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Human Defense Mechanisms
There are two types of human defense: innate resistance which includes natural barriers and the inflammatory response, and the adaptive (acquired) immune system.
First Line of Defense: Physical, Mechanical, and Biochemical Barriers
- Physical and mechanical barriers are the first lines of defense that prevent damage to the individual and prevent invasion by pathogens; these include the skin and mucous membranes.
- Antibacterial peptides in mucous secretions, perspiration, saliva, tears, and other secretions provide a biochemical barrier against pathogenic microorganisms.
- The normal bacterial flora provides protection by releasing chemicals that prevent colonization by pathogens.
Second Line of Defense: Inflammation
- Inflammation is a rapid and nonspecific protective response to cellular injury from any cause. It can occur only in vascularized tissue.
- The macroscopic hallmarks of inflammation are redness, swelling, hear, pain, and loss of function of the inflamed tissues.
- The microscopic hallmark of inflammation is an accumulation of fluid and cells at the inflammatory site.
The Mast Cell
- The most important activator of the inflammatory response is the mast cell, which initiates inflammation by releasing biochemical mediators (histamine, chemotactic factors) from preformed cytoplasmic granules and synthesizing other mediators (prostaglandins, leukotrines) in response to a stimulus.
- Histamine is the major vasoactive amine released from mast cells. It causes constriction of vascular smooth muscles, dilation of capillaries, and retraction of endothelial cells lining the capillaries, which increases vascular permeability.
Plasma Protein Systems
- Inflammation is mediated by three key plasma protein systems: the complement system, the clotting system, and the kinin system. The components of all three systems are a series of inactive proteins that are activated sequentially.
- The complement system can be activated by antigen-antibody reactions (through the classical pathway) or by other products, especially bacterial polysaccharides (through the lectin pathway or the alternative pathway), resulting in the production of biologically active fragments and target cell lysis.
- The most biologically portent products of the complement system are C3b (opsonin), C3a (anaphylatoxin), and C5a (anaphylatoxin, chemotactic factor).
- The clotting system stops bleeding, localizes microorganisms, and provides a meshwork for repair and healing.
- Bradykinin is the most important product of the kinin system and causes vascular permeability, smooth muscle contraction, and pain.
Cellular Components of Inflammation
- Many different types of cells are involved in the inflammatory process including neutrophils, monocytes and macrophages, eosinophils, natural killer (NK) cells, and platelets.
- Phagocytic cells (neutrophils and macrophages) engulf and destroy microorganisms by enclosing them in phagocytic vacuoles (phagolysosomes), within which toxic products (especially metabolites of oxygen) and degradative lysosomal enzymes kill and digest the microorganisms.
- Opsonins, such as antibody and complement component C3b, coat microorganisms and make them more susceptible to phagocytosis by binding them more tightly to the phagocyte.
- The polymorphonuclear neutrophils (PMN), the predominant phagocytic cell in the early inflammatory response, exits the circulation by diapedesis through the retracted endothelial cell junctions and moves to the inflammatory site by chemotaxis.
- The macrophage, the predominant phagocytic cell in the late inflammatory response, is highly phagocytic, responsive to cytokines, and promotes wound healing.
- Eosinophils release products that control the inflammatory response and are the principal cell that kills parasitic organisms.
- Natural killer cells recognize and eliminate cells infected with viruses, cancer cells, and other abnormal cells.
- Platelets interact with proteins of the clotting system to stop bleeding and release a number of mediators that promote and control inflammation.
- Phagocytosis is a multistep cellular process for the elimination of pathogens and foreign debris. The steps include recognition and attachment, engulfment, formation of a phagosome and phagolysosome, and destruction of pathogens or foreign debris.
- The cells involved in inflammation stimulate other cells by secreting cytokines, which include interleukins, interferons, and other molecules.
- Interferons are produced by cells that are already infected by viruses. Once released from infected cells, interferons can stimulate neighboring healthy cells to produce substances that prevent viral infection.
- Chemokines are synthesized by a number of different cells and induce leukocytes chemotaxis.
Local Manifestations of Acute Inflammation
- Local manifestations of inflammation are the result of the vascular changes associated with the inflammatory process, including vasodilation and increased capillary permeability. The symptoms include redness, heat, swelling, and pain.
- The functions of the vascular changes are to dilute toxin molecules produced by dying cells or contaminating microorganisms, carry plasma proteins and leukocytes to the injury site, carry debris away from the site, and initiate healing and repair.
Systemic Manifestations of Acute Inflammation
The principal systemic effects of inflammation are fever and increases in levels of circulating leukocytes and plasma proteins (acute phase reactants).
- Chronic inflammation can be a continuation of acute inflammation that lasts 2 weeks or longer. It also can occur as a distinct process without much preceding acute inflammation.
- Chronic inflammation is characterized by a dense infiltration of lymphocytes and macrophages. The body may wall off and isolate the infection to protect against tissue damage by formation of a granuloma.
Resolution and Repair
- Resolution (regeneration) is the return of tissue to nearly normal structure and function. Repair is healing by scar tissue formation.
- Damaged tissue proceeds to resolution (restoration of the original tissue structure and function) if little tissue has been lost or injured tissue is capable of regeneration. This is called healing by primary intention.
- Tissues that sustained extensive damage or those incapable of regeneration heal by the process of repair resulting in the formation of a scar. This is called healing by secondary intention.
- Resolution and repair occur in two separate phases, the reconstructive phase in which the wound begins to heal and the maturation phase in which the healed wound is remodeled.
- Dysfunctional wound healing can occur as a result of abnormalities in either the inflammatory response or the reconstructive phase of resolution and repair.