Physical and chemical defenses compose the innate immune system and are the first line of defense against pathogens.
The skin is the primary method of physical defense. Alterations in the skin allow for an easy portal of entry for pathogens.4 Burns and abrasions are common examples that alter the physical defense of the skin; however medications can also alter this nonspecific system (drug-associated Stevens Johnson syndrome—see Table 11-2). The low pH of the stomach serves as a major defense to pathogen entry through the gastrointestinal system. Medications that alter the pH of the stomach may change the gastrointestinal bacterial flora and increase risk of infections. Antisecretory agents such as proton pump inhibitors have been associated with pH changes in the stomach and subsequent development of bacterial infections.5 The rapid turnover of gastrointestinal cells also limits systemic infection, as cells are frequently sloughed. Cell-cycle antineoplastics that disrupt the sloughing process may leave the patient at increased risk for infections. The respiratory tract has forms of physical defense such as coughing, mucous coating the epithelial cells, and the cilia lining the epithelium of the lungs. The combination of coughing, cilia, and mucus provide a barrier to invasion of the respiratory tract. Disruption of the respiratory physical defense through mechanical ventilation can increase the risk for penetration by a pathogenic organism (pneumonia) or anti-infectives that alter gastrointestinal flora leaving the patient at an increased risk of infection (eg, Clostridium difficile infection).6 Other examples of nonspecific defenses include: normal urine flow, lysozymes in tears and saliva, and the normal flora in the throat, gastrointestinal tract, and genitourinary tract.
TABLE 11-2 Stevens Johnson Syndrome ||Download (.pdf)
TABLE 11-2 Stevens Johnson Syndrome
|Stevens Johnsons Syndrome (SJS) is a rare, serious disorder in which the skin and mucous membranes react severely to a medication or infection. Often SJS begins with flu-like symptoms, followed by a painful red or purplish rash that spreads and blisters, eventually causing the top layer of skin to die and shed. Examples of drug-induced SJS are:|
|Nonsteroidal anti-inflammatory drugs (NSAID)|
Cellular Components Defense
If a pathogen invades and is able to infiltrate through a host's physical defense system, innate immunity (cellular) is used to halt progression of the pathogen. Innate immunity cells include the leukocytes or white blood cells (monocytes, neutrophils, basophils, and eosinophils).2 Other white blood cells (lymphocytes) are involved in adaptive immunity.2, 3 The innate cells are one of the most widely monitored clinical laboratory tests. Innate cells may be evaluated by ordering a complete blood count (CBC). When a CBC is ordered, part of the laboratory test reports a tally of the total white blood cells (WBCs) in a given volume of blood plus the relative percentages that each cell type contributes to the total. Table 11-3 provides a breakdown of the different types of WBCs and their usual cell counts in peripheral blood for an adult.
TABLE 11-3 Normal White Blood Cell Count and Differential in Adults ||Download (.pdf)
TABLE 11-3 Normal White Blood Cell Count and Differential in Adults
|Cell Type||Normal Range|
|Total white blood cell count||4.4-11.3 × 103 cells/mm3|
|Polymorphonuclear neutrophils (polys, segs, PMN)||2.3-7.7 × 103 cells/mm3|
|Band neutrophils (immature neutrophils, bands, stabs)||0-10 × 103 cells/mm3|
|Eosinophils||0.0-0.7 × 103 cells/mm3|
|Basophils||0.0-0.2 × 103 cells/mm3|
|Monocytes||0.3-0.8 × 103 cells/mm3|
|Lymphocytes||1.6-2.4 × 103 cells/mm3|
Granulocytes are phagocytes (engulfing cells) and derive their name from the presence of granules within the cytoplasm.2, 3 The granules store lysozymes and other chemicals needed to produce the oxidative and nonoxidative burst to lyse the pathogen. Granulocytic leukocytes include neutrophils, eosinophils, basophils, and monocytes. Granulocytes are formed in large numbers in the bone marrow, undergo numerous steps in the marrow, and are usually released into the peripheral blood in their mature form. Neutrophils, eosinophils, and basophils die in the course of destroying pathogens, yielding pus. In contrast, monocytes do not die when destroying pathogens because they play a critical role in activating the adaptive immune response via antigen presentation.
Neutrophils represent the majority of granulocytes and leukocytes and serve as the primary defense against bacterial infections. Neutrophils, also termed segs or polymorphonuclear cells, migrate from the bloodstream into infected or inflamed tissue. In this migration process known as chemotaxis, neutrophils reach the desired site and adhere to, recognize, and phagocytose pathogens.2 During phagocytosis, the pathogen is internalized within the phagocyte. The neutrophil releases its granular contents which lead to destruction of the engulfed pathogen. The less mature form of a neutrophil is a band. During an acute infection there is an increase in the percentage of neutrophils as they are released from the bone marrow. Less mature band forms may also be released. These immature neutrophils are still considered active. The appearance of band cells is called a shift to the left. The actions of cytokine medications such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) may intensify neutrophil activity. G-CSF (filgrastim [Neupogen]) and long-acting G-CSF (pegylated filgrastim [Neulasta]) are granulocyte colony-stimulating factors licensed to prevent chemotherapy-induced neutropenia or to stimulate granulocyte production among patients with severe chronic neutropenia. GM-CSF (sargramostim [Leukine]) is a granulocyte-macrophage colony-stimulating factor licensed to shorten the time to neutrophil recovery in acute myelogenous leukemia and stem cell transplantation.
Eosinophils and Basophils
The major role of eosinophils is in host defense against parasitic infections; however, eosinophils can phagocytize, kill, and digest bacteria and yeast, but not as efficiently as neutrophils. Eosinophils account for less than 7% of circulating leukocytes and are present in the intestinal mucosa and lungs, two locations where foreign proteins enter the body.2, 3 Elevations of eosinophil counts are highly suggestive of parasitic infections.1-3 Along with mast cells, eosinophils play an important role in allergies and allergic asthma.
Basophils are the least common granulocyte, accounting for 0.1% to 0.3% of granulocytes. They contain heparin, histamine, and leukotriene B4.7 Along with eosinophils and mast cells, basophils play a role in allergies and allergic asthma. Basophils may also be associated with immediate hypersensitivity and delayed hypersensitivity reactions, and increased chronic inflammation and leukemia.2, 3
Functions of monocytes include removal of necrotic apoptotic tissues, lysis of cancer cells, and antigen presentation.2 They account for 1% to 10% of circulating leukocytes. Monocytes migrate to tissues (lymph nodes, spleen, liver, lung), where they mature into macrophages.8 After engulfing pathogens, monocytes/macrophages are transformed into antigen-presenting cells (APC). These transformed macrophages present antigen (lysed pathogens) to CD4(+) helper T lymphocytes; therefore, macrophages and other antigen presenting cells (eg, dendritic cells) activate the adaptive immune response (Figure 11-1). Dendritic cells are the most potent antigen presenting cell; however, they make up less than 1% of circulating leukocytes. Dendritic cells, like macrophages, are found more commonly in tissues (eg, spleen, liver). Tissue macrophages also salvage iron from hemoglobin of old erythrocytes and return iron to transferrin for delivery to bone marrow.
Activation of the adaptive immune response. Macrophage and/or dendritic cells present antigen to the CD4+ helper T cell. If the CD4+ T cell recognizes the antigen by its T cell receptor (TCR), the CD4+ helper T cell becomes activated to secrete cytokines to stimulate either a CD8+ cytotoxic T cell response or a CD20+ B cell response to produce antibody.