Host Parasite Interactions

Koch’s Postulates

The organism (“parasite”) must be present in every case of the infectious disease.

The organism (“parasite”) must be isolated in pure culture from the diseased host.

Inoculation of the organism in pure culture into animals (hosts) must produce a similar disease.

The same species of organism (“parasite”) must be recovered from the diseased animal (host)

Primary pathogen

an organism that regularly causes infection and disease when it enters a healthy host.

Opportunistic pathogen

an organism that rarely causes disease in healthy humans but may in a host whose defense mechanisms have been compromised or weakened.

Microbiome

A community of microorganisms living in a particular environment. The human microbiome comprises of parasites, fungi, bacteria, archaea, and viruses that inhabit and colonize the human body.

Commensal (or colonization)

an organism living in or on a host where neither derives benefit or harm. Part of the microbiome. Example: Escherichia coli in the GI tract.

Symbiosis (or mutualism)

an organism living in or on a host where both derive mutual benefit. Example: Lactobacilli in the urogenital tract of females. The bacteria prevents other pathogenic organisms.

Parasitism

an organism living in or on a host where the organism gains benefit at the host’s expense. Example: a uropathogenic Escherichia coli in the urinary tract

Infection

invasion and multiplication of microorganisms in or on a host. A disease process may or may not be apparent. It may cause an immune response. Symptoms may be sub-clinical.

Virulence

the degree of pathogenicity and extent to which a microorganism can cause damage to the infected host (variable due to individual host, infectious dose, and portal of entry).

Carrier

an infectious host that, because of inherited genetic traits, either does not develop symptoms of disease or carries an organism in a latent state. (Symptoms may develop later, such as Herpes reactivation following stress).

Establishment of a disease

1. Reach the host and find a portal of entry

2. Overcome host defenses

3. Invade and proliferate in the host tissues and produce toxins or other virulence factors

4. Be capable of resisting host defenses

Anatomic barriers to disease

1. skin: sweat, lactic acid, free fatty acids

2. respiratory tract: mucus and ciliated epithelium

3. GI tract: Stomach acid, mucus, peristalsis, villi, and microvilli

How microbiome is a barrier to disease

Examples:

1. influence on metabolic functions

2. protect against invading pathogens

3. educate the immune system

Things that effect the microbiome development

1. Microbiome is very fragile, the human intestinal microbiome has coevolved with its hsot to establish a stable homeostatic relationship

2. Age, diet, geographical location, health status, and environmental influences contribute to the variability in the microbial communities among individuals

3. Higher diversity is generally linked to improved gut health and potential resilience against certain diseases.

The microbiome plays a fundamental role in stimulating, educating, and supporting the immune system.

i. The microbiota promotes and calibrates all aspects of the immune system.

ii. Gut dysbiosis – changes in the gut bacterial composition and functional abilities, which lead to adverse effects on the host’s health.

iii. Dysbiosis may lead to increased neutrophil recruitment and excessive production of proinflammatory cytokines.

Things in the body that act as a host defense

Automatic movements in the body

a. Cilia in the respiratory tract

b. Peristalsis in the gastrointestinal tract

c. Flow of the genitourinary tract

The mucus layer lining the gut

Stomach acid

Innate immune responses

a. White blood cells, such as neutrophils, monocytes, and macrophages

b. Chemical inhibitors, such as lysozymes in saliva and tears

c. Humoral substances such as complement and opsonins

Adaptive immune responses (i.e., learned)

a. B-cells (type of white blood cell) produce antibodies that bind to antigens

b. T-cell (type of white blood cell) mediated responses

Host factors that leading to disease

1. Behaviors (promiscuous activity, IV drug usage, alcohol misuse disorder, nutritional status) 2. Occupation 3. Age/genetics/sex 4. Prior viral infections (virus induces dysfunction of phagocytes, T suppressor cells, etc.) 5. Foreign body (IV catheter, prosthetic valves, indwelling urinary catheter, etc.) 6. Splenectomy 7. Diabetes 8. Hematoproliferative disorders 9. Autonomic dysfunction 10. Burns 11. Medications: a. Steroid therapy b. Prior course of antibiotics c. Immunosuppressive drugs (oncology or bone marrow transplant patients)

Microbial Factors Leading to Disease

1. Evade immune response (capsules, antigen shedding, antigenic variation, antibody cleaving) 2. Antibiotic cleaving (i.e. Beta-lactamase) 3. Can inhibit chemotaxis, phagocytosis (leukocidins) 4. Exotoxins 5. Endotoxins 6. Enterotoxint 7. Elicit production of tumor necrotic factor

Exotoxins

Exotoxins: produced in the cell and excreted

Endotoxins

Endotoxins: toxin derived from the cell wall of gram-negative rods

Enterotoxins

Enterotoxin: toxins that give rise to gastrointestinal symptoms when ingested or formed in the gu

Tissue tropism:

ability to penetrate and survive within tissue

Capsules

a. Inhibits the organism from phagocytosis, evading immune response

b. Usually made of polysaccharides

c. Capsular material appears mucoid on an agar plate

Enzymes excretion

a. Hyaluronidase splits hyaluronic acid, a component of connective tissue b. Collagenase, as above c. Coagulase causes formation of fibrin which may deposit on surface to inhibit phagocytosisd. d. Hemolysins lyse red blood cells e. Fibrinolysin, ketatinase, lecithinase, iga proteases, etc.

Ability to attach (not for locomotion)

a. Extracellular substances such as slime layer may be important in adhering to host tissue b. Pili i. Unique to prokaryotic cells ii. Protein fibers that are for exchange of genetic information.c. Fimbriae i. Specialized pili ii. Unique to prokaryotic cells iii. Protein fibers that are for attachment.

Chain of Infection RESERVOIRS

A “holding environment” for an infectious agent. 1. Capable of causing disease 2. Examples of environmental reservoirs: a. soil, water, plants 3. Examples of diseases with human only reservoirs: a. Measles, mumps, streptococcal infections 4. Zoonosis is an infectious disease that is transmissible under natural conditions from vertebrate animals to humans, Examples of diseases with animal reservoir: a. Brucellosis - cows and pigs, anthrax -sheep, plague – rodents

Chain of Infection Disease Transmission