Microbial Immune Evasion Mechanisms Flashcards
- What is meant by “Balanced Pathogenicity”?
The balance between properties of the microbe (pathogenic mechanisms) and properties of the host (defensive mechanism) determine the pathogenicity
- Explain what pathogenic mechanisms can help the pathogen increase its pathogenicity?
- Adhesion Molecules
- Toxins
- Capsules
etc. ..
- Explain what defensive mechanisms are in place to reduce the pathogenicity of the virus?
- Natural Barriers (eg mucous, tight epithelial junctions, antimicrobial peptides)
- Defensive Cells (Lymphocytes, macrophages)
- Immune response (Complement system)
- Adaptive immune response (B cell and T cell)
- Do all organisms (eg humans) experience the same virulence if disease, if not , why?
We all experience different levels of disease, this is because we have different defensive mechanisms
- What are Virulence factors?
Components of an organism that drive pathogenesis
- What is the difference between pathogenesis and Virulence?
Pathogenesis = It can cause disease Virulence= The degree to which it causes disease
- Give some examples as to what a virulence factor could be?
- Something that promotes colonisation and adhesion—>establishes infection eg Adhesins
- Something that promotes tissue damage —-> for transmission eg toxins
- What are some roles of the compliment system?
- Induces inflammatory response (releasing factors that chemoattract the effector cells )
- Increases phagocytosis by opsonisation ( binding the surface of pathogens and allows them to be phagocytosed by macrophages and killed)
Increases vascular permeability –> allow in immune defensive cells to kill pathogen
Mast cell degranulation
Lysis of cell membranes
- How do pathogens fight against our immune response specifically complement using LPS and capsules?
-Fail to activate the compliment pathway (polysaccharides on their surface and endotoxins (LPS) don’t allow the early stage of the compliment system to bind to their surface so it blocks the triggering of the compliment activated cascade
10.How do pathogens fight against our immune response specifically complement using Factor H sequestration?
Fails to allow the assembly of the complement – (particular bacteria that causes meningitis ) have a protein encoded in their genome called Factor H (a negative regulator of the complement cascade) SO if a bacteria has a protein on its surface bound to Factor H, it will stop compliment from being activated on the surface of the bacteria
- How do pathogens fight against our immune response specifically complement by coating with non-fixing with IgA?
Can coat themselves with non-fixing immunoglobulins , one of the things of complement is that certain antibodies can bind to compliment and that drives opsonisation of that antigen-antibody complex. Certain bacteria can coat themselves with antibodies that CANNOT bind to complement and therefore cannot be opsonised eg IgA
- How do pathogens fight against our immune response specifically complement by capsules blocking C3b
Polysaccharide capsules on some bacteria walls can block C3b binding- c3b is one component released when compliment is activated , it is a powerful opsonin- it binds to surfaces and allows opsonisation– macrophages
- How do pathogens fight against our immune response specifically complement by creating C5a proteases?
C5a- component after compliment is activated, certain bacteria have enzymes that degrade C5a and C3b . C5A is chemo attractant factor —>minimizes the amount of inflammation–> tips balance in favor of pathogen
- Another way of pathogens defensive mechanisms to the immune response ,is to hide from it! How can they do that?
- > Intracellular pathogens eg viruses enter the cells macrophages
- > Need a mechanism to kill cytotoxin T cells
- Advantageous of the pathogen because If your virus /bacteria lives inside cells , then its difficult for the immune system to recognise that the pathogen is there and how to have a killing effect
- Give three examples of pathogens that ‘hide’ from the immune system ?
Mycobacterium tuberculosis
Listeria
Salmonella
- Which toxins can pathogens produce to prevent phagocytosis by killing the cell- how?
Some bacteria contain toxins (leucocidins eg Staphylococcus) that produce extracellular type 2 toxin – damage membrane of white cells eg macrophages (prevent phagocytosis of themselves)
- Another way of pathogens preventing phagocytosis is by preventing opsonisation first-how?
