Transcript chapter19
Host-Microbe Interactions Chapter 19 19.1 Anatomical Barriers As Ecosystems Some bacteria have symbiotic relationships with their hosts Mutualism - both benefit (K and B vitamins) Commensalism - bacteria benefit with no harm to the host Parasitism - microbe grows at the expense of the host 19.2 Normal Flora The normal flora are those bacteria that are commonly found on/in the body of a healthy host Many play critical protective roles for the host Staphylococcus aureus and scalded skin syndrome Clostridium difficile and aggressive antibiotic therapy 19.3 Principles of Infectious Disease Infection - usually parasitic colonization by a microbe Clinical manifestations Subclinical (apathogenic) - none apparent Clinical (pathogenic) - symptoms of disease Course of infection Primary - disease caused by the initial infection Secondary - because of the initial infection, another microbe can establish an infection Example: Influenza virus infection can be followed by Klebsiella pneumoniae pneumonia 19.3 Principles of Infectious Disease Pathogenicity The capacity for a microbe to cause disease Some microbes are primary pathogens and usually cause disease after colonization Others are opportunistic pathogens and cause disease only in conjunction with some other unusual event Immunocompromised status Compromised normal flora 19.3 Principles of Infectious Disease Characteristics of infectious disease Communicable or contagious diseases are readily transmitted person to person (e.g., influenza, measles, pertussis Other diseases are not contagious (including West Nile virus, anthrax) since they are not transmitted person to person Infection is also a function of quantity of microbes The infectious dose is expressed as ID50 The ID50 for a microbe is the number of bacteria or viruses needed to infect 50 of 100 people given the dose This number varies among pathogens (anthrax = 10,000) Incubation period - no symptoms 19.3 Principles of Infectious Disease Illness - phase of disease Convalescence - recovery from disease Some people can be carriers for some infectious agents (”Typhoid Mary”) Duration of Symptoms Acute - rapid onset, short duration Chronic - slow onset, long duration Latent - agent is never eliminated Recrudescence is the recurrence of a latent viral infection 19.3 Principles of Infectious Disease Distribution of the pathogen Most are localized to a specific tissue Others can be systemic Some localized infections can become systemic; often a poor prognostic indicator Microbes and their products in the blood Bacteremia - bacteria in blood Viremia - virus in the blood Toxemia - toxins in the blood Septicemia - life-threatening; bacteria replicating in the blood 19.4 Establishing the Cause of Infectious Disease Koch’s postulates of infectious disease etiology The microbe must be present in every instance of the disease The microbe must be isolated and cultured from a diseased animal Introduction of the microbe into a susceptible animal must result in the disease The microbe must be reisolated from the animal 19.4 Establishing the Cause of Infectious Disease Molecular postulates of infectious disease etiology The virulence factor or gene(s) must be detected in pathogenic members of a species, but not nonpathogenic members Introduction of the gene(s) that encodes the virulence factor into a nonpathogen must convert the microbe into a pathogenic strain The gene(s) must be expressed when introduced into a susceptible animal Antibodies or immune cells (e.g., Tc cells) must protect the animal from the disease 19.4 Establishing the Cause of Infectious Disease The mechanisms of disease Production of exotoxins that are ingested Colonization of the host surface (skin or mucosa), followed by exotoxin production Invasion of host tissues Invasion of host tissues, followed by exotoxin production 19.5 Establishment of Infection Adherence Mediated by glycoproteins termed adhesins Typically have specificity for host cell surface proteins Colonization Replication of bacteria at the site of adherence Secretion of factors that impair the host response, such as IgA proteases (enzymes that digest IgA dimers) Expression of iron-binding molecules, termed siderophores Delivery of effector molecules into host cells Often virulence factors that damage the host cell 19.6 Invasion - Breaching the Anatomical Barriers Penetration of the skin Cuts, abrasions, or burns Vector (flea, mosquito) Penetration of the mucous membranes Directed uptake by cells Exploitation of antigen sampling by immune cells Dendritic cells Macrophages 19.7 Avoiding the Host Defenses Hiding within a host cell avoids antibodies Avoiding killing by complement system proteins Neisseria gonorrhoeae inactivates the C3b complement protein Avoiding destruction by phagocytes Bacillus anthracis kills macrophages Streptococcus pyogenes produces streptolysin O that damages phagocytic cell membranes Polysaccharide capsules are resistant to phagocytosis Strep pyogenes (protein G) and Staph aureus (protein A)secrete proteins that bind to Fc portions of antibodies, thus neutralizing them 19.8 Damage to the Host Exotoxins Proteins secreted by various pathogenic bacteria Can be local or systemic Fatal in small amounts 1 gram of botulinum toxin is sufficient to kill the Earth’s human population Potent antigens, but exert their effect before antibodies can be synthesized A-B toxins - two parts; A is toxic, B dictates target Membrane-damaging toxins - hemolysin disrupts RBC membranes Superantigens “trick” large numbers of helper T cells into producing inflammatory cytokines 19.8 Damage to the Host Endotoxins Endotoxins are lipopolysaccharides (LPS) Lipid A (toxic) Polysaccharide Normally found as outer cell membrane component of Gram- bacteria Bind to Toll-like receptors on phagocytic cells, which results in the release of tumor necrosis factor from the cells TNF causes capillary leakage and inflammation This can lead to hypotension and disseminated intravascular coagulation - aka, septic shock 19.9 Mechanisms of Viral Pathogenesis Viruses do not encode toxins Their principal cause of damage is death of the cell In some viral infections, the immune response is so aggressive that it causes immunopathology Many viruses encode immune-modulating proteins that subvert the immune response Shut down MHC class I processing and presentation Impair the interferon pathway Viral cytokines Interference with apoptosis (death signals from T and NK cells)