Immune function is reduced by many diseases, injuries, and medical therapies. Reduction of immune function may be temporary or permanent, but it always endangers the patient’s health. Chapter 21 discusses issues related to reduced protection from inadequate immunity or inflammatory responses. Other problems occur when immunity overfunctions or functions at inappropriate times, at which time this normally protective response becomes an enemy (Braun, 2010; Stevens, 2009). Chapters 20 and 22 discuss issues related to damage from excess or inappropriate inflammatory or immune responses.

Overview

Immunity is composed of many cell functions that protect people against the effects of injury or invasion. People interact with many other living organisms in the environment. The size of these organisms varies from large (other humans and animals) to microscopic (bacteria, viruses, molds, spores, pollens, protozoa, and cells from other people or animals). As long as organisms do not enter the body, they pose no health threat. The body has some defenses to prevent organisms from entering, such as intact skin and mucous membranes, skin surface normal flora, and natural chemicals that inhibit bacterial growth. These defenses are not perfect, and invasion of the body by organisms occurs often. Invasion occurs much more often than does an actual disease or illness because of proper immune functioning.

The purpose of inflammation and immunity is to provide protection by neutralizing, eliminating, or destroying organisms that invade the internal environment. To protect without harming the body, immune system cells use protective actions only against non-self proteins and cells. Immune system cells can distinguish between the body’s own healthy self cells and other, non-self proteins and cells.

Self Versus Non-Self

Non-self proteins and cells include infected body cells, cancer cells, cells from other people, and invading organisms. Recognizing self versus non-self, which is necessary to prevent healthy body cells from being destroyed along with the invaders, is called self-tolerance. The immune system cells are the only cells capable of determining self from non-self. Self-tolerance is possible because of the different proteins present on cell membranes.

Each cell is surrounded by a plasma membrane with different proteins protruding through the surface (Fig. 19-1). For example, in liver cells, many different protein types are present on the cell membrane surface. The amino acid sequence of each protein type differs from that of all other protein types. Some of these proteins are found on the liver cells of all animals (including humans) that have livers, because these protein types are specific to the liver and serve as a marker for liver tissues. Other protein types are found only on the liver cells of humans, because these protein types are specific markers for human tissues. In addition, each person’s liver cells have surface proteins that are specific to that person. These unique proteins would be identical only to the proteins of an identical sibling. These unique proteins, known as human leukocyte antigens (HLAs), are found on the surface of all body cells of that person and serve as a “universal product code” or a “cellular fingerprint” for that person. One person’s HLAs are recognized as “foreign,” or non-self, by the immune system of another person. Because the cell-surface proteins are non-self to another person’s immune system, they are antigens, which are proteins capable of stimulating an immune response.

FIG. 19-1 Proteins on human cell plasma membranes.

Human leukocyte antigens are on the surfaces of most body cells—not just on leukocytes. They are a normal part of the person and act as antigens only if they enter another person’s body. These antigens determine the tissue type of a person. Other names for these cellular fingerprints are human transplantation antigens, human histocompatibility antigens, and class I antigens.

Humans have about 40 major HLAs that are determined by a set of genes called the major histocompatibility complex (MHC). The specific antigens that any person has (of a large number of possible antigens) are determined by which MHC gene alleles were inherited from his or her parents (Nussbaum et al., 2007).

The HLAs are key for recognition and self-tolerance. The immune system cells constantly come into contact with other body cells and with any invader that enters the body. At each encounter, the immune system cells compare the surface protein HLAs to determine whether the encountered cell belongs in the body (Fig. 19-2). If the encountered cell’s HLAs perfectly match the HLAs of the immune system cell, the encountered cell is “self” and is not attacked by the immune system cell. If the encountered cell’s HLAs do not perfectly match the HLAs of the immune system cell, the encountered cell is non-self, or foreign. The immune system cell then takes action to neutralize, destroy, or eliminate this foreign invader.

FIG. 19-2 Determination by immune system cell of self versus non-self cells.

