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Infection and Disease IIInfection and Disease II
Pathogenicity and InfectionPathogenicity and Infection
ELISAELISA -- Enzyme-Linked Immunosorbent -- Enzyme-Linked Immunosorbent
AssayAssay
Direct ELISADirect ELISA -- detects __________ (i.e. virus, -- detects __________ (i.e. virus,
bacterium)bacterium)
Indirect ELISAIndirect ELISA -- detects ______________ to -- detects ______________ to
the antigen. HIV ELISA is an example.the antigen. HIV ELISA is an example.
Antibody-based detection methodsAntibody-based detection methods
HIV Indirect ELISA animationHIV Indirect ELISA animation
http://www.biology.http://www.biology.arizonaarizona..eduedu/immunology/activities//immunology/activities/elisaelisa/technique.html?/technique.html?
Pathogenicity and InfectionPathogenicity and Infection
• Non-specific host defensesNon-specific host defenses
• Entry of the pathogen into the hostEntry of the pathogen into the host
• Colonization and growthColonization and growth
• VirulenceVirulence
• ToxinsToxins
Some termsSome terms
PathogenPathogen (or ‘true pathogen’) -- can cause infection and (or ‘true pathogen’) -- can cause infection and
disease in a _____________ hostdisease in a _____________ host
Opportunistic pathogenOpportunistic pathogen -- only pathogenic to non- -- only pathogenic to non-
______________ individuals or when introduced into a ______________ individuals or when introduced into a
normally ___________ part of the bodynormally ___________ part of the body
VirulenceVirulence -- degree of __________________ of a parasite -- degree of __________________ of a parasite
Virulence factorsVirulence factors -- _________________ of the pathogen -- _________________ of the pathogen
which allow it to successfully invade and colonize a hostwhich allow it to successfully invade and colonize a host
Non-specific host defensesNon-specific host defenses
• Anatomical defensesAnatomical defenses
• Effect of age, stress, and diet on Effect of age, stress, and diet on susceptibilitysusceptibility
Physical Barriers and Anatomical DefensesPhysical Barriers and Anatomical Defenses
Compound in Saliva Protects Against Compound in Saliva Protects Against E. coliE. coli
Scientists from the University of Calgary have identified aScientists from the University of Calgary have identified a protein produced by protein produced by salivary glands that, when administered orally, can significantly reduce salivary glands that, when administered orally, can significantly reduce diarrhea and weight loss associated with diarrhea and weight loss associated with Escherichia coliEscherichia coli infection infection. They . They report their findings in the October 1998 issue of the journal report their findings in the October 1998 issue of the journal Infection and Infection and ImmunityImmunity..
In the study, the researchers investigated the ability of the protein, known as In the study, the researchers investigated the ability of the protein, known as epidermal growth factor (EGF), to protect rabbits from the effects of an epidermal growth factor (EGF), to protect rabbits from the effects of an experimental experimental E. coliE. coli infection. The researchers found that daily treatment with infection. The researchers found that daily treatment with EGF prevented the occurrence of diarrhea and weight loss. They also found EGF prevented the occurrence of diarrhea and weight loss. They also found lower colonization rates in the intestines of treated rabbits.lower colonization rates in the intestines of treated rabbits.
"The findings demonstrate that oral EGF administration inhibits the production of "The findings demonstrate that oral EGF administration inhibits the production of diarrhea and reduction in weight gain seen in weanling rabbits infected with diarrhea and reduction in weight gain seen in weanling rabbits infected with attaching-effacing attaching-effacing E. coliE. coli, " say the researchers. "These observations suggest a , " say the researchers. "These observations suggest a role for EGF in protecting the gastrointestinal tract from colonization from role for EGF in protecting the gastrointestinal tract from colonization from bacterial pathogens.”bacterial pathogens.”
(A. Buret, M.E. Olson, D. Grant Gall, and J.A. Hardin. 1998. Effects of orally administered epidermal growth factor on (A. Buret, M.E. Olson, D. Grant Gall, and J.A. Hardin. 1998. Effects of orally administered epidermal growth factor on enteropathogenic Escherichia coli infection in rabbits. Infection and Immunity. 66:4917-4923.)enteropathogenic Escherichia coli infection in rabbits. Infection and Immunity. 66:4917-4923.)
