Immune System: Anatomy, Physiology, and Function | PDF

Chapter 18 INTRODUCTION Immunity refers to the body's ability to resist infection and disease. Innate and adaptive immune responses provide three lines of defense against unwanted antigens (Fig. 18.1). Innate (natural) immunity provides the first and second lines of defense. The first line consist...

Chapter 18 INTRODUCTION Immunity refers to the body's ability to resist infection and disease. Innate and adaptive immune responses provide three lines of defense against unwanted antigens (Fig. 18.1). Innate (natural) immunity provides the first and second lines of defense. The first line consists of physical, biochemical, and mechanical barriers that offer surface protection to prevent the invasion of microbes. When those barriers are breached, the second line of defense, the inflammatory response, is initiated to prevent and/or limit infection, clean out the debris of dead cells, and initiate tissue healing. The first and second lines are nonspecific, responding the same way for any invasion. The third line, adaptive (acquired) immunity, occurs by natural exposure; infection, transfer of maternal antibodies, or artificial exposure; vaccination; or infusion of immune serum globulin. This type of immunity is specific and protects by way of cellular-mediated and humoral-mediated mechanisms. When competent, the immune system wards off the penetration of foreign microbes and the proliferation of abnormal or malignant cells. When the system is incompetent, the failure can lead to allergies, infection, cancer, and autoimmune and immunodeficiency disorders. Age, medications, nutrition, genetics, physical or emotional stress, and illness can all affect immunity and how the immune system functions. OVERVIEW OF ANATOMY AND PHYSIOLOGY Anatomy of the Immune System Components of the immune system include the lymphatic system, primary and secondary lymphoid organs, and the cells and proteins involved in the immune response. The lymphatic system consists of lymphatic vessels and collecting ducts. Primary lymphoid, or central, organs include the thymus and bone marrow. Secondary lymphoid, or peripheral, organs include the spleen, lymph nodes, tonsils, adenoids, and Peyer's patches (Fig. 18.2). The cells and proteins include leukocytes (white blood cells \[WBCs\]), T and B lymphocytes (T cells and B cells), cells involved in the inflammatory response, antibodies, signaling proteins (cytokines), and other protein systems (complement system) that support the immune response. See Table 18.1 for an overview of the cells involved in the immune response. Lymph Nodes and the Lymphatic System Fluid continually filters out of the blood and into the interstitial space, the majority of which is reabsorbed back into the bloodstream. The lymphatic system is a network of vessels that transports excess interstitial fluid that has not been reabsorbed (lymph fluid) back to the bloodstream, helping to maintain fluid balance. This system contains thousands of lymph nodes strategically located superficially and deep within the tissues near the lymphatic vessels (Figs. 18.3, 18.4, and 18.5). The nodes are small glandular structures that house macrophages, lymphocytes, and monocytes that actively filter and phagocytize microorganisms and other invading particles from circulating lymphatic fluid. The lymph fluid moves through the lymphatic vessels, eventually emptying into the lymphatic ducts, the right lymphatic or thoracic duct, and returning to the general circulation through the subclavian veins. This filtering process prevents unwanted substances from reentering the bloodstream. Thymus The thymus is a soft organ located within the chest cavity near the heart. It starts off large in children and decreases in size into adulthood. It is the central lymphoid organ that produces thymosin (a hormone that stimulates T-cell production) and is where T-cell development takes place. Bone Marrow Within bone cavities resides bone marrow or myeloid tissue, consisting of red (active) marrow and yellow (inactive) marrow. This is where B- and T-lymphocyte formation and differentiation of B cells and T cells occur. B cells stay within the bone marrow to mature. T cells migrate to the thymus to mature and become active as regulatory T cells (suppressor T cells) or effector T cells (helper T cells and cytotoxic T cells; Fig. 18.6). Spleen Approximately the size of a fist, the spleen is located in the left upper quadrant of the abdominal cavity. As a part of the lymphatic system, it serves as a blood filter. It is divided into compartments that contain red and white splenic pulp. The red pulp serves as the filtering site for old or damaged red blood cells. It can also store blood. The white pulp of lymphoid tissue houses lymphocytes and macrophages, filtering unwanted debris like a lymph node. Although it is a redundant organ in the immune system, if it is removed due to accident or disease, the patient