Microbial immune evasion mechanism Flashcards
What are the properties of microbes which drive pathogenic processes?
- Microbes have properties which drive pathogenic processes:
- Adhesins
- Toxins
- Capsule
What mechanism do host cells have that act as natural barriers?
- Host cells have defence mechanisms which act as natural barriers:
- Natural barriers
- Defensive cells
- Complement
- Immune response
What does a balance of the properties of microbes and mechanism of host cells lead to?
A balance of these 2 properties lead to the clinical course of disease
What is virulence?
Virulence is the degree to which a pathogen causes a disease
What are some virulence factors there to promote?
- Some virulence factors are there to promote colonisation and adherence in order to establish an infection
- Some virulence factors are there to promote tissue damage
What are some virulence factors involved in the evasion of?
Some virulence factors are involved in evading host defence mechanisms
What are examples of non-adaptive/innate immunity?
- Complement
- Phagocytosis
- Protection against antibodies
What does complement induce?
Induces an inflammatory response
What does complement promote?
Promotes chemotaxis by recruiting macrophages/neutrophils to the site of infection
What does complement increase phagocytosis by?
Increase phagocytosis by opsonisation
What does complement increase?
Increase vascular permeability
What does complement cause to the membrane?
Causes lysis of membranes
What are the bacterial defences against complement?
- Bacteria can fail to activate the complement pathway
- Have a factor H sequestration property
- Maybe coated with non-complemented fixing antibodies(IgA)
- Polysaccharide capsules can block C3b binding/preventing C3b receptor access
- Has enzymes which degrade activated products of complement
How can bacteria fail to trigger the complement pathway?
Bacteria have LPS and polysaccharide capsule on their surface which prevents the early stage of the complement cascade from binding to their surfaces, hence failing to trigger the complement cascade
What is the factor H sequestration pathway and how does this protect bacteria against complement?
Bacteria have a protein encoded in their genome, located on its surface, which binds to factor H
-Factor H is a negative regulator of complement, and this stops complement from activating
What drives opsinisation of antigen-antibody complex which protects bacteria against complement?
One of the steps of the complement cascade is that certain antibodies can bind to the complement cascade
-This drives opsonisation of the antigen-antibody complex
What is C3b, when is it released and what does it do?
C3b is a potent opsin which is released when complement cascade has been activated which binds to the surface of the bacteria and allows opsonisation into macrophages
What is C5a and what is it important in and what is it released after?
C5a is a chemoattractant factor which is important in inflammation and is released after complement cascade has been activated
How do certain pathogens evade antibody neutralisation?
Certain pathogens have proteins on their surface which mimics Fc receptor and bind to Fc portion of the antibody the wrong way round and this evades antibody neutralisation
What do intracellular pathogens hide from?
Hide from serum killing, complement and antibodies
Why do intracellular pathogens have an advantage?
Intracellular pathogens have an advantage as its difficult for the immune system to recognise them
What is the role of intracellular pathogens?
- Promote their own safe uptake
- Prepares cell for its invasion
- Negative phagolysosome fusion
- Escape phagolysosome and enters cytoplasm
- Resistive oxidative killing
How does adaptive immunity work?
-Concealment of antigen
-Immunosuppression
-Antigenic variation
-Persistence/latency/
reactivation
Where do antigens hide in the concealment of antigens?
Hide inside cells
Where do antigens enter in the concealment of antigens?
Enter immunologically privileged sites like nerve cells
What is blocked in the concealment of antigen?
Block MHC antigen presentation
What is downregulated in immunosuppression?
- Downregulate MHC presentation
- Downregulate receptors on surface of cells
What does immunosuppression prevent?
Prevent cells from undergoing apoptosis
What do IgA proteases degrade in immunosuppression?
IgA proteases degrade secretory IgA which is a key antibody defence mechanism
What happens in the colonisation of the nasopharynx with streptococcus pneumoniae?
- Have specific adhesion molecules which allow them to adhere
- Secrete IgA proteases which stop immune antibodies
What happens when streptococcus pneumoniae is inhaled into lungs?
- By-pass surfactant molecules
- Still producing secretory IgA proteases which block our antibody defences
- Induce and switch on the genes for pneumolysin and toxins are released by bacteria
- Pneumolysin lyses the membrane and causes pores in membranes of pneumocytes in the lungs and destroys the defensive barriers
- Bacteria has now created a niche for its own replication and induces an inflammatory response which can result in pneumonia
What happens when streptococcus pneumoniae reaches lungs?
- Escapes phagocytosis
- Its capsulated structure allows it to block complement from binding hence not phagocytosed - Inflammation
- Pneumolysin forms pores in membranes of pneumocytes
- Teichoic acids drive an ineffective inflammatory process which creates a niche for bacteria to grow and survive - Damage to endothelial cells
- Inflammation caused by pneumolysin forming pores in membranes of pneumocytes
What can streptococcus pneumoniae lead to?
Can lead to pneumonia
How many serotypes does streptococcus pneumonia has and due to what?What is this known as?
Streptococcus pneumonia has more than 80 serotypes as there are slight changes In the structure of its membrane polysaccharide
-This is known as antigenic diversity
What are the different methods of viral immune evasion?
- Latency
- Decreased antigenic presentation
- Decreased MHC expression
- Mutation of epitopes
When does VZV become latent and where and due to what reason?
Varicella-zoster virus(VZV) becomes latent in nerve ganglia after chicken pox because nerve cells have little immune surveillance
What can certain viruses bind to in order to block antigen presenting?
Certain viruses can bind to TAP protein and block antigen transfer to MHC molecules which can block antigen presenting
What are epitopes?
Epitopes are parts of an antigen which are recognised by antibodies or T cell receptors
What are anitgenic diversity/polymorphisms?
Antigenic diveristy/polymorphisms are genetically stable forms of antigens in a population of microbes
Structure of influenza virus?
Segmented negative single stranded RNA genome=has 8 segments with 10 genes
What do the genes of the influenza virus code for?
Genes code for the surface protein
- Haemagglutin(15types)
- Neuraminidase(9 types)
What happens as a virus replicates itself and what does it create?
As virus replicates itself, it makes errors and creates antigenic variation of surface components
What is the key defence mechanism against influenza?
The key defence mechanism against influenza virus is neutralising antibodies which recognise haemagglutin or neuraminidase
What will a mutation of H or N result in?
A mutation in H or N means antibodies can no longer recognise the antigen
What does the flu virus undergo every year and hence what does this lead to?
Flu virus in a population gradually undergoes minor mutational changes every year and hence immunity becomes less and less
Steps involved in antigenic shift?
- 2 viruses infect a single cell and undergo recombination of the genome which creates combinations of genes which have never been seen before
- This generate a gene re-assortment and new virus particles that very little people in the population have an immune response against
- Results in pandemic flu
