Host-Microbe interactions

The human body and microbes

• the human body exists in a state of dynamic equilibrium

• Many interactions between human body and microorganisms involve the development of biofilms

• Colonization of the body involves a constant “give and take”

Contact, Colonization, Infection, Disease

• Microbes that engage in mutual or commensal associations - normal (resident) flora, Indigenous flora, microbiota

• Infection - a condition in which pathogenic microbes penetrate host defenses, enter tissues, and multiply

• Pathogen - infectious agent

• Infectious disease - an infection that causes damage or disruption to tissue and organs

Resident flora

• Most areas of the body in contact with the outside environment harbor resident microbes

• Internal organs, tissues, and fluids are microbe-free

• Transients - microbes that occupy the body for only short periods

• Resident - microbes that become established

• Bacterial flora benefit host by preventing overgrowth of harmful microbes - microbial antagonism

• Endogenous infections - occur when normal flora is introduced to a site that was previously sterile

Initial colonization of the newborn

• Uterus and contents are normally sterile and remain so until just before birth

• breaking of fetal membrane exposes the infant

• All subsequent handling and feeding continue to introduce what will be normal flora

Flora of the human skin

• Skin is the largest and most accessible organ

• Two cutaneous populations

  • Transients - influenced by hygiene

  • Residents - Stable, predictable, less influenced by hygiene

Flora of the gastrointestinal tract

• GI tract is a long hollow tube, bounded by mucous membranes

  • Tube is exposed to the environment

• Variations in flora distribution due to shifting conditions (pH, Oxygen, tension, anatomy)

• Oral cavity, large intestine, and rectum harbor appreciable flora

Flora of the mouth

• Most diverse and unique flora of the body

• Numerous adaptive niches

• Bacterial count of saliva (5 × 10⁹ cells per milliliter)

Flora of the large intestine

• Has complex and profound interactions with host

• 10⁸-10¹¹ microbes per gram of feces

• Intestinal environment favors anaerobic bacteria

• Intestinal bacteria contribute to intestinal odor

Flora of the respiratory tract

• Oral streptococci, first organisms to colonize

• Nasal entrance, nasal vestibule, anterior nasopharynx - S. aureus

• Mucous membranes of nasopharynx - Neisseria

• Tonsils and lower pharynx - Haemophilus

Flora of the gentiourinary tract

• Sites that harbor microflora

  • Females - Vagina and outer opening of urethra

  • Males - anterior urethra

• Changes in physiology influence the composition of the normal flora

  • Vagina (estrogen, glycogen, pH)

Maintenance of the normal resident flora

• Normal flora is essential to the health of humans

• Flora create an environment that may prevent infections and can enhance host defenses

• Antibiotics, dietary changes, and disease may alter flora

• Probiotics - introducing known microbes back into the body

Major factors in the development of infection

• Portal of entry

• Adhesion

• Invasion

• Multiplication

• Infection of target

• Disease

• Portal of exit

True pathogens

Capable of causing disease in healthy person with normal immune defenses. i.e. Influenza virus, plague bacillus, malarial protozoan

Opportunistic pathogens

Cause disease when the host’s defenses are compromised or when they grow in a part of the body that is not natural to them. i.e. Pseudomonas sp. & Candida albicans

Virulence factor

Characteristic or structure that contributes to the ability of a microbe to cause disease - total severity of a disease depends on the “virulence” of the pathogen

Becoming established (Portal of entry)

• Portals of entry - Characteristic route a microbe follows to enter the tissues of the body

• Exogenous agents - originate from source outside the body

• Endogenous agents - already exist on or in the body (normal flora)

Different portals of entry

• Skin

  • Nicks, abrasions, punctures, incisions

• Gastrointestinal tract

  • Food, drink, and other ingested materials

• Respiratory tract

  • Oral and nasal cavities

• Urogential tract

  • Sexual, displaced organisms

• Transplacental

Pathogens that infect during pregnancy

• STORCH

  • Syphilis

  • Toxoplasmosis

  • Other diseases (hepatitis B, AIDS, and Chlamydia)