Immune function changes during a person’s life, according to nutritional status, environmental conditions, drugs, disease, and age. Immune function is most efficient when people are in their 20s and 30s and slowly declines with increasing age (Graham et al., 2006; Touhy & Jett, 2010). Older adults have decreased immune function, increasing their risk for many health problems (Chart 19-1).

Chart 19-1 Nursing Focus on the Older Adult

Changes in Immune Function Related to Aging

IMMUNE COMPONENT	FUNCTIONAL CHANGE	NURSING IMPLICATIONS
Inflammation	There is a probable defect in neutrophil function.	Neutrophil counts may be normal, but activity is reduced or impaired, increasing the risk for infection.
	Leukocytosis does not occur during episodes of acute infection.	Patients may have an infection but not show expected changes in white blood cell counts.
	Older adults may not have a fever during inflammatory or infectious episodes.	Not only is there potential loss of protection through inflammation, but also minor infections may be overlooked until the patient becomes severely infected or septic.
Antibody-mediated immunity	The total number of colony-forming B-lymphocytes and the ability of these cells to mature into antibody-secreting cells are diminished.	Older adults are less able to make new antibodies in response to the presence of new antigens. Thus they should receive immunizations, such as “flu shots,” the pneumococcal vaccination, and the shingles vaccination.
	There is a decline in natural antibodies, decreased response to antigens, and reduction in the amount of time the antibody response is maintained.	Older adults may not have sufficient antibodies present to provide protection when they are re-exposed to microorganisms against which they have already generated antibodies. Thus older patients need to avoid people with viral infections and need to receive “booster” shots for old vaccinations and immunizations, especially tetanus and pertussis (whooping cough).
Cell-mediated immunity	Thymic activity decreases with aging, and the number of circulating T-lymphocytes decreases.	Skin tests for tuberculosis may be falsely negative. Older patients are more at risk for bacterial and fungal infections, especially on the skin and mucous membranes, in the respiratory tract, and in the genitourinary tract.

Organization of the Immune System

The immune system is not located in any one body area but, rather, is influenced by many systems, especially the nervous system, the endocrine system, and the GI system. Most immune system cells come from the bone marrow. Some cells mature in the bone marrow; others leave the bone marrow and mature in different body sites. When mature, many immune system cells are released into the blood, where they circulate to most body areas and have specific effects.

The bone marrow is the source of all blood cells, including immune system cells. The bone marrow produces immature, undifferentiated cells called stem cells (Abbas et al., 2010, Kaufman, 2011). Stem cells are pluripotent, meaning that each cell has more than one potential outcome. When the stem cell is first created in the bone marrow, it is undifferentiated. The cell is not yet committed to maturing into a specific blood cell type. At this stage, the stem cell is flexible (pluripotent) and could become any one of many mature blood cells. Fig. 19-3 shows the possible outcomes for maturation of stem cells. The type of mature cell that the stem cell becomes depends on which pathway it follows.

FIG. 19-3 Stem cell differentiation and maturation.

The maturational pathway of any stem cell depends on body needs and on the presence of specific growth factors that direct the cell to a pathway. For example, erythropoietin is a growth factor for red blood cells (RBCs). When immature stem cells are exposed to erythropoietin, they commit to the erythrocyte pathway and eventually become mature RBCs.

White blood cells (leukocytes or WBCs) protect the body from the effects of invasion by organisms. These cells are the immune system cells—the knight and soldiers protecting the castle inhabitants after invaders get through the castle wall. Table 19-1 lists the functions of different immune system cells. The leukocytes provide protection through many defensive actions (Abbas et al., 2010; Stevens, 2009). These actions include:

• Recognition of self versus non-self

• Destruction of foreign invaders, cellular debris, and unhealthy or abnormal self cells

• Production of antibodies directed against invaders

• Complement activation

• Production of cytokines that stimulate increased formation of leukocytes in bone marrow and increase specific leukocyte activity