Prevent opsonisation — non fixing complement antibody OR antibody A (binds antibodies the wrong way round – Fc receptors bind instead of antibody recognition site) , cant be opsonised by a macrophage , organism has overcome opsonisation
- Another way of pathogens preventing phagocytosis is by blocking contact - how?
-polysaccharide capsules –non antigenic , pathogen cant be recognised, use capsules to avoid phagocytosis
- How does the Shigella or E.coli toxin evade macrophages and enter the cell?
Some pathogens (Shigella, E.Coli) inject proteins into the macrophage – act as receptors for the bacteria , bacteria can bind to its own receptor – internalised that overcomes killing mechanism of macrophages
- How doesM. tuberculosis survive intracellularly?
M.T blocks phagalysome fusion (-ve P-L fusion) , once its in early endosome, starts to secrete proteins to block that phagalysosome mechanism . Stops acidification of early endosome – > cant phagocytose
- How does Listeria survive intracellularly?
Listeria , escapes phagolysosome into cytoplasm – escapes all killing mechanism – grows and replicate
- How does producing your own catalases/peroxidases help to survive intracellularly?
Some pathogens produce their own catalyses/peroxides’ that neutralise the enzymes in the phagalysosome , specific components in their genome -> virulence components
- How does you use CR3 and mannose lectin receptors to survive intracellularly?
Intracellular pathogens enter macrophages through receptors that don’t activate the macrophages
- How does the production of Fc receptors by microbes, help them against our immune system?
Normally:
Once an antibody binds to the surface of a pathogen, the Fc component binds to the Fc receptor on the pathogen, it gets internalised and killed through acidification , phagocytosis and respiratory burst
-CERTAIN pathogens (Staph,Herpes HHV-1 and HHV-3) they have proteins on their surface that mimics the Fc receptor so they bind the Fc receptors the wrong way round
-protective mechanism
-allow them to evade antibody neutralisation
Fc receptor mimics
- What are the four main ways a pathogen can invade our adaptive immunity?
1.Concealment of antigen
2 .Immunosuppression
3. Antigenic Variation (changing antigen slightly)
4. Persistence/latency/reactivation (stays in the body for a long time)
- How can a pathogen conceal their antigen?
hiding inside cells, go to parts of the body that we call immunologically privileged sites –typically nerves so nerve cells really don’t have much immune response because if they did and we damaged our nerves we would loose our ability to survive so they are immunologically privledged sites so they hide their antigen here – eg Herpes can live in our nervous system for many years to be reactivated later or shed
- Block presentation of antigen through MHC (in dendritic cells, macrophage) so after the virus has been processed in macrophage, the antigens are presented on their surface – so certain viruses can block this antigen presentation, inhibit protein called Tap protein
- surface uptake of host molecules e.g. CMV and beta2microglobulin
- How do pathogens cause immunosuppression?
Suppress immunity-down regulating the MHC presenting antigen cells or by down regulation receptors eg interferon gamma .
- Interfere apoptosis so they can continue dying
- Certain pathogens induce apoptosis so they can escape via cell lysis
- Interfere cytokine balance= tip whole immune response in favour of pathogen
- neutralise IgA using proteases
- What does Streptococcus pneumoniae cause?
Pneumonia
Otitis media
meningitis
- What are the 4 main pathogenic mechanisms of Streptococcus pneumoniae?
Colonisation
By-pass defences
Survival
Damage
- Explain the process by which you get infected by Streptococcus Pneumoniae
- So we breathe the organism in
- Colonised by our naso-pharynx (due to Adhesion molecules)
- Secrete igA proteases that stop our immune antibodies at our mucosal surface from aggregating and evading the SP
- Gives them the ability to be retained
- Once you get viral infection–> defence mechanism in our respiratory tract damaged->so were breathing in SP into our lungs -> but our main defence mechanism against SP is surfactant molecules and mucous inside the lungs.
- How does overcome the immune response? in detail?
