The development of the components required for immunity begins early in fetal life when the fetal liver produces stem cells, which in turn produce all cells of the hematopoietic system. Bone marrow assumes this role after birth (Figure 3-3). Some of the stem cells migrate to the thymus gland, where they become T cells (T lymphocytes), which multiply and develop the capacity to combine with specific foreign antigens derived from viruses, fungi, tumors, or transplanted tissue (Figure 3-4). Those T cells coded to recognize self-antigens are destroyed. The remaining T cells are coded to seek out foreign invaders. The body produces several types of T cells; each has a different function:

FIGURE 3–3 Bone marrow formation of lymphocytes.

• Cytotoxic T cells (killer T cells) directly destroy virus-infected cells, tumor cells, and allograft cells by releasing certain toxins or by inducing apoptosis. These cells also may be referred to as CD8 cells because they carry the CD8 glycoprotein on their surface.

• Helper T cells stimulate the B cells to differentiate into plasma cells and to produce more antibodies. They also activate cytotoxic T cells and macrophages. Helper T cells carry the CD4 glycoprotein on their surface.

• Suppressor T cells inhibit both B- and T-cell activities and moderate the immune response.

• Memory T cells remain dormant until they are reactivated by the original antigen, allowing a rapid and more potent response years after the original exposure.

T cells are the major component of the type of acquired immunity known as cell-mediated immunity. The mononuclear phagocytic system, formerly termed the reticuloendothelial system, initiates this immune response. Macrophages, which develop from monocytes, are found in the tissue of the liver, lungs, and lymph nodes. These large cells intercept and engulf the foreign invader antigens, then process and present them to the T cells. Cell-mediated immunity defends the body against viral and fungal attacks, mediates graft rejection and tumor cell destruction, and helps or suppresses an antibody-mediated response to infection.

The remaining stem cells develop into B cells (B lymphocytes) to produce the antibody-mediated (humoral) immunity that protects the body against bacterial and viral infections and reinfections (see Figure 3-4). Once activated by exposure to an antigen, B cells are stimulated to proliferate and form a clone of cells that respond to that specific antigen. Some B cells become antibody-secreting plasma cells, whereas others become memory B cells, ready for a quick response if the target antigen presents itself again. The plasma cells are responsible for producing antibodies that attach to invading foreign antigens, thus marking the antigens for destruction by other cells of the immune system.

B cells are coated with immunoglobulins, giving them the ability to recognize foreign protein and stimulate an antigen-antibody reaction. The five classes of immunoglobulins or antibodies are IgM, IgG, IgA, IgD, and IgE (Table 3-1). These immunoglobulins are usually all present during an antigenic response, although in varying amounts, depending on the stimulant and the health of the patient. Actions of the antigen-antibody complex include the following:

TABLE 3–1

Classes of Antibodies

CLASS	PERCENT OF TOTAL	LOCATION	FUNCTION
IgG	75-85	Blood plasma	Major antibody in primary and secondary immune responses; inactivates antigen; neutralizes toxins; crosses placenta to provide immunity for newborn; responsible for Rh reactions
IgA	5-15	Saliva, mucus, tears, breast milk	Protects mucous membranes on body surfaces; provides immunity for newborn
IgM	5-10	Attached to B cells; released into plasma during immune response	Causes antigens to clump together; responsible for transfusion reactions in the ABO blood typing system
IgD	0.2	Attached to B cells	Receptor sites for antigens on B cells; binding with antigen results in B-cell activation
IgE	0.5	Produced by plasma cells in mucous membranes and tonsils	Binds to mast cells and basophils, causing release of histamine; responsible for allergic reactions

From Applegate EJ: The anatomy and physiology learning system, ed 3, St Louis, 2006, Saunders.

• Inactivation of the pathogen or its toxin through direct binding.

• Stimulation of phagocytosis through complement fixation, the process by which an antibody targets an infected cell for destruction by binding to the cell surface. (Phagocytic cells recognize the antibody marker and engulf the infected cell.)

