BIOLOGY & SCIENCE: article : Summary of Host-Parasite Interactions

I. NATURAL HABITATS FOR MICROBES

Soil; Water; Air

Animals and Animal Products

II. MICROBIAL FLORA OF HUMAN BODY

Skin: Gram-positive bacteria are most common

Respiratory Tract (actually external to body)

Mouth and oropharynx

Saliva

Teeth and gums (gingiva)

Nose and nasopharynx
Microorganisms can be aspirated into the lower respiratory tract

Larynx, trachea and bronchial tubes (bronchi)

Lungs: Superior and inferior lobes (also middle lobe in right lung); Alveoli

Eye (Conjunctivae)
Ear: Inner, middle and exterior; Exterior commonly colonized

Gastrointestinal Tract (actually external to body): Intestinal flora play a significant role in: Digestion; Vitamin production (e.g., vitamin K); Ecological competition (see below) with potentially pathogenic microorganisms

Esophagus: Not typically colonized
Gastric mucosa of stomach: Acid tolerant organisms
Small intestine: Extends from pylorus to ileo-cecal junction (about 20 feet in length); Colonized by mostly anaerobes

Villi (plural of villus) and microvilli are finger-like projections that protrude through the mucous membrane throughout the length of the small intestine and are responsible for absorption

Peyer’s patch: Aggregations of lymphoid tissue concentrated in the ileum

M (microfold) cells: specialized cells in the Peyer’s patches that sample the microenvironment and uptake foreign antigens for processing by underlying macrophages

Duodenum: Upper portion of small intestine (about 10 inches in length) encompassing the superior, descending, transverse and ascending portions, in that order; Hepatic ducts (from liver), pancreatic duct, and cystic duct (from gallbladder) join and enter into the intestine at the descending duodenum

Jejunum (middle portion): Upper two-fifths of remaining length of small intestine

Ileum (lower portion): Remaining three-fifths of length of small intestine

Large intestine: Extends from ileo-cecal valve to anus (about 5 feet in length); >10¹¹ bacteria per gram of feces with anaerobes 1000-fold more common than other microbes

Cecum (a.k.a., Caecum): Large, blind pouch just posterior to the ileo-cecal junction

Colon: Ascending, transverse, descending, and sigmoid portions

Rectum

Anus

Special conditions of intestinal tract

Intestinal tract of newborn

Antibiotic alteration of flora

Genitourinary Tract

External genitalia
Anterior urethra: Normally colonized by avirulent organisms; May be transiently colonized by fecal organisms that can cause disease; Neisseria gonorrhoeae and Chlamydia trachomatis may cause disease or asymptomatically colonize
Urinary bladder: Not normally colonized; May be transiently colonized with urethral organisms
Vagina: Microbial population influenced by hormones
Cervix: Not normally colonized; Neisseria gonorrhoeae and Chlamydia trachomatis are important pathogens

III. NORMALLY STERILE SITES IN THE HUMAN BODY: Colonization of one of these sites generally involves a defect or breach in the natural defenses that creates a portal of entry

Brain; Central nervous system

Blood; Tissues; Organ systems

Sinuses; Inner and Middle Ear

Lower Respiratory Tract: Larynx; Trachea; Bronchioles (bronchi); Lungs; Alveoli

Kidneys; Ureters; Urinary Bladder; Posterior Urethra

Uterus; Endometrium (Inner mucous membrane of uterus ); Fallopian Tubes; Cervix and Endocervix

IV. ECOLOGY DEFINITIONS

Ecological Niche: Unique environmental position occupied by a particular species, perceived in terms of actual physical space occupied and function performed within the community or ecosystem

Flora (Microbiology Definition) = Microbiota: Microorganisms present in or characteristic of a special location (Flora more generically refers to plants; Fauna generically refers to animals)

Normal flora = Indigenous or resident microbiota: Microbial flora typically occupying a particular niche; Organisms tend to segregate given diversity of environmental conditions; Many normal flora perform important functions for the host, including: digestive and nutritional functions and competition with pathogenic microorganisms
Transient flora: Microbial flora only temporarily associated with a particular niche
Endogenous flora: Microbial flora occupying niches that are in or on the body of the host
Exogenous flora: Microbial flora normally existing externally to the body of the host

V. ECOLOGICAL RELATIONSHIPS

Independence: Living free from the influence, guidance, or control by another organism

Benign Relationship (Commensalism): Carrier

Malignant Relationship (Parasitism): Disease

Benign: Referring to a non-life or non-health threating condition; commensalism between host and parasite
Carrier: Symptomless individual who is host to a pathogenic microorganim and has the potential to pass the pathogen to others
Malignant: Disease tending to become progressively worse (Morbidity = illness) and potentially result in death (Mortality = death)

