Host- Pathogen Responses - Weapons of Mass Infection

Question 1

What does LD 50 mean

Answer 1

lethal dose amount of an agent that will kill 50% of animals in a test group, describes virulence

Question 2

If an animal has a higher lethal dose (LD50) is it more or less virulent?

Answer 2

less because a higher amount is needed for the same effect

Question 3

What is the ID 50?

Answer 3

number of pathogen cells or visions required to cause active infection in 50% of inoculated animals, higher ID50 means it’s less infective does not consistently correlate with virulence

Question 4

primary pathogens vs opportunistic pathogens

Answer 4

primary pathogens –> cause disease in healthy host
opportunistic pathogens –> cause disease in compromised hours or following entry into unprotected sites (usually harmless or can be fought off pretty easily except for exceptional cases or a loss of homeostatic balance)

Question 5

What is an infection how does it happen?

Answer 5

any time where a non local microorganism is established and growing, it doesn’t always mean disease, some can even enter a latent state during infection where the organism can’t be found by culture

Question 6

What is immunopathogensis?

Answer 6

“friendly fire” by our immune system contributes to pathology and disease by causing major damage (symptoms)

Question 7

Infection cycles

Answer 7

Horizontal transmission:
direct (handshaking, kissing etc.), indirect (sharing contaminated objects or space)
fomites: inanimate objects (pathogen lives there for a while and infects people who come in contact, like doorknobs and utensils)

Vertical transmission:
from mother to fetus during pregnancy or birth

Question 8

What are the steps to pathogenesis

Answer 8

Infection process:
1. exposure
2. adherence
3. invasion (through epithelium)
4. multiplication (growth and production of virulence factors and toxins)

Disease process
toxicity (toxin effects are local or systemic) or invasion (further growth at original and distant sites)

Question 9

Portals of Entry

Answer 9

mouth, respiratory tract, conjunctiva and mucous membranes, wounds, injuries and skin lesions and parenteral route (direct into bloodstream)

Question 10

Septicemia

Answer 10

blood borne systemic infection, can lead to inflammation septic shock etc,

Question 11

bacteremia

Answer 11

bacteria in blood not always harmful

Question 12

invasiveness

Answer 12

ability of a pathogen to grow in host tissue in large enough quantities that it’s a problem and inhibits host function

Question 13

Types of virulence factors

Answer 13

adherence: adhesion, capsule, fimbriae, pili, flagella etc.
Invasion: enzymes, cytolytic exotoxins
Growth and toxicity: virulence plasmid, exotoxins, endotoxins, antiphagocytic proteins immune inhibitors, T3SS and effector proteins

Question 14

What is an adhesin

Answer 14

glyco or lipoprotein on pathogen surface that allow it to bind to host cell by interacting with receptors on host cell membrane
ex. pili, flagella, fimbraie

Question 15

How do pili (fimbriae) attach

Answer 15

Type I: adhere to carbs on host mb
static attachment growing from outer mb of gram -ve

Type IV: twitching motility
dynamic attachment that assemble and disassemble , grow from inner mb of gram -ve bacteria

Question 16

What are non-pilus adhesins

Answer 16

S. pyogenes: M protein (binds to fibronectin)
B.pertussis: pertactin (binds to integrin)
P.areuginosa: MAM7 (binds to phospholipids and fibronectin)
- can bee why some people are more susceptible: receptor availability, immunocompetence, person-person differences in receptor structures are possible

Question 17

How do capsules contribute to pathogenicity?

Answer 17

no capsule no pathogenicity
sticky and has receptors for attachment
protect the bacteria phagocytosis
they inhibit opsonization because they block bacterial receptors from opsonins
- block antibody/complement interaction
- reduce entry into endocytic pathways by lessening antigen presentation (hiding the bacteria)
- mimics self molecule, preventing antibody/complement response

Question 18

How do biofilms contribute to infections

Answer 18

• play a role in chronic infections by enabling persistent adherence, resistance to host defences and tolerance to Abx agents

Question 19

Enzymes as virulence factors

Answer 19

pathogens often have to break down host tissues, this is often done through enzymes that attack host cell like hyaluronidase which breaks down host tissues,
other examples are coagulase and streptokinase used by S.aureus which clots itself to avoid immune system or S. pyogenes to dissolves the clot to release pathogen into blood stream

Question 20

Exotoxins

Answer 20

proteins produced and secreted by bacteria which kill host cells and unlock their nutrients
ex: ab toxins, cytolysis and
superantigens

mostly gram positive bacteria can. be both, proteins, cell specific, heat labile, low LD50

Question 21

Cytotoxin

Answer 21

protein that bacteria produce that usually inhibits protein synthesis and will kills cells, or cause cell injury

Question 22

hemotoxins

Answer 22

Toxins that destroy red blood cells, disrupt blood clotting, cause hemolysis

Question 23

endotoxin

Answer 23

• LPS of gram -ve bacteria
• lipoteichoic acid on gram +ve
  hyperactive the host immune systems to harmful levels

Question 24

Effector Proteins

Answer 24

proteins that have a function that will help the bacteria manipulate the host to its advantage (invasion, immune evasion)
they can help with colonization, invasion, cytotoxicity, immunity, they carry out the virulence strategy

Question 25

Cytolysins

Answer 25

exotoxins that disrupt host cell membranes
2 mechanisms:

pore-forming proteins: insert themselves into membranes by binding cholesterol and membrane receptors
ex. hemolysins and leukocidins or streptolysin S which is indiscriminate

Phospholipase enzymes: hydrolyse phospholipids into fatty acids

Question 26

AB toxins general mechanism

Answer 26

A subunit toxicity associated factor
B subunit binds host cell, delivers “A” subunit

Question 27

Cholera toxin

Answer 27

AB5 exotoxin, made by V. cholerae, disrupts signalling
1. Bs bind to intestinal cell membrane and trigger endocytosis of cholera toxin complex

2. As ADP-ribosylate a host cell target that leads to sharp increase is second messenger cAMP
3. cAMP activates ion transporters which push ions out making the cell hypotonic and water leaves leading to watery diarrhea

Question 28

Diphteria Exotoxin

Answer 28

produced by Corynebacterium diphtheria that blocks protein synthesis
- destroys healthy tissues in respiratory system
-causes thick gray psuedomembrane coating that makes it very hard to breathe and swallow
-can get into blood stream and damage other systems heart, kidneys nerves

Question 29

Neurological Exotoxins

Answer 29

Botulinum toxins and tetanus toxins
- disrupt transport
B causes loss of contraction
T constant state od contraction

Question 30

Endotoxins

Answer 30

• only made by gram -ve
• lipid A a part of the LPS is the endotoxin part,
• general systemic symptoms of inflammation and fever
  -heat stable
  -high LD50
• immunopathogenic
• less immunogenic (less good for vaccines essentially) –> maybe cause they are so immunopathogenic
  can lead to toxic shock and systemic infections

Septic shock: induced by pathogen associated molecular patterns other than endotoxins

Question 31

Type II secretion system

Answer 31

• homologous to Type 4 pili
• secretion structures extend and extract like pili using polymerization and depolymerization
• protein is secreted into the periplasm gets folded than secreted out via an outer membrane pore

Question 32

Type III secretion system

Answer 32

• homologus to flagellar synthesis mechanism
• bacterial pathogens use them to insert their receptor into target cells
  –> inject toxin(effectors) into eukaryotic host cells
• secretion is triggered by cell-cell contact bwt host and bacterium
• genes located within pathogenicity island