Activation of the complement system (complement fixation) involves several proteins found in plasma or body fluids. The antigen-antibody reaction initiates a series or cascade of reactions that activate the complement system, fixing the complement and consequently permitting the destruction of pathogens by the process of phagocytosis or lysis of the pathogen’s cell membrane. This activation occurs during an immune reaction mediated by IgG or IgM.

The human body is protected by two types of acquired specific immunity: active immunity and passive immunity. Active immunity results when a person has had previous exposure to a disease or pathogen, or when a person receives immunizations against a disease to stimulate the production of a specific antibody. Active immunity affords the person acquired permanent protection. Passive immunity bypasses the body’s immune response to afford the benefit of immediate antibody availability. A person gains passive immunity by being given immune substances created outside that person’s body for temporary immunity, such as antibodies received through the placenta, when breast milk is fed to a child, or when immune globulin, an antibody-containing preparation made from the plasma of healthy donors, is given to help a person combat disease (Figure 3-5).

FIGURE 3–5 Acquired immunity. (From Applegate EJ: The anatomy and physiology learning system, ed 4, Philadelphia, 2011, Saunders.)

Immunodeficiency Diseases

An absent or inadequate response of the immune system results in immunodeficiency conditions and increased susceptibility to other diseases and opportunistic infections. Immunodeficiency can occur in any of the following major components of the immune system: B cells, T cells, complement, or phagocytes. Although the deficiency may be in either the humoral (antibody-related) or the cell-mediated responses, the consequences are similar: the individual does not have the capability to dispose of foreign and harmful substances. In general, an increased susceptibility to bacterial infections results from a B-cell deficiency, whereas recurrent viral, fungal, and protozoan infections are usually due to decreased T-cell function. Some of the conditions are genetic and present at birth, whereas other defects are not manifested until later in life or are acquired. Acquired immunoincompetence may result from a bacterial or viral insult to the body, malnutrition, or exposure to radiation or certain drugs. The severity of the immunodeficiency disease depends on the type of cell or cells that are affected. It can range from annoying chronic infections to severe life-threatening or fatal conditions. E3-2

Enrichment

Malignancies and Common Opportunistic Infections and Conditions in Patients With AIDS

• Kaposi sarcoma is an aggressive malignancy of the blood vessels that appears as purple or blue patches on the skin, in the mouth, or anywhere else on the body

FIGURE 3–6 Kaposi’s sarcoma of distal heel and lateral foot. (Courtesy The Centers for Disease Control and Prevention, 1992. From Mudge-Grout C: Immunologic disorders—Mosby’s clinical nursing series, St Louis, 1992, Mosby.)

• Lymphomas are cancerous lesions of lymphoid tissues.

• Pneumocystis carinii pneumonia (PCP) is a lung infection that can progress to be life threatening. It is the most common lung disease in persons with AIDS.

• Tuberculosis is a bacterial infection of the lungs or other organs.

• Herpes simplex consists of painful blisterlike lesions of the mouth, genitalia, or anus caused by the herpes virus

FIGURE 3–7 Primary perineal herpes with methylene blue stain. (Courtesy The Centers for Disease Control and Prevention, 1992. From Mudge-Grout C: Immunologic disorders—Mosby’s clinical nursing series, St Louis, 1992, Mosby.)

• Herpes zoster (shingles) is characterized by clusters of red blisterlike skin lesions that follow an inflamed nerve path.

• Candida albicans causes a fungal infection of the mucous membranes of the mouth, genitalia, or skin.

• Toxoplasmosis is an infection caused by a protozoan intracellular parasite. A rash and lymphadenopathy can be present, and the central nervous system, heart, or lungs can become involved.

• Neurologic complications include inflammation of nerves, neuropathy, neoplasms, and AIDS dementia complex.

• Diarrhea is a symptom of a host of bacterial and viral infections of the gastrointestinal tract, liver, or gallbladder.

• Epstein-Barr virus causes hairy leukoplakia that is characterized by white plaque visible on the tongue.

