I. THE INNATE IMMUNE SYSTEM
D. EARLY INDUCED INNATE IMMUNITY
a. An Overview of Phagocytic Defense
The overall purpose of this Learning Object is to learn how phagocytes within the body encounter microbes.
LEARNING OBJECTIVES FOR THIS SECTION
D. Early Induced Innate Immunity
Early induced innate immunity begins 4 - 96 hours after exposure to an infectious agent and involves the recruitment of defense cells as a result of pathogen-associated molecular patterns or PAMPS (def) binding to pattern-recognition receptors or PRRs (def). These recruited defense cells include:
Unlike adaptive immunity, innate immunity does not recognize every possible antigen. Instead, it is designed to recognize molecules shared by groups of related microbes that are essential for the survival of those organisms and are not found associated with mammalian cells. These unique microbial molecules are called pathogen-associated molecular patterns or PAMPS (def) and include LPS from the gram-negative cell wall, peptidoglycan and lipotechoic acids from the gram-positive cell wall, the sugar mannose (a terminal sugar common in microbial glycolipids and glycoproteins but rare in those of humans), bacterial and viral unmethylated CpG DNA, bacterial flagellin, the amino acid N-formylmethionine found in bacterial proteins, double-stranded and single-stranded RNA from viruses, and glucans from fungal cell walls. In addition, unique molecules displayed on stressed, injured, infected, or transformed human cells also act as PAMPS. (Because all microbes, not just pathogenic microbes, possess PAMPs, pathogen-associated molecular patterns are sometimes referred to as microbe-associated molecular patterns or MAMPs.)
Most body defense cells have pattern-recognition receptors or PRRs (def) for these common PAMPS (see Fig. 1) and so there is an immediate response against the invading microorganism. Pathogen-associated molecular patterns can also be recognized by a series of soluble pattern-recognition receptors in the blood that function as opsonins and initiate the complement pathways. In all, the innate immune system is thought to recognize approximately 103 of these microbial molecular patterns.
We will now take a closer phagocytosis, beginning with an overview of phagocytic defense.
a. An Overview of Phagocytic Defense
Phagocytic cells include neutrophils, eosinophils, monocytes, macrophages, dendritic cells, and B-lymphocytes.
Phagocytosis is the primary method used by the body to remove free microorganisms in the blood and tissue fluids. The body's phagocytic cells are able to encounter these microorganisms in a variety of ways:
a. Infection or tissue injury stimulates mast cells, basophils, and other cells to release vasodilators (def) to initiate the inflammatory response (discussed later in Unit 4). Vasodilation results in increased capillary permeability, enabling phagocytic white blood cells such as neutrophils, monocytes, and eosinophils - as well as other leukocytes - to enter the tissue around the injured site. The leukocytes are then chemotactically attracted to the area of infection. In other words, inflammation allows phagocytes to enter the tissue and go to the site of infection. Neutrophils are the first to appear and are later replaced by macrophage.
b. Lymph nodules are unencapsulated masses of lymphoid tissue containing fixed macrophages and ever changing populations of B-lymphocytes (def) and T-lymphocytes (def). They are located in the respiratory tract, the liver, and the gastrointestinal tract and are collectively referred to as mucosa-associated lymphoid tissue or MALT. Examples include the adenoids and tonsils in the respiratory tract and the Peyer's patches on the small intestines. Organisms entering these systems can be phagocytosed by fixed macrophages (def) and dendritic cells (def) and presented to B-lymphocytes and T-lymphocytes to initiate adaptive immune responses.
c. Tissue fluid (def) picks up microbes and then enters the lymph vessels as lymph. Lymph vessels carry the lymph to regional lymph nodes (see Fig. 1). Lymph nodes contain many reticular fibers that support fixed macrophages and dendritic cells as well as everchanging populations of circulating B-lymphocytes (def) and T-lymphocytes (def). Microbes picked up by the lymph vessels are filtered out and phagocytosed in the lymph nodes by these fixed macrophages (def) and dendritic cells (def) and presented to the circulating B-lymphocytes (def) and T-lymphocytes to initiate adaptive immune responses. The lymph eventually enters the circulatory system at the heart to maintain the fluid volume of the circulation.
d. In addition, Langerhans' cells - immature dendritic cells (def) - are located throughout the epithelium of the skin, the respiratory tract, and the gastrointestinal tract where in their immature form they are attached by long cytoplasmic processes. Upon capturing antigens through pinocytosis and phagocytosis and becoming activated by proinflammatory cytokines, the dendritic cells detach from the epithelium, enter lymph vessels, and are carried to regional lymph nodes. By the time they enter the lymph nodes, they have matured and are now able to present antigen to the everchanging populations of naive T-lymphocytes (def) located in the cortex of the lymph nodes.
e. The spleen contains many reticular fibers that support fixed macrophages (def) and dendritic cells (def), as well as everchanging populations of circulating B-lymphocytes and T-lymphocytes. Blood carries microorganisms to the spleen where they are filtered out and phagocytosed by the fixed macrophages and dendritic cells and presented to the circulating B-lymphocytes (def) and T-lymphocytes (def) to initiate adaptive immune responses.
To view a diagram of the lymphatics system, see the Innerbody.com Webpage.
f. As mentioned above under fixed macrophages, there are also specialized macrophages and dendritic cells located in the brain (microglia), lungs (alveolar macrophages), liver (Kupffer cells), kidneys (mesangial cells), bones (osteoclasts), and the gastrointestinal tract (peritoneal macrophages).
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Updated: Sept., 2007
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