A parasitic organism is one that lives at the expense of its host; the relationship of host and parasite is called parasitism
Host-parasite interactions
Ectoparasite-lives on the surface of the host
Endoparasite-lives within the host
Final host-the host on (or in) which the parasite either gains sexual maturity or reproduces
Intermediate host-a host that serves as a temporary but essential environment for parasite development
Transfer host-a host that is not necessary for development but that serves as a vehicle for reaching the final host
Reservoir host-an organism that is infected with a parasite that can also infect humans
Infection-the state occurring when a parasite is growing and multiplying on or within a host
Infectious disease-a change from a state of health as a result of an infection by a parasitic organism
Pathogen-any parasitic organism that produces an infectious disease
Pathogenicity-the ability of a parasitic organism to cause a disease
Primary (frank) pathogen-organism that causes disease in the host by direct interactions with the host
Opportunistic pathogen-organism that is normally free-living or part of the host's normal microbiota, but which adopts a pathogenic role under certain circumstances
Some infectious organisms can enter a latent state; this can be intermittent (e.g., cold sores) or quiescent (e.g., chickenpox/shingles)
The final outcome of most host-parasite relationships is dependent on three main factors:
The number of pathogenic organisms present
The virulence of the organism
The host's defenses or degree of resistance
Virulence-the degree or intensity of pathogenicity of an organism; it is determined by three characteristics of the pathogen (invasiveness, infectivity, and pathogenic potential)
Invasiveness-the ability of the organism to spread to adjacent tissues
Infectivity-the ability of the organism to establish a focal point of infection
Pathogenic potential-the degree to which the pathogen can cause morbid symptoms (e.g., toxigenicity)
Virulence is often measured experimentally by lethal dose 50 (LD50) or infectious dose 50 (ID50)
Disease can also result from exaggerated immunological responses to a pathogen (immunopathology)
Pathogenesis of Viral Diseases
In order to cause disease, a virus must:
Enter a host
Contact and enter susceptible cells
Replicate within the cells
Spread to adjacent cells
Cause cellular injury
Engender a host immune response
Be either cleared from the body of the host, establish a persistent infection, or kill the host
Be shed back into the environment
Entry, contact, and primary reproduction-entrance can be gained through one of the body surfaces or as the result of medical procedures (e.g., needle stick, blood transfusion), or by insect vectors; some viruses replicate at site of entry; others spread to distant sites
Viral spread and cell tropism
Mechanisms of viral spread vary, but most common routes are bloodstream and lymph system; presence of virus in blood is called viremia
Tropisms-specificity of a virus to a type of cell, tissue, or organ; specificity usually results from presence of specific receptors or host cells that bind virus
Cell injury and clinical illness
Destruction of virus-infected cells in target tissues and changes in host physiology lead to development of viral disease and clinical illness; damage can be temporary or permanent
Four accepted patterns of viral infection
Lytic-virus multiplies, kills host cell immediately, and releases new virions
Persistent-virus lives in host cell and releases small number of viruses over a long time; little damage to host
Latent-virus resides in host cell but produces no virions; at later time, virus is activated and lytic infection occurs
Transformation-virus transforms host cell into cancer cell
Host immune response-both humoral and cellular components of immune response control viral infection
Recovery from infection-host either succumbs or recovers; recovery mechanisms involve numerous components of immune system and the importance of any individual component varies with the virus
Virus shedding-necessary to maintain a source of viruses in a population of host; can occur at same body surface used for entry; for some viral infections (e.g., rabies) humans and other animals are dead-end hosts (no shedding of virus)
Pathogenesis of Bacterial Disease
In order to cause disease a bacterium must (Note: the first five influence infectivity and invasiveness; toxigenicity plays a major role in the sixth step):
Maintain a reservoir (a place to live before and after causing an infection)
Initially be transported to the host
Adhere to, colonize, or invade the host
Multiply or complete its life cycle on or in the host
Initially evade host defense mechanisms
Possess ability to damage the host
Leave the host and return to the reservoir or enter a new host
Transport of the bacterial pathogen
Direct contact (e.g., coughing, sneezing, body contact)
Indirect transmission
Vehicles include soil, water, food
Vectors include living organisms that transmit a pathogen (e.g., insects)
Fomites-inanimate objects contaminated with a pathogen and that can spread the pathogen
Attachment and colonization by the bacterial pathogen-bacterium must be able to adhere to and colonize (but not necessarily invade) host cells and tissue
Depends on ability of bacterium to successfully adhere to host and compete with normal microbiota for essential nutrients
Adhesins-molecules on bacterium's surface that bind to complementary receptors on host cell surface
Invasion of the bacterial pathogen