FIGURE 3–8 Hairy leukoplakia on the tongue of a patient with AIDS. (Courtesy J.S. Greenspan, DDS, University of California-San Francisco; courtesy The Centers for Disease Control and Prevention, 1992. From Mudge-Grout C: Immunologic disorders—Mosby’s clinical nursing series, St Louis, 1992, Mosby.)

Acquired Immunodeficiency Syndrome (AIDS)

Description

Acquired immunodeficiency syndrome (AIDS) is a progressive impairment of the immune system caused by the human immunodeficiency virus (HIV). This gradual destruction of the immune system affects many organ systems and is ultimately lifethreatening for the person infected.

ICD-9-CM Code 042

ICD-10-CM Code B20 (Human immunodeficiency virus (HIV) disease)

Symptoms and Signs

Initially it is not possible to tell whether people are infected with HIV by simply observing them. They may remain healthy for years during the latent period and may therefore unknowingly transmit the virus to other people. Within 1 to 4 weeks after exposure, the patient may experience a flulike illness with sore throat, fever, and body aches that often lasts about 2 weeks. Lymphadenopathy, weight loss, fatigue, diarrhea, and night sweats are common as the clinical course progresses. The body’s number of T cells becomes lower and allows for frequent infections, especially opportunistic infections, pneumonia, fever, and malignancies (see the Enrichment box for Malignancies and Common Opportunistic Infections and Conditions in Patients with AIDS). Often, in the later stages, encephalopathy and malignancy lead to dementia and death (Figure 3-9).

FIGURE 3–9 Pathologic changes associated with acquired immunodeficiency syndrome (AIDS). (From Damjanov I: Pathology for the health-related professions, ed 4, St Louis, 2011, Saunders.)

Patient Screening

An individual who complains of weight loss, fatigue, swollen glands, night sweats, and/or a persistent flulike syndrome needs an appointment with a physician for a medical evaluation as soon as possible. When an individual reports a known HIV exposure through unprotected sexual contact or puncture with a contaminated needle, immediate medical care should be arranged.

Etiology

AIDS is caused by HIV, type 1 or 2 (HIV-1 is found worldwide, HIV-2 is mainly in West Africa) retroviruses that contain RNA; they cannot survive apart from human cells. HIV attacks helper T lymphocytes (CD4 cells), the body’s safeguard against tumors, viruses, and parasites. The destruction of T cells and the proliferation of HIV leave the body defenseless against infection and malignancy by reducing cell-mediated immunity. The virus also directly damages the nervous system. AIDS first was recognized in the United States in 1981. Since then, it has become a top killer of young men and a worldwide threat to humankind. It is estimated that close to 35 million people are currently infected with the AIDS virus and more than 30 million have already died from the illness. Without treatment, the time from infection with HIV to death is approximately 10 years. To date, neither a cure nor an effective vaccine has been found for this disease, although use of highly active antiretroviral therapy (HAART) has significantly prolonged the life span of those infected.

HIV is spread most readily by direct contact with the blood or semen of an infected person. It is not transmitted by casual contact, such as touching, handshaking, and hugging. Sexual contact is the primary means of transmission. Although AIDS initially was associated with homosexual activity, now most people are infected through heterosexual transmission. AIDS also can be transmitted through blood and blood products. Infants of infected mothers can contract the disease in utero through the placenta, during the birth process, and from breast milk. Sharing of needles by intravenous drug users also leads to infection. The risk of transmission of HIV to and from health care workers and patients is minimized by strict adherence to the universal precautions for infection control.

Diagnosis

A common laboratory screening test used to detect the presence of HIV antibodies in the blood is the enzyme-linked immunosorbent assay (ELISA). If the findings are positive, the test is repeated, and the result is then confirmed by using a Western blot test. A positive p24 antigen test indicates circulating HIV antigen. ELISA tests are often negative during the first month of infection, although a p24 antigen test or polymerase chain reaction (PCR) assay may be positive. Rapid HIV antibody testing has become the preferred method of testing as the results are often available within 5 minutes. Although a negative test is regarded as a true negative, a positive result requires confirmatory testing by Western blot. A viral titer and CD4 T-cell count are usually obtained following a positive test to determine the patient’s disease burden and risk for opportunistic infections. Transmission of HIV is possible during all stages of infection, even before it can be detected by laboratory tests.

