Bacterial pathogenesis.pdf

By / Reem Abdelrahman Lecturer of microbiology and immunology, faculty of medicine, Helwan university  continued Objectives: — Understand the meaning and types of pathogen. — Identify the meaning, types, sites and effect of bacteria...

By / Reem Abdelrahman Lecturer of microbiology and immunology, faculty of medicine, Helwan university  continued Objectives: — Understand the meaning and types of pathogen. — Identify the meaning, types, sites and effect of bacterial carrier. — Understand the meaning of infection and disease. — Explain factors that govern disease production. — Recognize the meaning of bacterial pathogenicity. — Identify virulence factors of bacteria. — Differentiate between exotoxin and endotoxin. — Understand Koch’s postulate.  Microorganism is pathogen when it is able to cause disease Saprophytic: live Parasitic: live in/on freely on nature living host Pathogenic: Commensal: live in/on living host cause disease without causing disease Opportunistic: under certain conditions commensals cause disease. How can commensals become opportunistic ? Lowered host defense Alteration of the host tissue Change in natural habitat of the Lowered host defense organism Alteration of the host tissue Bacterial carrier  Carrier — Healthy or diseased? — Healthy. — Possess microorganism or no? — Possess microorganism. — Transmit microorganism or no? — Transmit microorganism.  Carrier Transient Permanent (incubation (chronic) period) Are carriers serious? Why carriers are serious? Not confined No manifestations. to bed. Communicate normally with Carry organism in the entire epidemic period. public.  Infection and disease — Infection: relation between microorganism and host. — Disease: destruction of host tissue by the organisms due to: 1- Invasion of tissue. 2-Toxin production. 3-Other virulence factors.  source The Portal infection of to occur needs: exit reservoir Mode of multiplication transmission Portal of entry Factors that govern disease production Microbial Host resistance factors factors Virulence pathogenicity Natural Acquired immunity immunity Microbial factors — Pathogenicity: the ability to cause disease. — Virulence: Degree of pathogenicity. It is genetically determined through genes carried on plasmids, phages, pathogenicity island or the chromosome.  Bacteria Virulent Moderately Avirulent virulent Cause disease Cause no Mild disease disease  Virulence factors of bacteria Invasive Adherence Survive factors intracellularly factors Antigenic Toxin variation production I- Adherence factors: Pili Fimbriae Glycocalyx N.Gonorrhea Streptococci Staph.epidermidis E.coli attachment to Adherence to Adherence to urinary tract endothelium buccal mucosa. epithelium. of heart valves.  I- Invasive factors:the ability to invade tissues, multiply and spread rapidly causing the inflammatory process. Partialy due to the following Antiphagocytic Extracellular enzymes Collagenase Capsule hyalouronidase Lecithenase M.protein: over 150 antigenic type, protrude Phospholipase. from outer surface in hairy like projections. coagulase Streptokinase Protein A :bind Fc portion of IgA preventing Streptodornase complement activation. IgA protease  III- Ability to survive intracellularly thus escape intacellular killing by phagocytic cells. — M. tuberculosis and Legionella: Inhibit phagosome-lysosome fusion. — Lesteria: Escape phagosome to cytoplasm before phagosome-lysosome fusion. IV- Antigenic variation —Pathogens change their surface antigen and evade the immune system. V- Toxin production — Bacterial products which have direct harmful action on tissue cells. Exotoxin Endotoxin  continued Exotoxin: — Nature: Protein. — Bacteria: living. — Site of action: diffuse extracellularly to surrounding medium. — Control of production: genes on plasmids and bacteriophage. — Action: specific, neurotoxin, enterotoxin or exotoxin. — Mechanism of action: (A-B) two component toxin Cytolysin. Super antigen.  Modes of action of exotoxin: — (A-B) two component protein toxin: B-part: Bind specific receptor. Facilitate enternalization of A part. A-part: Active toxic component usually enzyme as ADP ribosyl transferase. Diphtheria toxin, cholera toxin, tetanus toxin —Cytolysin: Lyse cells from outside by damaging membrane. Example: Cl.perfringens. —Superantigens: üStaphylococcal TSST and enterotoxin. üStreptococcal pyrogenic exotoxin. Endotoxin: — Nature: Lipopolysaccharide. — Bacteria: dead. — Site of action: general effect. — Control of production: genes on chromosomes. — Action (generalized) (endotoxic or septic shock): Fever. Hypotention. DIC. Shock and death due to massive organ failure. — Mechanism of action: macrophage activation Complement C3a, C5a Hageman factor — Mechanism of action: 1- Macrophage activation IL-1, IL-6, TNFα, nitric oxide fever, hypotention, tissue damage, shock. — 2- Complement C3a, C5a bradykinin induced vasodilatation, increase vascular permeability, hypotention and shock. — 3- Hageman factor (early component of coagulation cascade) DIC, thrombosis, purpuric rash, tissue ischemia. Property Exotoxin Endotoxin Location of genes Composition Action Heat stability Diffusibility Immunogenicity Toxicity Convertibility to toxoid Produced by Property Exotoxin Endotoxin Location of Plasmid, Bacterial chromosome bacteriophage, PAIs. genes Composition Proteins Lipopolysaccharide Action Specific Non0specific Heat stability Labile, destroyed at Stable at 100 °C for 1 60°C. hour. Diffusibility Diffusible Not diffusible Excreted by living cell Integral part of cell wall Immunogenicity Strong induce high titer Weak immunogenicity of antitoxin Toxicity Strong Weak Convertibility to Yes No toxoid Produced by Gram positive mainly. Gram negative. —Define! übacterial carrier. üPathogen. üParasitic. üCommensal. —Illustrate chain of infection! —Innumerate bacterial virulence factors! —Differentiate between exotoxin and endotoxin!