Microbial immune Evasion Mechanisms Flashcards
What is balanced Pathogenicity?
Balance between the microbe and the host
Properties of the microbe (Pathogenic mechanisms) • Adhesins • Toxins • Capsule
clinical course of disease
Properties of the host Defensive mechanisms • Natural barriers • Defensive cells • Antibacterial peptides • Innate and adaptive Immune response
Virulence Factors
Promote colonisation and adhesion - To establish infection e.g. adhesins
evade host defences
Promote tissue damage -
Growth, Transmission?
e.g. toxins
Immune response against these may protect from disease
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
antibodies T cells – CD4 helper cells and CD8 cytotoxic cells
• Pathogen diversity
• Multiple immune evasion
strategies
complement system
diagram
Innate Immunity - complement
failure to trigger
negative binding
disrupt regulation
block/expel MAC
LPS, capsules coating with non-fixing IgA Capsule blocks C3b binding Capsule prevents C3b receptor access Factor H sequestration C5a proteases , blebbing
Roles of Complement
induces inflammatory response promotes chemotaxis increased phagocytosis by opsonisation increased vascular permeability mast cell degranulation lysis of cell membranes
Living inside cells protects bacteria
Intracellular pathogens:- e.g. Mycobacterium tuberculosis Listeria Salmonella Hidden from serum killing, complement, antibodies
innate immunity
Phagocytosis Macrophages + PMNs
kill cell - leucocidins - Staphs
prevent opsonisation - protein A (binds Fc portion of IgG) - Staphs
block contact - capsules -meningococcus, Hib
Intracellular pathogens:
Promote own uptake (safe) - CR3; mannose lectin receptors
Prepares cell for invasion - Shigella
Inhibit Phagosome-lysosome fusion - M. tuberculosis
Escape Phagosome-lysosome to cytoplasm - Listeria
Resist oxidative killing - produce catalases/peroxidases
Immune response depends on localisation within cell
Hidden from serum killing, complement, antibodies
Mechanisms that enable life inside macrophages
- Directs phagocytosis via CR3 – no ROI
- Actin rearrangement - +ve engulfmant
- Type 3 secretion systems – prepares cell
- Resists digestion and ROIs in PLs - SOD, catalase
- Escape into cytoplasm
e.g. Listeria - Inhibits PL fusion maintains early endosome Blocks acidification e.g. mycobacteria
- Controls antigen presentation- Stops CTLs or
P activation
Production of Fc receptors by microbes leading to
antibody inhibition
diagram
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. MHC, receptors, apoptosis, cytokine switch IgA proteases
Antigenic variation
Persistence/latency/reactivation
Streptococcus pneumoniae
Pathogenic mechanisms
• Colonisation • By-pass defences • Survival • Damage Pneumonia; Otitis media; meningitis
diagrams
Viral Immune Evasion
Intracellular pathogens - requires adaptive cell mediated immunity
- Latency - VZV, herpes simplex
- decrease antigenic presentation by binding to TAP - inhibits peptide transfer to MHC - Herpes simplex
- decrease MCH expression - Cytomegalovirus (CMV)
- Mutation of epitopes
B cells - neutralisation escape
T cells -CD8+ escape mutants of HIV
Ophthalmic Zoster
chickenpox - VZ V becomes latent in the nerve ganglia
shingles- reactivated years later
Persistence as an immune evasion strategy
Persistent microbes e.g. Varicella-zoster virus
- Microbes infects susceptibles
- Microbe remains latent
- Microbes reactivates (zoster) and infects next generation of susceptibles
Herpes simplex virus I
Nerves and immunologically privileged site
Poor protective immunity for reactivation
Note creeping lesions and scars from previous episodes
Viral Immune Evasion - herpes
Intracellular pathogens - requires adaptive cell mediated immunity
- decrease antigenic presentation by binding to TAP - inhibits peptide transfer to MHC- Herpes simplex
- decreased MCH expression - Cytomegalovirus (CMV)
Phenotype changes
colony morphology, virulence, serotype loose flagella, change surface sugars
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
Neisseria gonorrhoeae
Surface components interact with host cells
Components vary at high frequency in a population of bacteria
Variation to avoid immune response
Phase and antigenic variation in Neisseria affects
cell surface components
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 H haemaglutinin - 18 types N neuraminidase- 11 types Segmented –ve ssRNA genome 8 segments, at least 10 genes Up to 14 proteins
Antigenic drift
– mutation + selection
Epidemics
Antigenic shift
- gene reassortment
Pandemics
