Determinants of disease

Question 1

Virulence factors

Answer 1

adhesion
invasion
evasion of host defense
obtaining nutrients from host
toxicity

Question 2

Measuring virulence

Answer 2

ID50- dose to infect 50% of hosts

LD50- dose to kill 50% of hosts

Question 3

Types of transmission

Answer 3

Direct-host to host transmission (eg respiratory, body contact, faecal-oral, body fluids, vertical transmission)

Indirect- host to host through living or inanimate objects (eg soil, contaminated water/food, fomites)

Question 4

Portals of entry

Answer 4

Skin- though not if it’s healthy

Mucousal barrier-warm, moist, every bacterium’s wet dream!

Question 5

Bacterial adhesins

Answer 5

Proteins: fimbrial, afimbrial surface proteins

Polysaccharides: capsule compenents, techoic/lipotechoic acid

Question 6

Extracellular invasion

Answer 6

Gets to niches in tissue that aid in proliferation and spreading

Produces enzymes that: attacks extracellular matrix, degrades carb/protein complexes and disrupt cell surface

Question 7

Intracellular invasion

Answer 7

Rickettsia spp and mycobacteria leprae are obligate intracellular

Phagocytic cells invaded through phagocytosis, while non phagocytic cells are induced into doing phagocytosis

Question 8

Phagocytosis

Answer 8

1. Bacterium binds to cell surface of phagocyte
2. Cytoskeleton pushes membrane around bacterium creating large vesicle
3. Phagosome moves into cytoplasm
4. Phagosome fuses with lysosome forming a phagolysosome
5. Bacterium gets rekt and digested

Question 9

Surviving phagocytosis

Answer 9

Stay in phagolysome

Prevent formation of phagolysosome (salmonella)

Destroy/escape phagosome and live in cytosol

Question 10

Invading non-phagocytic cells

Answer 10

1. Bacterial proteins recruit host proteins to induce phagocytosis
2. Secretion system used by g-ve bacteria (salmonella, psuedemonas)
3. Invasion proteins injected
4. Activate host signalling and recruit actin

Question 11

Biofilms

Answer 11

Attach to surface and become enveloped in matrix

Protects from phagocytosis, antibiotics, disinfectants

High bacterial density produces virulence factors through quorum sensing

Question 12

Nutrition

Answer 12

Limiting nutrient is iron contained in transferrin, lactorferrin, ferritin, haemoglobin

Uptake using cell surface proteins TBP (Transferrin) and HBP (haemoglobin)

Or by secreting small compound with very high affinity for iron to capture iron from host proteins or insoluble ferric salts

Question 13

Siderophores

Answer 13

Produced when iron concentration is low

Has a low molecular weight and competes for both free and bound iron

Transports iron into cell

Enterobactin is an example of a siderophore

Question 14

Evading complement

Answer 14

Capsule around cell- thick polysaccharide layer to prevent complement activation

LPS O antigen has extended O chains prevent complement activation

Question 15

Resisting phagocytes

Answer 15

Prevent contact with phagocytes

Affect phagocyte migration- S.pyogenes peptidase cleaves complement factor C5a

Destroy phagocytes- using leukocidins

Question 16

Evade host-antibody response

Answer 16

Bind host proteins so its not seen as foreign- M protein S.pyogenes

Use surface protein to make antibodies bind backwards- Protein A by S.aureus and Protein G S. Pyogenes to prevent opsonisation

Question 17

Toxin damage

Answer 17

Cause host damage and induce inflammation

Exotoxin: Toxins secreted during growth

Endotoxin: Toxins released on lysis

Question 18

Types of exotoxin tranmission

Answer 18

Ingestion of preformed exotoxin- food poisoning

Tissue is infected and then exotoxin release occurs

Question 19

Exotoxins

Answer 19

Usually proteins therefore heat labile

Host site specific exotoxins
Usually AB toxins: A is the toxin, B is for targetting

Question 20

Membrane disrupting toxins

Answer 20

Pore forming toxin- Exotoxin forms pore in membrane and uncontrolled entry of water occurs causing lysis

Bilayer disruption- Phospholipase exotoxin cause disruption of bilayer leading to lysis

Question 21

Superantigen

Answer 21

Produced by staphylococci and streptococci
Staph produces TSST, Strept produces 6 pyrogenic toxin

Causes a massive non specific inflammatory response

Leads to endothelial damage, circulatory shock and multi organ failure

Question 22

Lipid A component of LPS

Answer 22

Heat stable and in the outermembrane of g-ve bacteria

Released when bacteria die inducing fever, complement activation, clotting cascades and toxic shock

Question 23

Regulation by numbers: quorum sensing

Answer 23

Many microbes only produce virulence factors until a quorum (min no of cells) is reached

Question 24

Quorum sensing

Answer 24

Autoinducer (AI)- small diffusable molecule

R protein- activates gene transcription when it binds to AI at high concentrations of AI
High Ai concentrations only occur at high cell densities