HIV RT PCR, a nucleic acid amplification test for HIV RNA, has recently been shown to be the most valuable test for a) monitoring a patient’s progress during triple drug therapy and b) determining the chances of progression to AIDS. A viral load of 750,000 copies per ml significantly increases the chance of progression to AIDS within 5 years. The other tests listed do not accurately predict progression to AIDS. The figure below shows the basic structure of HIV including the enzyme, reverse transcriptase:

Parvovirus B 19 is the causative agent of erythema infectiosum (fifth disease). It is associated with transient aplastic crisis in persons with hereditary hemolytic anemia. In adults, it is also associated with polyarthralgia.

The advent of triple therapy or a therapeutic “cocktail” has had a marked effect on AIDS patients. The combination of drugs work together as reverse transcriptive inhibitors and a protease inhibitor.

Many patients with high viral loads do very well on triple therapy, although resistance to one or more of the agents may subsequently occur. A low CD4 count does not predict progression to AIDS but does indicate increased chance of opportunistic infection such as those listed. Kaposi’s sarcoma, which has been linked to herpesvirus type 8, pneumocystis, and mycobacterial disease are three of the most prevalent opportunistic infections. While HIV-positive patients contract pneumococcal pneumonia, they are probably at no more risk than the general population, as protection against pneumococcal disease is linked to the presence of anticapsular antibody.

All of Koch’s postulates have been verified for the relationship between infectious mononucleosis and Epstein-Barr virus, a herpesvirus. However, the relationship between this virus and Burkitt’s lymphoma, sarcoid, and systemic lupus erythematosus (SLE) is less clear. Infectious mononucleosis is most common in young adults (14 to 18 years of age) and is very rare in young children. Heterophil antibody titer is helpful in diagnosis, but is not expressed as a function of clinical recovery.

Rubella virus does not produce cytopathic effects (CPEs) in tissue-culture cells. Moreover, rubellainfected cells challenged with a picornavirus are resistant to subsequent infection and thus would not exhibit CPEs. Monkey kidney cells infected only with picornavirus would show CPEs.

Arboviruses (arthropodborne viruses) may or may not be surrounded by a lipid envelope, although most are inactivated by lipid solvents such as ether and may contain either double-stranded or single-stranded RNA. Physicochemical studies have demonstrated a great heterogeneity among these viruses. Arboviruses cause disease in vertebrates; in humans, encephalitis is a frequent arbovirus illness. Most human infections with arbovirus, however, are asymptomatic.

Interferon is a protein produced by cells in response to a viral infection or certain other agents. Entering uninfected cells, interferon causes production of a second protein that alters protein synthesis. As a result of inhibition of either translation or transcription, new viruses are not assembled following infection of interferon-protected cells.

The delta agent was first described in 1977 and has recently been shown to be an incomplete RNA virus that requires HBsAg for replication. It is found most often in persons who have multiple parenteral exposures, for example, intravenous (IV) drug abusers, hemophiliacs, and multiply transfused patients.

As an intravenous agent, ribavirin is effective against Lassa fever in the first week of onset of the disease. It may also be administered as an aerosol that is quite useful in infants with RSV. Unlike amantadine, which is efficacious only with influenza A, ribavirin has activity against both influenza A and B if administered by aerosol in the first 24 h of onset.

Echoviruses were discovered accidentally during studies on poliomyelitis. They were named enteric cytopathogenic human orphan (ECHO) viruses because, at the time, they had not been linked to human disease and thus were considered “orphans.” Echoviruses now are known to infect the intestinal tract of humans; they also can cause aseptic meningitis, febrile illnesses, and the common cold. Echoviruses range in size from 24 to 30 nm in diameter and contain a core of RNA.

HSV meningitis or encephalitis is difficult to diagnose by laboratory tests as there is a low titer of virus present in the CSF. Neonatal HSV infects the child during the birth process. While culture, Tzanck smear, and even antibody tests may be useful in adults, particularly those with HSV-rich lesions, they are not useful for CSF testing. Only PCR is sensitive enough to detect HSV DNA in the CSF. Once diagnosed rapidly, HSV encephalitis or meningitis can be treated with acyclovir.

Enterovirus and Coxsackievirus A can be recovered from conjunctival scrapings of patients with acute hemorrhagic conjunctivitis (AHC) during the first 3 days of illness. Isolation rates are somewhat higher for enterovirus than Coxsackievirus. Less than 5% of throat swab or fecal specimens have been positive for either virus.

