Unit 3

Role of "Host" in Health and Disease

The host animal has a number of different defense mechanisms by which it deals with the onslaught of infectious agents. They can be broken into three parts, based on the specificity of response.

First Line of Defense -- skin & mucus membranes

Temperature -- the surface temperature of skin is lower than the core body temperature of an animal and is also lower than the temperature required for many infectious agents to multiply.

Surface layer of cells -- the skin has an outer layer of dry, dead, keratinized cells that do not provide a hospitable environment for infectious agents. Likewise, many mucus membranes are covered with a mucus layer that traps infectious agents and physically prevents them from interacting with the epithelial cells lining the mucus membrane. This mucus layer in the respiratory tract is swept up from the deeper regions of the lung to the oropharynx of the animal by cilia on the surface of the epithelial cells lining the bronchioles and bronchi.

Secretions and excretions -- the anti-microbial action of gastric acid and bile secreted into the gastrointestinal tract; peristaltic movement of ingesta through the intestinal tract and flushing and antimicrobial action of urine and tears prevents the attachment and proliferation of infectious agents in many parts of the body.

Second Line of Defense -- nonspecific immune response (Hoopes and Thwaits, chapter 5; Mims, chapter 3 -- inflammatory response)

Inflammation -- an increase in blood circulation at site of infection leads to the classic signs of inflammation -- redness, swelling, heat, pain. This is due to:

• increase in the permeability of blood vessels in the area. This results in a buildup of the following compounds in the effected tissues:
  • complement
  • proteins, such as fibrinogen, histamine, kinins
  • cytokines (interferon, interleukins, etc.)
  • leukocytes (white blood cells-WBC)
    • phagocytes -- monocytes (macrophages)
    • polymorphs
    • lymphocytes -- B & T cells

Inflammation is a two-edged sword for the host animal.
The benefit of the inflammatory reaction is that there is a very quick response to the disease agent which may stop further progression of the disease. The downside of the inflammatory reaction is that it is nonspecific and the inflammatory compounds released are also harmful to the host.

Because of this, inflammation is under tight regulatory control in the body.

Increase in lymph circulation -- this results in:

1. transport of "agent" to local lymph node
2. ingestion by macrophages (phagocyte) in marginal sinus of lymph node
3. presentation of "antigenic units" to lymphocytes
4. beginning of specific immune response
5.  

Third Line of Defense -- Specific Immune Response

There are two different parts, or branches to this response. They consist of:

• Cell-mediated immunity (CMI) - T lymphocytes, Natural Killer (NK) cells
• Humoral immunity (antibody) - B lymphocytes

Humoral Immunity

Role of antigen presenting cell (APC)

• monocyte, macrophage, histiocyte, dendritic cell
• "process" proteins from agent
• present the processed proteins to T "helper" lymphocyte, or B lymphocyte

Role of B lymphocyte

• circulate and bind some specific antigens or processed proteins from T helper lymphocytes
• differentiate into "memory" cells
• differentiate into plasma cells -- produce antibody (immunoglobulin)

Immunoglobulin M (IgM)

• produced first by the B lymphocytes
• very large - stays in bloodstream
• activates complement - kills cells (membrane attack complex)
• short lived - isotype switch to IgG, E, A production by B lymphocytes
• relatively nonspecific - cross reactions
• only immunoglobulin produced by fetus

Immunoglobulin G (IgG)

• takes longer to produce - requires B cell switch
• smaller molecule (monomer) - gets into tissues
• "opsonizes" agent to aid in phagocytosis
• long lived in body - varies with agent
• more specific

Immunoglobulin A (IgA)

• "mucosal" antibody
• also requires B cell switch to produce
• present as a dimer - secreted onto the mucosal surface
• poor at opsinization but binds and neutralizes agent

Immunoglobulin E (IgE)

• produced in allergic and parasitic reactions
• binds to mast cells beneath epithelium
• stimulates degranulation of mast cells

Functions of IgG and IgA

• Neutralize bacterial toxins
• Neutralize viral agent by binding to specific receptor used to enter cell
• Neutralize bacterial agent by binding to "adhesin" - especially IgA
• "Opsinize" bacteria - function of IgG

Cell-mediated Immunity

Role of T lymphocyte (2 types)

CD4 "helper" T lymphocyte

• helps B cells produce immunoglobulins (antibodies)
• activates macrophages
• activates polymorhs
• activates NK (natural killer) cells
• helps CD8 "cytotoxic" T cells

CD8 "cytotoxic" T lymphocyte

• destroys infected host cells

Host Reactions as indirect mechanisms of disease

Immune complexes -- may be deposited onto cell membranes and cause damage (kidney disease, arthritis)

Anti-host antibody production -- cross-reacting haptans

Cell-mediated immunity -- destroys host cells

Review of Interactions between Agent and Host

Persistent Infection

A. Ways in which agent out-maneuvers the host

1. antigenic variation - influenza virus
   
   
2. become "latent" until immunity wanes
   a. intracellular bacteria, viruses - herpes
   b. stress, hormonal changes, etc. lead to reactivation
   
   
3. resistance to or exploitation of host defense
   a. live & multiply within phagocyte
   b. live & multiply within lymphocyte

AIDS - T lymphocyte
mouse mammary tumor - B lymphocyte

B. Immunosuppression contributes to persistence

1. stress - cortisol inhibits B cell differentiation
2. Staphylococcal toxins are immunosuppressive
3. other agents also suppress immune system

C. Failure of host defense system

1. Inherited Immunodeficiency
   
   a. BLAD (bovine leukocye adhesion deficiency)
   b. Chediak-Higashi Syndrome - failure of intracellular killing - Aleutian mink disease
   c. SCID (severe combined immune deficiency) - mice
   
   
2. Acquired Immune Deficiency
   
   a. AIDS - human
   b. SIV - monkey
   c. FeLV - cat
   d. BLV - cattle
   
   
3. "Immaturity" of Immune System - Neonate
   
   a. importance of colostrum
   b. role of maternal antibodies in blocking active immunity

Role of Host -- Practical Aspects of Immune Function

Classification of Immunity -- Natural vs Acquired

Natural Immunity is the innate or inborne resistance of an animal to certain types of disease. This does not require antibody (immunoglobulin) production. Natural immunity could be due to lack of receptors for the infectious agent within the host cell, or nonspecific immune responses.

Acquired Immunity is an immunity to specific infectious agents that the animal acquires, either actively or passively. Acquired immunity is usually evaluated by measuring antibodies in the blood of the animal.

Passive Immunity is the result of passive transfer of antibodies from an immune individual to a susceptible individual. It provides immediate protection against the infecting agent, however the protection is short-lived and wanes as antibodies are catabolized.

1. "Colostrum" is the primary means of transfer of passive immunity to neonatal animals in domestic species.

2. Transplacental transfer of antibodies occurs in rabbits and primates; there is limited transplacental transfer in dogs and cats and essentially no transplacental transfer in domestic livestock.

3. Passive immunity can also be obtained by injecting immune antiserum into the susceptible animal.

Active Immunity is developed by an animal in response to exposure to an agent, or by vaccination. Active immunity takes longer to develop (4-5 or 7-10 days), but it is also longer lived in the animal. Protection can be increased by "boosting" (anamnestic response).

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