Porth's Pathophysiology, 9e

Chapter 13 Innate and Adaptive Immunity    283

saliva, and human milk, which is capable of cleaving the walls of bacterial cells by hydrolyzing the 1,4 beta-linkages between residues in peptidoglycan. The complement sys- tem is found in the blood and is essential for the activity of antibodies. It is comprised of 20 different proteins, many of which act as precursors of enzymes. An antigen–antibody complex initiates this system. Activation of the comple- ment system increases bacteria aggregation, which renders them more susceptible to phagocytosis through activation of mast cells and basophils and through the direct release of lytic complexes that rupture cell membranes of invad- ing organisms (Fig. 13.1). In addition, recent research has shown that complement plays a key role in bridging the innate–adaptive immune responses through the release of C3 and C5 from DCs. 12 In the stomach and intestines, death of microbes results from the action of digestive enzymes, acidic conditions, and secretions of defensins , small cat- ionic peptides that kill within minutes both gram-­positive and gram-negative microorganisms by disrupting the microbial membrane. When pathogens overcome the epithelial defenses, the innate immune response is initiated by the body’s leukocytes by the recognition of common surface receptors present on the invading microorganisms. Cells of Innate Immunity The cells of the innate immune response are capable of recog- nizing microbes that share common surface receptor charac- teristics and in response initiate a broad spectrum of responses that target the invading microorganisms. The key cells of innate immunity include neutrophils, macrophages, DCs, NK cells, and intraepithelial lymphocytes.

Neutrophils and Macrophages The leukocytes involved in the innate immune response are derived from myeloid stem cells and subdivided into two dis- tinct groups based upon the presence or absence of specific staining granules in their cytoplasm. Leukocytes that contain granules are classified as granulocytes and include neutro- phils, eosinophils, and basophils. Cells that lack granules are classified as agranulocytes and include lymphocytes, mono- cytes, and macrophages. Neutrophils, which are named for their neutral-staining granules, are the most abundant granulocytes found in the body and make up approximately 55% of all white blood cells. They are also known as polymorphonuclear neutrophils (PMNs). They are phagocytic cells and are capable of ame- boid-like movement. They function as early responder cells in innate immunity. They are rare in the tissues and in body cavities and lay predominantly dormant in the blood and bone marrow until they are needed in the immune response. 13 Eosinophils have large coarse granules and normally com- prise only 1% to 4% of the total white cell count. In contrast to neutrophils, these cells do not ingest cellular debris but rather antigen–antibody complexes and viruses. They frequently become active in parasitic infections and allergic responses. Basophils make up less than 1% of the total white cell count and contain granules that release a multitude of substances including histamine and proteolytic enzymes. There function is not completely understood, but they are believed to play a role in allergy and parasitic infection as well. The agranulocytes involved in innate immunity are part of the mononuclear phagocyte system (MPS) and include the monocytes and macrophages. Monocytes are the largest in size of all the white blood cells but make up only 3% to 7% of the total leukocyte count. They are released from the bone

Bacterium

Bacterium

Leukocyte Lysosome

Vesicle

Lysosome

Blood

Digestive products

Erythrocyte

Residue

Capillary wall

Epithelial cell

A

B

FIGURE 13.1  •  Phagocytosis. ( A ) A phagocytic white blood cell moves through a capillary that is in an infected area and engulfs the bacteria. ( B ) The lysosome digests the bacteria that was in a vesicle. (From Cohen B. J. (2013). Memmler’s the human body in health and disease (12th ed.) Philadelphia, PA: Lippincott Williams & Wilkins.)