Host Microbe Interactions

Host Microbe Interactions daily we ingest thousands of microorganisms on the food we eat inhale hundreds of thousands of microorganisms in the air we breath have microorganisms stick to us wherever we go most of these invaders have no ill effect on us as we cough, urinate and defecate them away we are also protected by the “friendly” resident microorganisms found throughout our body

Host Microbe Interactions microorganisms very easily colonize the warm, moist, nutrient rich environment we call the human body usually they live as normal flora in some cases, they are able to overcome the bodies defenses, and cause disease organisms that can cause any noticeable damage, invade tissue, or produce toxins are called pathogens

Anatomical Barriers in addition to providing barriers to the microbial world, skin and mucous membranes also create an environment for interacting microorganisms and the human body these interactions are referred to as symbiosis, which means living together

Anatomical Barriers symbiotic relationships between microorganisms and a host include mutualism commensalism parasitism

Mutualism in this type of relationship, both partners benefit E. coli synthesizes vitamin K in the intestine in exchange the large intestine provides nutrients necessary for survival of the microorganisms E. coli

Commensalism one organism is benefited and the other is unaffected by this type of relationship many of the microorganisms that make up our normal flora inhabit places like the eyes, ears, and external genitalia these bacteria live on secretions and sloughed off cells they bring no benefit to the host and yet the microorganisms benefit greatly from the environment they inhabit

Parasitism one organism benefits at the expense of the other all pathogens are parasites parasitic microorganisms

Normal Flora microorganisms that colonize a host without causing disease two types of normal flora exist resident flora are microorganisms that inhabit sites on the body for extended periods transient flora are microorganisms that are temporary

Normal Flora the presence of normal flora cover potential adherence sites for invading microorganisms consume the available nutrients produce compounds toxic to other microorganisms bacteria found on skin

Normal Flora when the balance between normal flora and pathogens is upset, disease can result the normal bacterial microorganisms of the adult human vagina maintain the pH at about 3.4 – 4.5 the presence of this normal flora inhibits the overgrowth of Candida albicans, yeast

Normal Flora if the presence of the normal flora is eliminated by antibiotics, or excessive douching, the pH of the vagina becomes nearly neutral, creating an environment very conducive to the growth of C. albicans C. albicans

Principles of Infectious Disease a parasitic relationship between a microorganism and a host is called an infection infections can be subclinical or inapparent: meaning no symptoms or the symptoms are so mild as to be noticed infection that causes impairment of body function is called disease

Principles of Infectious Disease the more virulent a pathogen is the more disease promoting attributes it possesses virulence factors are substances or features of a microorganism that help it infect and cause disease they may include ability to adhere ability to overcome host defense ability to evade host defense

Establishing the Cause of Infectious Disease Koch’s Postulates criteria for establishing the fact that specific microbes cause specific diseases determined by Robert Koch in 1877 while looking for the causative agent for anthrax

Establishing the Cause of Infectious Disease Koch’s Postulates in order to determine that a microbe causes a particular disease, the following postulates must be met: The microorganism must be present in every case of the disease. The organism must be grown in a pure culture from diseased hosts. The same disease must be produced when a pure culture of the organism is introduced into a susceptible host. The organism must be recovered from the experimentally infected hosts.

Mechanisms of Pathogenesis pathogenesis is the manner in which a disease develops patterns that disease-causing microorganisms may follow include production of ingested toxins foodborne intoxication the causative agent must produce toxins few organisms are capable of causing disease this way, the few that can include Clostridium botulinum or Staphylococcus aureus

Mechanisms of Pathogenesis colonization of host surface, then toxin production invading pathogen is able to grow to high numbers on host surfaces such as the respiratory and intestinal tract they then produce a toxin that is damaging to the cells organisms that use this mechanism include Vibrio cholerae, which causes cholera or Corynebacterium diphtheriae, which causes diphtheria

Mechanisms of Pathogenesis invasion of host tissue breaching body’s barriers then multiplies in the body’s tissues these organisms have mechanisms that allow them to avoid macrophage destruction some are also capable of avoiding detection by antibodies organisms that use this mechanism include Mycobacterium tuberculosis, causative agent for tuberculosis, and Yersinia pestis, causative agent for plaque

Mechanisms of Pathogenesis invasion of tissue, then toxin production breach the body’s barriers, then make toxins in addition to invasion, these organisms also make toxins organisms that use this mechanism include Shigella dysenteriae and Streptococcus pyogenes

