Host-Parasite Interactions

Question 1

Principal Pathogen

Answer 1

• Regularly causes disease in a proportion of susceptible hosts who have normal specific and non-specific defense mechanisms
• Ex: Streptococcus Pneumoniae, Neisseria meningitidis

Question 2

Commensal Organism

Answer 2

• Lives within or on the surface of the host, almost never perturbing homeostasis
• Ex: Diphtheroids, Lactobacilli

Question 3

Opportunistic Pathogen

Answer 3

• Rarely causes disease except in hosts who have defects in specific or non-specific defense mechanisms
• Ex: Pseudomonas Aeruginosa, Staphylcoccus Epidermidis

Question 4

Virulence

Answer 4

• A measure of the tendency of an organism to cause disease

- LD50 - dose of microorganism that will kill 50% of a susceptible population

Question 5

Koch’s Postulates

Answer 5

1) the organism must be found in all cases of disease but generally not in healthy animals.
2) the organism must be isolated from diseased animals and grown in pure culture
3) the disease must be reproduced when the isolated organism is inoculated into susceptible animals
4) the organism must be isolated in pure culture from the experimentally infected animals

Question 6

Kock’s Postulate (Molecular)

Answer 6

1) the gene(s) encoding the phenotype should be associated with pathogenic strains
2) inactivation of the gene(s) results in a reduction in virulence
3) restoration of the gene(s) into the avirulent mutant re-establishes virulence

Question 7

Goal of all organisms

Answer 7

• Proliferation

- in the case of infectious agents, this requires both multiplication within a host and transmission to another host

Question 8

Outcomes of Infection

Answer 8

• asymptomatic (most common)
• disease (reflects details of survival strategy by microbe)
• Death (unfavorable for both host and microbe)

Question 9

Microbial Factors in Emergence of New Infections

Answer 9

• Short generation time
• Mutations
• Acquisition of new genetic elements
• Changes in vector distribution

Question 10

Host Factors in Emergence of New Infections

Answer 10

• Changes in behavior
• Expanding populations
• Increased travel
• Contamination of environment
• Food and Water distribution
• Immunosuppression

Question 11

Infectious Cycle

Answer 11

• Entry
• Establishment
• Persistence
• Damage
• Exit

Question 12

Entry

Answer 12

• Entry sites

- Overcoming barriers both anatomical/functional and ecological

Question 13

Anatomical Barriers to Microbe Entry

Answer 13

• Skin (thick, dry, acidic, constant shedding)
• Mucosa (mucin, motility, sIgA)
• Respiratory tract (hair, mucocilia, lysozyme, cough/sneezing)
• Alimentary Tract (saliva, acidic pH, digestive enzymes, sIgA, shedding)
• GU Tract (urine flow, pH)

Question 14

Ecological Barriers to Entry

Answer 14

• Vast Microbiome

- Density of surface area

Question 15

Salmonella infection through inflammation

Answer 15

• inflammation induced by Salmonella converts S2O3 into S4O6 via NO/ROS from PMNs
• confers a selective advantage to increase colonization within the gut out competing the microbiome

Question 16

Establishment

Answer 16

• requires adherence
• a result of the specific molecular interaction between microbial adhesins and receptors on the epithelium
• non-adherent mutants are generally avirulent

Question 17

Adherence - Role of the host

Answer 17

• host polymorphisms play major role in disease susceptibility
• surface carbohydrates including blood group antigens can alter risk of recurrent UTIs and norovirus infection

Question 18

Biofilm

Answer 18

• composed of bacteria and ECM on a foreign body
• constitutes a site protected from phagocytes and the actions of antibiotics
• Staphylococcus Epidermidis can become established in biofilm

Question 19

Persistance - Avoidance of host defenses

Answer 19

• Complement evasion
• Invasion
• Avoidance of phagocytosis
• Survival in the phagocyte
• Antigenic Variation
• Inactivation of antibodies
• Iron acquisition

Question 20

Neisseria Meningitidis

Answer 20

• binds factor H

- Results in un-regulated complement activation by avoiding opsonization and contributes to vascular damage

Question 21

Cellular Invasion - Trigger

Answer 21

• microbe engages host signaling proteins that regulate actin and causes the cell to form ruffles that engulf the organisms
• Ex: Salmonella and Shigella