may become immunocompromised, with high-risk patients requiring lifetime antibiotics. Tonsils, Adenoids, and Peyer's Patches Additional lymphoid tissues, such as the tonsils, the adenoids, and Peyer's patches, are located in close proximity to mucosal surfaces within the body and provide another means of protection against invading microorganisms. The tonsils are located between the palatine arches on either side of the pharynx. They function as traps to protect against bacteria and viruses that are inhaled. Located at the nasopharyngeal border, the adenoids also defend against inhaled bacteria and viruses. Peyer's patches are lymphoid follicles located on the mucosa of the small intestine. They are known as intestinal immune sensors and defend against pathogens that gain entry to the intestinal tract. Cells Leukocytes White blood cells, or leukocytes, are formed in the bone marrow and lymph tissue; mature in the thymus or bone marrow; and are found in the blood, lymphatic system, spleen, and other body tissues. Leukocytes are mobile units traveling through the bloodstream to defend the body against infection. There are five types of leukocytes: neutrophils, monocytes, eosinophils, basophils, and lymphocytes (B and T cells). They are further classified as granulocytes or agranulocytes depending on their function. Granulocytes have granules in the cytoplasm and release histamines and other substances to defend the body against foreign materials by increasing capillary permeability through vasodilatory effects and mediating the inflammatory response. Neutrophils, basophils, and eosinophils are all phagocytic (cells that engulf bacteria and debris) granulocytes. Neutrophils are phagocytes of early inflammation that destroy bacteria. Basophils release heparin as an anticoagulant and histamine during the early inflammatory response. Eosinophils are phagocytes that destroy allergens and combat parasitic infections. Agranulocytes (without granules in the cytoplasm) include monocytes and lymphocytes. In the bloodstream, monocytes are a part of the adaptive immune response, presenting pathogens to T cells for destruction. In the tissue, they develop into macrophages and are a part of the tissue macrophage system. Macrophages are phagocytes and initiators of the inflammatory response that digest and destroy, or phagocytize, microorganisms and other debris. They also activate helper T cells by secreting signaling proteins, called cytokines, and presenting processed antigens for destruction by the T cell. Lymphocytes Lymphocytes are active in both humoral immune responses and cell-mediated immune responses. They are formed in the bone marrow and are found in the lymph nodes, spleen, and thymus and enter the bloodstream through the lymphatic system. B Lymphocytes B lymphocytes (B cells) are the cells involved in humoral immune responses. They are a subset of lymphocytes that mature in the bone marrow and produce antibodies, or immunoglobulins. Antibodies bind with specific antigens, marking them for destruction by other components of the immune system, or directly neutralize the antigen by inhibiting an essential function necessary for its survival. Once B cells are exposed to a specific antigen for the first time, they proliferate and differentiate into plasma cells and memory cells. Plasma cells secrete antibodies after the first exposure to the antigen. Memory cells, restimulated by the same antigen, mount a specific antigen--antibody response, sometimes long after the initial exposure. B cells can function independently but typically require the help of T lymphocytes. Immunoglobulins The immunoglobulins (Igs), or antibodies, that B cells produce include the following five classes: IgA, IgD, IgE, IgG, and IgM. Immunoglobulin A is found in exocrine-gland secretions such as breast milk and tears. Immunoglobulin D plays a role in B-cell activation, and IgE is associated with allergic reactions and parasitic infections. Immunoglobulin G is effective against bacteria, viruses, and other toxins, and IgM is the initial antibody produced after an infection (Table 18.2). T Lymphocytes T lymphocytes (T cells) are participants in cellular-mediated immune responses. T-cell activation occurs when macrophages present the T cell with a phagocytized antigen. Their main functions include the elimination of cells infected by pathogens, continued activation of the inflammatory response against persistent infections, and regulation of innate and adaptive immune responses. T cells include cytotoxic T cells, suppressor T cells, and helper T cells. Cytotoxic T cells respond to foreign cells, including tumors, non-self cells, and virus-laden cells. Helper T cells are important cells in both adaptive and innate immunity. They augment the effectiveness of the innate immune response by activating macrophages. They augment both humoral and cellular immunity through the activation of B cells to produce antibodies. They also activate cytotoxic