TABLE 19-1 IMMUNE FUNCTIONS OF SPECIFIC LEUKOCYTES

VARIABLE	LEUKOCYTE	FUNCTION
Inflammation	Neutrophil	Nonspecific ingestion and phagocytosis of microorganisms and foreign protein
	Macrophage	Nonspecific recognition of foreign proteins and microorganisms; ingestion and phagocytosis
	Monocyte	Destruction of bacteria and cellular debris; matures into macrophage
	Eosinophil	Weak phagocytic action; releases vasoactive amines during allergic reactions
	Basophil	Releases histamine and heparin in areas of tissue damage
Antibody-mediated immunity	B-lymphocyte	Becomes sensitized to foreign cells and proteins
	Plasma cell	Secretes immunoglobulins in response to the presence of a specific antigen
	Memory cell	Remains sensitized to a specific antigen and can secrete increased amounts of immunoglobulins specific to the antigen on re-exposure
Cell-mediated immunity	Helper/inducer T-cell	Enhances immune activity through secretion of various factors, cytokines, and lymphokines
	Cytotoxic/cytolytic T-cell	Selectively attacks and destroys non-self cells, including virally infected cells, grafts, and transplanted organs
	Natural killer cell	Nonselectively attacks non-self cells, especially body cells that have undergone mutation and become malignant; also attacks grafts and transplanted organs

The three processes needed for human protection through immunity are (1) inflammation, (2) antibody-mediated immunity (AMI), and (3) cell-mediated immunity (CMI). Each process uses different defensive actions, and each influences or requires assistance from the other two processes (Fig. 19-4). Therefore full immunity (immunocompetence) requires the function and interaction of all three processes.

FIG. 19-4 The three divisions of immunity: inflammation, antibody-mediated immunity, and cell-mediated immunity. Optimal function of all three divisions is necessary for complete immunity.

Inflammation

Inflammation, also called innate-native immunity or natural immunity, provides immediate protection against the effects of tissue injury and invading foreign proteins. Innate-native immunity is any natural protective feature of a person. It can be a barrier to prevent organisms from entering the body or can be an attacking force that eliminates organisms that have already entered the body. This type of immunity cannot be developed or transferred from one person to another and is not an adaptive response to exposure or invasion by foreign proteins.

The inflammatory responses are part of innate immunity. Other parts of innate immunity include skin, mucosa, antimicrobial chemicals on the skin, complement, and natural killer cells (Abbas et al., 2010; Stevens, 2009).

The ability to produce an inflammatory response is critical to health and well-being. Inflammation differs from AMI and CMI in two important ways:

• Inflammatory protection is immediate but short-term against injury or invading organisms. It does not provide true immunity on repeated exposure to the same organisms.

• Inflammation is a nonspecific body defense to invasion or injury and can be started quickly by almost any event, regardless of where it occurs or what causes it.

So, inflammation triggered by a scald burn to the hand is the same as inflammation triggered by bacteria in the middle ear. How widespread the symptoms of inflammation are depends on the intensity, severity, and duration of exposure to the initiating event. For example, a splinter in the finger triggers inflammation only at the splinter site, whereas a burn injuring 50% of the skin leads to an inflammatory response involving the entire body.

Inflammatory responses start tissue actions that cause visible and uncomfortable symptoms. Despite the discomfort, these actions are important in ridding the body of harmful organisms. However, if the inflammatory response is excessive, tissue damage may result (Landis, 2009). Inflammatory responses also help start both antibody-mediated and cell-mediated actions to activate a full immune response.

Infection

A confusing issue about inflammation is that this process occurs in response to tissue injury, as well as to invasion by organisms. Infection is usually accompanied by inflammation; however, inflammation can occur without infection. Examples of inflammation without infection include joint sprain injuries, myocardial infarction, and blister formation. Examples of inflammation caused by noninfectious invasion include allergic rhinitis, contact dermatitis, and other allergic reactions. Inflammations from infection include otitis media, appendicitis, and viral hepatitis, among many others. Inflammation does not always mean that an infection is present.

Cell Types Involved in Inflammation

The leukocytes involved in inflammation are neutrophils, macrophages, eosinophils, and basophils. Neutrophils and macrophages use phagocytosis to destroy and eliminate foreign invaders. Basophils and eosinophils release chemicals that act on blood vessels to cause tissue-level responses that help neutrophil and macrophage actions.