Clinical manifestations of cytomegalovirus (CMV) infection may not be readily apparent at birth. Thus, in a newborn infant with a 1:32 titer of CMV, it is necessary to determine whether the antibodies were passed transplacentally from the mother (these antibodies would be IgG) or produced by the fetus in response to an in utero infection (IgM). A newborn infant who is infected excretes large numbers of virus particles in the urine and, therefore, places other neonates at risk for contracting CMV disease.

Koplik’s spots are pathognomonic for measles. The measles virus is a paramyxovirus. In industrialized countries, vaccination has reduced the importance of this childhood infection (although U.S. incidence increased in 1989 and 1990). In developing countries, however, measles is a major killer of young children. In America, most states now require proof of immunity before school enrollment, and this has reduced the incidence of disease.

Human papillomavirus (HPV) is the cause of genital warts. It is one of the most pervasive of all the sexually transmitted diseases. There is no specific cure or vaccine. There are multiple serotypes of papillomavirus and some serotypes are linked to cervical cancer. New techniques for molecular diagnosis of HPV show promise for rapid and sensitive detection and perhaps more aggressive treatment.

Parainfluenza viruses are important causes of respiratory diseases in infants and young children. The spectrum of disease caused by these viruses ranges from a mild febrile cold to croup, bronchiolitis, and pneumonia. Parainfluenza viruses contain RNA in a nucleocapsid encased within an envelope derived from the host cell membrane. Infected mammalian cell culture will hemabsorb red blood cells owing to viral hemagglutinin on the surface of the cell.

In a small number of patients with acute hepatitis B infection, HBsAg can never be detected. In others, HBsAg becomes negative before the onset of the disease or before the end of the clinical illness. In such patients with acute hepatitis, hepatitis B virus infection may only be established by the presence of antihepatitis B core IgM (anti-HBc IgM), a rising titer of anti-HBc, or the subsequent appearance of anti-HBsAg.

Varicella-zoster virus, a member of the herpesvirus group, causes a usually mild, self-limited in children. Recurrent disease in adults who possess circulating antibody against varicella-zoster virus may be more severe and cause an inflammatory reaction in the sensory ganglia of spinal or cranial nerves. This disease, shingles, appears to result from the reactivation (by trauma or other stimuli) of latent varicella-zoster virus.

Rhinovirus is a major cause of the common cold. The primary mode of transmission is the contact of contaminated hands, fingers, or fomites with the conjunctiva or nasal epithelium. While several studies have shown no evidence of aerosol transmission, a study by Dick and associates in 1986 did show aerosol transmission can occur. This is not, however, the main mode of transmission.

The definitive diagnosis of rabies in humans is based on the finding of Negri bodies, which are cytoplasmic inclusions in the nerve cells of the spinal cord and brain, especially in the hippocampus. Negri bodies are eosinophilic and generally spherical in shape; several may appear in a given cell. Negri bodies, although pathognomonic for rabies, are not found in all cases of the disease.

Kuru and CreutzfeldtJakob disease (CJD) are similar but not identical diseases with very different epidemiology. Kuru is prevalent among certain tribes in New Guinea who practiced ritual cannibalism by eating the brains of the departed. CJD is found worldwide and has been transmitted by corneal transplants and in pituitary hormone preparations. There is some association between CJD and Mad Cow Disease in England. Prions are unconventional selfreplicating proteins, sometimes called amyloid. It is now thought that CJD, Kuru, and animal diseases such as scrapie, visna, and bovine spongiform encephalopathy (Mad Cow Disease) are caused by prions.

Routine vaccination of infants and children for smallpox has been discontinued in the United States, both because the risk of contracting the disease is so low and because the complications of smallpox vaccination, including generalized vaccinia eruption, postvaccinal encephalitis, and fetal vaccinia, are significant. Owing to the extremely effective eradication of smallpox worldwide by the World Health Organization, U.S. citizens traveling abroad no longer require vaccination. Pregnancy, immune deficiencies, and eczema and other chronic dermatitides are contraindications to smallpox vaccination.

Hepatitis D virus is a defective virus with an RNA genome and a hepatitis B surface antigen envelope. Two types of HDV infection occur: simultaneous HDV and HBV infection, or HDV superinfection with chronic HBV infection. Diagnosis is made by demonstrating IgM or IgG antibodies, or both.

