molecular basis of parasite host-cell interactions

Question 1

pathogenicity

Answer 1

• not all micro-organisms cause disease
• most are never pathogenic
• few can be, and few are always pathogenic
• very few can cause death

Question 2

process of infection

Answer 2

• growth/multiplication of microbe in host
• doesn’t always result in injury of the host i.e. disease
• classed by site of infection:
  
  • localised - sore throat
  • generalised - influenza

Question 3

outcomes of infection

Answer 3

• infection without illness
• infection will illness but no long term consequences
• infection, illness and death
  
  • not in the microorganism’s best interest to kill the host
  • host can’t transmit infection
  • e.g. rabies
    
    • humans can never transmit rabies so doesn’t matter if it dies or not - dead end so they kill host

Question 4

asymptomatic infection

Answer 4

• common
• microorganism often cannot multiply for several reasons
  
  • temperature non-optimal
  • killed by immune system
  • unable to attach
  • lack of food source

Question 5

recurrent illness

Answer 5

• can occur when relationship is established between host and pathogen
• host controls microorganisms but doesn’t eliminate it
• e.g. chicken pox
  
  • remains in host for lifetime
  • if host’s immune system weakens disease returns in the form of shingles

Question 6

host defences

Answer 6

• physical and mechanical barriers
• chemical barriers
• innat eimmuntiy
• acquired/adaptive immuntiy (vertebrates only)

Question 7

host toleration

Answer 7

• host allows colonisation but restricts it to certain regions where there will be no harm
• e.g. staph aureus - sore throat
• e.g. strep pneumoniae - usually restricted to pharynx, but spread to lungs causes severe disease
• progression beyond colonisation and breaching of defences = infection

Question 8

requirements of a disease-causing microorganism

Answer 8

• transmission between hosts
• entry and adherence to target tissues
• evasion of host defences and multiplication in host tissues
• obtain iron and other essential nutrients
• produce symptoms
• exit the host

Question 9

target tissue adherence

Answer 9

• shapes the infection
• different influenza strains have different surface molecules
• allow adherence to different regions of respiratory tract
• lower respiratory tract infection much more dangerous
  
  • site of oxygen exchange

Question 10

host parasite relationships

Answer 10

• highly dynamic
• determines outcome of infection
  
  • parasite pathogenicity and host susceptibility
• each modifies activites functions and genetics of the other
• genetic variability of both host and pathogen is important
  
  • symptoms and severity differs between individuals

Question 11

stages of the infectious process

Answer 11

• entry
  
  • oral, respiratory, parenteral
• attachment
  
  • pili, capsules, proteins
• colonisation
  
  • metabolism, replication, clearance evasion
• tissue damage
  
  • toxins, invasion, immune repsonse

Question 12

route of entry

Answer 12

• depends on microorganism’s ability to survive in the environment
• some can survive for months
  
  • mycobacterium - oral transmission
• some very sensitive to the environment and die upon exposure
  
  • HIV - transmission by sexual intercourse
• some can only use arthropod vectors
  
  • malaria
  • also helps bypass main host barrier (skin)

Question 13

infection routes

Answer 13

• depend on biology of organism
• respiratory and salivary spread - aerosol transmission for more durable microorganisms
• fecal-oral spread common - humidity and nutrient availability
• animal vectors or vertebrate reservoirs
• some combine vector, vertebrate reservoir and human host
  
  • plague, yellow fever

Question 14

attachment

Answer 14

• key factor in determining entry route and localisation within the host
• adhesion molecules must bind host cell membranes
• inability to attach to mucosa means the microorganism will die and be washed away

Question 15

colonisation

Answer 15

• involves multiplication and use of host resources
• host cell remodelling to establish closer relaitonship
• counteracting host immune system
• phagocytosis - microorganisms can:
  
  • inhibit fusion
  • escape phagolysosome
  • multiply within it - mycobacterium

Question 16

tissue damage

Answer 16

• improtant for release of nutrients
• destroy cell membrane or connective matrix
• can use exotoxins
  
  • often bipartite - one component binds cell, induces phagocytosis, other component allows escape and has toxic effect e.g. diphtheria toxin, blocks protein synthesis

Question 17

dynamics of attachment

Answer 17

• specific interaction between receptor and ligand
• number and density of each is important
• individual binding forces are weak so high numbers are needed to decrease probability of interactions breaking
• dynamic
  
  • rates of attachment and detachment determine rate of invasion

Question 18

avidity

Answer 18

• tendency for multiple receptors or multiple ligands to combine
• represents cumulative strength of all receptor ligand pairs
• RL pairs are not independent in terms of binding
  
  • binding of one pair increases chance of another binding event
• dissociation requires multiple bonds to be broken simultaneously

Question 19

RL density

Answer 19

• density = sum of all receptors/surface area
• the smaller the surface, the lower the density and the higher the probability of detachment
  
  • inverse relationship

Question 20

kinetics of parasite-host binding

Answer 20

Question 21

parasitic binding affinity

Answer 21

• driving force is avidity so affinity constant is low
• high abundance of ligands/receptors
• pili/fimbriae must recognise abundant ligands
• likely to involve glycosaminoglycan family
  
  • host receptors for various microorganisms

Question 22

proteoglycans

Answer 22

• extreme form of protein glycosylation
• carbohydrate units are polysaccharides that contain amino sugars (glycosaminoglycans)
• GAGs - repeating disaccharide chains of 3 types
  
  • chondroitin sulfate, dermatan sulfate, heparan sulfate

Question 23

GAG heterogeneity

Answer 23

• highly heterogeneous in structure
• every N-linked glycan subject to extensive modification in golgi
• different GAGs in tissues explains variable infection regions of different strains e.g. influenza
• high heterogeneity between tissues and cells

Question 24

P. falciparum

Answer 24

• infected RBCs must attach to endothelium
• mediated by knob structures containing variable surface antigens that bind GAGs
• parasite expresses different antigens to evade immune system
  
  • also alters specificity - different GAGs are bound
  • interact with different endothelial regions of host

Question 25

PfEMP1

Answer 25

• P. falciparum surface antigen
• specifically interacts with chondritin sulfate
• when on knob surface, if pregnant womanis infected, chondritin sulfate on placenta surface is bound causing stillbirth of the foetus