Microbial Interactions: Complex relationships among species; Neutral, Antagonistic, or Synergistic

Host-Parasite Interactions: Commensalism (+/0); Mutualism (+/+); Parasitism (+/-)

Symbiosis: A relationship in which two dissimilar organisms (Symbiotes, Symbionts) live in close association with one another
Commensalism: A relationship between two species in which one is benefited and the other is not affected, neither negatively nor positively
Mutualism: Mutually beneficial relationship between two species
Parasitism: A relationship between two species in which one benefits (Parasite) from the other (Host); Usually involves some detriment to the host

True pathogen (a.k.a., Strict pathogen): Any microorganism capable of causing disease; An infecting agent

Opportunistic pathogen: A usually harmless microorganism that becomes pathogenic under favorable conditions; Often a member of the normal microbial flora

VI. EPIDEMIOLOGY: Study of factors influencing occurrence, transmission, distribution, prevention and control of disease

Epidemic: Occurring suddenly in numbers clearly in access of normal expectancy
Endemic: Present or usually prevalent in a population or geographic area at all times
Pandemic: Widespread epidemic distributed or occurring widely throughout a region, country, continent, or globally

Acquiring Infectious Agents

Portals (Routes) of entry: Ingestion, inhalation, direct penetration
Carrier state: Symptomless individual (host) that is colonized by a pathogenic microorganism and who has the potential to pass the pathogen to others; Carriage may be transient or (semi-) permanent
Nosocomial infections: Infection acquired in a hospital setting that was not present in the host prior to admission, generally occurring within 72 hours of admission
Opportunistic infections: Infection caused by a normally harmless microorganism when certain predisposing conditions (disease or conditions that increase host susceptibility) exist

Transmission of Disease

Portals of entry/exit
Vector: Living carrier, especially the animal that transfers an infectious agent from one host to another; Commonly an Arthropod
Fomite: Inanimate object capable of transmitting microbes from one host to another, e.g., soiled bed linens, diapers, tissues and handkerchiefs, hospital respiratory equipment, etc.

VII. FACTORS CONTROLLING GROWTH OF ORGANISMS

Nutrient Availabilty: The accessibility of a necessary resource, substance or compound providing nourishment to maintain life, i.e. capable of conversion to energy and structural building blocks

Fastidious: an organism that has complex nutritional or cultural requirements, making isolation and culture more difficult

Physico/Environmental Parameters

Water activity/Osmotic pressure:

Water activity (a_w): Represents the available water

Osmotic pressure (p): Expressed in atmospheres; Reflects the concentration of solute in an aqueous solution

Oxygen: Pathogenic microorganisms may have metabolic oxygen requirements that are Obligate or Facultative, Anaerobic or Aerobic, or somewhere in between, Microaerophilic
pH: Power of hydrogen; Measurement of the amount of hydrogen ion in solution; Logarithm of the reciprocal of the hydrogen ion concentration in an aqueous solution used to express its acidity or alkalinity (0-14)
Temperature:

Psycrophile (psychrophilic): Liking cold temperatures; Optimal growth at 15o to 20oC

Mesophile (mesophilic): Liking moderate temperatures; Optimal growth at 20o to 45oC

Thermophile (thermophilic): Liking elevated temperatures; Optimal growth at 50o to 70oC

Competition: Simultaneous demand by two or more organisms or species for a necessary, common resource or physical space (niche) that is in limited or potentially limited supply, resulting in a struggle for survival

Host Immune System: The cells and tissues involved in recognizing and attacking foreign substances in the body

VIII. PATHOGENICITY vs. VIRULENCE

Pathogenicity: Quality of producing or the ability to produce pathologic changes or disease

Virulence: Measurement of the degree of disease producing ability of a microorganism as indicated by the severity of the disease produced; Measure of the dosage (inoculum size) required to caused a specific degree of pathogenicity; One general standard is the LD50

Virulence factors: Microbial characteristics that enhance the ability to cause disease
Dosage (Inoculum size): Number of pathogenic microorganisms entering the host
LD50 = Lethal Dose 50: Number of microorganisms required to cause lethality in 50% of the test host

IX. INFECTION vs. DISEASE

Infection: Colonization and/or invasion and multiplication of pathogenic microrganisms in the host with or without the manifestation of disease

Colonization: Successful occupation of a new habitat by a species not normally found in this niche
Multiplication: Ability of a microorganism to reproduce and increase in numbers during an infection

Disease: Abnormal condition of body function(s) or structure that is considered to be harmful to the affected individual (host); Any deviation from or interruption of the normal structure or function of any part, organ, or system of the body; Dependent upon the dosage and virulence of the organism/agent and varies inversely with the resistance of the host

X. MICROBIAL PATHOGENICITY

Factors that Influence the Degree of Pathogenicity and the Progression of Infection and Disease

Host factors: Age, sex, ethnicity, nutrition (diet), hormonal status; personal hygiene and immune status; Underlying disease or medical condition; Antibiotic or drug usage; Presence of foreign object (e.g., splinter, catheter, sutures, etc.); Innate differences between hosts
Microbial factors: Bacterial virulence factors; Inoculum size (dosage)
External factors (e.g., crowding; seasonal variations; hygiene, sanitation and public health; food processing, storage and preparation; etc.)