The e antigen seems to be related to the Dane particle, which is presumed to be the intact hepatitis B virus. Possession of the e antigen suggests active disease and, thus, an increased risk of transmission of hepatitis to others. HBsAg and e antigen are components of hepatitis B and are not shared by other hepatitis viruses.

St. Louis encephalitis, yellow fever, and dengue are caused by flaviviruses. Western equine encephalitis is caused by an alphavirus. Laboratory diagnosis is usually made by demonstration of a fourfold rise in specific antibody titer in paired sera.

Ribavirin is effective to varying degrees against several RNA- and DNA-containing viruses in vitro. It has been approved for aerosol treatment of respiratory syncytial virus infections in infants. Intravenous administration has proved effective in treating Lassa fever.

Herpes simplex virus causes primary and recurrent disease. The typical skin lesion is a vesicle that contains virus particles in serous fluid. Giant multinucleated cells are typically found at the base of the herpesvirus lesion. Encephalitis, which usually involves the temporal lobe, has a high mortality rate. Severe neurologic sequelae are seen in surviving patients.

Contact with infected secretions such as saliva can result in infection with EBV, thus the term kissing disease. Laboratory diagnosis of EBV-induced infectious mononucleosis is usually determined by presence of atypical lymphocytes, heterophile antibodies, or specific antiviral antibodies such as VCA (viral capsid antibody).

The highest risk of fetal infection with rubella occurs during the first trimester. In seronegative patients, the risk of infection exceeds 90%. However, before other measures (such as termination of pregnancy) are considered, a rubella immune status must be performed. A rubella titer of 1:10 is protective.

Mad Cow Disease is related to both scrapie in sheep and bovine spongiform encephalopathy virus. The fear in Great Britain is the potential for acquiring Creutzfeldt-Jakob disease, which is a slowly progressive neurodegenerative disease. Theoretically, such acquisition could be through ingestion of beef from infected cows. A prion consists of protein material without nucleic acid. While related to a virus, a prion is a proteinaceous infectious particle that replicates within cells.

Hepatitis E virus (HEV) is a single-stranded RNA virus. It is transmitted enterically, and the disease is often referred to as enteric hepatitis C. There is no test for HEV routinely available. Diagnosis is clinical and also one of exclusion.

Staphylococcus aureus is the most common cause of postinfluenzal secondary bacterial pneumonia. It most often affects the elderly, although patients of any age may be afflicted. The pneumococcus as well as group A streptococci and Haemophilus influenzae may also cause pneumonia.

In 1993, an outbreak of a fatal respiratory disease occurred in the southwestern United States. This disease is caused by a Hantavirus endemic in deer mice. It is not transmitted from person to person. The mortality rate is 60%. Ribavirin has been used but is not effective. A vaccine is not available.

Parvovirus B19 causes the common disease erythema infectiosum, characterized by a “slapped cheek” rash. Called fifth disease, it is the fifth childhood rash disease; the other four are measles, rubella, scarlet fever, and roseola.

Only two human viruses have been confirmed as human tumor viruses. They include human T-cell lymphoma/leukemia virus (HTLV) and papillomavirus. Others, such as EBV, HSV, and hepatitis B and C, have been implicated as tumor viruses. The virus that causes chicken pox (VZV) is not know to be oncogenic.

Although infection with cytomegalovirus (CMV) is common, it only rarely causes clinically apparent disease. Lesions characteristic of infection with CMV are found in up to 10% of stillborn babies; however, CMV, which can be transmitted transplacentally, usually is not the cause of death. Children and adults with immunosuppressive problems are susceptible to active disease. In severely immunodeficient patients such as those with AIDS, CMV ocular disease may occur. The patient suffers blurring of vision or vision loss, and ophthalmic examination reveals large yellowish-white areas with flame-shaped hemorrhages. Ganciclovir is now licensed for treatment of CMV retinitis in AIDS patients.

Rotaviruses were initially identified by direct electron microscopy (EM) of duodenal mucosa of infants with gastroenteritis. Subsequent studies in several countries have shown them to be the cause of 30 to 40% of acute diarrhea in infants. They are non-lipid-containing RNA viruses with a double-shelled capsid. Although the virus has been serially propagated in human fetal intestinal organ cultures, cytopathic changes are minimal or absent; multiplication is detected by immunofluorescence. Numerous methods for rotavirus antigen detection, including radioimmunoassay, counterimmunoelectrophoresis, and enzyme-linked immunosorbent assay, have been developed and found to be about as effective as EM.