Neutrophils

Mature neutrophils make up between 55% and 70% of the normal total white blood cell (WBC) count. Neutrophils come from the stem cells and complete the maturation process in the bone marrow (Fig. 19-5). They are also called granulocytes because of the large number of granules present inside each cell. Other names for neutrophils are based on their appearance and maturity. Mature neutrophils are also called segmented neutrophils (“segs”) or polymorphonuclear cells (“polys,” PMNs) because of their segmented nucleus. Less mature neutrophils are called band neutrophils (“bands” or “stabs”) because of their nuclear shape.

FIG. 19-5 Stem cell maturation into fully functional segmented neutrophils.

Usually, growth of a stem cell into a mature neutrophil requires 12 to 14 days. This time is shortened by the presence of specific growth factors (cytokines), such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF). The purpose and action of cytokines are described on p. 314 in the Cytokines section.

In the immunocompetent healthy person, more than 100 billion fresh, mature neutrophils are released from the bone marrow into the circulation daily (Abbas et al., 2010; Stevens, 2009). This huge production is needed because the life span of each neutrophil is short—about 12 to 18 hours.

Neutrophil function provides protection after invaders, especially bacteria, enter the body. Although the neutrophils are the largest group of circulating leukocytes, each cell is small. This powerful army destroys invaders by phagocytosis and enzymatic digestion, although each cell is small and can take part in only one episode of phagocytosis.

Mature neutrophils are the only stage of this cell capable of phagocytosis. Because this cell type is responsible for continuous, instant, nonspecific protection against organisms, the percentage and actual number of mature circulating neutrophils are used to measure a patient’s risk for infection: the higher the numbers, the greater the resistance to infection. This measurement is the absolute neutrophil count (ANC), also called the absolute granulocyte count or total granulocyte count.

The differential of a normal white blood cell count shows the number and percent of the different types of circulating leukocytes (Table 19-2). Usually, most neutrophils released into the blood from the bone marrow are segmented neutrophils; only a small percentage are band neutrophils. Less mature neutrophil forms should not be in the blood. Some problems, such as sepsis, cause the neutrophils in the blood to change from being mostly segmented neutrophils to being less mature forms. This situation is termed a left shift or bandemia because the segmented neutrophil, which is seen at the far right of the neutrophil pathway (see Fig. 19-5), is no longer the most numerous type of circulating neutrophils. Instead, more of the circulating cells are bands—the less mature cell type found farther left on the neutrophil pathway.

TABLE 19-2 VALUES OF A WHITE BLOOD CELL DIFFERENTIAL FOR PERIPHERAL BLOOD REPRESENTING A NORMAL COUNT

WBC TYPE	%	/MM³
TOTAL WBC	100	10,000
Segs	62	6200
Bands	5	500
Monos	3	300
Lymphs	28	2800
Eosins	1.5	150
Basos	0.5	50

A left shift indicates that the patient’s bone marrow cannot produce enough mature neutrophils to keep pace with the continuing infection and is releasing immature neutrophils into the blood. Unfortunately, most of these immature cells are of no benefit because they are not capable of phagocytosis.

Macrophages

Macrophages come from the committed myeloid stem cells in the bone marrow and form the mononuclear-phagocyte system. The stem cells first form monocytes, which are released into the blood at this stage. Until they mature, monocytes have limited activity. Most monocytes move from the blood into body tissues, where they mature into macrophages. Some macrophages become “fixed” in position within the tissues, whereas others can move within and between tissues. Macrophages in various tissues have slightly different appearances and names (Table 19-3). The liver, spleen, and intestinal tract contain large numbers of these cells.

TABLE 19-3 TISSUE MACROPHAGES

TISSUE	MACROPHAGE
Lung	Alveolar macrophage
Connective tissue	Histiocyte
Brain	Microglial cell
Liver	Kupffer cell
Peritoneum	Peritoneal macrophage
Bone	Osteoclast
Joint	Synovial type A cell
Kidney	Mesangial cell