Monday, July 2, 2007

Innate Immunity

Innate immunity has four types of defensive barriers; anatomic, physiologic, endocytic and phagocytic, and inflammatory.

Anatomic barriers: Physical and anatomic barriers that tend to prevent the entry of pathogens are an organism’s first line of defence against infection.

The skin and the surface of mucous membranes are included in the category because they provide an effective barrier to the entry of most microorganisms. The skin consists of two distinct layers; a relatively thin outer layer- the epidermis and a thicker layer the dermis. The epidermis contains several layers of tightly packed epithelial cells. The outer layer consists of dead cells and is filled with a waterproofing protein called keratin. The dermis, is composed of connective tissue, contains blood vessels, hair follicles, sebaceous glands. The sebaceous glands secrete an oily substance called sebum. Sebum consists of lactic acid, which maintains the pH of the skin between 3 and 5. Thus intact skin not only prevents the penetration of most pathogens but also inhibits most bacterial growth due its low pH.

The conjunctiva and the alimentary, respiratory, and urinogenital tracts are lined by mucous membranes, not by the dry, protective skin covering the exterior of the body. These membranes consist of an outer epithelial layer and an underlying connective tissue layer. The secretions of these mucus membranes wash away potential invaders and also contain antibacterial or antiviral substances. The viscous fluid called mucus, which is secreted by epithelial cells of mucous membrane, entraps foreign microorganisms.

Physiologic barriers: The physiologic barriers that contribute to innate immunity include temperature, pH, oxygen tension and various soluble factors. Many species are not susceptible to certain diseases simply because their body temperature inhibits pathogen growth. Gastric acidity also provides an innate physiologic barrier to infection because very few ingested microorganisms can survive the low pH of the stomach. One reason newborns are susceptible to some diseases that do not afflict adults is that their stomach contents are less acid than that of adults. Among the soluble proteins are lysozyme, interferon, and complement. Lysozyme, a hydrolytic enzyme found in mucous secretions, is able to cleave the peptidoglycan layer of the proteins of the bacterial cell wall. Interferon comprises a group of proteins produced by virus-infected cells. Among the many functions of the interferons is the ability to bind to nearby cells and induce a generalized antiviral state. Complement is a group of serum proteins that circulate in an inactive proenzyme state. These proteins can be activated by a variety of specific and nonspecific immunological mechanisms that convert the inactive proenzymes into active enzymes. The activated complement components participate in a controlled enzymatic cascade that results in damage to the membranes of pathogenic organisms, either destroying the pathogens or facilitating their clearance.

Endocytic and Phagocytic Barriers: Another important innate defense mechanism is the ingestion of extracellular macromolecules via endocytosis and of particulate material via phagocytosis. These tow internalization processes not only bring different types of extracellular material into the cell, they also differ in several other ways.

In endocytosis, macromolecules within the extracellular tissue fluid are internalized by cells via the invagination (inward folding) and pinching off of small regions of the plasma membrane. Phagocytosis involves the ingestion of particulate material, including whole pathogenic microorganisms.

Barriers created by the Inflammatory Response:
Tissue damage caused by a wound or by invasion by a pathogenic microorganism induces a complex sequence of events collectively known as the inflammatory response. In the first century A.D. the Roman Physician Celsus described the four cardinal signs of inflammation are rubor (redness), tumor (swelling), calor (heat) and dolor (pain). Afterwards the fifth sign functio laesa (loss of function) was added in second century A.D. Inflammatory response includes three events:

1. Vasodilation: an increase in the diameter of blood vessels – occurs as the vessels that carry blood away from an affected area constrict, resulting in engorgement of the capillary network. The engorged capillaries are responsible for tissue redness (erythema) and an increase in tissue temperature.
2. An increase in capillary permeability facilitates an influx of fluid and cells form the engorged capillaries into the tissue. The fluid that accumulates (exudate) has a much higher protein content than fluid normally released from the vasculature. Accumulation of exudate contributes to tissue swelling (edema).
3. Influx of phagocytes from the capillaries into the tissues is facilitated by the increased capillary permeability. The emigration of phagocytes involves a complex series of events including adherence of the cells to the endothelial wall (margination) followed by their emigration between the capillary endothelial cells into the tissue (diapedesis or extravasation) and, finally, their migration through the tissue to the site of the inflammatory response (chemotaxis). As phagocytic cells accumulate at the site and begin to phagocytose bacteria, they release lytic enzymes, which can damage nearby healthy cells. The accumulation of dead cells, digested material, and fluid forms a substance called pus.

The events in the inflammatory response are initiated by a complex series of interactions involving a variety of chemical mediators. One of the principal mediators is histamine, a chemical released by a variety of cells in response to tissue injury. Histamine binds to receptors on nearby capillaries and venules, causing vasodialtion and increased permeability. Once the inflammatory response has subsided and phagocytic cells have cleared most of the debris away, tissue repair and regeneration of new tissue occur.

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