T cells and natural killer cells. Suppressor T cells are activated by helper T cells when the immune response is no longer needed. Natural killer (NK) cells, another form of T cell, targets virus-infected and tumor cells. As individuals age, the number of NK cells increases. Dendritic and Mast Cells Dendritic cells are a type of macrophage that reside in lymphoid tissue and are the most potent of the antigen-presenting cells (APCs). APCs capture and engulf antigens, producing a molecule, the major histocompatibility complex (MHC), that identifies the antigen to aid in T-cell and B-cell recognition and response. The MHC process is discussed later in this chapter. When APCs attack an antigen, such as bacteria or a virus, they secrete signaling proteins (cytokines) that stimulate both the innate and adaptive immune response. Mast cells are heavily granulated and are found in the skin and lining of the respiratory and gastrointestinal tracts. Similar to basophils, they release heparin and histamine during the early inflammatory response. Mast-cell degranulation is responsible for many allergic reactions, including anaphylaxis, a severe systemic allergic reaction that is rapid in onset and can be fatal. Proteins Cytokines Cytokines, which include interleukins (ILs), interferon (IFN), and tumor necrosis factor alpha (TNFα), are small proteins that act to regulate immune responses. They are produced in response to specific antigens by cells of the acquired immune system. They have systemic and local signaling effects that enable them to signal cells of the immune system. The production of ILs occurs predominantly by macrophages and lymphocytes in response to the initiation of the inflammatory response. They are responsible for the general enhancement or suppression of inflammation and the stimulation of leukocyte production and maturation. Interferons are proteins that protect against viral infections and tumor growth. They do not destroy a virus directly; rather, they prevent the virus from infecting the surrounding healthy cells and interfere with its ability to replicate. Tumor necrosis factor alpha, produced primarily by macrophages, enhances inflammation, and is involved in the regulation and production of immune cells. Interleukins and IFNs rely on TNFα to mount an effective inflammatory response. Complement System Complement, a complex system of proteins, provides cell-killing effects for both innate and acquired immunity. Initiation of the complement can activate every component of the inflammatory response as well as "complement" the antibacterial function of antibodies. Complement proteins are synthesized primarily in the liver and circulate in the bloodstream in an inactive form until activated by bacteria, viruses, fungi, tumor cells, antigen--antibody complexes, or endotoxins. The complement system is activated through classic, lectin, and alternative pathways. The classic pathway is activated by antibodies of the acquired immune system bound to their specific antigens to form an antigen--antibody complex. The lectin pathway is activated through exposure to bacteria rather than antibodies. The alternative pathway is activated by polysaccharides in gram-negative bacterial and fungal cell walls. Physiology of the Immune Function Innate Immune Response Innate immunity provides protective barriers and an inflammatory response that is immediate, nonspecific, and without memory as first and second lines of defense against threats that are foreign. An important first step in the immune response is to differentiate whether an invader is self (a self-antigen on the host's cells) or non-self (a foreign antigen). If recognized as non-self (i.e., from antigens such as a pathogen, pollen, or foreign tissue or blood product), an attack is mounted to stop and destroy the invading microorganism or toxin. To aid in the identification of self versus non-self, and to identify antigens to allow for a specific adaptive immune response, a group of proteins, the major histocompatibility complex (MHC), codes for the antigens on APC cell surfaces to aid in recognition by the immune cells. That coding occurs when an APC cell, most commonly a dendritic cell, encounters an antigen, consumes it, and "presents" it on its surface to allow recognition by the immune cells. In humans, this process is called the human leukocyte antigen (HLA) system. Physical, Mechanical, and Biochemical Barriers The first line of defense relies on anatomical and biochemical barriers for protection. These all work in concert to mount a passive defense against pathogens. The epithelial cells of the skin, mucous membranes, and protective linings of the organs provide protection through the mechanisms of sloughing, coughing, sneezing, vomiting, and urination. Working with the physical and mechanical barriers, biochemical surface and glandular secretions such as tears, saliva, perspiration, and earwax provide additional means of protection. Inflammatory