22: bacterial pathogenesis

Question 1

How do we resist microbes?

Answer 1

physical barriers, limits nutrient availability, innate and adaptive immunity

Question 2

How do pathogens evade restriction?

Answer 2

adhere/invade host tissue, secrete toxins/effectors, steal host nutrients, SEC

Question 3

What is a primary pathogen?

Answer 3

always cause disease

Question 4

What is an oppurtunistic pathogen?

Answer 4

cause disease only in compromised host or following entry into unprotected sites

Question 5

What is lochs postulate?

Answer 5

1. microbe only found in disease but is absent from healthy individuals
2. microbe is isolated from diseased host and grown in pure culture
3. microbe in new host, same disease occurs
4. same strain of microbe is isolated from dead host

Question 6

What must a pathogen do to cause disease?

Answer 6

enter host, find unique niche, SEC defenses, multiply, transmit susscebtibilty via virulence factors

Question 7

Whats a pathogenicity island?

Answer 7

virulence genes in pathogens clustered in islands with unique GC/AT ration, linkage to tRNA gene or association with gene homology to plasmid
horizontally transferred via transduction and conjugation

Question 8

What are lochs molecular postulates?

Answer 8

inactivation of virulence genes should be associated w? decrease in pathogenesis
replacement of gene should restore pathogenicity

Question 9

Microbial attachment

Answer 9

adhesion via adhesion protons cell attachment, bind to specific host factor (pilus or nonpilus proteins)

Question 10

chemical defenses of mucosal colonization:

Answer 10

lysozyme: modify pG to be resistant to it
antimicrobial peptides: bacteria change charge of membrane to repe positively charged defension, prevent pores
obtain nutrients: specific receptors (lactoferrin, transferrin) to harvest essential molecules

Question 11

adaptive immunity:

Answer 11

antibody degradation (iGA protease) or antigenic variation(type 4 pilus)

Question 12

Portals of entry: skin

Answer 12

pathogen invasion via damaged skin

Question 13

portals of entry: mucus membrane

Answer 13

entry through damaged epithelium
-forced uptake: use of type 3 secretion system to induce uptake in non phagocytotoxic cells
-M cell transcytosis: antigen/bacteria taken up by M-cell, exit M-cell for macrophage uptake

Question 14

SEC: subvert

Answer 14

effectors/toxins employed to block signaling pathways or to remove key immune cells

Question 15

What are toxins?

Answer 15

secreted into extracellular place
- can damage cellular membranes via pore
- can inhibit protein synthesis via iron starvation

Question 16

What are effectors?

Answer 16

proteins injected into host cell via type 3 ss
enteropathic e.coli attaches via type 1 pilus. inject TirA effect which binds to intimin on membrane, Air phosphorylated, actin polymerization, pedestal formation

Question 17

SEC: evade

Answer 17

mask MAMPS to avoid immune detection
- capsular polysaccharide: barrier to MAMP, protect from PRR and toll receptors
- on glycosyl chains of gram -

Question 18

SEC: counteract

Answer 18

shields used to render host useless: antibodies and ROS
phagocytes can break down ROS
FC region and receptor: aid in linking antibodies at FC region
antibodies link bacteria and macrophage

Question 19

immune evasion of yrsenia pestis

Answer 19

gamma proteobacteria, g- rod with LPS in outer membrane is a MAMP that binds to PRR TLR4 to induce inflammation
- lipid A core of LPS is conserved in g-, sensed by TLR4

Question 20

temp dependency of yrsenia pestsis

Answer 20

hexa acetylated when in host but tetra acetylated in host, TLR4 cannot recognize it so it goes undetected

Question 21

Yrsenia and lysozyme

Answer 21

When sensed by lysozyme, yrsenina resists it and kills macrophage, enters lymphoid tissue, develops T3SS
-> T3 needly protein binds to formyl peptide receptor on phagocytes and uinhects w effectors, blocks cytokine production and disrupts actin polymerization-> no phagocytosis