Penetration of the host's epithelial cells or tissues
Pathogen-associated mechanisms involve the production of lytic substances that:
1) Attack the ground substance and basement membranes of integuments and intestinal linings
2) Degrade carbohydrate-protein complexes between cells or on cell surfaces
3) Disrupt cell surfaces
Passive mechanisms of entry involve:
1) Breaks, lesions, or ulcers in the mucous membranes
2) Wounds, abrasions, or burns on the skin surface
3) Arthropod vectors that penetrate when feeding
4) Tissue damage caused by other organisms
5) Endocytosis by host cells
Invasion of deeper tissues can be accomplished by production of specific products or enzymes that promote spreading (these are one type of virulence factor) or by entry into the circulatory system
Growth and multiplication of the pathogen-pathogen must find an appropriate environment; presence of bacteria in blood stream is called bacteremia; release of toxins by bacteria into blood stream can cause septicemia
Leaving the host-must be able to leave host or disease cycle will be interrupted and the bacterium will not be perpetuated; most bacteria leave host by passive mechanisms (e.g., in feces, urine, or saliva)
The clonal nature of bacterial pathogens-many virulence genes can be transferred by horizontal gene transfer; some transfer processes result in insertion of virulence genes into chromosome; this leads to the formation of different clonal types, some that cause disease and some that don't
Regulation of bacterial virulence factors-some bacteria are adapted to both free-living state and parasitic state; these bacteria have complex signal transduction pathways that regulate virulence genes; expression of virulence genes may be under control of phages or under control of environmental factors
Pathogenicity islands-large segments of DNA that carry virulence genes acquired during evolution by horizontal gene transfer; are not present in nonpathogenic members of same genus or species
J. Toxigenicity-the capacity of an organism to produce a toxin
Intoxications-diseases that result from the entry of a specific toxin into the host
Toxin-a specific substance, often a metabolic product of the organism, that damages the host in some specified manner
Toxemia-symptoms caused by toxins in the blood of the host
Exotoxins-soluble, heat-labile proteins produced by and released from a pathogen; may damage the host at some remote site
Can be grouped into four types based on structure and physiological activities
1) AB toxins can be separated into two distinct portions: one that binds the host cell and one that causes toxicity (e.g., diphtheria toxin-binds host cell surface receptor by the B portion and is taken into the cell by the formation of clathrin-coated vesicles; toxin is then cleaved, releasing A fragment, which enters cytosol; A fragment inhibits protein synthesis)
2) Host site specific exotoxins: neurotoxins damage nervous tissue (e.g., botulinum toxin and tetanus toxin), enterotoxins damage the small intestine (e.g., cholera toxin), and cytotoxins do general tissue damage (e.g., shiga toxin); some host site specific exotoxins are also AB toxins (e.g., cholera toxin)
3) Membrane-disrupting exotoxins-two subtypes, those that bind cholesterol in the host cell membrane and then form a pore (e.g., leukocidins and hemolysins) and those that are phospholipases (e.g., gas gangrene-associated toxin)
4) Superantigens
Roles of exotoxins in disease-can cause disease when they are ingested as preformed exotoxins (e.g., staphylococcal food poisoning), when produced after colonization of host (e.g., cholera), and when produced at a wound site (e.g., gas gangrene)
Endotoxins- LPS of many gram-negative bacteria
Released only when the microorganism lyses or divides
Usually capable of producing fever, shock, blood coagulation, weakness, diarrhea, inflammation, intestinal hemorrhage, and/or fibrinolysis; many of these effects are indirect and are mediated by host molecules and cells (e.g., macrophages, endogenous pyrogens, host cytokines)
Microbial Mechanisms for Escaping Host Defenses
Evasion of host defenses by viruses
Antigenic drift-mutations cause change in antigenic sites on the virion (e.g., influenza virus)
Infection of T cells (e.g., HIV)
Fusion of host cells-allows spread from cell to cell without exposure to antibody-containing fluids (e.g., HIV, measles virus, cytomegalovirus)
Infection of neurons having little or not MHC molecules (e.g., herpesvirus)
Production and release of antigens that bind neutralizing antibodies-ties up neutralizing antibodies so there is insufficient antibody to bind complete viral particle (e.g. hepatitis B virus)
Evasion of host defenses by bacteria
Evading the complement system
Capsules prevent complement activation
Lengthened O chains in LPS prevent complement activation
Serum resistance-features on surface of bacterium prevent formation of membrane-attack complex (e.g., Neisseria gonorrhoeae)
Evading phagocytosis
Capsules
Specialized proteins (e.g., M protein of Streptococcus pyogenes)
Prevention of phagolysosome formation (e.g., Chlamydia)
Production of leukocidins (e.g., staphylococci)
Production of enzymes that destroy complement-derived chemoattractants for phagocytes
Evading specific immune response
Capsules that are not immunogenic (e.g., Bordetella pertussis)
Phase variation-alteration in antigens (e.g., N. gonorrhoeae)
Production of IgA proteases (e.g., N. gonorrhoeae)
Production of proteins that interfere with antibody-mediated opsonization (e.g., staphylococcal protein A)