  • Rubella

  • Cytomegalovirus

  • Herpes simplex virus

Requirement for an Infectious Dose (ID)

• Minimum number of microbes required for infection to proceed

• Microbes with small IDs have greater virulence

• Lack of ID will not result in infection

Attaching to host (Adhesion)

• Microbes gain a stable foothold at the portal of entry

• Dependent on binding between specific molecules on host and pathogen

• Fimbrae

• Flagella

• Glycocalyx

• Cilia

• Suckers

• Hooks

• Barbs

Surviving host defenses

• Initial response of host defenses comes from phagocytes

• Antiphagocytic factors - used to avoid phagocytes

• Species of Staphylococcus and Streptococcus produce leukocidins, toxic to white blood cells

• Slime layer or capsule - makes phagocytosis difficult

• Ability to survive intracellular phagocytosis

Entering host tissues

Some pathogens produce a secretion system to insert specialized virulence proteins directly into the host cells

Causing disease

• Virulence factors

  • Traits used to invade and establish themselves in the host, also determine the degree of tissue damage that occurs - severity of disease

• Exoenzymes

  • Dissolve extracellular barriers and penetrate through or between cells

• Taxigenicity

  • Capacity to produce toxins at the site of multiplication

Bacterial toxins

• Two types:

  • Endotoxin

    • Toxin that is not secreted but is released after the cell is damaged

    • Composed of lipopoylsaccharide (LPS), part of the outer membrane of gram-negative cell walls

  • Exotoxin

    • Toxin molecule secreted by a living bacterial cell into the infected tissue

    • Strong specificity for a target cell

    • Hemolysins

    • A-B toxins (A - active, B - binding)

    • The A component is attached to the B component to get into the cell

    • Then, the A component is released from the vacuole and inhibits a cellular protein to cause damage

The process of infection and disease

• 4 distinct stages of clinical infections:

  • Incubation period

    • Time from initial contact with the infectious agent to the appearance of first symptoms

    • Agent is multiplying, but damage is insufficient to cause symptoms

    • Several hours to several years

  • Prodromal stage

    • Vague feelings of discomfort

    • Nonspecific complaints

  • Period of Invasion

    • Multiplies at high levels, becomes well-established

    • More specific signs and symptoms

  • Covalescent period

    • As person begin to respond to the infection, symptoms decline

Localized infection

Microbes enter the body and remains confined to a specific tissue

Systemic infection

Infection spreads to several sites and tissue fluids usually in the bloodstream

Focal infection

When infectious agent breaks loose from a local infection and is carried to other tissues

Mixed infection

Several microbes grow simultaneously at the infection site - polymicrobial

Primary infection

Initial infection

Secondary infection

Another infection by a different microbe

Acute infection

Comes on rapidly, with severe, but short-lived effects

Chronic infections

Progress and persist over a long period of time

Signs and symptoms of inflammation

• Edema

  • Accumulation of fluid

• Granulomas and abscesses

  • Walled-off collections of inflammatory cells and microbes

• Lymphadenitis

  • Swollen lymph nodes

Earliest Symptoms of disease

• Result from the activation of body defenses:

  • Fever

  • Pain

  • Soreness

  • Swelling

Signs of infection in the blood

• Changes in the number of circulating white blood cells

  • Leukocytosis

    • Increase in white blood cells

  • Leukopenia

    • Decrease in white blood cells

  • Septicemia

    • Microorganisms are multiplying in the blood and present in large numbers

      • Bacteremia - Small numbers of bacteria present in blood not necessarily multiplying

      • Viremia - Small number of viruses present not necessarily multiplying

Infections that go unnoticed

• Asymptomatic (subclinical) infections

  • Although infected, the host doesn’t show any signs of disease

• Inapparent infection, so the person doesn’t seek medical attention

Portals of exit

• Pathogens depart by a specific avenue

• Greatly influences the dissemination of infection

• Respiratory

  • Mucus, sputum, nasal drainage, saliva

• Skin scales

• Fecal exit

• Urogenital tract

• Removal of blood

Persistence of Microbes and pathologic conditions

• Apparent recovery of host does not always mean the microbe has been removed

• Latency

  • After the initial symptoms in certain chronic diseases, the microbe can periodically become active and produce a recurrent disease