SSPE is a late and rare manifestation of measles. It is a progressive encephalitis involving both white and gray matter. Demyelination is seen only at an advanced stage of the disease in a few cases. In 1985, viral RNA was demonstrated in brain cells from a patient with SSPE by the use of in situ hybridization.

Rotavirus is a viral entity that is similar to Nebraska calf diarrhea virus and is thought to be a major cause of acute diarrhea in newborn infants. Three-quarters of all adults have antibodies against rotavirus; passive transfer of these antibodies to the baby, especially through the colostrum, seems to be protective. Although vaccination would be expected to be of little use to the neonate, it might effectively immunize pregnant mothers.

Papillomavirus infects the skin or mucosa and causes benign tumors. The lesion is termed condyloma acuminatum. These tumors may undergo malignant conversion and become squamous cell carcinomas. Classification of the human papillomavirus is done by DNA hybridization, and to date 46 types have been recognized. Some types, such as 16 and 18, are more frequently associated with carcinoma, while others, such as 6 and 11, are associated with benign tumors or warts.

The replication of a retroviral genome is dependent on the reverse transcriptase enzyme, which performs a variety of functions. It builds a complementary strand of DNA for the viral RNA template; it builds a second DNA strand complementary to the previous DNA; it degrades the original RNA, leaving a DNA-DNA duplex; and, finally, it is responsible for integrating the new viral DNA hybrid into the host genome.

Presently, cytomegalovirus (CMV) is the most common cause of congenital and perinatal viral infections. Culture of the virus is a sensitive diagnostic technique; in the case of a neonate with classic symptoms, serum samples from the mother and neonate are obtained at birth. The IgM antibody titer in the infant’s serum should be higher than the mother’s titer, but they may be similar. For this reason, another sample from the infant at 1 month of age is tested simultaneously with the initial sample. The results should indicate a rise in IgM titer. Measurement of total IgM in the infant’s sera at birth is nonspecific and may show false-negative and false-positive reactions.

Viral cytopathic effects are thought to include a change in the host cell’s macromolecular synthesis and the structure of the cell membrane. Viruses may produce cytopathic changes without forming infectious virions and without replicating infectious virus, although the cytopathology is usually fatal to the cell. A particular cytopathic effect is not necessarily associated with a specific virus.

With an acute case of primary infection by Epstein-Barr virus (EBV), such as infectious mononucleosis, IgM antibodies to VCA should be present. Antibodies to EBNA should be absent, as they usually appear 2 to 3 months after onset of illness. Culture is not clinically useful because it (1) requires freshly fractionated cord blood lymphocytes, (2) takes 3 to 4 weeks for completion, and (3) is reactive in the majority of seropositive patients.

A therapeutic regimen that includes appropriately administered gamma globulin is effective in the treatment of viral hepatitis A and B. Hyperimmune rabies antiserum prolongs the incubation period of rabies and allows the patient more time to mount an immune response to the vaccine. Although it is not a primary form of treatment for patients with poliomyelitis, passive immunization with pooled gamma globulin can offer adequate protection against the disease.

Atypical lymphocytes are the hematologic hallmark of infectious mononucleosis with 90% or more of the circulating lymphocytes being atypical in some cases. These abnormal lymphocytes are not pathognomonic for infectious mononucleosis. They are also seen in other diseases, including cytomegalovirus infection, viral hepatitis, toxoplasmosis, rubella, mumps, and roseola.

Dengue (breakbone fever) is caused by a group B togavirus that is transmitted by mosquitoes. The clinical syndrome usually consists of a mild systemic disease characterized by severe joint and muscle pain, headache, fever, lymphadenopathy, and a maculopapular rash. Hemorrhagic dengue, a more severe syndrome, may be prominent during some epidemics; shock and occasionally death result.

HCV is a positive-stranded RNA virus, tentatively classified as a flavivirus. About half of HCV patients develop chronic hepatitis. A large number of infections appear among IV drug abusers. About 90% of the cases of transfusion-associated hepatitis are thought to be caused by HCV.

Advances in the serodiagnosis of viral hepatitis have been dramatic, and the findings of specific viral antigens have led to further elucidation of the course of infections. The “Australia antigen,” discovered in 1960, was first renamed hepatitis-associated antigen (HAA) and then, finally, hepatitis B surface antigen (HBsAg). It appears in the blood early after infection, before onset of acute illness, and persists through early convalescence. HBsAg usually disappears within 4 to 6 months after the start of clinical illness except in the case of chronic carriers.