Question 22

Cellular Invasion - Zipper

Answer 22

• tight binding of bacterial ligand to a receptor that is coupled to the cytoskeleton results in recruitment of more receptors which in turn bind to ligand
• eventually the organism is completely surrounded by the host membrane
• Ex: Yersinia pseudotuberculosis, Y. enterocolitica, and Listeria monocytogenes

Question 23

Type III Secretion Systems

Answer 23

• prevalent on gram negative pathogens
• allows delivery of virulence factors directly into the cytoplasm of host cells (triggered by contact with host cells)
• mediates invasion, avoidance of phagocytosis, and cytotoxicity
• Ex: Salmonella, Shigella, Yersinia, Pseudomonas, and some E. Coli

Question 24

Inhibition of phagosome/lsysosome fusion

Answer 24

• Legionella pneumophila
• Toxoplasma gondii
• histoplasma capsulatum

Question 25

Survival in phagocytic environment

Answer 25

- Leishmania | - Coxiella Burnetii

Question 26

Antigenic Variation

Answer 26

- avoiding immune system by changing surface components recognized by thehost - Neisseria Gonorrheaa posses several different alleles of opa genes; changes in opa expression occur with high frequency in the bacterial population

Question 27

Antibody inactivation

Answer 27

- Protein A (staph Aureus) - -binds immunoglobulins - -inhibits phagocytosis - -causes B cell apoptosis - -inhibits immune response Many mucosal pathogens make Ig proteases

Question 28

Iron Scavenging

Answer 28

- Iron required for microbe survival | - transferrin receptors or Siderphores used to get iron

Question 29

Siderophores

Answer 29

- small molecules secreted by bacteria that compete with host iron-binding proteins for iron, and bind to receptors on the bacterial membrane which in turn transport iron across the membrane

Question 30

Host Damage

Answer 30

- Direct - -Exotoxins (proteins (typically enzymes) liberated by growing bacteria) - B subunit binds specifically to cellular receptor; A subunit enters cell and causes characteristic effect - Indirect - -superantigens - -endotoxins

Question 31

Diphtheria Toxin

Answer 31

- single polypeptide chain that is cleaved to form A and B subunits - B subunit binds to epithelial growth factor like precursor and is taken up by membrane via clatherin coated pits - Acidification of endosome changes conformation to activate A subunit - A subunit catalyses the transfer of ADP ribosyl group to NAD to elongation factor 2 causes protein synthesis to halt and cell death

Question 32

Shiga Toxin

Answer 32

- produced by Shigella Dysenteriae - 5 identical B subunits and a single A - B subunit binds to globotrioacyl ceramide - toxin enters endosome and is transported retrograde to ER - A subunit catalyzes the depurination of adenine4324 of the 28S ribosomal subunits halting protein synthesis and resulting in cell death

Question 33

Membrane Damaging Toxins

Answer 33

- Direct pore forming toxins (hemolysins) | - phospholipases - contain enzymes that hydrolyze phospholipids

Question 34

Cholera Toxin

Answer 34

- produced by Vibrio Cholerae and heat labile protein of enterotoxigenic E. Coli - B subunit binds to glycolipid GM1 ganglioside - A subunit catalyzes the ADP ribosylation of Gs protein, locks it in GTP bound active state, which in turns activates adenylate cyclase - increase in cAMP ultimately leads to increase in CFTR in the membrane leading to chloride secretion

Question 35

Toxins that affect small GTPases

Answer 35

- large cytotoxins of Clostridium Difficile - single peptide with binding, translocation, and enzymatic domains - catalyze the transfer of glucose from UDP-glucose to Rho, Rac, and CDC42 causes them to become inactive - results in depolymerization of actin, cell rounding, and loss of tight junctions causing diarrhea

Question 36

Damage due to Host

Answer 36

- superantigens | - Endotoxin

Question 37

Endotoxin

Answer 37

- lipid A component of LPS associated with gram negative bacteria - binding of LPS-binding protein to CD14 receptor activates pro-inflammatory cytokines - leads to activation of complement cascade, and release of inflammatory mediators - can lead to DIC and shock