Response The second line is the inflammatory response that occurs due to tissue damage, such as a break in the skin, that introduces microorganisms. Inflammation may also be initiated through noninfectious processes, such as trauma or exposure to noxious compounds. The goal of inflammation is to prevent and/or limit infection and further damage to the involved area, remove debris, and prepare the area of injury for healing. Cellular mediators involved in the inflammatory response include those in the circulation (neutrophils, eosinophils, basophils, platelets, monocytes, and lymphocytes) and those in tissue (macrophage and mast cells). The proteins involved include complement, clotting factors, kinins (inflammatory mediators generated after tissue injury), and cytokines. Initiation of the inflammatory response includes vasodilation and increased permeability of the capillaries stimulated by histamine released by mast cells, kinins, and other inflammatory mediators, such as prostaglandins and leukotrienes. Vasodilation increases blood flow to the inflamed area, facilitating leukocyte movement (chemotaxis) to the affected site. Increases in permeability allow the leukocytes to move into the tissues. Once in the tissue, invading organisms are engulfed and phagocytized. In order to limit infection and further damage, an area of margination or a border is created through the formation of fibrinogen clots around the area. The action of the inflammatory cells creates excess fluid and debris that are then removed by lymphatic vessels. Moving through the lymphatics, offending antigens identified through this process come in contact with lymphocytes residing in the lymph nodes, initiating the adaptive immune response with the production of antibodies. Last, a promotion of fibrous scarring to facilitate tissue repair and healing is seen. Clinical evidence that can be observed as a result of this response includes the cardinal signs of inflammation: redness and heat due to the increased blood flow and increased metabolic activity, edema due to the accumulation of fluid in the affected area, and pain due to the injury and swelling. Drainage, serous exudate, or pus (a combination of dead immune cells and digested bacteria) may also be seen. Systemically, fever, chills, malaise, and an elevated WBC count (leukocytosis) may also occur as a result of the inflammatory response (Fig. 18.7). Adaptive Immune Response The adaptive immune response to foreign antigens consists of cellular and humoral responses. The cellular response is mediated by the T lymphocytes, and the humoral response is mediated by the B lymphocytes. For an immune response to be initiated, the foreign antigen must be recognized as non-self on presentation by APCs via the MHC molecule on its surface. Each T or B cell recognizes only one antigen, but together as a group, they can recognize a host of foreign antigens (Fig. 18.8). Acquired after birth, the adaptive immune response develops through active or passive immunity. In active immunity, antibodies or T cells are produced either after natural exposure to an antigen during illness or infection or after immunization. Passive immunity happens when preformed antibodies or T lymphocytes are transferred from one individual to another. For example, a newborn acquires immunity from their mother through the placenta, or an individual can acquire immunity through transfusion of antibody-laden blood products. Different from the immediate and nonspecific innate response, the adaptive immune response is delayed and very specific. It also has memory, which confers long-term protection (Table 18.3). Adaptive immunity works in tandem with innate immunity and relies on antigen-specific receptors on T and B cells to mount a response against exposure to a threat or disease (see Fig. 18.8). Cellular-Mediated Response After formation in the bone marrow, undifferentiated T cells move to the thymus and develop specific surface antigen receptors in the process of maturation. Naive effector T cells (helper and cytotoxic T cells) leave the thymus and move to lymphatic tissue throughout the body, ready for activation. This activation, followed by subsequent proliferation, occurs when there is binding of an antigen to a T-cell receptor following recognition through the MHC after presentation by the APCs. This allows direct destruction of foreign or abnormal cells and activation of other cells such as macrophages. This function is carried out by cytotoxic T cells. Activated T helper cells release signaling cytokines to other activated cells, B cells and cytotoxic T cells. This facilitates the process of proliferation and direct binding of the helper T cells to the B cells, which facilitates B-cell division to plasma cells and memory cells. T memory cells are also produced during this process to stimulate secondary cell-mediated immune responses. These memory cells have the ability to respond rapidly to additional exposures to the