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Host-Microbe Interactions Chapter 14 • Disease • Etiology • Pathogen – Primary vs. opportunistic • Virulence • Contamination • Infection vs. Infestation • Pathogenesis • Pathology • Symptoms • Signs • Syndrome • Sequelae Anatomical Barriers as Ecosystem • Skin and mucous membranes are physical barriers to infection – May supply foundation for microbial ecosystem • Humans are usually sterile in utero • Soon after birth, microbial populations begin to establish • Normal microbiota – Resident flora – Transient flora • Isolated colonies in specific body regions •Factors that influence distribution: •Nutrient availability, salinity, oxygen availability, host defenses, mechanical factors •Dominant type of organism may change with age and situation – Normal flora play a role in defenses • protection from colonization by pathogens • microbial antagonism » Competitive exclusion » Bacteriocins • Symbiotic relationships form between microbes and host – Relationships may change depending on state of host and attributes of microbes – Mutualism (++) – Intestinal bacteria – Probiotics – Commensalism (+ neutral) – Flora on skin and conjunctiva – Parasitism (+-) – Pathogens Pathogenicity – State of host resistance usually determines extent of infection • primary infection • secondary infection (typically opportunistic) • Sub-clinical (inapparent) infection Distribution of pathogens – Local infection – Systemic (generalized) infection • Septicemia can result from: – Bacteremia – Toxemia – Viremia • Many people are carriers of pathogens – Viruses; Neisseria; Salmonella; Streptococcus • Why are they less affected or not at all? • Predisposing factors: – gender – genetic background – climate and weather – inadequate nutrition – age – habits and lifestyle – chemotherapy – emotional disturbances • Characteristics of infectious disease: – communicable • contagious • Often reflects ID50 – non-communicable disease Etiology of Infectious Diseases • Robert Koch demonstrated that specific microbes caused specific diseases – experimented with grazing animals infected with anthrax • Koch’s postulates – Same pathogen must be present in each case of disease – Pathogen is isolated from diseased host and grown in pure culture – Pure culture must cause disease when inoculated into healthy animal – Pathogen must be re-isolated from inoculated animal • Exceptions to Koch’s postulates – some bacteria have unique culture requirements – some diseases are caused by multiple pathogens • Polymicrobial diseases (mixed infections) – Ethical considerations Stages of an Infectious Disease Duration of a Disease – acute diseases – chronic diseases – latent disease Establishment of Infection • In order to cause disease pathogen must follow a series of steps – Gain entrance to host – Adherence – Colonization – Avoid Host Defenses – Cause host damage Portals of entry 1. Mucus membranes • • • • Respiratory tract Gastrointestinal tract Genitourinary tract Placenta 2. Skin 3. Parenteral route • Bite, puncture, injection, wound • Most microbes have a preferred portal of entry – Streptococci when inhaled may cause pneumonia; when ingested they do not • A few microbes cause illness no matter how they enter – May cause different illness based on portal – Plague has 2 forms; bubonic and pneumonic – Anthrax has three forms • Adherence – Critical Step – Binding of adhesins to host receptors is highly specific • Virulence factors – Capsules – Incomplete phagocytosis – Fimbrae – Components of cell wall • Extra-cellular enzymes (exoenzymes) – Coagulases & Kinases • Form or dissolve blood clots – Hyaluronidase & Collagenase • Dissolve hyaluronic acid and collagen fibers – IgA proteases & Leukocidins • Destroy antibodies or WBCs Damage to the Host • Damage often facilitates dispersal of pathogen – Diarrhea or coughing • Main sources of damage: – – – – Steal nutrients Binding to and invading host cells Induce hypersensitivity reactions (allergies) Production of toxins (Toxigenicity) • Exotoxins – G+ bacteria • Produced as part of their metabolism • Secreted externally or following cell lysis • Among most lethal substances – Proteins • Enzymatic nature • Highly soluble • Heat Liable – Toxoids • Inactivated exotoxins • Induce antitoxins that provide immunity – Antibodies against a specific toxin • Passive immunity in form of antitoxin can be given as treatment – Grouped into functional categories • Neurotoxins • Enterotoxins • Cytotoxins • Staphylococcus aureus – enterotoxin; exofoliatin toxin; Toxic Shock Syndrome toxin • Vibrio cholera – cholera enterotoxin • Clostridium species – botulinum neurotoxin; tetanus neurotoxin; gangrene toxin • Endotoxins – G- bacteria – Released when cells die and their cell walls lyse – Lipopolysaccharide (LPS) outer membrane • The lipid portion (lipid A) is toxin – Heat stable; not suitable for use as toxoids • Do not cause formation of antitoxins – All endotoxins produce the same symptoms • Chills, fever, weakness, aches • May activate blood clotting proteins • May cause septic shock that can be fatal – Salmonella, Proteus, Klebsiella and Neisseria Portals of Exit • Mucus membranes – Respiratory & gastrointestinal are most common • Skin/wounds • Biting insects • Contaminated needles and syringes