Monday, August 29, 2011

Immune Response to Pathogens

Innate Immune Function
The innate subdivision of the immune system is the most primitive. An important component consists of anatomic barriers such as intact skin and mucous membranes.
The most important cells of the innate immune system are the neutropbils (polymorphonuclear cells), macrophages (transformed monocyte cells located in tissues), and lymphocytes known as natural killer cells.
These cells roam in all body tissues and are able to identify microbes via recognition signals of patterns of surface molecules indigenous to microorganisms. Invading microbes are identified and attacked by the release of toxic molecules or by phagocytosis and destruction following ingestion.
Innate cells initiate the process of inflammation following infection or tissue damage. Inflammatory mediator molecules such as histamine are released that produce local vasodilatation and increased blood flow, accompanied by increased capillary permeability.
Circulating complement protein molecules are also activated and turn into complexes that enhance inflammation and, along with the mediator molecules released by the innate cells, act as chemoattractants, drawing more immune cells into the area. The outcome of inflammation is the destruction of invading microbes, clearance of damaged tissues, and activation of the adaptive immune system.
Adaptive Immune Function
The response of the adaptive division of lymphocyte immune cells is characterized by delay. Lymphocytes must be activated in a days-long process before they can respond; specificity—cells and antibodies are generated targeted to unique proteins found on an invading microbe; and memory dormant cells are generated that can quickly mount a defense against the invader on re exposure.
Each CD4 "helper" lymphocyte (T-helper or Th) carries T-cell receptors that respond to a single antigen microbial protein component; on exposure, the CD4 cells begin secreting activator "helper" molecules that can further enhance macrophage function and activate the CD8 (cellular immunity) and B-lymphocyte cells (humoral immunity). CD8 lymphocytes ("cytotoxic"
cells, cellular adaptive response) seek out and destroy body ceils infected with the microbe specific to its T-cell receptor. These cells are the body's primary defense against intracellular invaders such as viruses and some bacteria .
B lymphocytes, when activated by the antigen specific to the B-cell receptor and molecules from Th cells, begin the process of secreting their receptors into the plasma as soluble antibodies (humoral adaptive response) that attack invading microbes.
To "turn on" the adaptive response, specialized antigen-presenting and innate macrophage cells present in tissues migrate to regional lymph nodes, therein displaying antigens bonded to major histocompatibility complex class 1 or class II surface molecules for recognition by antigenically specific lymphocyte T-cell receptors.
In the specialized environment of the lymph node, the interactions of these cells result in the clonal expansion of lymphocyte populations and antibodies, generated to attack and destroy invading microbes.
In summary, the physiologic objective of the integrated innate and adaptive immune response is to detect and prevent infection and clear damaged cells. There is a complex and partially reciprocal relationship between
these arms of the immune system: the first-line innate immune system response is necessary to activate the adaptive immune cells, yet produces inflammatory mediator molecules that restrain lymphocyte function.
Activated Th lymphocytes produce cytokines that enhance macrophage and neutrophil function.

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