- Decrease MHC
- Decrease receptors
- Stops apoptosis
- Cytokine switch
- IgA proteases
Mechanisms of immune evasion
Describe 4 mechanisms in how viral immune evasion can occur + examples of diseases that use for these for each one?
- IC pathogens: Require adaptive cell mediated immunity
- Latency (VZV, herpes simplex)
- Decreases antigenic presentation (binds TAP -> inhibits peptide transfer to MHC - HS)
- Decreased MCH expression (CMV)
- Mutation of epitopes (B cells - neutralisation escape, T cells - CD8+ escape mutants of HIV))
Paradigms of immune evasion + examples - Streptococcous pneumonia
State the pathogenic effects + causes from Streptococcous pneumonia? VD
- Effects: Colonisation, by-pass defences, survival + damage
- Causes: Pneumonia, otitis media (IF), meningitis
VZV + herpes simplex
Describe how varicella-zoster virus uses persistance as an immune evasion strategy?
Microbes infects susceptibles -> Remains latent -> reactivates (zoster) + infects next generation of susceptibles
Antigenic variation - definitions
State the type of phenotypes that changes occur in when antigenic variation arises?
- Colony morphology
- Virulence
- Serotype
- Loose flagella
- Change surface sugars
Define antigen diversity polymorphism?
Genetically stable and alternative forms of an antigen in a population of microbes
Define antigenic variation?
Successive expression of alternative forms of an antigen in a specific clone or its progeny
What is phase variation and when does it occur?
- Bacteria undergo frequent and reversible phenotypic changes resulting from genetic alterations in specific loci of their genomes
- ON/OFF of an antigen at low frequency
- Occurs during infection OR spread of microbe through a communitv
Describe how neisseria gonorrohoea uses variation to avoid immune response?
- Surface components interact with host cells -> cell surface components undergo Phase + antigenic variation at increased frequency -> avoids immune response
Influenza virus
Describe how influenza virus has the potential for variation?
- Antigenic drift -> point mutation + immune selection
- Antigenic shift -> gene reassortment