  • Person may or may not shed it during the latent stage

• Chronic Carrier

  • Person with a latent infection who sheds the infectious agent

• Sequelae

  • Long-term or permanent damage to tissues or organs

Sources and transmission of microbes

• Reservoir

  • Primary habitat of pathogen in the natural world

  • Human or animal cell, soil, water, plants

• Source

  • Individual or object from which an infection is actually acquired

Living Reservoirs

• Carrier

  • An individual who inconspicuously shelters a pathogen and spread it to others

  • may or may not have experienced disease due to the microbe

• Asymptomatic carrier

  • Shows no symptoms

• Passive carrier

  • Contaminated healthcare provider picks up pathogens and transfers them to other patients

Asymptomatic Carriers

• Show no symptoms

• Incubation carriers

  • Spread the infectious agent during the incubation period

• Convalescent carriers

  • Recuperating without symptoms

• Chronic carrier

  • Individual who shelters the infectious agent for a long period

Animals as reservoirs and sources

• Vector

  • A live animal (other than human) that transmits an infectious agent from one host to another

• majority of vectors are arthropods - fleas, mosquitoes, flies, and ticks

• Some larger animals can also spread infection - mammals, birds, lower vertebrates

Biological vectors

Actively participate in a pathogen’s life cycle

Mechanical vectors

Not necessary to the life cycle of an infectious agent and merely transports it without being infected

Zoonosis

• An infection indigenous to animals but naturally transmissible to humans

• Humans don’t transmit the disease to others

• At least 150 zoonoses exist worldwide

• Make up 70% of all new emerging diseases worldwide

• Impossible to eradicate the disease without eradicating the animal reservoir

Communicable disease

• When an infected host can transmit the infectious agent to another host and establish infection in that host

• Highly communicable disease is contagious

Non-communicable infectious disease

• Infectious disease that does not arise through transmission from host to host

• Occurs primarily when a compromised person is invaded by his or her own normal microflora

• Contact with organism in natural, non-living reservoir

Patterns of transmission

• Direct contact - Physical contact or fine aerosol droplets

• Indirect contact - Passes from infected host to intermediate conveyor and then to another host

  • Vehicle - inanimate material, food, water, biological products, fomites

  • Airborne - droplet nuclei, aerosols

Nosocomial infections

• Diseases that are acquire or developed during a hospital stay

• From surgical procedures, equipment, personnel, and exposure to drug-resistant microorganisms

• 2 to 4 million cases per year in the US with approximately 90000 deaths

Universal blood and body fluid precautions

• Stringent measures to prevent the spread of nosocomial infections from patient to patient, from patient to worker, and from worker to patient - universal precautions

• Based on the assumption that all patient specimens could harbor infectious agents, so must be treated with the same degree of care

Epidemiology

• The study of the frequency and distribution of disease and health-related factors in human populations

• Surveillance - collecting, analyzing, and reporting data on rates of occurrence, mortality, morbidity, and transmission of infections

• Reportable, notifiable diseases must be report to authorities

• Centers for Disease Control and Prevention (CDC) in Atlanta, GA - principal government agency responsible for keeping track of infectious diseases nationwide

Prevalence

Total number of existing cases with respect to the entire population usually represented by a percentage of the population

Incidence

Measure the number of new cases over a certain time period, as compared with the general healthy population

Mortality rate

The total number of deaths in a population due to a certain disease

Morbidity rate

Number of people afflicted with a certain disease

Endemic

Disease that exhibits a relatively steady frequency over a long period of time in a particular geographic locale

Sporadic

When occasional cases are reported at irregular intervals

Epidemic

When prevalence of a disease is increasing beyond what is expected

Pandemic

Epidemic across continents

Koch’s Postulates

• Used to determine the causative agent of a disease

• Method:

  1. Find evidence of a particular microbe in every case of a disease

  2. Isolate that microbe from an infected subject to cultivate it artificially in the laboratory

  3. Inoculate a susceptible health subject with the laboratory isolate and observe the resultant disease

  4. Reisolate the agent from this subject