The hepatitis B core antigen (HBcAg) is found within the nuclei of infected hepatocytes and not generally in the peripheral circulation except as an integral component of the Dane particle. The antibody to this antigen, anti-HBc, is present at the beginning of clinical illness. As long as there is ongoing HBV replication, there will be high titers of anti-HBc. During the early convalescent phase of an HBV infection, anti-HBc may be the only detectable serologic marker (window phase), if HBsAg is negative and antiHBsAg has not appeared.

Hepatitis B  antigen (HBeAg) appears during the early acute phase and disappears before HBsAg is gone, although it may persist in the chronic carrier. Persons who are HBeAg-positive have higher titers of HBV and therefore are at a higher risk of transmitting the disease. HBeAg has a high correlation with DNA polymerase activity.

The hepatitis B core antigen (HBcAg) is found within the nuclei of infected hepatocytes and not generally in the peripheral circulation except as an integral component of the Dane particle. The antibody to this antigen, anti-HBc, is present at the beginning of clinical illness. As long as there is ongoing HBV replication, there will be high titers of anti-HBc. During the early convalescent phase of an HBV infection, anti-HBc may be the only detectable serologic marker (window phase) if HBsAg is negative and antiHBsAg has not appeared.

Cytomegalovirus causes cytomegalic inclusion disease (CID), especially congenital abnormalities, in neonates. Malformations include microencephaly. Seizures, deafness, jaundice, and purpura can also occur. CID is also one of the leading causes of mental retardation in the United States.

Orchitis, a complication of mumps virus infection in postpubertal males, can cause sterility if bilateral.

Respiratory syncytial virus (RSV) is the leading cause of pneumonia and bronchiolitis in infants. Viremia does not occur and treatment in several ill infants is aerosolized ribavirin.

The vaccine for hepatitis A virus (HAV) is prepared from virus grown in culture and inactivated with formalin.

Influenza usually occurs in successive waves of infection with peak incidences during the winter months. If only minor antigenic drift is expected for the next influenza season, then the most recent strains of A and B viruses representative of the main antigens are included in the vaccine. Influenza vaccine consists of killed viruses.

The original vaccine for hepatitis B was prepared by purifying hepatitis B surface antigen (HBsAg) from healthy HBsAg-positive carriers and treating it with viral-inactivating agents. The second-generation vaccine for hepatitis B is produced by recombinant DNA in yeast cells containing a plasmid into which the gene for HBsAg has been incorporated.

Similar mononucleosis-like diseases are caused by cytomegalovirus (CMV) and Toxoplasma gondii, a parasite. CMV causes fewer than 10% of infectious mononucleosis-like diseases. CMV “mono” is primarily characterized by fatigue. Congenital infection with CMV almost always causes serious sequelae, such as retardation and hearing loss. T. gondii also causes a variety of clinical problems, among them encephalitis in AIDS patients and food poisoning from the ingestion of raw meat. Although CMV and T. gondii are relatively rare causes of infectious mononucleosis, they must be ruled out, particularly when EBV tests are nonreactive.

EBV causes a variety of other syndromes including Burkitt’s lymphoma, the most common childhood cancer in Africa, and nasopharyngeal carcinoma, commonly seen in China.

A number of viruses that cause gastroenteritis are now being recognized ( rotavirus, Norwalk virus, adenovirus, calicivirus, and astrovirus, only gastroenteritis – Adenovirus 40/41.

Detection of anti-HAV IgM in a single serum specimen obtained in the acute or convalescent stage is the quickest and most reliable method to diagnose hepatitis A infection. This antibody is usually present at onset of symptoms and may persist 3 to 6 months.

Hepatitis E virus is an RNA virus. Transmission is by the fecal-oral route although maternal-fetal transmission has recently been described. Prognosis is usually favorable with rare cases of fulminant HEV reported.

HPV (Human papillomavirus) and polyomavirus have icosahedral capsids and DNA genomes. JC virus, a polyomavirus, was first isolated from the diseased brain of a patient with Hodgkin’s lymphoma who was dying of progressive multifocal leukoencephalopathy (PML). This demyelinating disease occurs usually in immunosuppressed persons and is the result of oligodendrocyte infection by JC virus. JC virus has also been isolated from the urine of patients suffering from demyelinating disease. Cryotherapy and laser treatment are the most popular therapies for warts, although surgery may be indicated in some cases. At the present time, there is no effective antiviral therapy for treatment of infection with polyomavirus or HPV. West Nile virus is an arbovirus. While prevalent in Europe, Africa, and the Middle East, it was not seen in the United States until the summer of 1999. It is transmitted by mosqitoes and birds, especially crows; these animals are a reservoir. WNV causes a rather mild encephalitis in humans, the exception being older patients or those who may be immunocompromised.

