Microbial Immune Evasion Flashcards
Define the terms
- Pathogenicity
- Virulence
- Virulence Factors
- Pathogenicity → Abillity of an organism to cause disease
- Virulence → Degree to which the pathogen causes disease
- Virulence Factors → Molecules produced by virus, fungi, protozoa which add to their effectiveness
List some potential mechanisms bacteria can use to avoidn immune responses
- Inhibit opsonisation
- C3a and C5a proteases (anti-inflammatory and anti chemoattractant
- Prevent opsin binding
- Inhibit complement activation
- Create Ig binding proteins (protein A)
- SIgA proteases
- Inhibit antigen presentation
- Express superantigens and inappropriate immune activation
- Induce/inhibit apoptosis
- Survive inside macrophages
- Phase and antigenic variation
List some potential mechanisms viruses can use to evade the immune response
- MHC mimic - blocks NK cels
- Downregulate MHC
- Block antigen processing by TAP
- Induce immune supression
- Host mimicry
- Cytokine mimics and binding proteins
- Hide/survive inside cells
- Block cell cycle progression
- Induce/inhibit apoptosis
- Latency reactivation
- Antigenic variation
List some examples of virulence factors
- Promote adherance and colonisation
- Promote tissue damage (e.g produce toxins)
- Evade host defences
What is complement and what are its roles?
Complement system/cascade is a group of serum proteins which enhances the abillity of antibodies and phagocytic cells to clear microbes and damaged cells from an organism through
- Induce an inflammatory response (C5a)
- Promote chemotaxis (movement of leucocytes to area of inflammation)
- Increase phagocytosis by opsonisation (C3b)
- Increase vascular permeabillity
- Cell lysis
- Mast cell degranulation
What are some ways in which pathogens can evade the non adaptive (innate) immune response? (complement)
- Affect the COMPLEMENT CASCADE
- Block the trigger of the complement cascade (via endotoxins (LPS) or capsule)
- Factor H Sequestration (removal) (Factor H is involved in activation of complement, if bacteria has a protein that binds factor H (negative binding) there will be no complement activation)
- Bacteria will coat themselves with non-fixing IgA
- IgG and IgM are fixing + will drive complement and opsonisation, non-fixing IgA wont bind complement and drive opsonisation
- Some capsules can block C3b binding (potent opsin)
- C3b can coat bacteria and make and make them more suceptible to phagocytosis as phagocytes have a binding site for C3b
- Block and expel MAC (membrane attack complex) - capsule can prevent C3b binding and C5a proteases can be encoded by the bacteria genome
What is the role of Factor H, C3b and C5a proteases?
They are all involve din the complement
Factor H = initiation of the complement cascade
C3b = Is a potent opsin, it can coat bacteria and contains binding sites for phagocytes making them more susceptible
C5a proteases = are encoded by the bacterial genome and involved in immune evasion
What is opsonisation?
Opsonisation is a molecule that will enhance phagocytosis by marking an antigen for an immune response or marking dead cells for recycling
e.g C3b is a potent opsin and can bind to surface antigens and recognised by phagocyte receptors for phagocytosis
What is the role of C5a?
C5a is released via complement activation
- It is a strong chemoattractant and involved in recruitment of inflammatory cells (neutrophils, eosinophils, macrophages and T-lymphocytes)
- This is blocked by C5a proteases reducing an effective inflammatory response
What are some ways in which pathogens can evade the innate immune response (hiding)
- They can evade the immune system by HIDING
- They can live inside immune cells (if intracellular, it is difficult for immune system to recognise pathogens
Provide some examples of intracellular pathogens
Mycobacterium tuburculosis, Listeria and Salmonella
These can all hide from serum killing, complement and antibodies
What are some immune evasion mechanisms of innate immunity? (Phagocytosis)
- Bacteria will produce extracellular toxins type II leucocidins
- Will damage the membrane of leukocytes (monocytes and neutrophils) preventing phagocytosis
-
Protein A = binds to the Fc part of human IgG preventing opsonisation (found in Staphyloccocus Aureus)
- binds the antibody the wrong way round
- Capsules = Block contact and avoid phagocytosis (meningococcus)
What are some immune evasion machanisms of intracellular pathogens?