Mechanisms of Pathogenesis in order to cause disease microorganisms need to be able to adhere and colonize host tissue avoid the innate defenses avoid the adapted defenses cause damage related to the disease

Adherence to establish disease the causative agent needs to adhere difficult to overcome our first-line defenses so adherence is imperative many bacteria have adhesions, generally found on the pili

Colonization causative agent needs to multiply in order to colonize to multiply, they must compete successfully with the normal flora for space and nutrients toxins that may be produced by the normal flora must be overcome

Avoiding Innate System while some bacteria are able to cause disease while remaining on the surface of the skin or mucosa, many need to penetrate that barrier once this is done, those pathogens have it on easy street, exclusive rights to rich nutrition and multiplying without any competition penetrating the skin is extremely difficult bacteria take advantage of trauma to provide a break in the skin West Nile Virus is transmitted to the host through a mosquito bite, a penetration of the skin

Avoiding Innate System mucous membranes penetration is the most common entry for most microorganisms one method that is used is referred to as ruffling once the microorganism attaches to the membrane, it can direct the that cell to engulf the bacterium: this is referred to as ruffling ruffling on the surface of mucous membrane

Avoiding Innate and Adaptive System several mechanisms can be used by microorganisms to avoid the potentially lethal effects of our immune system hide inside a host cell phagocytes, complement and antibodies can’t find them: remember self and non-self! interfere with the activation of complement (which attracts phagocytes)

Avoiding Innate and Adaptive System avoid destruction by phagocytes by simply preventing encounters with phagocytes C5a peptides are an enzyme that is made by some bacteria C5a peptide destroys the complement component if the complement is not activated, neither are the phagocytes some bacteria produce membrane-damaging toxins that kill phagocytes

Avoiding Innate and Adaptive System avoid recognition and attachment to phagocytes by producing capsules to prevent phagocytosis Streprococcus pneumoniae procduces capsules survive in the phagocyte they don’t worry about being engulfed, simply enjoy the “free ride” some microorganisms can escape from the phagosome before being fused with the enzyme lysosome

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Avoiding Innate and Adaptive System survive in the phagocyte some microorganisms can block the fusion of the phagosome and lysosome a few organisms can actually survive the lysosome environment

Avoiding the Adaptive System avoiding antibodies which integral to the adaptive system; this can be accomplished several ways including IgA protease cleaves IgA class of antibodies found in mucus and other secretions antigenic variation alter structure of antigens stay ahead of antibody production and destruction by altering the structure the antibodies are searching for mimic host molecules some microorganisms have the ability to cover themselves with molecules similar to “self”

Host Damage in order for disease to happen damage of some sort must happen to the host in most cases damage to the host facilitates dispersal of the pathogen damage to the host can occur either directly indirectly

Direct Host Damage toxins produced by the invading pathogen cause direct damage to the host which results in disease toxins capable of causing damage include exotoxins a protein toxin released from a living cell mostly found in Gram + cells Bacillus anthraxis produces an exotoxin

Toxins Some bacteria release poisons known as toxins which cause food poisoning. Some toxins, known as exotoxins multiply in food. These toxins are not easily destroyed by cooking and may remain in food once they have developed. Other bacteria produce toxins inside the human body only after the food has been eaten. These are called endotoxins 34

Exotoxins exotoxins are secreted by the bacteria or released following lysis exotoxins are soluble in body fluids which makes them easily diffused into blood and then are rapidly transported throughout the body exotoxins work by destroying particular parts of the host cells or by inhibiting certain metabolic functions

Exotoxins exotoxins are highly specific exotoxins are among the most lethal substances known to man 1 gram of the exotoxin produced from Clostridium botulinum is capable of killing the entire population of the United States, close to 300 million people the danger with exotoxins is not the ingestion of the bacterium, but the ingestion of the toxin Clostricium botulinum

Exotoxins most exotoxins are grouped according to the tissues they adversely impact neurotoxins damage the nervous system entereotoxins upset the intestinal system cytotoxins afflict their damage on many different types of cells by disrupting cellular function of by lysing the cell

Endotoxins endotoxins are lioopolysaccharides (LPS) found in the lipid portion of the outer wall of Gram – bacteria endotoxins are released when Gram – bacteria die and the cell wall undergoes lysis antibiotics that are used to treat Gram – diseases can lyse the bacterial cells, releasing the endotoxin this can lead to an immediate worsening of the symptoms these symptoms usually improve as the endotoxins break down