Progression of Infection and Disease

Entrance (Portal of entry)
Colonization (Adherence; Adhesion; Attachment)
Multiplication with or without dissemination (spread)
Penetration (Invasion) (Note: Not all pathogens are invasive)
Signs and symptoms of disease (Morbidity; Mortality)
Resolution or chronic state may be established
Elimination and/or exit of pathogen (Carrier state may be established)

Damage to Host

Direct damage

Tissue damage

Cell components and metabolic by-products
Toxins
Enzymes

Organ necrosis: Sum of morphological changes indicative of cell death and caused by the progressive degradative action of cellular components, metabolic by-products, enzymes and/or toxins

Metabolic Effects: Pathogenic organisms can affect any of the body systems with disruptions in metabolic processes

Indirect Damage: Damage to host from excessive or chronic immune response (immunopathogenesis)

XI. VIRULENCE FACTORS

Colonization Factors

Attachment/Adherence: Close association of bacterial cells and host cells generally characterized by receptors and target sites
Surface Receptors/Target Sites: Receptor sites present on both host (Receptor) and bacterial surfaces (Adhesins)

Adhesins: Bind Specific Host Receptors; Often involve fimbriae as structural cell component; Host cell receptors are often sugar moieties; Lectin: Adhesin specific for polysaccharide target receptor (sugar residues)

Fimbriae (plural): Modern term for short, hair-like, protein (pilin) appendages extending outward from the surface of certain bacteria (formerly and a.k.a., pili)
Pili (plural); Pilus (singular): Short, hair-like protein (pilin) appendages extending outward from the surface of certain bacteria; Term more properly applied to those organelles (F-pilus) responsible for bacterial conjugation (transfer of nucleic acids between closely related strains or species = "bacterial sex")

Invasive Factors: Invasins enable a pathogenic microorganism to enter and spread throughout the cells and/or tissues of the host body; Specific recognition of receptor sites on target cells enhances pathogenic advantage

Degradative Enzymes: Class of protein capable of catalytic reactions

Bacterial growth requires food and energy: Growth is achieved by enzymatic catalysis of catabolic (breakdown) reactions of host tissues (resulting in tissue damage) linked to catalysis of anabolic (buildup) reactions in the bacterial cell

Bacterial and host enzymes both play roles in the disease process

Toxigenicity: the ability of a microorganism to cause disease as determined by the toxin it produces which partly determines its virulence

Toxin-like pyrogenic (fever inducing) cell components (e.g., peptidoglycan and peptidoglycan fragments; Teichoic acid or lipoteichoic acid of Gram-positive cell wall)
Endotoxin: Complex bacterial toxin; Lipid A portion of lipopolysaccharide from Gram-negative cell walls; LPS is composed of Lipid A + Core Polysaccharide + O Antigen (a.k.a., O polysaccharide side chain) and is released upon lysis of the cell during infection (FIGURE 3-11); Lipid A component is responsible for endotoxin activity effects on the host; O side chain is the antigenic portion of the LPS molecule

Effects of endotoxin: Binds to specific receptors on macrophages, B lymphocytes (a.k.a., B cells) and other cells stimulating production and secretion of acute phase immunoreactants and lymphokines (e.g., IFN-gamma, IL-1, TNF-alpha, IL-6, histamine, prostaglandins); Stimulates growth of B cells (mitogenic)

Lymphocyte: Agranular leukocyte that is concentrated in lymphoid tissue and is active in immunological responses in the body, including the production of lymphokines (cytokines) and antibodies

Septic shock (sepsis): Endotoxemia; Endotoxin in the blood; Associated with overwhelming infection resulting in vascular system failure with sequestration of large volumes of blood in capillaries and veins; Activation of the complement and kinin systems and the release of histamines, prostaglandins, and other mediators may be involved
Fever (Pyrogenicity): Any elevation of the body temperature above the normal; Functions to speed up immune reactions and to limit/slow bacterial growth and multiplication
Leukopenia and then Leukocytosis: Abnormal reduction in the number (-penia) of leukocytes in the blood, (specifically a count of 5000 or less per cubic millimeter) / Abnormal increase in the number (-cytosis) of leukocytes in the blood, as during hemorrhage, infection, inflammation, or fever (specifically a count of 12,000 or more per cubic millimeter), respectively
Activation of alternate complement pathway: C3a; C5a
Increased vascular permeability (vasodilation); Decreased peripheral circulation; Decreased perfusion (blood flow) of blood to major organs