Susceptibility to Infectious DiseaseSusceptibility to Infectious Disease
AgeAge -- ___________ and ____________ more susceptible. Why? -- ___________ and ____________ more susceptible. Why? infants -- undeveloped normal flora,undeveloped immune systeminfants -- undeveloped normal flora,undeveloped immune system elderly -- immune response declines, anatomical changeselderly -- immune response declines, anatomical changes
StressStress -- in rats: fatigue, exertion, poor diet, dehydration, drastic -- in rats: fatigue, exertion, poor diet, dehydration, drastic climatic changes increase_________________ climatic changes increase_________________ and___________________ of infections. and___________________ of infections. Hormone imbalance plays important role.Hormone imbalance plays important role.
DietDiet -- famine and infectious disease correlated (e.g. cholera). -- famine and infectious disease correlated (e.g. cholera). OvereatingOvereating may have also an effect. may have also an effect. Key may be disruption of __________________ ______________Key may be disruption of __________________ ______________ Not eating a particular substance needed by normal flora can have effect Not eating a particular substance needed by normal flora can have effect
(e.g. a vitamin)(e.g. a vitamin)
How they get inHow they get in
Tissue specificity (of the pathogen) is a serious barrier to the Tissue specificity (of the pathogen) is a serious barrier to the entry of most microorganisms (more on this later)entry of most microorganisms (more on this later)
Discussed in viruses, also true of other pathogenic Discussed in viruses, also true of other pathogenic microorganisms: often (usually) only infect specific tissues and microorganisms: often (usually) only infect specific tissues and cell types.cell types.
Notable (mainly bacterial) exceptions exist, e.g. Notable (mainly bacterial) exceptions exist, e.g. Streptococcus Streptococcus pyogenespyogenes and and Staphylococcus aureus.Staphylococcus aureus.
So, how So, how dodo microorganisms “get into” (colonize and establish microorganisms “get into” (colonize and establish in) the host??in) the host?? In the first place some of them don’t have to “get in” to be In the first place some of them don’t have to “get in” to be
pathogenic… How can this be?pathogenic… How can this be?
They might already be there (in the normal flora or as They might already be there (in the normal flora or as latent latent infectionsinfections) Called infection from an ) Called infection from an ““endogenousendogenous” ” sourcesource
Exogenous infectionsExogenous infections
SkinSkin: portals are bites, digestive : portals are bites, digestive enzymes, needles, surgery, enzymes, needles, surgery, wounds, and catheters. wounds, and catheters.
High speed photo of unstifled sneezeHigh speed photo of unstifled sneeze
Respiratory tractRespiratory tract: location (upper or : location (upper or lower) somewhat dependent on size, lower) somewhat dependent on size, attachment. attachment. Portal of entry to the Portal of entry to the greatest ________________ of greatest ________________ of pathogenspathogens..
GI tractGI tract: : ________ production ________ production (e.g. (e.g. Staph. aureus, Clostridium Staph. aureus, Clostridium perfringensperfringens) or directly through ) or directly through intestinal (and stomach, in the case intestinal (and stomach, in the case of of HelicobacterHelicobacter) epithelium) epithelium
Exogenous Infectious AgentsExogenous Infectious Agents
• Entering via the Entering via the skinskin:: Staph. aureusStaph. aureus; ; Strep. pyogenesStrep. pyogenes; herpes ; herpes
simplex type I, HIV, and various viruses; assorted fungi; simplex type I, HIV, and various viruses; assorted fungi; ClostridiumClostridium tetanitetani and and C. perfringensC. perfringens; ; Haemophilus aegyptumHaemophilus aegyptum, , Acanthamoeba Acanthamoeba and assorted protozoa, etc.and assorted protozoa, etc.
• Entering through the Entering through the GI tractGI tract:: various Gram-negative rods various Gram-negative rods
((Salmonella, Campylobacter, E. coli, Shigella dysenterae, Vibrio Salmonella, Campylobacter, E. coli, Shigella dysenterae, Vibrio choleraecholerae, etc.); assorted viruses (poliovirus, hepatitis A, rotaviruses), etc.); assorted viruses (poliovirus, hepatitis A, rotaviruses)
• Entering via the Entering via the respiratory tractrespiratory tract:: Group A Group A Strep. pyogenesStrep. pyogenes; ;
meningitis-causing bacteria such as meningitis-causing bacteria such as Neisseria meningitidisNeisseria meningitidis, and , and Haemophilus influenzaeHaemophilus influenzae; ; Corynebacterium diphtheriaeCorynebacterium diphtheriae; ; Bordetella Bordetella pertussispertussis; pneumonia-causing agents like ; pneumonia-causing agents like Strep. pneumoniaeStrep. pneumoniae and and various viruses and fungi; various viruses and fungi; Mycobacterium tuberculosisMycobacterium tuberculosis; viruses of ; viruses of chickenpox, measles, mumps, rubella, influenza, and common cold.chickenpox, measles, mumps, rubella, influenza, and common cold.