Endotoxins endotoxins can also activate blood-clotting proteins, causing the formation of small blood clots blood clots obstruct capillaries, resulting in decreased blood supply, which can lead to tissue death this is referred to as disseminated intravascular coagultaion endotoxins also cause fever (pyrogenic response) and rapid blood pressure decrease

Immune Response Damage inflammatory response can destroy tissue antibody-antigen complexes formed during the immune response settle in kidneys and joints activates complement, which produces damaging inflammation

Thank you

Principles of Infectious Disease pathogenicity is the ability of a microorganism to cause disease by overcoming the host defenses this can be accomplished with a primary pathogen: microorganism capable of causing disease in a healthy host opportunistic pathogen: is only capable of causing disease when the immune system is overcome, or the organism is introduced to an unusual location opportunistic organisms can be part of the normal flora or found in the environment

A closer look at intestinal bacteria Staphylococcus Lactobacillus  E. coli This slide shows a closer look at some of our intestinal bacteria by scanning electron microscope. It is estimated that the colon of healthy adults harbors more than 100 species of bacteria. C. perfringens  Bacteroides Bifidobacterium Source : Yakult Research Institute - Japan

Viral Pathogenesis Mechanisms viral pathogenesis is very dependent on gaining access to the host evading the host’s defenses causing damage to or death of the host cell while continuing to reproduce themselves viral access to the host was discussed in the virus lecture; remember viral attraction is specific to the host viruses bind more successfully to organisms found in mucous membranes

Viral Evasion of Host interferons play a role in limiting the ability of viruses moving from neighbor cell to neighbor cell once infected cells are capable of producing a protein that can regulate and limit viral replication some viruses are able to encode proteins to shut down this cellular protective device

Viral Evasion of Host though limited in the ability to control viruses, those few antibodies that are used can be circumvented by viruses that have developed methods to transfer directly from one cell to its immediate neighbor since antibodies control viruses by neutralizing extracellular viral particles, the above renders this useless

Terminology of Infectious Diseases communicable disease that spreads from one host to another, either through direct or indirect contact infectious dose # of microbes needed to establish infection some microorganisms are less contagious than others and as a result require a larger number of pathogens present to establish disease

Terminology of Infectious Diseases sign objective changes that are observable and measurable examples of signs include swelling, fever, paralysis symptoms subjective effects experienced by patient examples of symptoms include pain or nausea

Terminology of Infectious Diseases disease stages incubation the time between the initial infection and the first appearance of any signs or symptoms this time can vary depending on the pathogen and the condition of the host illness signs and symptoms of the disease are experienced if the disease is not successfully overcome or treated, the patient dies during this period convalescence person regains strength and the body returns to its pre-diseased state

Terminology of Infectious Diseases types of infectious diseases acute disease rapid onset, short duration influenza is an acute disease chronic disease develop slowly, last longer the body’s reaction may be less severe hepatitis B is a chronic disuse latent disease causative agent is never completely eliminated remains inactive, but can become reactivated and symptomatic if immune response is diminished shingles is a latent disease

Terminology of Infectious Diseases localized infections invading microorganisms are limited to a small area boils and abscesses are local infections systemic infections infectious agent spread throughout body by blood or lymph measles is a systemic infection

Virus and Host Damage some viruses take-over and destroy the cell virus causes inflammatory response – more damage – more activation of inflammatory response often times, in particular with the case of the common cold, the inflammatory response initiated by the virus causes much less effect than the domino effect of the inflammatory response that follows

Mechanisms of Eukaryotic Pathogenesis these mechanisms are not clearly understood, though the mechanisms include colonization of the host, evasion of the host defenses and damage to the host fungi these organisms are generally opportunistic, taking advantage of a weakening or change in our immune system excessive growth of Candida albicans is often a result in immunocompormised hosts C. albicans is the causative agent of thrush, a common occurrence in AIDS patients

Mechanisms of Eukaryotic Pathogenesis eukaroytic parasites are generally found in the intestinal tract or have gained access through an insect bite attach with specific receptors are capable of hiding within the host cell the damage they can inflict varies some cause malnutrition by competing for nutrients some can cause direct damage by the enzymes they produce