Treatment

Currently, no cure exists for AIDS. After a patient has been diagnosed, he or she will have periodic measurement of the number of CD4 T cells and the amount of HIV RNA (viral load) present in the bloodstream. These are both markers of disease progression from the initial infection with HIV to the development of AIDS. These numbers can also be used to determine when to begin HAART. HAART consists of a three drug combination: two nucleoside reductase inhibitors and either a nonnucleoside reductase inhibitor or a protease inhibitor. There are currently 20 antiretroviral drugs approved for use in HAART, so many different drug combinations are possible. Although these drugs have been effective at prolonging life and maintaining the quality of life for patients, they are associated with a number of toxicities and serious side effects so patients on HAART must be followed closely. In the later stages of the disease, patients will require prophylactic antibiotics. Addressing the psychological needs of the patient with AIDS is essential.

Health care practitioners who are involved in various forms of patient care with exposure to body fluids and blood should follow the principles of infection control and universal precautions (see the Alert box for Infection Control and Universal Precautions). All body fluids and blood from any patient should be handled with extreme care, as if the patient were known to be infected with HIV.

Prognosis

Although AIDS is ultimately a fatal disease, the number of Americans dying of AIDS each year has dropped. Treatment strategies that result in better prognosis include use of HAART, use of prophylactic antibiotics, and care by a physician experienced with HIV care.

Prevention

Because HIV is transmitted directly from human to human, prevention measures relate to avoiding risk factors for sexually transmitted diseases and practicing infection control through the use of universal precautions. Use of condoms and not sharing needles are highly recommended. The drugs used in highly active antiretroviral therapy (HAART) can be administered as postexposure prophylaxis after a needlestick injury.

Patient Teaching

Describe the diagnostic tests and inform the patient concerning when to expect test results. Assure the patient of medical confidentiality. Make sure the HIV-positive individual knows how the disease is transmitted. Stress important aspects of the medication regimen and the dangers of noncompliance. Explain side effects of the therapeutic drugs, and encourage him or her to contact the health care worker with questions or concerns. Other teaching points will include how to minimize infections, the need for lifelong therapies, and the responsibility to inform health care providers about the HIV diagnosis. The psychological, social, and financial ramifications of having HIV require referrals for community support. Eventually, referrals will be required to meet a variety of home care needs.

Alert

Infection Control and Universal Precautions

Guidelines: Treat blood and body fluids as if infected and remember to use the following precautions:

1. Practice frequent and thorough hand washing.

2. Report any accidental needlesticks.

3. Wear personal protective equipment, including mask or face shield, gown, gloves, and goggles. Change equipment between patients.

4. Use caution with laboratory specimens.

5. Dispose of contaminated sharps in designated biohazard containers. Caution: Do not recap or break needles.

6. Use proper linen disposal containers.

7. Use clean mouthpieces and resuscitation bags.

8. Obtain hepatitis B vaccination to protect against occupational exposure to blood.

9. Use proper decontamination techniques.

10. Absorb blood spills with paper towels, then clean the area with soap and water, followed by disinfection of the area with a 1 : 10 solution of household bleach. E3-3

NOTE: Pathogens can be bloodborne or airborne. Standard Precautions, which correlate with Universal Precautions, are recommended and posted for hospitals and patient care institutions.

Children with DiGeorge’s anomaly often have a set of structural abnormalities. These include abnormally wide-set, downward slanting eyes; low-set ears with notched pinnas; a small mouth (Figure 3-10); abnormalities of the palate; and cardiovascular defects such as tetralogy of Fallot. The thymus and parathyroid glands are absent or underdeveloped. The infant exhibits signs of tetany due to hypocalcemia caused by hypoparathyroidism. Some degree of cognitive impairment often is present. The patient is susceptible to severe viral, fungal, and protozoan infections. The most common of these are pneumonia and thrush in infants.