Exogenous infections (cont.)Exogenous infections (cont.)
UrogenitalUrogenital: Enter through skin or mucosa of penis, : Enter through skin or mucosa of penis,
vagina, urethra, etc. Syphilis vagina, urethra, etc. Syphilis (Treponema (Treponema
pallidum),pallidum), gonorrhea gonorrhea (Neisseria gonorrhoeae),(Neisseria gonorrhoeae),
genital warts, chlamydia, herpes simplex Type II, genital warts, chlamydia, herpes simplex Type II,
HIV, etc.HIV, etc.
Birth-related infectionsBirth-related infections: Placental (e.g. syphilis) or : Placental (e.g. syphilis) or
during birth: STORCH (syphilis, toxoplasmosis, during birth: STORCH (syphilis, toxoplasmosis,
other [HIV, hepatitis B, chlamydia], rubella, other [HIV, hepatitis B, chlamydia], rubella,
cytomegalovirus, herpes simplex II virus)cytomegalovirus, herpes simplex II virus)
Adherence, colonization, invasion, growth, diseaseAdherence, colonization, invasion, growth, disease
AdherenceAdherence
Fimbriae (non-sex pili) of Fimbriae (non-sex pili) of enteropathogenicenteropathogenic E. coliE. coli
http://www.bc.ic.ac.uk/mcbap.htmlhttp://www.bc.ic.ac.uk/mcbap.html
Enteropathogenic strains are able to colonize the ___________ Enteropathogenic strains are able to colonize the ___________
intestine and cause ________________ by expressing specific intestine and cause ________________ by expressing specific
colonization factor antigenscolonization factor antigens (proteins) on their fimbriae (proteins) on their fimbriae
Intestinal Infection by Enteropathogenic bacteria
Intestinal Infection by Enteropathogenic bacteria
Enteropathogenic Enteropathogenic E. coli infection animationE. coli infection animation
Salmonella invasion animationSalmonella invasion animation
(Howard Hughes Institute web site:(Howard Hughes Institute web site:
http://www.hhmi.org/grants/lectures/biointeractive/animations.html)http://www.hhmi.org/grants/lectures/biointeractive/animations.html)
Pathogens must first become established at site of infection. _____________ must be Pathogens must first become established at site of infection. _____________ must be compatible with the microorganism.compatible with the microorganism.
An infecting microorganism can’t adhere to _______ cells or hosts. An infecting microorganism can’t adhere to _______ cells or hosts.
Tissue and host specificity as factors in infection
Tissue and host specificity as factors in infection
Disease Tissue infected OrganismDiphtheria Throat epithelium Corynebacterium
diphtheriaeGonorrhea Urogenital
epitheliumNeisseriagonorrhoeae
Cholera Small intestineepithelium
Vibrio cholerae
Dental caries Oral epithelium Strpetococcusmutans, S.sobrinus, S.sanguis, S. mitis
Spontaneous abortion(cattle)
Placenta Brucella abortus
AIDS T helperlymphocytes
HIV
Malaria Blood (erythrocytes) Plasmodium sp.
Some cells are pathogenic due to the toxins Some cells are pathogenic due to the toxins
they produce (e.g. they produce (e.g. ClostridiaClostridia) but most ) but most
need to actually ___________ and need to actually ___________ and
______________ in host tissues in order ______________ in host tissues in order
to cause disease.to cause disease.
Colonization, Growth, and VirulenceColonization, Growth, and VirulenceColonizationColonization -- ____________________ of a -- ____________________ of a
microorganism after it has attached to host tissues microorganism after it has attached to host tissues or other surfacesor other surfacesThe initial inoculum of cells is rarely sufficient to cause The initial inoculum of cells is rarely sufficient to cause
disease; needs to ____________.disease; needs to ____________.
