Medical Microbiology Host-Parasite Relationships BIOL 533 1 Lecture One Agents That Cause Disease. Pathogens Viruses Bacteria Parasites Fungi Lecture One Characteristics of Parasitism • • • • • Encounter: agent meets host Entry: agent enters host Spread: agent spreads Multiplication: agent multiplies Damage: agent, host response, or both cause damage • Outcome: agent or host wins, or coexist BIOL 533 3 Lecture One Encounter • In utero – Do not normally come in contact with organisms • Protection of fetal membranes • Do not normally come in contact with organisms from mother – Normally only present sporadically – Exceptions: sexual diseases, virus causes, rubella BIOL 533 4 Lecture One Encounter • At moment of birth – Come in contact with organisms present in vaginal canal and on skin • Previously, antibodies passed from mother to fetus • Defenses are good for a period of time, then they wane BIOL 533 5 Lecture One Encounter • Challenge between man and microbe wages many times during lifetime – Most disappear rapidly – Some become part of normal flora – Only a few cause disease BIOL 533 6 Lecture One Later Encounters • Exogenous: encountered in environment • Endogenous: encountered in or on body – Organisms present on skin can cause disease when they go into deeper tissues BIOL 533 7 Lecture One Later Encounters • Example: – Staphylococcus aureus enters cut and forms boil – In this case, encounter took place long before disease (at time skin was colonized) • Encounter is not always sharply demarcated BIOL 533 8 Lecture One Normal Flora • What constitutes normal flora? – Some people possess Streptococcus pyogenes in their throat for long periods, but rarely contract disease • Opportunistic pathogen existence (carrier state) – 95% of people never have this bacterium, and when they do, they get sick BIOL 533 9 Lecture One Normal Flora Defined • Constitutes normal flora if definition is “any organism present that is not causing disease” • Not normal flora if used to mean organisms present in majority of population BIOL 533 10 Lecture One Host-Parasite Interaction • Exposure to virulent agents does not always lead to disease – Typhus and Black Plague epidemics: only half of population became sick, even though most likely exposed BIOL 533 11 Lecture One Host-Parasite Interaction • Response of particular microbe to particular host – Depends on factors unique to each interaction – Within a single individual – Changes with: • Age • Nutritional state • Other factors BIOL 533 12 Lecture One Entry • Much of inside of body is connected to the outside; for example: – Lumen of intestine – Alveoli of lung – Tubules of kidney • Almost all organs within thorax and abdomen are topologically connected to the outside BIOL 533 13 Lecture One Entry • Mechanisms to keep out invaders – Sphincters and valves – With exception of digestive and genitourinary systems, these sites are normally sterile – Organism that resides on lumen side of intestine or lung alveoli has not penetrated body BIOL 533 14 Lecture One Entry Defined • Ingress of microbes into body cavities contiguous with outside BIOL 533 15 Lecture One Digestive System • Enter through eating – Numbers of organisms are reduced one million or more in stomach • Bacillary dysentery can result from only a few hundred organisms – Not many survive in intestine because of digestive enzymes and strong force of peristalsis BIOL 533 16 Lecture One Digestive System • More survive in ileum, but need mechanisms to prevent expulsion – Surface components serve as adhesins to allow adherence to epithelial cells • Pili and surface polysaccharides – Diseases such as cholera and “traveler’s diarrhea” are caused without penetrating epithelium • Toxins that affect epithelial cells BIOL 533 17 Lecture One Respiratory System • Enter through being inhaled – Air containing microbes goes through air passages (nasal turbinates, oropharynx, larynx) – Microbes reaching lower respiratory system face powerful epithelium sweeping action – Colonization requires adhesion mechanisms BIOL 533 18 Lecture One Other • No term for urinary or genital entry • By bypassing epithelial tissue, microbes can cause disease without