Petechiae: Round, purple lesions caused by intradermal or submucosal microvascular hemorrhaging; capillary leakage; microhemorrhage
Hypotension: Low blood pressure
Shock

Effects on metabolic and liver functions

Decreased iron
Hypoglycemia: Abnormally low glucose levels

Activation of clotting pathway

Thrombocytopenia: Abnormally low numbers of blood platelet
Thrombosis: formation of blood clot (thrombus) in heart or blood vessel
(DIC) Disseminated intravascular coagulation: Disorder characterized by a reduction in the elements involved in blood coagulation due to their utilization in widespread blood clotting within the vessels; Late stages marked by profuse hemorrhaging

Shock: Characterized by failure of the circulatory system to maintain adequate blood flow to the vital organs; Symptoms include: Hypotension; Weak pulse; Rapid and shallow breathing; Low body temperature; CNS (central nervous system) effects (e.g., nausea)
Death

Exotoxins: Potent toxic substance formed and secreted extracellularly by species of certain bacteria; Genetic control can be encoded either chromosomally, on a plasmid, or by a lysogenic bacteriophage

Toxoid: Toxin that can be altered with formaldehyde to lose physiological toxicity while retaining antigenicity; used as a vaccine

Bacterial Cytolysins (a.k.a., Cytotoxins; Cytolytic toxins; Cytolytic enzymes): Responsible for hemolysis and tissue necrosis; May be lethal when administered intravenously

Three major types based on mechanism of action:

Hydrolyze membrane phospholipids (e.g., phospho-lipases of Clostridium, Staphylococcus)
Thiol-activated cytolysins (oxygen-labile) alter membrane permeability by binding to cholesterol; e.g., Streptococcus, Clostridium
Detergentlike activity on cell membranes; e.g. Staphylococcus, rapid rate of lysis

Two-Component (Bipartite; Two domain) Toxins (A-B or A-5B): Usually one component is a receptor-binding domain (B) associated with absorption to target cell surface and transfer of active component across cell membrane; Second component is an enzymatic domain (A) (active component) that enzymatically disrupts cell function

Conform to general structural model: Prototype is diphtheria toxin of Corynebacterium diphtheriae

Bipartite structure (B, binding; A, active)
Receptor-mediated endocytosis (host cell uptake and internalization of exotoxin
ADP-ribosylation of intracellular target host molecule (e.g., host EF-2 (elongation factor-2) is ADP-ribosylated by C. diphtheriae exotoxin)

Other types of exotoxins (e.g., PA, EF, LF protein toxins of Bacillus anthracis)

Bacterial Defenses against Host Responses to Infection

Encapsulation and antigenic mimicry, antigenic masking, and antigenic shift are important bacterial defense mechanisms
Evasion or incapacitation of phagocytic and/or immune clearance

Phagocytosis inhibitors: Mechanisms enabling an invading microorganism to resist being engulfed, ingested, and or lysed by phagocytes/ phagolysosomes; Patients with a defective/compromised monocyte-macrophage system (formerly, RES, reticuloendothelial system) are particularly susceptible to infection
Capsule (Slime layer)

Avoid recognition and killing

Inhibit opsonization, chemotaxis, and/or phagocytosis
Inhibit phagolysosomal fusion and/or resist lysosomal killing
Block activation of phagocytes by interferon-gamma

Destroy (lyse) phagocytic cell

Inactivate/evade complement and antibody

Evade alternate complement system
Survive opsonization in presence of complement and PMNs and survive inside phagocytic cells
Avoid antibody or proteolytically cleave immunoglobulins

Avoid immune response by growing intracellularly

Direct invasion of cells
Resist lysosomal enzymes and antibacterial substances and multiply intracellularly
Escape phagosome; Adapt to cytoplasmic growth

Nonspecific T cell activation and/or mast cell stimulation: Bind TCR on T cell and MHCII on APC without presence of antigen; Life-threatening release of excess interleukins and mediators; Toxin-like, autoimmune-like responses or loss of immunoresponsiveness
Induction of excess or chronic inflammation; Fibrosis (walling-off) of site of infection (e.g., granuloma formation seen in mycobacterial infections)
Resistance to antibiotics: Intrinsic resistance; Plasmid-mediated; Chromosomally-mediated