Microbial Immune Evasion Mechanisms

Question 1

1. What is meant by “Balanced Pathogenicity”?

Answer 1

The balance between properties of the microbe (pathogenic mechanisms) and properties of the host (defensive mechanism) determine the pathogenicity

Question 2

2. Explain what pathogenic mechanisms can help the pathogen increase its pathogenicity?

Answer 2

• Adhesion Molecules
• Toxins
• Capsules
  etc. ..

Question 3

3. Explain what defensive mechanisms are in place to reduce the pathogenicity of the virus?

Answer 3

• 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)

Question 4

4. Do all organisms (eg humans) experience the same virulence if disease, if not , why?

Answer 4

We all experience different levels of disease, this is because we have different defensive mechanisms

Question 5

5. What are Virulence factors?

Answer 5

Components of an organism that drive pathogenesis

Question 6

6. What is the difference between pathogenesis and Virulence?

Answer 6

Pathogenesis = It can cause disease
Virulence= The degree to which it causes disease

Question 7

7. Give some examples as to what a virulence factor could be?

Answer 7

1. Something that promotes colonisation and adhesion—>establishes infection eg Adhesins
2. Something that promotes tissue damage —-> for transmission eg toxins

Question 8

8. What are some roles of the compliment system?

Answer 8

• 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

Question 9

9. How do pathogens fight against our immune response specifically complement using LPS and capsules?

Answer 9

-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

Question 10

10.How do pathogens fight against our immune response specifically complement using Factor H sequestration?

Answer 10

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

Question 11

11. How do pathogens fight against our immune response specifically complement by coating with non-fixing with IgA?

Answer 11

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

Question 12

12. How do pathogens fight against our immune response specifically complement by capsules blocking C3b

Answer 12

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

Question 13

13. How do pathogens fight against our immune response specifically complement by creating C5a proteases?

Answer 13

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

Question 14

14. Another way of pathogens defensive mechanisms to the immune response ,is to hide from it! How can they do that?

Answer 14

• > 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

Question 15

15. Give three examples of pathogens that ‘hide’ from the immune system ?

Answer 15

Mycobacterium tuberculosis
Listeria
Salmonella

Question 16

16. Which toxins can pathogens produce to prevent phagocytosis by killing the cell- how?

Answer 16

Some bacteria contain toxins (leucocidins eg Staphylococcus) that produce extracellular type 2 toxin – damage membrane of white cells eg macrophages (prevent phagocytosis of themselves)

Question 17

17. Another way of pathogens preventing phagocytosis is by preventing opsonisation first-how?

Answer 17

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

Question 18

18. Another way of pathogens preventing phagocytosis is by blocking contact - how?

Answer 18

-polysaccharide capsules –non antigenic , pathogen cant be recognised, use capsules to avoid phagocytosis

Question 19

19. How does the Shigella or E.coli toxin evade macrophages and enter the cell?

Answer 19

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

Question 20

20. How doesM. tuberculosis survive intracellularly?

Answer 20

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

Question 21

21. How does Listeria survive intracellularly?

Answer 21

Listeria , escapes phagolysosome into cytoplasm – escapes all killing mechanism – grows and replicate

Question 22

22. How does producing your own catalases/peroxidases help to survive intracellularly?

Answer 22

Some pathogens produce their own catalyses/peroxides’ that neutralise the enzymes in the phagalysosome , specific components in their genome -> virulence components

Question 23

23. How does you use CR3 and mannose lectin receptors to survive intracellularly?

Answer 23

Intracellular pathogens enter macrophages through receptors that don’t activate the macrophages

Question 24

24. How does the production of Fc receptors by microbes, help them against our immune system?

Answer 24

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

Question 25

25. What are the four main ways a pathogen can invade our adaptive immunity?

Answer 25

1.Concealment of antigen 2 .Immunosuppression 3. Antigenic Variation (changing antigen slightly) 4. Persistence/latency/reactivation (stays in the body for a long time)

Question 26

26. How can a pathogen conceal their antigen?

Answer 26

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

Question 27

27. How do pathogens cause immunosuppression?

Answer 27

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

Question 28

28. What does Streptococcus pneumoniae cause?

Answer 28

Pneumonia Otitis media meningitis

Question 29

29. What are the 4 main pathogenic mechanisms of Streptococcus pneumoniae?

Answer 29

Colonisation By-pass defences Survival Damage

Question 30

30. Explain the process by which you get infected by Streptococcus Pneumoniae

Answer 30

1. So we breathe the organism in 2. Colonised by our naso-pharynx (due to Adhesion molecules) 3. Secrete igA proteases that stop our immune antibodies at our mucosal surface from aggregating and evading the SP 4. Gives them the ability to be retained 5. 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.

Question 31

31. How does overcome the immune response? in detail?

Answer 31

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

Question 32

32. What are two examples of viruses that use latency as a viral immune evasion?

Answer 32

- VZV /Opthalmic Zoster (Chicken pox as child, remaining latent for years and reactivates to form shingles-dangerous) - Herpes Simplex

Question 33

33. How can viruses use persistence as an immune evasion strategy?

Answer 33

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

Question 34

34. How does the Herpes Simplex Virus I stay latent?

Answer 34

-Hides in nerves cells (immunologically privileged site) -Poor protective immunity for reactivation -Note creeping lesions and scars from previous episodes

Question 35

35. How can pathogens achieve a decrease in antigenic presentation and MCH expression?

Answer 35

Herpes can bind to a Tap protein Blocks antigen transfer to MHC molecules Blocks antigen presentation CMV (cytomegalovirus)= down regulate MHC regulation

Question 36

36. What is the mutation of epitopes and how does this evade the immune response?

Answer 36

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

Question 37

37. Give some examples of phenotype changes?

Answer 37

colony morphology, virulence, serotype loose flagella, change surface sugars

Question 38

38. What is Antigenic Diversity/Polymorphisms?

Answer 38

- genetically stable and alternative forms of antigens in a population of microbes e. g. serotypes of Strep.pneumoniae

Question 39

39. What is Antigenic Variation?

Answer 39

- successive expression of alternative forms of an antigen in a specific clone or its progeny

Question 40

40. What is Phase Variation?

Answer 40

ON/OFF of an antigen at low frequency | - occurs - during course of infection in an individual host- during spread of microbe through a community

Question 41

41. What is Gonorrhoea?

Answer 41

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

Question 42

42. What are some symptoms of Gonorrhoae?

Answer 42

dysuria, redness, swelling, pain on urination, destruction of mucosa prostatitis, orchitis, strictures, ovaritis, fistulas, PID, proctitis, sterility Disseminated infections ---> arthritis, endocarditis, meningitis

Question 43

43. What is the bacteria that causes Gonorrhoae?

Answer 43

Neisseria gonorrhoeae

Question 44

44. What does Neisseria gonorrhoeae | do to evade the immune cells?

Answer 44

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

Question 45

45. Explain the structure of the influenza virus?

Answer 45

``` Segmented –ve ssRNA genome 8 segments, 10 genes Has the surface proteins: H haemaglutinin- 15 types N neuraminidase- 9 types ```

Question 46

46. Influenza uses antigenic drift and shift, explain the difference ?

Answer 46

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

Question 47

47. Give four examples of how BACTERIA might avoid the immune system?

Answer 47

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 ```

Question 48

48. Give four examples of how VIRUSES might avoid the immune system?

Answer 48

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