Introductory Content

Question 1

1. Order the following in most morbid to least:

• Malaria
• Diarrhoeal diseases
• Acute respiratory infections
• STIs
• Pertussis
• Tropical diseases
• HIV/AIDS
• Tuberculosis
• Measles

Answer 1

Acute respiratory infections
Diarrhoeal diseases
HIV/AIDS
Malaria
Measles
Tuberculosis
STIs
Pertussis
Tropical Diseases

Question 2

2. What are 3 examples contributing to the spread of epidemics?

Answer 2

Mass travel
Modern high density living
Animal husbandry: close proximity with pigs, birds

Question 3

3. Infectious diseases whose incidence in humans has increased in the past 2 decades or threatens to increase in the near future, include:

a) New infections resulting from changes or evolution of existing organisms
b) Known infections spreading to new geographic areas/populations
c) Previously unrecognised infections appearing in areas undergoing ecologic transformation
d) Old infections re-emerging as a result of antimicrobial resistance in known agents or breakdowns in public health measures
e) all of the above

Answer 3

e) all of the above

Question 4

4. Which is NOT a major factor contributing to the emergence of infectious diseases?

a) human demographics & behaviour
b) economic development & land use
c) breakdown of public health measures
d) regular sanitary measures
e) international travel & commerce

Answer 4

d) regular sanitary measures, although, extreme sanitary measures can prevent the development of the human immune system…

other major factors include:

• technology & industry
• microbial adaptation & change

Question 5

5. What are the two most common diseases affecting tourists?

a) respiratory infections & gonorrhoea
b) diarrhoeal diseases & fever (cause unknown)
c) diarrhoeal diseases and gonorrhoea
d) respiratory infections & diarrhoeal diseases
e) fever & malaria

Answer 5

d) respiratory infections (8%) & diarrhoeal diseases (64%).

Other major tourists diseases (to a lesser extent) are gonorrhoea, hepatitis, fever (cause unknown) and malaria.

Question 6

6. What are 3 major microbial species exhibiting extensive antimicrobial resistance?

Answer 6

Malaria, Tuberculosis and Staphylococcus.

For example, Malaria already exhibits complete resistance to some antibiotics in Thailand.

Question 7

7. What are the AIMS of ACTIVE IMMUNISATION? Have they been achieved?

Answer 7

• to produce long-lasting immunity to pathogens in individuals & the community
• to eliminate the pathogen (where possible)
• successes: smallpox, polio
• less effective: BCG vaccine for TB, whooping cough vaccine
• major deficiencies - no vaccine for: HIV, malaria

Question 8

8. Which is correct regarding COMMENSALISM, MUTUALISM and PARASITISM?

a) commensalism is where one partner benefits and the other is harmed
b) parasitism can exist when the host is unaffected
c) mutualism is where one partner benefits and the other is harmed
d) none of the above

Answer 8

d) none of the above:

• ‘commensal’ = lives in / on another, i.e. interaction bw normal flora & host: one partner benefits, other partner not affected
• ‘mutualist’ / ‘symbiont’: both partners benefit (often obligatory eg ruminants, GIT flora)
• ‘parasitic organisms’: one partner benefits, other harmed (pathogen = parasitic organism causing specific disease)

Question 9

9. SYMBIOSIS SPECTRUM

Answer 9

Mutualism-Commensalism-ParasitismShift right: initiate disease Shift left: re-establish a healthy host.

The spectrum is DYNAMIC. (see #10 & 11)

Question 10

10. Describe VIRULENCE.

Answer 10

Degree or intensity of pathogenicity, i.e. increase virulence –> likely to cause harm; a shift towards Parasitism. A standard strain of an organism may change, acquiring new virulence factors and mechanisms for damaging the host. Can lead to epidemics.

Question 11

11. What are 3 factors governing symbiosis?

Answer 11

1. No. organisms: increase numbers = shift to parasitism, e.g. poor hygiene.
2. Virulence of organisms: increase virulence = shift to parasitism
3. Host’s defence / resistance: healthy = high resistance, decreases resistance = shift to parasitism.