same antigen Humoral-Mediated Response After maturation in the bone marrow, B cells circulate through the lymphatic system as naive B cells with specific membrane-bound antibodies attached to their surface. When they encounter an antigen that "matches" their antibody, they become activated and divide into plasma and memory cells. This process is commonly assisted by the helper T cell. Plasma cells are the effector cells, secreting antibodies to bind to the antigen. They have a short life span. Memory cells have the same membrane-bound antibody as the parent B cell. They remember and respond to the same antigen if there is repeated exposure. They have a longer life span. Antibodies defend against foreign substances in several ways. They can react between two antigens, causing them to clump, which is termed agglutination. Agglutination facilitates phagocytosis and enables the body to clear itself of the invading organism. Opsonization, a process in which the antigen--antibody binding is coated with a pasty substance, also facilitates phagocytosis and assists in the clearing of the invading organism. ASSESSMENT Obtaining a comprehensive history and performing a thorough physical examination will assist the nurse in assessing a patient's immune function. Laboratory and other diagnostic tests are also helpful in the assessment of immune function. History Pertinent information to obtain from the patient or significant other includes the patient's age, current medications, allergies, and the current problem they are experiencing. Medications that have immune system side effects include antibiotics, anti-inflammatory and immunosuppressive agents, antimetabolites, antineoplastic agents, and thyroid-suppressive therapy. The medical and surgical history is also important to obtain in addition to the family and social history because some immunological problems are genetic or chemically induced. Also included should be nutritional status, infection history, prior immunizations, chronic illnesses, autoimmune disorders, and cancers. Nutritional status is important to assess because suboptimal nutrition can negatively affect the immune system. Adequate vitamins and minerals are vital for the maturation of immune cells and their function. A fatty acid imbalance can have suppressive effects. Illness leading to inadequate oral intake may negatively alter nutritional status and the body's ability to fight off infection and disease. Childhood and adult immunizations should be assessed to make sure adequate protection is present. Tuberculin test administration and results and recent exposure to infections, including sexually transmitted diseases, are also important to assess. Box 18.1 details a comprehensive patient history. Table 18.4 details risk factors for immune system malfunction. Physical Examination Physical assessment includes the taking of vital signs; an inspection of the skin and mucous membranes; palpation of lymph nodes; and an examination of the neurological, respiratory, cardiovascular, gastrointestinal, genitourinary, and musculoskeletal systems. In a patient with immune dysfunction, the normal inflammatory responses may be blunted, and subtle changes may be present. Inspection The nurse should perform a thorough assessment, inspecting each area of the patient's body for evidence of an immune disorder. Look for signs of hypothermia or hyperthermia, enlarged lymph nodes, or edema. Inspection of changes in skin color and skin integrity, rashes, dermatitis-type lesions, hematomas, petechiae, or purpura is equally important. Changes in level of consciousness, cognition, gait, and vision and hearing are important to note. Also important are changes in the respiratory system, such as tachypnea, air hunger, retractions, coughing, and nasal flaring. Collect and examine the urine for sediment, odor, and blood. Stool samples should be assessed for blood, smell, and the presence of diarrhea. Auscultation Listen to the lungs for adventitious (abnormal) breath sounds such as crackles, wheezing, rubs, or rhonchi. Also note if there is any decrease in or absence of breath sounds. Listen to heart sounds; note if tachycardia, rubs, or irregularity of heart rhythm is present. Check for bowel sounds and note if they are hyperactive, hypoactive, or absent. Palpation and Percussion Palpate the skin to check the temperature and whether clamminess is present. Also examine the lymph nodes for evidence of enlargement or tenderness. With light palpation, move the skin over the areas where nodes may be palpable. Nodes are not easily palpable in a healthy adult. If nodes are noted to be enlarged, tender, or fixed in position, this is cause for concern. Explore the adjacent area and regions that are drained by the enlarged node for signs of infection or malignancy. Cancerous nodes are not usually as tender as those from an infection or inflammatory process. To assess the abdomen, perform light and deep palpations with percussion to assess