Pathogenesis Introduction PDF

Over View  Consequences of Adaptive Response Humoral – B-cell activation – Antibody production to extracellular pathogens – Immune memory Cellular – Cytotoxic T-cell Activation – Migration – Immune memory Types of Immunity Host Microbe Interactions Introduction...

Over View  Consequences of Adaptive Response Humoral – B-cell activation – Antibody production to extracellular pathogens – Immune memory Cellular – Cytotoxic T-cell Activation – Migration – Immune memory Types of Immunity Host Microbe Interactions Introduction to disease Principles of Infectious Disease Infection – colonization of host with microorganisms – Infection does not always lead to noticeable adverse effects – Infectious Disease – infection that results in disease – Disease – Deviation from normal health Usually due to damage or injury to host  Two Main Types of Infections Beneficial – normal flora – Microbes living on and in body – Over a trillion microbes associated human body – 500 to 1000 different species in gut alone – Outnumber all cells in your body 10:1 or more! Harmful – Pathogenic Microbes  Pathogenicity Pathogenicity – Ability to cause disease True Pathogens are organisms that can cause disease in otherwise healthy people That pathogen termed primary pathogen Opportunistic Pathogen - Microbes that cause disease when the body’s defenses are down May be part of normal flora or common in environment Mechanisms of Pathogenicity Virulence factors Figure 15.9  Virulence – Virulence is quantitative term referring to pathogen’s disease-causing ability – Measure of ability to cause disease Highly virulent organisms have high degree of pathogenicity – These organisms more likely to cause disease – Example: Streptococcus pyogenes » Causes disease from strep throat to necrotizing fasciitis  Virulence Factors Biotic factors that lead to increased virulence Often additive or synergistic – Morphological characters – Metabolic pathways (e.g. antibiotic resistance) – Toxins – Enzymes  Infectious Disease Characteristics of infectious disease – Disease that spreads from host to host termed communicable or contagious – Virulence or ease of spread reported as infectious dose Infectious dose is number of organisms required to establish infection Diseases with small infectious dose more easily spread than those requiring large numbers  How bad is the bug? Microbes – ID50: Infectious dose for 50% of the test population Toxins or poisons – LD50: Lethal dose (of a toxin) for 50% of the test population Smaller LD or ID more toxic or virulent  Bacillus anthracis Portal of entry ID50 Skin 10-50 endospores Inhalation 10,000-20,000 endospores Ingestion 250,000-1,000,000 endospores  Virulence Factors Virulence is determined by combination of factors Often additive or synergystic More factors = more virulent – Examples: Fimbriae Glycocalyx Enzymes Toxins Host  I. Adherence factors Adhesions/ligands bind to receptors on host cells Most adhesins – glyco- or lipoproteins – Glycocalyx Streptococcus mutans – Fimbriae Escherichia coli – M protein Streptococcus pyogenes Facilitate binding to host cells or tissues Figure 15.1a Figure 15.1b Figure 15.2  II. Exoenzymes/Proteins – Enzymes or proteins secreted by bacteria Digestive enzymes – Proteases, nucleases, lipases – Used to penetration/invasiveness – Used to degrade host defense proteins Antibodies Complement Cytokines Penetration into the Host Cell Figure 15.2  III. Toxins Toxin Substances that contribute to pathogenicity Toxigenicity Ability to produce a toxin Toxemia Presence of toxin the host's blood Toxoid Inactivated toxin used in a vaccine Antitoxin Antibodies against a specific toxin  Toxins Endotoxins – Found in cell walls or cells – Released after death – Examples?? Exotoxins – Secreted by organism – Highly toxic!! Endotoxin Figure 15.4b  Endotoxin Source Traditionally Gram – Metabolic product Lipopolysacharide cell wall (teichoic acids) Chemistry Carbohydrate and lipid Fever? Yes Neutralized by antitoxin no LD50 Large Exotoxins Figure 15.4a  Exotoxin Source Gram + and Gram – (most gram +) Metabolic product By-products of growing cell Chemistry Protein Fever? Depends on Toxin Neutralized by antitoxin Yes LD50 Small  IV. Metabolic Pathways Enzymes to degrade antibiotics – Beta-lactamases Export pumps for antimicrobials Glycogen degradation – Use intramuscular polysaccharides as carbon source  Summarize What are the 4 major factors that influence virulence Difference between Endotoxin and exotoxin Who makes them?  Next Time More Virulence Toxins