Question 12

12. When is a disease an infectious disease?

Answer 12

Koche’s Postulates:

1. The same pathogen must: be PRESENT IN EVERY CASE of the disease
2. The pathogen must: be ISOLATED FROM THE DISEASED HOST and grown in pure culture
3. The pathogen from the pure culture must: CAUSE THE DISEASE when inoculated into a healthy, susceptible laboratory animal
4. The pathogen must: again be ISOLATED FROM THE INOCULATED ANIMAL and must be shown to be the original organism

Question 13

13. Give examples diseases of the following:

a) Outbreak
b) Endemic
c) Epidemic
d) Pandemic
e) Sporadic

Answer 13

a) Sudden, unexpected occurrences: Hendra virus Qld 2012 & 2013, Ebola in West Africa
b) Usually within a population; steady, at fairly low levels without any peaks: common cold, TB, malaria
c) Sudden occurrence; sudden increase above a baseline: influenza
d) Disease increases within large widespread populations usually worldwide: SARS
e) Random & irregular: Salmonella food poisoning outbreak

Question 14

14. Explain the concept of “Herd Immunity”

Answer 14

Scenario when people immunised or have recovered from the disease and developed natural immunity block susceptible individuals from the index case or spread of disease. If an infected individual however comes into contact with the susceptible individual they will become sick. In an unprotected population, herd immunity does not (yet) exist, and a disease will spread rapidly.

Question 15

15. Explain the differing functions of the HA & NA proteins of the Influenza Virus, and how they contribute to endemics.

Answer 15

Haemagglutinin protein - for attaching the virus to epithelial cells in our respiratory tract.

Neuraminidase - punches a hole in the outer surface of epithelial cells & allows the cells to enter & thus replicate.

These 2 proteins can change & give way to different versions of the virus, which can allow it to overcome immune response (host cells no longer immune).

Question 16

16. Explain the differences between antigenic SHIFT and DRIFT.

Answer 16

Drift = SMALL antigenic changes, e.g. altered protein which leads to ineffective recognition by the immune system (mutation)

Shift = DRASTIC antigenic changes e.g. large scale altered proteins, leading to complete non-recognition by the immune system. Coinfection with animal & human strains of influenza can generate very different virus strains by genetic reassortment (sharing/incorporation of virulence-causing DNA). Can lead to major epidemics/pandemics.

Question 17

17. Which of the following is not an example of vector-borne transmission?

a) malaria
b) flu
c) trypanosomiasis
d) none of the above

Answer 17

b) flu is air-borne transmission, on aerosols or ‘fomites’ (air-borne particles which carry infectious organisms). The flu can transmit via coughing, talking or sneezing, as examples. Other air-borne examples include chicken pox, mumps & measles. (even dust can be a factor, e.g. in hospitals, can lead to nosocomial infections).

NB trypanosomiasis = any tropical disease caused by trypanosomes and typically transmitted by biting insects, especially sleeping sickness and Chagas’ disease. Other examples include dengue fever & zika virus, transmitted via mosquitos.

Question 18

18. How do CONTACT & VEHICLE modes of transmission differ?

Answer 18

Contact: direct, usually skin to skin, or utensils; includes STIs.

Vehicle: contaminated food/water; e.g. cholera & food poisoning

Question 19

19. What is the most important step in Control of Disease?

a) The pathogen
b) Source of the pathogen
c) Transmission to host
d) Host susceptibility
e) Exit from the host

Answer 19

c) Controlling TRANSMISSION: stopping the spread from one host to the next:
- change behaviour: HIV protection
- destroy insect vectors: DDT mosquitos
- control animal vectors: cattle: brucellosis, TB

Question 20

20. How are VIRULENCE and MODE OF TRANSMISSION related?

Answer 20

Virulence = intensity of pathogenicity OR degree of ability to cause disease. It is affected by the ability to live outside a host. If virulence is low e.g. in the common cold, the host is still active, moves around, and can spread the virus. If the virulence is increased to the point the host is bed-ridden, the transmission drops.

Conversely, vector transmission eg African sleeping sickness: the host can’t transmit as the pathogen is reliant on a vector. I.e. the virulence is not connected with transmission.

Question 21

21. How do Virulence Factors assist pathogenic microbial survival?

Answer 21

1. Aid colonisation (eg capsule, pili/fimbriae)
2. Allow penetration of host tissue
3. Prevent/reduce host response
4. Cause direct damage eg toxicity

Question 22

22. What is the difference between specific and non-specific attachment/adhesion?

Answer 22

Specific - between particular proteins (e.g. flu virus protein spikes receptors)

Non-specific - just ‘sticking on a membrane’, eg slime/capsule/glycocalyx; dental plaque

Question 23

23. How might an organism penetrate a host cell for further growth?

Answer 23

Uptake via:

• Invasins: bacterial surface proteins (promote ingestion)
• Endocytosis: non-phagocytic cells (exocytosis: actin tail propulsion)
• Phagocytosis

e. g. Flu virus: endocytic uptake
e. g. Measles virus: membrane fusion uptake

Question 24

24. What are some of the microbial enzymes that promote survival, penetration & damage to the host?

Answer 24

Coagulase: Coagulates blood
Kinases: Digests fibrin clots
Hyaluronidase: Hydrolyses hyaluronic acid
Collagenase: Hydrolyses collagen
IgA proteases: Destroys IgA antibodies = survival

Other important factors for penetration & growth:

• Siderophores: Take iron from host (iron-binding proteins)
• Antigenic variation: Alter surface proteins

Question 25

25. What is one of the most significant microbial defences against immunological clearance that contributes to high virulence capacities?