- They promote their own (safe) uptake (Shingella + E.Coli)
- Secrete proteins into the macrophage which act as receptors allowing bacteria to be internalised overcoming killing process
- E.g via CR3 and mannose lectin receptors on macrophage
- Secrete proteins into the macrophage which act as receptors allowing bacteria to be internalised overcoming killing process
- Block phagolysosome fusion - once bacteria is in endosome number of proteins secreted and early acidification prevent endosome fusing with lysosome (myob. TB)
- Escape the phagolysosome to the cytoplasm (Listeria) where they will replicate and escape the killing mechanism of the macrophage allowing it to grow and replicate
- Resist oxidative killing (produce catalases and peroxidases) = neutralise reactive oxygen intermediates produced by phagolysosome fusion
How can microbes protect themselves from antibodies?
- Normal situation
- Antibody will contain receptors which will bind to antigens. This will eliminate them through Fc receptor mediated phagocytosis
- Virus + Bacteria containing a microbial Fc receptor
- This allows the antibody to bind backwards blocking the access to surface antigen and preventing opsonisation + phagocytosis
What are some of the ways in which pathogens can evade adaptive immune responses?
- Concealment of antigens
- Immunosuppresion
- Antigenic Variation
- Persistence, Latency, Reactivation
How does concealment of antigens work so pathogens can evade the adaptive immune response?
- They can hide inside cells that are immunologically priveleged sites e.g nerve cells
- Block MHC antigen presentation on dendritic cells and macrophages (e.g herpes)
- These pathogens do this by inhibiting TAP protein which is involved in antigen processing
What is the role of TAP protein?
It is involved in antigen processing, concealment of antigens can occur through blocking this protein on dendritic cells and macrophages
How can immunosuppression evade the adaptive immune response?
They will
- Downregulate expression of MHC
- Downregulate receptors (e.g interferon gamma receptors) = activation of these enhance killing mechanism
- Interfere with apoptotic pathway of cells or induce apoptosis so that they can grow and suvive and escape from the cell
- Cytokine switch = Microbes can cause disbalance of cytokines
- IgA proteases (will degrade IgA antibodies at mucosal sites)
Describe antigenic variation
- This is the succesive expression of alternative forms of an antigen in a specific clone or its progeny
- This will allow it to avoid its host immune response aswell as allowing re-infection of previously infected hosts
Describe phase variation
ON/OFF of an antigen at low frequency occurs during course of infection of an individual host during spread of microbe through a community
Describe how steptococcus pneunomiae causes disease in a person?
- We will breath the organism in and will colonise in our nasopharynx because of special receptors (NAc-hex-gal)
- They also contain IgA proteases which will block the secretion of IgA
- Sp will then be breathed into the lungs and by-pass sufactant molecules and mucus by secreting IgA and pneumolysin which will damage pnuemocytes
- An inflammatory response will be triggered
- Bacteria will also contain a capsule which blocks complement + antibody binding
- Bacteria contain techtoic acids = lung damage + inflammation
- There will be damage to endothelial cells due to inflammation
This can lead to lobar pneunomia = develop into meningitis and septicaemia, inflammation and toxic shock
How has streptoccoccus pneunomiae survived in the population?
- There are multiple antigen serotypes (changesin the polysaccharide structure to its capsule)
- It is able to survive in the population by having multiple serotypes
- = ANTIGENIC DIVERSITY
Describe viral immune evasion mechanisms
- Latency
- Decreased antigenic presentation (binds to TAP protein, inhibits transfer to MHC = herpes simplex)
- Decreased MHC expression
- Mutation of epitopes
Why is latency important?
- If everyone were to be infected at the same time it would result in a population immune to subsequent attack
- For a pathogen to survive in a small population without dying out it will need to have evolved a latency strategy to evade immune clearance
Describe how pathogens will evade B-cells and T-cells?
- Viruses will escape B and T cells by undergoing rapid mutation of their epitopes to evade immune mechanisms
- HIV is an example of this
- B cells → neutralisation escape
- T cells → CD8+ escape mutants of HIV
Describe antigenic diversity/polymorphisms
Genetically stable and alternative forms or antigens in a population of microbes
E.g serotypes of Strep.pneumoniae
How does gornorrhoae evade the immune response?
- The virus surface components interact with the host ce;s
- The components vary at a high frequency in a population of bacteria
- This variation is to avoid a triggering immune response
Describe how the influenza virus has potential for variation
- Segmented single stranded RNA genome
- These genes are about 10 genes which code for haemagglutinins and neuraminidases
- The virus evades immunity at a population level via anitgenic drift
- The virus will gradually undergo small mutations every year so antibodies from last year will not recognise the newly mutated version
- Antigenic drift = can cause epidemic flus
- Antigenic shift = where two viruses will infect a single cell and undergo recombination of the genome and generate gene reassortment = new virus population
- This can cause pandemic flus