Must therefore find appropriate nutrients and Must therefore find appropriate nutrients and environment. This not always as easy as it appears (e.g. environment. This not always as easy as it appears (e.g. iron)iron)
Virulence factorVirulence factor -- any characteristic of a pathogen -- any characteristic of a pathogen that enables it to establish itself and cause disease. that enables it to establish itself and cause disease. These are often extracellular enzymes such as These are often extracellular enzymes such as hemolysinhemolysin, ,
hyaluronidasehyaluronidase, , collegenasecollegenase,, and and coagulasecoagulase. The first 3 . The first 3 of these allow for spread (and nutrition, to some of these allow for spread (and nutrition, to some extent), the 4th promotes localization and, probably, extent), the 4th promotes localization and, probably, protection.protection.
Summary of virulence factors important in Salmonella pathogenesis
Summary of virulence factors important in Salmonella pathogenesis
Some pathogens are much more virulent than others
Some pathogens are much more virulent than others
Infectious Dose -- minimum number of agents (cells, viruses) needed to cause disease
Infectious Dose -- minimum number of agents (cells, viruses) needed to cause disease
Varies from 1 Varies from 1 RickettsiaRickettsia cell in Q fever to 10 cells in cell in Q fever to 10 cells in tuberculosis to 10tuberculosis to 1033 cells in gonorrhea, 10 cells in gonorrhea, 104 4 cells in cells in typhoid, and 10typhoid, and 1099 cells in cholera. cells in cholera.
Smaller infectious dose = more _________ pathogenSmaller infectious dose = more _________ pathogen
If number of cells < infectious dose no infectionIf number of cells < infectious dose no infection
If number of cells >> inf. dose more rapid __________If number of cells >> inf. dose more rapid __________
ToxinsToxins
Exotoxin Exotoxin -- toxin ___________ into tissue-- toxin ___________ into tissue
Diphtheria toxinDiphtheria toxin -- extremely potent (one molecule will kill a -- extremely potent (one molecule will kill a
cell). Disrupts _____________ synthesis. Caused by cell). Disrupts _____________ synthesis. Caused by
lysogenic phage in lysogenic phage in Corynebacterium diphtheriae.Corynebacterium diphtheriae.
Tetanus and botulism toxinsTetanus and botulism toxins -- Causal organisms ( -- Causal organisms (Clostridium Clostridium
tetanitetani and and C. botulinumC. botulinum) don’t generally ______________ ) don’t generally ______________
very much in infected tissues but instead release potent very much in infected tissues but instead release potent
neurotoxins. neurotoxins.
Action of Tetanus NeurotoxinAction of Tetanus Neurotoxin
Tetanus causes irreversible muscle _________________ (‘spastic paralysis’ or ‘lockjaw’)Tetanus causes irreversible muscle _________________ (‘spastic paralysis’ or ‘lockjaw’)
Action of Botulinum NeurotoxinAction of Botulinum Neurotoxin
Botulinum toxin, the most poisonous substance known, causes Botulinum toxin, the most poisonous substance known, causes irreversible muscle _________________ (‘flaccid paralysis’).irreversible muscle _________________ (‘flaccid paralysis’).
Toxins (cont.)Toxins (cont.)EndotoxinEndotoxin -- toxin released only upon cell ________ and lysis -- toxin released only upon cell ________ and lysis
These are These are lipopolysaccharideslipopolysaccharides and thus are found only in Gram-negative and thus are found only in Gram-negative
organisms. Most studied in organisms. Most studied in Salmonella, E. coli, Salmonella, E. coli, and and Shigella.Shigella.
Toxins (cont.)Toxins (cont.)
EnterotoxinEnterotoxin -- toxin that acts specifically on -- toxin that acts specifically on the ______________. the ______________.
Enterotoxins are found in Enterotoxins are found in S. aureus, S. aureus,
enteropathogenic enteropathogenic E. coli, Clostridium E. coli, Clostridium
perfringens, Salmonella spp., etc.perfringens, Salmonella spp., etc.
Most studied: cholera toxin from Most studied: cholera toxin from Vibrio Vibrio choleraecholerae
Action of cholera enterotoxinAction of cholera enterotoxin
Action of cholera enterotoxin (cont.)Action of cholera enterotoxin (cont.)
Patterns of InfectionPatterns of Infection