Answer 25

CAPSULES. They are PROTECTIVE and ANTI-PHAGOCYTIC. They mask antigenic sites & evade detection. E.g. glycocalyx layer around E. coli, a protection & important attachment mechanism on intestinal tissue. E.g. polysaccharide coat around pathogenic yeast (Cryptococcus neoformans), appears as a 'shiny halo' under microscopy; very thick & protective, a hydrophilic capsule that inhibits phagocytosis & evades immune response.

Question 26

26. Other than capsules, what are other microbial defences against immunological clearance?

Answer 26

Antigenic change: shift, mimicry (mimicry = coat themselves in host protein so not seen as 'non-self') Produce antibody proteases: destroy immunoglobulins Intracellular survival Affect phagocytosis: destroy phagocyte, or inhibit phagocytosis (prevent chemotaxis / inhibit phagosome/lysosome fusion / resist lysosomal enzymes)

Question 27

27. Describe the following characteristics of exotoxins: a) source b) metabolic product c) chemistry d) fever e) neutralised by antitoxin

Answer 27

a) mostly G+ b) by-products of growing cell (diffuse / actively transported out) c) protein d) none e) yes

Question 28

28. What are the 3 types of microbial exotoxins based on structure & action?

Answer 28

1. A-B 2. Membrane-disrupting 3. Superantigens

Question 29

29. How do membrane-disrupting exotoxins lead to cell death?

Answer 29

If exotoxin is pore/channel-forming: cytoplasmic contents will leak out and water will enter the cell (osmotic effects), leading to swelling, host cell lysis and death. If exotoxin is Phospholipase: will hydrolyse the membrane, and destabilise the lipid bilayer. Destroyed integrity will lead to cell lysis & death.

Question 30

30. Describe the following characteristics of endotoxins: a) source b) metabolic product c) chemistry d) fever e) neutralised by antitoxin

Answer 30

a) G- (mostly*) - LPS b) present in LPS of outer membrane (part of the cell wall) c) lipid (lipopolysaccharide) d) occurs (inflammatory mediators) e) no (not proteins, so can't use Ab's) *G+ sources exist, but far less virulent - peptidoglycan, LTA, TA

Question 31

31. Why are endotoxin releasing organisms difficult to treat?

Answer 31

The SHOCK (septic) of breaking up bacteria with antibiotics, and the resultant release of the membrane blebs in the blood stream, can be in some cases considered worse than an individual's current infection with the organism.

Question 32

32. Provide an example of how Pathogenicity Islands contribute to characteristics of pathogenicity.

Answer 32

PI's are large segments of DNA that contain insertion-like sequences (mobile), encoding major virulence factors and associated with tRNA encoding genes. They are acquired by horizontal gene transfer and thus can be spread from cell to cell. E.g. Protein secretion by Yersinia pestis (plague) modulates host activities. Through a 'needle-like' structure, it delivers effector proteins, secreting plasmid-encoded outer membrane proteins into phagocytic host cells. This damages & counteracts natural defence mechanisms, helping Y. pestis multiply & disseminate in the host.

Question 33

33. Discuss COMPLEMENT and its roles in the innate immune system.

Answer 33

A component of blood, complement is always present in serum. Involves: - a series of 9 serum enzymes, act in cascade - activated when Ag/Ab rxn's occur - in association with Ab, causes bacterial lysis (kills cells) - aids phagocytosis Ultimate outcome is opsonisation/destruction of bacteria by a phagocytic cell. (opsonisation = molecular mechanisms where microbes/cells (etc.) are chemically modified to have stronger interactions with and "appear more delicious" to surface receptors on phagocytes and NKCs.