for hepatosplenomegaly (enlargement of the liver or spleen), palpable masses, and the presence of abdominal fluid or abdominal pain. The liver and spleen may be enlarged because of infections, primary or metastatic cancer, or diseases of the blood or lymph system. Joints should be examined for mobility, pain, swelling, warmth, and erythema. DIAGNOSTIC STUDIES Diagnostic studies, including blood tests, skin tests, bone marrow aspiration and biopsy, and radiological imaging, may be necessary to evaluate the state of an individual's immune competence. Immune deficiencies that may occur can be primary (due to aberrant development of immune cells or tissues) or secondary (due to outside interference of the normal immune system) in nature. The disorders that follow may be due to infection, autoimmunity, hypersensitivity, or gammopathies (caused by abnormal protein produced by plasma cells). AIDS, which is caused by HIV, is an example of a secondary immune deficiency caused by a viral infection. Autoimmunity refers to the body's attack against tissue that is self, causing organ or tissue dysfunction. Hypersensitivity occurs when an exaggerated response to an antigen is present, and gammopathies are caused by an overproduction of Igs from the plasma cell. Tests to evaluate immune disorders are obtained to identify antibody deficiencies, T-lymphocyte and neutrophil defects, and complement abnormalities. Specific tests to evaluate problems are based on the assessment and are related to the suspected deficiency or disorder. For example, if the patient has a history of chronic bacterial infections, a complete blood count (CBC) with differential to evaluate individual leukocyte counts may be ordered. If the patient is fighting an infection, a CBC to evaluate the WBC count and inflammatory markers such as C-reactive protein may be drawn to evaluate responsiveness to a prescribed antibiotic. If neutropenia (low neutrophil count) with a low absolute neutrophil count (ANC) is present, reverse isolation may be necessary to protect the patient from infections. Immune system deficiencies and disorders are more thoroughly discussed in additional chapters of this textbook. See Box 18.2 for a summary of the diagnostic priorities. Nursing Implications The patient undergoing an immunological workup requires adequate preparation, education, and counseling regarding the studies that are ordered. Teaching will allow the patient to be prepared for the procedure. Ideally, the patient should repeat what they have been taught to evaluate comprehension of the material and should be encouraged to ask questions if clarification is needed. Patients may feel anxious or frightened about the pain and discomfort they might experience while undergoing testing. They may also experience anxiety and distress over a diagnosis based on test results. The nurse and healthcare team should be ready to provide information and support. AGE-RELATED CHANGES Immune competence may decrease as the immune system changes and weakens with age. Aging has been noted to negatively affect both the innate and adaptive immune responses. Immunosenescence refers to those changes that occur with aging and their consequences---increased infection risk, increased risk of malignancy, and increased autoimmune disorders. Pneumonia and influenza are seen at much higher rates and are included in the top 10 causes of death for individuals 65 years of age and older. Atrophy of the thymus gland enhances with age, increasing the risk of viral infections. A greater incidence of shingles (herpes zoster virus) is seen in the older population; therefore, the shingles vaccine (Shingrix or Zostavax) is recommended for those 50 years of age and older. Innate and adaptive immune responses actively provide defense against tumor cells. These responses decline with aging, creating an increased incidence of cancers. Older adults are also noted to have a decline in T-cell production and function and in antibody production when exposed to specific antigen challenges. They also tend to have an increase in the production of autoantibodies, leading to autoimmune disorders. Autoimmune disorders such as polymyalgia rheumatica, rheumatoid arthritis, and systemic lupus erythematosus are examples of problems due to increased autoantibody production. A decrease in B-cell production and function and antigen-specific Ig activity may also be seen, creating a diminished immune memory and delayed hypersensitivity reactions. Malnutrition, which is associated with immune system defects, is sometimes seen in the older individual as a result of chewing and swallowing problems, blunted taste sensations, and chronic conditions that interfere with the absorption of food and nutrients. Additionally, economic factors, medication side effects, depressive moods, and decreased social interaction may all negatively affect oral intake and nutritional status in the aging population, negatively affecting the immune response.