Unit 2

Role of "Agent" in Health and Disease

Characteristics of an infectious agent (parasite or pathogen)

• ability to multiply - generation time of organism
• ability to spread from one animal to another
• ability to evolve quickly to outsmart host defenses
• ability to cause damage (pathogenicity, virulence)

Types of Agents (pathogens)

• Bacteria
• Viruses
• Fungi
• Protozoa
• Parasites

Steps that an Agent must complete to cause disease:

1. attach and enter host
2. evade host defenses/reach target tissue or organ
3. multiply
4. exit and enter another individual (transmission of disease)

Attachment +/or entry into the host body
means of attachment and entry vary, depending on the body site

Sites of attachment/entry

SKIN

• Characteristics of skin
  • difficult to penetrate when intact; easier under following circumstances
    • wounds, bites
    • softened by moisture
  • normally colonized by bacteria, fungi
  • keratin, sweat, sebum provide nutrients

MUCUS MEMBRANES

Line the lungs, gastrointestinal (GI) tract, and urogenital tract

Respiratory entry of agents into host

• host defenses

a. nasal turbinates

• temperature lower than required by most pathogens
• baffle
• agents are trapped in mucus and swallowed
• large particles are trapped at this level

b. intermediate level respiratory tract

• coated with a mucociliary blanket
• smaller particles are trapped at this level

c. lower respiratory tract

• alveolar macrophages phagocytize agents
• smallest particles may travel this far

Note that the size of the agent as well as the size of the water droplet or dust particle upon which it may be carried can determine what level of the lung is exposed to the agent.

• Agent's means of evading host defenses

a. bacteria/viruses attach to cells by specific receptors to prevent being swept out

• bacteria are able to attach to the cells lining the mucus membranes by structures called pili or fimbriae
• at the molecular level, adhesins on surface of agent bind to integrins or other receptors on surface of host cell (ex. S. typhimurium binding to EGF receptor)

b. agent may interfere with action of cilia/mucus

• Mycoplasma, Bordetella, Haemophilus inhibit ciliary action
• viruses kill epithelial cells

c. agent may interfere with action of alveolar macrophage

• respiratory virus, toxins

Gastro-Intestinal Entry of Agent

• Host defenses
  • acid, bile provide hostile environment for agent
  • movement of ingesta, constant flushing to prevent attachment
  • commensal bacteria (physical barrier)

• Agent's means of evading host defenses/causing disease
  • Attachment and adhesion to epithelial cells Enteropathogenic E. coli, Salmonella and Shigella
    • specific structures, receptor sites
    • invasive (enteropathogenic E. coli) and noninvasive
    • enveloped viruses fuse with cell membrane
    • some bacteria enter via specialized epithelial "M" cells over peyers patches
  • Toxin production  Bacterial Toxins:  Friends or Foes?
    • exotoxins
      • secreted by bacteria
      • acts by damaging host cell surface, causing death of cell
      • example -- Clostridium
    • endotoxins
      • released as agent dies
      • enterotoxin - secretory diarrhea
      • verotoxin - hemorrhagic diarrhea (EHEC)
  • Cause malabsorption of nutrients
    • direct damage to epithelial cells
    • villus atrophy (cryptosporidia)
    • bacterial overgrowth that inhibits absorption

Urogenital (UG) Entry of Agent

• Host defenses
  • flow of urine
  • long urethra
  • vaginal pH

• Agent's means of evading host defenses
  • attachment and adhesion
  • trauma to UG tract may facilitate entry

Conjunctival Entry of Agent

• Host defense -- tears, flushing and lysozyme

• Agent's means of evading host defenses
  • enzymes secreted by agent

• Environment effects -- dry, dusty conditions; flies

Multiplication and Spread of Agent Within Body

Tissue tropism
Some organisms do not normally spread beyond the tissue originally invaded

• skin -- ringworm
• lung -- Bovine Respiratory Syncytial Virus (BRSV)
• intestine -- Rotavirus

These organisms:

1. multiply locally
2. spread rapidly from cell to cell by liquid media (mucus membranes) in respiratory and GI tracts
3. often held at bay at site of entry by host immune defenses

Other agents have a distant site as target (ex. Salmonella pullorum for adult avian ovary)

Their location of growth and multiplication depends on specific requirements for microenvironment within the body

• temperature
• nutrition of disease agent (ex. Brucella - erythritol)
• oxygen tension in tissue
• migration of larval stages of internal parasites (round worm)

Means of travel of the "Agent" -- road

1. bloodstream
2. lymph
3. other routes (i.e. nerves for rabies, pseudorabies, tetanus)

Means of travel of the "agent" -- vehicle

1. extracellular - free in blood and lymph -- easy target for host immune defences
   
   a. recognized and "eaten" by phagocytes
   
   b. carried to lymph node where specific antibody production is stimulated
   
   c. stimulate immune response in animal -- cytokines, TNF, interferon, histamine, prostaglandins, acute phase proteins
   
2. intracellular - hidden from immune system within a host cell
   
   a. Phagocytes (white blood cells) -- must resist digestion - ex. Listeria, Brucella, Mycobacterium
   
   b. Erythrocytes (red blood cells) -- viruses cannot use
   ex. Eperythrozoon, Babesia, Hemobartonella
   
   c. Other host cells, such as epithelial cell of gut
   ex. Coccidia, Toxoplasma

Destination

1. determined by "address" receptor on capillary of blood vessels in target organ
2. local extension from site of entry

a. enzymes dissolve and liquefy tissue
(hyaluronidase, streptokinase, fibrinolysin)

EXIT of agent allows spread to other individuals

• Respiratory, salivary route of exit and spread
  • agents causing respiratory, systemic disease
    (PRV, rabies, foot and mouth disease, etc.)
  • increased density of animals, exertion, bawling, coughing, etc. exacerbate spread
    
    
• Fecal route of exit and spread
  • proper sanitation can minimize spread

• Venereal route of exit and spread
  • testing stock before introducing into herd
  • use of artificial insemination (AI)

• Blood as route of exit and spread
  • insect control
  • sterile needles, syringes, surgical instruments

• Spread without shedding from host
  • direct transmission to offspring in utero (vertical transmission)
  • eating tissues harboring agent (Trichina, Kuru, BSE)
  • environmental contamination by dead animal (Anthrax)

|| HOME || SYLLABUS || NOTES || PRESENTATIONS ||
|| RESOURCES || ANNOUNCEMENTS ||