Lec10 Colonization, Infection, and Disease

Colonization, Infection, and Disease

Colonization, Infection, and Disease

Colonization:

The action of an organism establishing itself in an area

Infection:

A condition in which pathogenic microorganisms penetrate host defenses, enter the tissues and multiply

Pathologic State:

  • Cumulative effects of infection damage

  • Disruption of tissues and organs

  • Results in disease

Disease:

  • Any deviation from health

  • Factors that cause disease:

    • Infections

    • Diet

    • Genetics

    • Aging

Infectious Disease:

Disruption of tissues or organs caused by microbes or their products

Resident Biota:

Normal Biota:

  • Large and diverse collection of microbes living on and in the body

  • Also known as resident, commensal, or indigenous biota, microbiome, microbiota, or normal flora

Include an array of bacteria, fungi, protozoa, viruses

  • These organisms protect us by occupying space that harmful bacteria could inhabit

  • “Sterile” sites (those lacking commensal microbes) are more susceptible to infection

Acquisition of Resident Microbiota

  • Benefits of normal biota:

    • Influence the development of organs

      • Gut/Intestinal tract-establishing tight junctions between gut epithelial cells

      • Immune tolerance

    • Prevent the overgrowth of harmful microorganisms

  • Microbial antagonism:

    • The general antagonistic effect “good” microbes have against intruder microorganisms

    • Take up nutrients that the intruder organisms could eat.

    • Microbes in a steady, established relationship are unlikely to be displaced by incoming microbes

Initial colonization of the newborn

  • Fetuses are likely inoculated w/ normal microbiota in utero

    • These microbes are important for healthy full term pregnancies and healthy newborns

  • Inoculated w/ mother’s flora during birth

    • Acquisition of Lactobacillus

  • Continued colonization of te baby through diet:

    • Breast milk contains around 600 species of bacteria and sugars that babies cannot digest

    • Sugars used by healthy gut bacteria

    • Breast milk may be necessary for maintaining a healthy gut microbiome in the baby.

Microbiota and Disease

Endogenous infections:

  • Caused by biota already on or in the body

  • Can occur when normal biota is introduced to a site that was previously sterile

    • Example: E. coli entering the bladder, resulting in a UTI

    • Example: Tear in intestines causes leaking of E. coli and other commensal gut organisms into blood, causing bacteremia

  • Can occur when other flora are disrupted

    • C. diff infection of the gut after antibiotic therapy

Pathogens and pathogensis

Pathogen:

  • Has a parasitic relationship w/ its host

  • Colonization may cause infection and disease

  • Type and severity of infection depend on both the pathogenicity of the organism and the condition of the host

  • Pathogenesis/Virulence factor - a trait that gives an organism some advantage over the immune system

Streptococcus pyogenes produces a hemolysin to disrupt red blood cells, enabling the acquisition of iron normally sequestered in the body by heme or transferrin

  • Pathogenicity

    • Organisms potential to cause infection or disease

  • (True) pathogen

    • Capable of causing disease in healthy persons w/ normal immune function

  • Opportunistic pathogen

    • Cause disease when host defenses are compromised, or when introduced into a body compartment they don’t normally occupy

      • Catheter associated UTI

      • Ventilator associated pneumonia

      • Infection after trauma, cancer chemotherapy

  • Virulence

    • Relative severity of the disease potential of a particular microorganism

Establishing infection: Step One - Portals of Entry

Portal of entry:

  • A characteristic route taken by a microbe to initiate infection

  • Usually through skin or mucous membranes

  • Exogenous: originating from outside the body

    • The enironment, another person, or animal

  • Endogenous: already existing in the body

    • Normal biota or a previously silent infection (i.e. controlled by immune system)

Infectious agents that enter the skin

  • Sites of entry:

    • Nicks

    • Abrasions

    • Punctures, some tiny and unapparent

    • Conjunctiva

  • Intact skin is a very tough barrier that few microbes can penetrate

The Gastrointestinal Tract as Portal

  • Entry through food, drink, or other ingested substances

    • Adapted to survive digestive enzymes and abrupt pH changes

  • Foodborne infection and intoxication

  • Heliobacter pylori survives stomach by local neutralization of acid by producing ammonia

The Respiratory Portal of Entry

  • Gateways to the respiratory tract:

    • Oral cavity

    • Nasal cavity

  • Continuous mucous membrane covering the upper respiratory tract, sinuses, and auditory tubes

    • Microbes often transferred from one site to another

Urogenital Portals of Entry

  • Sexually transmitted infections (STIs):

    • Pathogens transmitted by sexual means

    • Account for 4% of infections worldwide

    • 13 million new cases in the U.S. each year

  • Entry points through the skin or mucosa of:

    • Penis

    • External genitalia

    • Vagina

    • Cervix

    • Urethra

Infections During Pregnancy and Birth

  • The placenta is an exchange organ:

