41. Microbial Immune Evasion Mechanisms Flashcards
Give examples of pathogenic and defensive mechanisms
PATHOGENIC
- Adhesins
- Toxins
- Capsule
DEFENSIVE
- Natural barriers
- Defensive cells
- Complement
- Immune response
What are virulence factors and what do they cause?
•Virulence is the degree to which the pathogens cause disease – rather than the fact it can cause disease
1) Promote
Colonisation and adhesion
2) Evade host defences
3) Promote tissue damage
Roles of complement
- induces inflammatory response
- promotes chemotaxis
- inc. phagocytosis by opsonisation
- inc. vascular permeability
- mast cell degranulation
- lysis of cell membranes
How may bacteria fail to trigger the complement pathway, negative binding and block/expel MAC?
FAILURE TO TRIGGER
LPS, capsules
-VE BINDING
coating with non-fixing with IgA
Factor H sequestration
Capsule blocks C3b binding
BLOCK/EXPEL MAC
Capsule prevents C3b receptor access
C5a proteases
How may some pathogens overcome phagocytosis? and how do some become intracellular pathogens?
- kill cell - leucocidins - Staphs
- prevent opsonisation - protein A (binds Fc portion of IgG) ~ Staphs
- block contact - (polysaccharide) capsules ~ meningococcus, Hib
- promote own uptake (safe) ~ CR3; mannose lectin Rs
- prepares cell for invasion
- -ve P-L fusion
- escape P-L to cytoplasm
- resist oxidative killing ~ produce catalases/peroxidases
What are the effects of the production of Fc Rs by microbes?
The microbial Fc R means the antibody binds the wrong way round, and so the complex cannot be phagocytosed and killed.
How may pathogens overcome the adaptive immunity?
•Concealment of antigen
- hide inside cells - privileged sites - block MHC antigen presentation - Herpes -ve TAP protein - surface uptake of host molecules e.g. CMV and beta2microglobulin
•Immunosuppression
- e.g. dec. MHC, dec. receptors, apoptosis, cytokine switch, IgA proteases
- Antigenic variation
- Persistence/latency/reactivation
Expand on latency
1) Microbes infects susceptibles
2) Microbe remains latent
3) Microbes reactivates and infects next generation of susceptibles
- Herpes simplex virus 1 = nerves are immunologically privileged site. There is poor protective immunity for reactivation
Define antigenic diversity/polymorphisms and antigenic variation.
ANTIGENIC DIVERSITY/POLYMORPHISMS
- genetically stable and alternative forms of antigens
in a population of microbes
e.g. serotypes of Strep.pneumoniae
ANTIGENIC VARIATION
- successive expression of alternative forms of an antigen
in a specific clone or its progeny
- Phase variation - ON/OFF of an antigen at low frequency
- occurs - during course of infection in an individual host
- during spread of microbe through a community
Expand on Gonorrhoea
Gonorrhoea – a sexually transmitted disease
•Infects mucosal surfaces with columnar epithelium
- urethra, cervix, rectum, pharynx, conjunctiva
- dysuria, redness, swelling, pain on urination, destruction of mucosa
- prostatitis, orchitis, strictures, ovaritis, fistulas, PID, proctitis, sterility
•Disseminated infections -> arthritis, endocarditis, meningitis
Expand on Neisseria gonorrhoea pathogenesis
- Surface components interact with host cells
- Components vary at high frequency in a population of bacteria
- Variation to avoid immune response
Structure:
- Capsule
- Opa
- Pilus
- Inner membrane
- Outer membrane
•All of these structures can undergo either:
- Phase variation i.e. an ON-OFF switch (capsule, Opa’s)
- Antigenic variation e.g. pilins (or both phase and antigenic)
Influenza Virus potential for variation
Has 2 proteins on the surface, haemaglutinin (H) - 15 types and neuraminidase (N) - 9 types.
- Antigenic drift – mutation + selection ~ epidemics
- Antigenic shift - gene reassortment ~ Pandemics
Summarise how bacteria avoid the immune response – innate and adaptive
- Prevents opsonin binding
- C3a and C5a proteases
Anti-inflammatory and anti chemoattractant - Inhibits opsonisation
- Inhibit complement
activation - Ig binding proteins e.g. protein A
- sIgA proteases
- Inhibition of antigen presentation
- Superantigens and inappropriate immune activation
- Induction/inhibition of apoptosis
- Survival inside macrophages
•Phase and antigenic
variation
Summarise how viruses avoid the immune response – innate and adaptive
- Rapid growth and transmission
prior to adaptive immunity e.g. colds - Latency reactivation
e.g. VZV, Herpes simplex - CTL escape mutants –
quasi species swarms - Blockage of cell cycle progression
- Induction/inhibition of apoptosis
- Hide inside cells
- Survival inside cells
- MHC mimics – block killing by NK cells
- Downregulate MHC
- Block antigen
processing by TAP - Induce immune suppression dec. CMI, dec. CD4+
- Host Mimicry
- Cytokine mimics and binding proteins
•Antigenic variation