Question 34

34. What are GLYCOPROTEINS and how do they contribute to the innate immune system?

Answer 34

= proteins + polysaccharide moieties. e. g. Fibronectin: - mediates non-specific clearance (of foreign cells) - Coats foreign cells -> clotting - Blocks attachment of foreign organisms to epithelial cells RESULT: limits colonisation (maintains CT integrity)

Question 35

35. What are CYTOKINES and how do they contribute to the innate immune system?

Answer 35

- Intercellular signals - Bind to receptors on cells - Triggers cellular behaviours: - Initiate signal transduction pathway ○ Regulates specific transcription, translation events - Soluble small protein/glycoprotein - Can induce production of other cytokines - Produced in response to non-specific stimulus from: - Microbes: bacteria, viruses, parasites - Cancer - Inflammation - Action of specific immune cells

Question 36

36. Discuss COMPLEMENT and its roles in the innate immune system.

Answer 36

A component of blood, complement is always present in serum. Involves: - a series of 9 serum enzymes, act in cascade - activated when Ag/Ab rxn's occur - in association with Ab, causes bacterial lysis (kills cells) - aids phagocytosis Ultimate outcome is opsonisation/destruction of bacteria by a phagocytic cell. (opsonisation = molecular mechanisms where microbes/cells (etc.) are chemically modified to have stronger interactions with and "appear more delicious" to surface receptors on phagocytes and NKCs.

Question 37

37. What are GLYCOPROTEINS and how do they contribute to the innate immune system?

Answer 37

= proteins + polysaccharide moieties. e. g. Fibronectin: - mediates non-specific clearance (of foreign cells) - Coats foreign cells -> clotting - Blocks attachment of foreign organisms to epithelial cells RESULT: limits colonisation (maintains CT integrity)

Question 38

38. What are INTERFERONS and how do they contribute to the innate immune system?

Answer 38

- Antiviral proteins - Formed in response to viral infection - Excreted by infected cell; can be taken up by neighbouring cells, trigger them to not stimulate virus replication - Species-specific, not virus-specific (i.e. more general) - Interesting as anti-viral drug: - Expensive; genetic engineering RESULT: Protects other cells from viral infection.

Question 39

39. List the steps in Anti-viral Actions of Interferons.

Answer 39

1. Viral RNA enters the cell. 2. Infecting virus replicates. 3. The infecting virus induces RNA to produce alpha & beta interferon. 4. Interferons released by virus-infected cell bind to plasma membrane of neighbouring uninfected cells inducing them to produce anti-viral proteins (AVPs). 5. New viruses infect neighbouring cells. 6. AVPs degrade new viral mRNA, inhibiting protein synthesis & replication.

Question 40

40. What are BACTERIOCINS and how do they contribute to the innate immune system?

Answer 40

Proteinaceous/peptidic toxins produced by bacteria to inhibit the growth of similar or closely related bacterial strain(s). Normal flora as part of our Biological Barrier to infection provides competition with other organisms for nutrients & sites of colonisation. These antimicrobial compounds (bacteriocins) in combination to metabolic end products toxic to foreign/invading bacteria thus contribute to the innate immune system.

Question 41

41. Briefly describe the process of ACUTE INFLAMMATION and the end result.

Answer 41

- Results from tissue injury & infection - See redness, swelling, warmth, pain - 4 steps: 1. Increased blood flow & dilation 2. Rise in temperature 3. Formation of fibrin clot 4. Phagocytic action RESULTS: destruction of invader, localisation of infection.

Question 42

42. How does Capillary penetration by immune cells lead to the onset of acute inflammation?

Answer 42

Damaged tissue -> Inflammatory signals -> Dilation/permeability -> Chemotaxis -> Attraction of phagocytes to site -> Destruction of foreign microbe.

Question 43

43. The outcome of phagocytosis of SALMONELLA TYPHI would MOST LIKELY be: a) No uptake/endocytosis into the phagocyte b) Engulfed & pathogen is destroyed by lysosomal enzymes c) Engulfed & pathogen reproduce within phagocyte d) Engulfed but produce anti-phagocytic compounds that destroy the phagocyte

Answer 43

c) Engulfed & pathogen reproduce within phagocyte; some microbes can survive the lysosomal fusion and disseminate through the phagocyte (a severe virulence factor). Another example is Mycobacterium tuberculosis. Re (a): eg's include Streptococcus pneumoniae/pyogenes Re (b): eg's include most non-encapsulated bacteria Re (d): pathogens produce leukocidin and destroy the phagocyte, eg's include Staphylococcus aureus and Streptococcus pyogenes.

Question 44

44. What are NATURAL KILLER CELLS (NKCs) and how do they contribute to the innate immune system?

Answer 44

- Non-phagocytic lymphocytes - Recognise cells with defective MHC-I protein on cell surface - Result in production of pore-forming perforin proteins & granzymes = lyse target cells = apoptosis - Attack and destroy cells: - Malignant - Containing microbes - Opsonised with Antibody