Microbial Immune Evasion Mechanisms Flashcards
What are the microbial components that drive the pathogenesis of disease?
- Adhesins
- Toxins
- Capsules
What are the properties of the host defensive mechanisms
- Natural barriers
- Defensive cells
- Complement
- immune response
What is virulence?
The degree to which a pathogen causes disease
What are the roles of virulence factors?
Colonisation and adhesion
- Promoting adherence
- Promote receptor binding
- Promote internalisation of viruses
- Allow bacterial colonisation of mucosal surfaces
Promote Tissue damage
- Production of toxins and enzymes
- pharmacological cytopathic action
Evade host defences
How does each pathogen evade the immune defenses?
There are over 300 human pathogens that are dealt with different immune mechanisms - each pathogen tries to evade different parts of innate immune system
How do bacteria evade the immune response?
Bacteria try to overcome the complement system
What are the roles of the complement system?
- induces inflammatory response
- promotes chemotaxis
- ↑ phagocytosis by opsonisation
- ↑vascular permeability
- mast cell degranulation
- lysis of cell membranes
How does the complement system achieve its roles?
Releases factors that chemo attract effector cells e.g. macrophages, neutrophils
How do bacteria overcome the complement system?
- Failure to trigger complement cascade -ve binding
2. Block/expel MAC
How do bacteria inhibit complement cascade activation?
LPS, capsules inhibit early stages of complement to bind to their surfaces
Stops assembly of complex on surfaces; Factor H sequestration
Coating with non-fixing IgA - can’t be opsonized
How do bacteria block macrophages?
- Capsule blocks C3b binding (potent opsonin)
- Capsule prevents C3b receptor access
- C5a proteases (C5a is a chemoattractant factor)
Give examples of intracellular pathogens
Mycobacterium tuberculosis
Listeria
Salmonella
How do intracellular pathogens evade immune response?
Hidden from serum killing, complement, antibodies by hiding in a host cell
What are leukocidins?
cytotoxin created by some types of bacteria that forms pores in cells to kill them - cytopathic
e.g. Staphylococcus
How do intracellular pathogens prevent opsonisation?
Protein A (binds Fc portion of IgG)
How do intracellular pathogens block contact with immune cells?
capsules
meningococcus, Hib
Outline the immune evasion mechanisms in intracellular pathogens
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
How does TB evade immune mechanisms
TB evades phagolysosome fusion
Remains as an early non-acidified vacuole in which bacteria can replicate to v. high no.’s and infect other cells to cause disease
Describe the characteristics of antibodies
Antibodies are antigen specific, high affinity
How do antibody-antigen complexes work?
Fc receptors (on macrophage) bind to a bacteria Fc component
Bateria is internalised and killed due to antibody generation
> Fc receptor mediated phagocytosis
How do pathogens evade Fc receptor mediated phagocytosis?
Certain pathogens contain receptors on their surface that mimic Fc receptor of macrophages
What is the consequence of Fc receptor containing pathogens?
When antigen-specific antibodies are generated, bacterial Fc receptors bind them incorrectly so that antigen-antibody complex isn’t opsonized and killed - protective mechanism
What are the key mechanisms of pathogens evading adaptive immunity?
- Concealment of antigen
- Immunosuppression
- Antigenic variation
- Persistence/latency/reactivation
How do pathogens conceal antigens to evade adaptive immunity?
- hide inside cells
- privileged sites
- block MHC antigen presentation
- Herpes -ve TAP protein
- surface uptake of host molecules
e. g. CMV and beta2 microglobulin
How do pathogens evade adaptive immunity via immunosuppression?
↓ MHC, ↓ receptors, apoptosis, cytokine switch, IgA proteases
Outline paradigms of immune evasion
- Streptococcus pneumoniae
- Neisseria gonorrhoeae
- VZV and Herpes simplex
- HIV
- Influenza virus
- Mycobacterium tuberculosis
What is the consequence of Streptococcus pneumoniae infection?
Causes inflammatory processes: septicaemia, meningitis, osteomyelitis
What is a commonly occurring illness of streptococcus pneumoniae?
Common cause of lobar pneumonia
What is lobar pneumonia?
Whole lower lobe of lung is completely infiltrated by inflammatory exudate pus
In a CXR why does the lower lung lobe appear opaque in lobar pneumonia?
Large numbers of organisms (shows up opaque on X-ray)
Outline the pathogenesis of pneumonia
- Breath in Streptococcus pneumoniae
- Colonised in nasopharynx due to their adhesin
molecules - Secrete IgA proteases to stop immune mucosal
surfaces from degrading them - Inhalation into lungs
- Surfactant molecules overcome by pneumolysin
production - Bacteria creates niche for own replication within lungs
- Causes inflammation ⇒ pneumonia
Why do streptococcus pneumoniae infections develop into viral infections?
Streptococcus pneumoniae often followed by viral infections as defence mechanism structure of respiratory tract no longer intact (epithelial cell damage)
How does streptococcus evade immune response?
Streptococcus Pneumoniae evades inflammatory responses as it is capsulated:
- Blocks antibody binding
- Blocks complement binding
- Blocks phagocytosis
Gram +ve contain teichoic acids: pneumolysin
What is pneumolysin?
Pneumolysin is a toxin that lyses pneumocyte membranes
How does septic shock arise from pneumonia?
Pneumonia can spread from lungs into bloodstream ⇒ septicaemia, osteomyelitis, meningitis
Why does recovering from pneumonia not necessarily guarantee immunity?
Has multiple antigenic serotypes (slight changes in LPS capsule) to maximise survival within populations
What immune response is required for intracellular viral pathogens?
requires adaptive cell mediated immunity
How do viruses evade immune response?
- 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
What phenotypic changes arise to cause antigenic variantions?
Phenotype changes - colony morphology, virulence, serotype, loose flagella, change surface sugars
→ Strategy for :- immune evasion and pathogenesis
What is antigenic diversity?
Genetically stable and alternative forms of antigens in a population of microbes
e.g. serotypes of Strep.pneumoniae
What is antigenic variation?
Successive expression of alternative forms of an antigen in a specific clone or its progeny
What is phase variation?
ON/OFF of an antigen at low frequency
When does phase variation of a pathogen occur?
during course of infection in an individual host
during spread of microbe through a community
What is gonorrhoea?
a sexually transmitted disease
What are the signs of urethritis?
Discharge of pus, scanty to copious and purulent, Galen in 2ndC - “flow of seed”
What is urethritis?
Inflammatory and pyogenic infection of anterior urethra
What parts of the urogenital tract is affected by urethritis?
Infects mucosal surfaces with columnar epithelium
- urethra, cervix, rectum, pharynx, conjunctiva
What are the consequences of urethritis?
dysuria, redness, swelling, pain on urination, destruction of mucosa
prostatitis, orchitis, strictures, ovaritis, fistulas, PID, proctitis, sterility
What are the effects of disseminated gonorrhoea infection?
Disseminated infections → arthritis, endocarditis, meningitis
How does variation arise in Neisseria Gonorrhoeae?
Bacteria; 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)
How does influenza virus evade imunity?
Evades immunity at population levels:
Antigenic drift
– mutation + selection (Epidemics)
Antigenic shift
- gene reassortment (Pandemics)