Secreting iIgA proteases and now will start to secrete pneumolysin (toxin that’s released – lyse the membranes and cause pores of the pneumocytes of the lungs, once you’ve damaged them , then you’ve destroyed the defensive barrier, bacteria can create niche, cause inflammatory response, and then get pneumonia – spread to blood –septicaemia, meningitis
Producing toxin , inflammatory response will be activated but its capsulated so it can block phagocytosis
Teichoic acids= gram + has these molecules – immune defence mechanism
More than 90 types serotype , so we might have antibodies for some serotype but not the others , slight changes in polysaccharide capsule
- What are two examples of viruses that use latency as a viral immune evasion?
- VZV /Opthalmic Zoster (Chicken pox as child, remaining latent for years and reactivates to form shingles-dangerous)
- Herpes Simplex
- How can viruses use persistence as an immune evasion strategy?
Allows virus to exist in small populations
If the virus caused an infection at the same time then you would get a population that is immune to subsequent attack- pathogen would die out
So for a virus to exist for a long time in a population it needs to have developed this latency – evade immune clearance within a population
Remain latent to subsequently reactivate
- How does the Herpes Simplex Virus I stay latent?
-Hides in nerves cells (immunologically privileged site)
-Poor protective immunity for reactivation
-Note creeping lesions
and scars from previous episodes
- How can pathogens achieve a decrease in antigenic presentation and MCH expression?
Herpes can bind to a Tap protein
Blocks antigen transfer to MHC molecules
Blocks antigen presentation
CMV (cytomegalovirus)= down regulate MHC regulation
- What is the mutation of epitopes and how does this evade the immune response?
Epitopes- bites of antigen recognized by antibodies or T cell receptor
Viruses can escape both B cell or T cell by undergoing rapid mutation – mutated surface antigen = HIV is an example
B cells - neutralisation escape T cells - CD8+ escape mutants of HIV
- Give some examples of phenotype changes?
colony morphology, virulence, serotype loose flagella, change surface sugars
- What is Antigenic Diversity/Polymorphisms?
- 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
- occurs - during course of infection in an individual host- during spread of microbe through a community
- What is Gonorrhoea?
STD
Multiple re-infection
Asymptomatic
10% male
30% female
Causes Inflammatory and pyogenic infection of anterior urethra
Infects mucosal surfaces with columnar epithelium
- urethra, cervix, rectum, pharynx, conjunctiva
- What are some symptoms of Gonorrhoae?
dysuria, redness, swelling, pain on urination, destruction of mucosa
prostatitis, orchitis, strictures, ovaritis, fistulas, PID, proctitis, sterility
Disseminated infections —> arthritis, endocarditis, meningitis
- What is the bacteria that causes Gonorrhoae?
Neisseria gonorrhoeae
- What does Neisseria gonorrhoeae
do to evade the immune cells?
Surface components interact with host cells
Components vary at high frequency in a population of bacteria
Variation to avoid immune response
Phase and antigenic variation in Neisseria affects cell surface components
- Explain the structure of the influenza virus?
Segmented –ve ssRNA genome 8 segments, 10 genes Has the surface proteins: H haemaglutinin- 15 types N neuraminidase- 9 types
- Influenza uses antigenic drift and shift, explain the difference ?
at population level , series of mutation= ANTIGENIC DRIFT. As the virus replicates itself , it gets minor mutated , this is selected for (antibodies cant recognize and survive) . This is why we get continuous flu vaccine- epidemics of flu
Antigenic Shift – when two viruses affect a single cell and you get recombination of the cell, so now you get combinations of gene that we’ve never seen before – gene reassortment – infect everybody – spread quickly – PANDEMICS. Host population is immunologically naive = must more severe
- Give four examples of how BACTERIA might avoid the immune system?
Any four out of:
C3a and C5a proteases Anti-inflammatory and anti chemoattractant Inhibits opsonisation sIgA proteases Inhibition of antigen presentation Ig binding proteins e.g. protein A Survival insidemacrophages
- Give four examples of how VIRUSES might avoid the immune system?
Any four out of:
- Block antigen processing by TAP
- Downregulate MHC
- Latency reactivation e.g. VZV, Herpes simplex
- Blockage of cell cycle progression
- Hide inside host cell
