Host - Pathogen Interactions Normal Flora: commensal bacteria that are part of a normal, healthy host Different regions of the body are colonized with bacteria skin and mucous membranes upper respiratory tract GI tract urethra opening vagina external ear and eye Normal flora acquired during/after birth Resident flora: fixed types, found in defined areas Transient flora: derived from the environment Normal flora provide nutrients and prevent colonization by pathogens; in some cases normal flora can be pathogenicSterile Regions of the Body The presence of bacteria in normally sterile sites is indicative of an infection. May involve normal flora or pathogens Internal tissues and organs heart, liver, brain, lungs, kidney, bone, muscle, sinuses Body fluids blood, urine, cerebrospinal, amnioticPathogen: a microorganism capable of causing disease. True pathogen:Presence is always considered abnormal (eg. Mycobacterium tuberculosis, Yersinia pestis). Causes disease in hosts with normal immune defenses Opportunistic pathogen:causes infection/disease in immuno- compromised hosts. May be member of host’ s normal flora.Protection Disease eo Pathogens oe eee po ee Large inoculum ee oe gone SL tiers drags oe Lajertomation e <—— ‘by normal flora es Host factors < ee @ | ce, maize perisiatsic, "Waste prodlitforiation immune suppression} by normal flora es Physical destruction (eg. radian, chemiesl, burns) Mucosal celis Mucosal cells copyright Samuel Baron/Charles Patnick DavisCommon Infections Caused by Normal Flora Dental caries, petiociontal disease Absoasses and pharyngitis Sepsis Endocarcitis Pneumonia Gastroenteritis ‘and peritonitis, Urogenital infections: copyright Samuel Baron(Charies Patrick DavisNormal Flora in Rat GI TractPathogen (B) within normal flora of GI tractInfections Infection: The multiplication of an infectious agent (pathogen) within the body. Endogenous infection: an infection from the access of normal flora to sterile areas of the body. Exogenous infection: infection from extraneous organisms Acute (suppurative or purulent) infection: illicits inflamatory response with pus formation Granulomatous infection: chronic infection characterized by formation of granulomas (collection of macrophages)Infections - communicable Epidemic: occurs more frequently than normal Pandemic: infection that occurs worldwide Endemic: infection that is constantly present at low levels in a specific population. Inapparent or Subclinical: no overt symptoms; detected by Ab titer Latent: stage of infection in which organism is present but not multiplying or eliciting disease symptoms; can be reactivated Chronic: organisms continue to grow/multiple in host without eliciting symptoms (Typhoid Mary)Stages of Infection Incubation: time between acquisition and beginning of symptoms Prodrome: appearance of non-specific symptoms (fever, malaise) Specific: overt characteristic sions and symptoms Recovery: diminishing symptoms; immune controlKoch’s Principles - provide basis for clinical microbiology 1) Microbe present in every case of the disease; absent in healthy host 2) Microbe must be isolated and grown in pure culture 3) Inoculating host with pure microbe elicits disease 4) Same microbe must be isolated from newly infected hostVirulence A quantitative measure of the ability of a microorganism to cause disease (pathogenicity). LD,, (lethal dose 50%): The number of organisms needed to cause death in 50% of the infected hosts. ID.) (infectious dose 50): The number of organisms needed to cause an infection in 50% of the hosts. The degree of virulence expressed by each bacteria is related to the different virulent factors expressed by that organism.Bacterial Disease Mechanisms Bacteria cause disease by two primary mechanisms toxin production invasion and inflammation i Baclerie-Mediated Hoshitounted Patnegenssia Feviogenests Secreted Toxins oat & 4 #,°,¢¢ a Antigens Leukoaytes betenged maine and iarematery cell tesrursie ‘Somatic Gell BanagePathogen - Host Relationships cell =m Perr Facultative intrarelatar acter aimoreia ge Shigela eo retails Obligate intracellular bacteria: qu | rokertsia Chienydia Coxiella Extracellular bacteria’ Vilirio chovescee Peevdonoms Econ tereCy ooInfectious Disease Events and Pathogenic Determinants Encounter/Transmission Entry/evade primary defense Adhere Colonize/Spread Elicit disease symptoms Host response Outcome Transmissibility Adherence factors Invasive factors Avoidance of host defenses ToxigenicityTransmission Four main portals of entry: respiratory tract GI traet genital tract skin Bacteria transmitted by multiple means respiratory droplets fecal contamination insect/animal bites skin contact body fluids sexual contactAdherence to Cell Surfaces specialized bacterial structures aid in adherence tomucosal surfaces, catheters, heart valves, and artificial joints, predisposing individuals to infections pili glycocalyxInvasion Collagenase and Hyaluronidase: degrade proteins that comprise host’s extracellular matrix (collagen and hyaluronic acid), thereby spreading through subcutaneous tissue. Coagulase: accelerates the formation of fibrin clot. Clot can protect bacteria from host immune system. Integrins and Invasins: bacterial surface proteins that aid in attachment and invasion of host cellsAvoidance of Hosts Immune Response Immunoglobulin A (gA) protease: Ae | degrades host immunoglobulin ee eae Lp (antibody) allowing host to remain, \ ly adhere and colonize. light chain heavy ehain Proteins that bind to and inactivate antibody | function (Protein A, G) Leukocydins: destroy neutrophils and macrophages Capsule: prevents phagocytosisToxin Production Exotoxin secreted made up of protein (common 2 part structure) sensitive to high temperature derivatives can be used to produce vaccines cause several important diseases -tetnus, botulism, diphtheria Endotoxin (LPS) found only in Gram (-) bacteria not secreted heat stable made up of polysaccharideSpread of Virulence Factors Among Bacteria Avirulent E coli oy . 1. Transfer virulence 2, Change to virulence Transduction Transtormatton Phage 3. Intestinal disease dive to virulence: genes: Ee Bacterial DNA Adherence Enterotoxins Piasiia invasiveness Cyrotoxinity Virutent E colt