Microbial Immune Evasion Mechanisms Flashcards
Explain the concept of Balanced Pathogenicity
Properties of the microbe
(Pathogenic mechanisms):
Adhesins
Toxins
Capsule
Etc.
VS
Properties of the host
(Defensive mechanisms):
Natural barriers
Defensive cells
Complement
Immune response
Virulence Factors - describe 3 effects
Promote colonisation and adhesion
- To establish infection
e. g. adhesins
Evade host defences
Promote tissue damage
- Growth, Transmission?
e. g. toxins
Roles of Complement
induces inflammatory response promotes chemotaxis ↑ phagocytosis by opsonisation ↑vascular permeability mast cell degranulation lysis of cell membranes
Intracellular pathogens:- example
Intracellular pathogens:-
e.g. Mycobacterium tuberculosis
Listeria
Salmonella
Intracellular pathogens:- hidden from?
hidden from serum killing, complement, antibodies
Phagocytosis - functions
kill cell - leucocidins - Staphs
prevent opsonisation - protein A (binds Fc portion of IgG) - Staphs
block contact - capsules -meningococcus, Hib
intracellular pathogens:- function
Promote own uptake (safe)
- CR3; mannose lectin receptors
Prepares cell for invasion - Shigella
- ve P-L fusion
- M. tuberculosis
Escape P-L to cytoplasm - Listeria
Resist oxidative killing
- produce catalases/peroxidases
Describe phagocytosis
- Directs phagocytosis
via CR3 – no ROI - Actin rearrangement - +ve engulfment
- 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
Pφ activation
Effect of production of Fc receptors by microbes
Microbial antigen bind to antibody leading to elimination
However when microbial Fc receptors bind antibodies leads to binding specific + non-specific antibody by Fc portion
Access to surface antigen
by specific antibody blocked
Concealment of antigen - describe
Adaptive immunity
- hide inside cells
- privileged sites
- block MHC antigen presentation = Herpes -ve TAP protein
- surface uptake of host molecules e.g. CMV and beta2microglobulin
Effect of immunosuppression
Immunosuppression
- e.g. ↓ MHC, ↓ receptors, apoptosis, cytokine switch IgA proteases
Streptococcus pneumoniae - pathogenic mechanisms
Colonisation of nasopharynx
(adhesins; receptor NAc-hex-gal, sIgA proteases) = Otitis media
(inflammation)
Inhalation into lungs
By-passes defences: surfactants sIgA proteases; pneumolysin
Reaches lung
=
Escapes phagocytosis
(capsules)
Inflammation -Lung damage
(teichoic acids; pneumolysin)
Damage to endothelial cells
(inflammation; pneumolysin)
=
pneumonia
Bacteraemia
Meningitis + septicaemia
(Inflammation and toxic shock)
Viral Immune Evasion - describe
- Latency - VZV, herpes simplex
- ↓ antigenic presentation by binding to TAP
- Inhibits peptide transfer to MHC
- Herpes simplex - ↓MCH expression - Cytomegalovirus (CMV)
- Mutation of epitopes
B cells - neutralisation escape
T cells - CD8+ escape mutants of HIV
Intracellular pathogens - requires
Intracellular pathogens - requires adaptive cell mediated immunity
Ophthalmic Zoster - presentation
During chicken pox VZ V becomes latent in nerve ganglia
In shingles, reactivates years later
Ophthalmic Zoster - define
Shingles involving the eye. Symptoms = include a rash of the forehead with swelling of the eyelid.
There may also be eye pain, eye redness, and light sensitivity.
Explain infection of next generation susceptibles
Microbes infects
susceptibles
Microbe remains
latent
Microbes reactivates (zoster)
and infects next generation
of susceptibles
Explain immunological state of nerves
Nerves –
immunologically privileged site
Poor protective immunity for reactivation
Phenotype changes - list
Phenotype changes - colony morphology, virulence, serotype loose flagella, change surface sugars
Antigenic Diversity/ polymorphisms - define with an example
Antigenic Diversity/ polymorphisms
- genetically stable and alternative forms of antigens in a population of microbes
e. g. serotypes of Strep.pneumoniae
Antigenic Variation - define
Antigenic Variation
- successive expression of alternative forms of an antigen
in a specific clone or its progeny
Define phase variation - when does it occur
- 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
Gonorrhoea – a sexually transmitted disease = define
Inflammatory and pyogenic infection of anterior urethra
Infects mucosal surfaces with columnar epithelium
- urethra, cervix, rectum, pharynx, conjunctiva
Gonorrhoea – a sexually transmitted disease = effects
dysuria, redness, swelling, pain on urination, destruction of mucosa
prostatitis, orchitis, strictures, ovaritis, fistulas, PID, proctitis, sterility
Disseminated infections → arthritis, endocarditis, meningitis
Neisseria gonorrhoeae - characteristics
Surface components interact with host cells
Components vary at high frequency in a population of bacteria
Variation to avoid immune response
Neisseria gonorrhoeae - list cell surface components
Pilus Capsule Inner membrane Outer membrane Opa
Neisseria gonorrhoeae - cell surface structures can undergo what
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)
Epidemics cause
Antigenic drift
– mutation + selection
Pandemics cause
Antigenic shift
- gene reassortment
What effects do bacterium have on the body
Superantigens and inappropriate immune
activation
Induction/inhibition of apoptosis
Inhibition of antigen presentation
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
Survival inside macrophages
Induction/inhibition of apoptosis
What effects do viruses have on the body
MHC mimics – block killing by NK cells
Downregulate MHC
Block antigen processing by TAP
Induce immune suppression
↓CMI, ↓CD4+
Host Mimicry
Cytokine mimics and binding proteins
Hide inside cells
Survival inside cells
Induction/inhibition of apoptosis
Blockage of cell cycle
progression
CTL escape mutants –
quasi species swarms
Latency reactivation
e.g. VZV, Herpes simplex
Rapid growth and transmission prior to adaptive immunity e.g. colds