penetrating deep into tissues – Cholera, whooping cough, infection of urinary bladder BIOL 533 19 Lecture One Penetration into Deeper Tissues • Very few organisms can penetrate unbroken skin (worms are an exception) • Some organisms can penetrate epithelial tissue; for example: – S. pneumoniae, Treponema pallidum • Normally after some injury to tissue (many times caused by a virus) – Viruses, by receptors BIOL 533 20 Lecture One Carried in by Macrophage • Alveolar macrophage trap organisms in lung – Normally carry upward on ciliary epithelium – Some cases, can carry deeper into tissues • Some organisms can live, grow in macrophage: – Legionella – Bordetella pertussis – HIV (via virus-laden macrophage from semen) BIOL 533 21 Lecture One Penetration by Other Means • Insect bites: numerous viral and protozoan diseases • Cuts and wounds: don’t normally lead to disease – Brushing teeth or defecating vigorously causes minute abrasions of epithelium • Organisms quickly cleared from blood by reticuloendothelial system BIOL 533 22 Lecture One Penetration by Other Means – Injury to internal tissue disrupts defense mechanisms and serious disease can result; for example • Subacute bacterial endocarditis – Devastating before antibiotics – Caused by oral streptococci that became implanted on heart valves damaged by rheumatic fever BIOL 533 23 Lecture One Penetration by Other Means • Organ transplants or blood transfusions – Jakob-Cruetzfeldt disease from transplanted corneas – Cytomegalovirus from kidneys, probably in donor kidney • Because immunosuppressive drugs are used, virus may be endogenous • Hepatitis B, HIV transmitted by blood BIOL 533 24 Lecture One Disease Causation • Why are organisms adapted to various locations? – Temperature optima; athletes foot yeast cannot grow at 37°C – Oxygen requirements – Specialized factors important for causing disease (i.e., virulence factors) – Virulence: degree of pathogenicity BIOL 533 25 Lecture One Virulence Factor Examples • • • • • • Exotoxins Endotoxins Capsules IgA proteases Adhesins (pili) Motility BIOL 533 • Invasive properties • Ability to acquire iron • Serum resistance • Ability to survive inside phagocytes 26 Lecture One Inoculum Size • Inoculum size can determine whether organisms cause disease • Normally, high number needed to cause disease/overcome defenses; e.g. – Baths in contaminated hot tubs (veritable culture of bacteria—over one hundred million organisms per ml) BIOL 533 27 Lecture One Inoculum Size • Normally harmless organisms can overcome defenses; e.g., – People get boils all over body • If large number of organisms deposited in deeper tissues, infection usually results – Surgeon preps area to reduce numbers BIOL 533 28 Lecture One Spread of Disease • General: spread only if overcome host defenses • Sometimes precedes, sometimes follows microbial multiplication – Precede: parasite causes malaria disseminated before multiplication – Follow: S. aureus multiplies locally before being disseminated BIOL 533 29 Lecture One Spread of Disease • Types: – Direct lateral propagation to contiguous tissues – Dissemination to distant sites • Characteristics: – Anatomical factors (e.g., ear infections) – Active participation by pathogens— enzymes BIOL 533 30 Lecture One Multiplication • Factors that affect – Microbial nutrition: body is very nutritious, but it also has antimicrobial substances – Body contains very little free iron • Physical factors: temperature, etc. – Narrow temperature optima—prudence of lowering fever by “take two aspirin and call me in the morning” BIOL 533 31 Lecture One Damage • General: type and intensity depend on specific organism and tissue • Types: – Mechanical: mostly result of inflammation – Cell death: depends on: • Which cells • How many infected • How fast infection proceeds BIOL 533 32 Lecture One Damage • Types, continued: – Pharmacological: toxins alter metabolism – Damage due to host responses • Inflammation can lead to destruction of neighboring cells • Immune response BIOL 533 33 Lecture One Agents That Cause Disease. Pathogens Viruses Bacteria Parasites Fungi Lecture One • Outcome: agent or host wins, or coexist BIOL 533 35 Lecture One