Microbial Immune Evasion Mechanism Flashcards
List some potential mechanisms that bacteria can use to avoid immune response.
- inhibit opsonisation
- C3a and C5a proteases (anti-inflammatory
and anti chemoattractant) - prevent opsonin binding
- inhibit complement activation
- create Ig binding proteins, e.g. protein A
- sIgA proteases
- inhibit antigen presentation
- express superantigens and inappropriate immune activation
- induce/inhibit apoptosis
- survive inside macrophages
- host mimicry (M protein)
- phase and antigenic variation
List some potential mechanisms that viruses can use to avoid immune response.
- MHC mimics – block killing by NK cells
- downregulate MHC
- block antigen processing by TAP
- induce immune suppression, decrease CMI, decrease CD4+
- host mimicry
- cytokine mimics and binding proteins
- hide/survive inside cells
- block cell cycle progression
- induce/inhibit apoptosis
- rapid growth and transmission prior to adaptive immunity e.g. colds
- latency reactivation e.g. VZV, Herpes simplex
- CTL escape mutants - quasi species swarms
- antigenic variation
Describe balanced pathogenicity.
The microbe contains components that drive the pathogenic process of disease.
On the host, we have defence mechanisms that protect against disease.
Various things can tip the balance, either in favour of the host and recovery, or in favour of the pathogen and morbidity and mortality.
This affects the clinical course of the disease.
Describe virulence and virulence factors.
Virulence is the degree to which a pathogen causes disease, rather than the fact that it can cause disease.
If the immune system can recognise and destroy the virulence factors that contribute to the disease, we will be able to be protected against these diseases.
List some functions of virulence factors.
- promote colonisation and adhesion (to establish infection
e. g. adhesins) - promote tissue damage (growth, transmission?
e. g. toxins) - evade host defences
What are some ways in which pathogens can evade non-adaptive (innate) immune responses?
They can evade it by affecting the COMPLEMENT CASCADE:
- by failure to trigger the cascade (LPS, capsules)
- by negative binding (coating with non-fixing with IgA, Factor H sequestration, the capsule blocks C3b binding, etc.)
- block/expel MAC (the capsule prevents C3b receptor access, C5a proteases)
They can evade the immune system itself by HIDING:
- they can live inside immune cells (if intracellular, it is very difficult for the immune system to recognise the pathogens)
They can also evade PHAGOCYTOSIS:
- they kill the cell using leucocidins (e.g. Staphs)
- they prevent opsonisation (using protein A, which binds the Fc portion of IgG - e.g. Staphs)
- they block contact with the phagocyte (via capsules - e.g. meningococcus, Hib)
What are some immune evasion mechanisms of intracellular pathogens?
- they promote their own (safe) uptake (e.g. via CR3 and mannose lectin receptors on macrophages)
- prepares cell for invasion (e.g. Shigella injects its own receptors into the membrane)
- negative phagolysosome fusion (M. tuberculosis)
- escape the phagolysosome to the cytoplasm (Listeria)
- resist oxidative killing (produce catalases/peroxidases)
How do microbes protect themselves against antibodies?
Normally, the antibodies will be able to eliminate the pathogen by Fc-mediated phagocytosis.
However, some pathogens have evolved to be able to bind the antibody backwards (by displaying a mimic of an Fc receptor), so blocking the access to the surface antigen.
Thus, the pathogen complex can no longer be phagocytosed and killed.
What are some ways in which pathogens can evade adaptive immune responses?
CONCEALMENT OF ANTIGEN:
- hide inside cells that are immunologically privileged sites (essentially, nerves)
- block MHC antigen presentation (Herpes, -ve TAP protein)
- surface uptake of host molecules (e.g. CMV and beta2microglobulin )
IMMUNOSUPPRESSION:
- e.g. decreased MHC, decreased receptor presentation, apoptosis, cytokine switch, IgA proteases
ANTIGENIC VARIATION
PERSISTENCE/ LATENCY/ REACTIVATION:
where the disease can become latent, then resurface later on in life
Describe how Streptococcus pneumonia causes disease in a person.
The bacteria colonise us through our nasopharynx; this is because they have adhesion molecules. They also secrete IgA proteases that stop our immunal antibodies in our mucosal surfaces from degrading them.
Streptococcus pneumoniae normally follows a viral infection, which would have already damaged our respiratory tract. They also secrete pneumolysin, a toxin which damage the pneumocytes in the lung. This allows the bacteria to enter our lungs, bypassing the defences.
The bacteria escapes phagocytosis with the help of its capsules. It also causes inflammation, resulting in lung damage.
This collection of lung damage can ultimately lead to lobar pneumonia, which can further develop into meningitis and septicaemia, inflammation and toxic shock, and ultimately, death.
The way that Streptococcus pneumoniae survives within a population is by having a large number of serotypes (these are slight changes in the polysaccharide structure of its capsule). The antigen diversity allow for the bacterium to survive in our population, as we may have different antibodies to the antigens presented.
Why is latency as an immune evasion mechanism beneficial?
If the virus infected everybody in a population at the same time, it would result in a population immune to a subsequent attack.
For a pathogen to survive in a small population without dying out, it needs to have evolved a latency strategy to evade immune clearance within the population.
Describe how pathogens reduce antigenic presentation.
The Herpes virus (for example) can bind to and block the TAP protein.
The TAP protein is important in the peptide transfer to the MHC.
Without it, we don’t get antigen presentation.
Describe how pathogens can evade B-cells and T-cells.
Viruses may escape both T-cells and B-cells by undergoing rapid mutation of their epitopes to evade their immune mechanisms.
HIV is a great example.
Define antigenic diversity/ polymorphisms.
It is when there are genetically stable and alternative forms of antigens in a population of microbes (e.g. serotypes of Strep. pneumoniae).
Define antigenic variation.
It is the successive expression of alternative forms of an antigen in a specific clone or its progeny.
Within this we can have phase variation - when you can turn ON/OFF an antigen at low frequency. It occurs during the course of infection in an individual host, and also during the spread of a microbe through a community.