    • Formed by maternal and fetal tissues

    • Separates the blood of the developing fetus from that of the mother

    • Permits diffusion of dissolved nutrients and gases to the fetus

    • A few microbes cross the placenta and are spread by the umbilical vein into the fetal tissues

      • Zika virus

      • Listeria monocytogenes

    • Other infections are transmitted perinatally as the child passes through the birth canal

The Size of the Inoculum

  • Infection Dose (ID): a minimum number of microbes required for an infection to proceed

    • Determined experimentally for many microbes

    • Microbes w/ a smaller infectious dose have greater virulence

    • Often see as ID50, or the number of microbes needed to cause infection in 50% of a population

    • The lower the infectious dose, the less microbes needed to establish an infection

Establishing Infection: Step Two - Attachment to Host

  • Adhesion:

    • A process by which microbes gain a more stable foothold on host tissues

    • Dependent on binding between specific molecules on both the host and pathogen

    • A particular pathogen is limited to only those cells and organsims to which it can bind

    • Once attached, a pathogen can invade body compartments

Becoming Established: Step Three - Surviving Host Defenses

  • Phagocytes:

    • White blood cells that engulf and destroy pathogens by means of enzymes and antimicrobial chemicals

    • macrophages, neutrophils, …

  • Antiphagocytic factors:

    • Capsules

    • Protein

    • Antigen

Step Four: Causing Disease

  • Virulence Factors:

    • Structures, products, or capabilities that allow a pathogen to cause infection in the host

    • Adaptations that a microbe uses to invade and establsih itself in a host

    • Determine the degree of tissue damage that occurs, and extent of infection

Patterns of Infection

  • Localized Infection:

    • Microbe enters the body and remains confined to a specific tissue

  • Systemic Infection:

    • When an infection spreads to several sites and tissue fluids, usually in the bloodstream

    • Infectious agents can travel by means of nerves or cerebrospinal fluid

  • Focal Infection:

    • Exists when the infectious agent breaks loose from a local infection and is carried to other tissues

    • Examples:

      • Tuberculosis

      • Dental caries and systemic inflammation

      • Toxins are carried through the blood to the target tissue

  • Mixed Infection:

    • Several agents establish themselves simultaneously at the infection site

    • In synergistic infections, microbes cooperate in breaking down tissue

    • In other mixed infections, one microbe creates an environment that enables another microbe to invade

    • Polymicrobial diseases: gas gangrene, wound infections, dental caries, human bite infections

Inducing and Injurious Host Response

  • Many cases of microbial diseases are the result of indirect damage

    • Host’s excessive or inappropriate response to a microorganism

    • Pathogenicity is a trait not solely determined by microorganisms

    • Cause of septic shock during systemic infections

      • Immune reaction to LPS is inflammation

      • During systemic infection, LPS is spread through body in bloodstream

Vacating the Host: Step Five - Portals of Exit

  • Portal of Exit:

    • Avenue of departure for pathogens to exit the host

    • Secretion

    • Excretion

    • Discharge

    • Sloughed tissue

Respiratory and Salivary Portals

  • Escape media for pathogens that infect the upper and lower respiratory tract:

    • Mucus

    • Sputum

    • Nasal Drainage

    • Moist secretions

Fecal Exit

  • Some intestinal pathogens cause irritation in the intestinal mucosa that increases the motility of the bowel

    • Resulting diarrhea provides a rapid exit for the pathogen

    • Helminth worms release eggs and cysts through the stool

    • Feces containing pathogens creates public health problem

Fluid Loss - Urogenital Tract, Blood Loss

  • Agents involved in STIs leave the host in vaginal discharge or semen

  • Source of neonatal infections that infect infant as it passes through the birth canal

    • Herpes simplex

    • Chlamydia

    • Candida albicans

  • Blood removed or released through vasuclar puncture

  • Traumatic injury

  • Blood-feeding animals are the most common transmitters of pathogens:

    • Ticks

    • Fleas

    • Mosquitoes

Fomites

  • An inanimate object that harbors and transmits pathogens

  • Not a continuous source of infection

Animals as Reservoirs and Sources

  • Vector:

    • In epidemiology, a live animal that transmits an infectious agent from one host to another

    • Majority of vectors are arthropods:

    • Biological vector:

      • Actively participates in a pathogen’s life cycle

      • Serves as a site in which it can multiply or complete its life cycle

    • Mechanical vectors:

      • Not necessary to the life cycle of an infectious agent

      • Merely transport it without being infected

What Happens in Your Body

  • Incubation Period:

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

  • Prodromal Period:

    • When the earliest notable symptoms of infection appear

  • Period of Invasion:

    • Infectious agent multiplies at high levels and exhibits greatest virulence

  • Convalescent Stage:

    • Patient responds to infection and symptoms decline

Epidemiology - Study of Disease Transmission

  • Characterize how a disease is spreading

  • Locate source of disease

  • Remove source and/or control spread to stop an outbreak

Source Identification is necessary for control

  • Infections are traced back from patient to potential sources

  • Allows identification of common point of contamination