Orthomyxoviruses and paramyxoviruses are RNA viruses that contain a single-stranded RNA genome. The influenza viruses belong to the orthomyxoviruses. They cause acute respiratory tract infections that usually occur in epidemics. Isolated strains of influenza virus are named after the virus type (influenza A, B, or C) as well as the host and location of initial isolation, the year of isolation, and the antigenic designation of the hemagglutinin and neuraminidase. Both the hemagglutinin and neuraminidase are glycoproteins under separate genetic control, and because of this they can and do vary independently. The changes in these antigens are responsible for the antigenic drift characteristic of these viruses.

The primary constituent cells of the immune system are bone-marrow-derived lymphocytes (B cells) and thymus-derived lymphocytes (T cells). Cytokines are polypeptides that modulate the function of immunoresponsive cells, and interleukins are cytokines that are produced by mononuclear cells. Platelets appear not to be immunoresponsive and are involved in blood clotting.

The great heterogeneity in the B cell response is characterized by a wide variety of antigenic stimuli. The end result of this remarkable process is a set of very specific surface receptors on B lymphocytes. However, it is the hypervariable regions in the variable domain of these B cells that provide the amino acid residues that confer specificity by synthesis of surface immunoglobulin receptors. T cells, on the other hand, do not secrete immunoglobulins.

Recurrent severe infection is an indication for clinical evaluation of immune status. Live vaccines, including BCG attenuated from Mycobacterium tuberculosis, should not be used in the evaluation of a patient’s immune competence because patients with severe immunodeficiencies may develop an overwhelming infection from the vaccine. For the same reason, oral (Sabin) polio vaccine is not advisable for use in such persons.

The initial response to a new infection is with an IgM class antibody. IgM develops quickly and usually disappears within a few months. The secondary response is IgG and reflects the patient’s immune status or, in the case of chickenpox, a vaccination given.

A male patient with the presentation as outlined in question (fatigue, weight loss, and lymphadenopathy) must be tested for antibodies to HIV. While other antibody tests may be relevant after the primary diagnosis, they must be considered after HIV is ruled out. Certainly, infectious mononucleosis is a possibility, but its occurrence in this age group is not as frequent as HIV. Patients are tested first by an ELISA screening test.

Patients with complement deficiencies such as C5 through C9, which form the membrane attack complex (MAC), are predisposed to disseminated meningococcal disease. These patients may also be susceptible to gonococcal infection. There appears to be no disposition to AIDS or to fungal, parasitic, or pneumococcal infections.

There are at least 10 functions of the known cytokines, including mitogenesis, lymphocyte activation, pyrogenesis, lymphocyte proliferation, and T-cell differentiation. Not all cytokines (such as interleukins) are responsible for all of these functions. Cytokines do not activate LPS, but LPS may activate macrophages.

Natural immunity is nonspecific. The description of natural immune functions described are not specific for a certain antigen. For example, certain proteins such as C-reactive protein (CRP) are acute-phase reactants. While elevated CRP is seen in infection, it is not disease-specific. Maternal transfer of antibody, however, is passive but still confers specific immunity. It is termed acquired immunity.

T-cells do not synthesize antibody; that is the task of B cells. Recognition of certain epitopes, lymphokine production, and eradication of “foreign cells” are all functions of T cells. One of the best-recognized T cells is the CD4 cell. The importance of CD4 cells to the immune response is demonstrated by the effects of a specific inhibition of CD4 functions, that is, human immunodeficiency virus (HIV)

Whether an antigen will induce tolerance rather than an immunologic response is largely determined by immunologic maturity of the host, structure, dose of antigen, and administration of immunosuppressive drugs. Tolerance is best maintained by the presence of low concentrations of antigen. T cells become tolerant more readily than B cells

Except squamous epithelial cells, all of the cells listed exhibit CD4 glycoprotein on their cell surface, although at lower levels, than do helper T cells. This explains, in part, how HIV infection may be neurotropic. Because of the low levels of CD4 glycoprotein, these cells, as well as colon epithelial cells, are susceptible to HIV infection. Suppressor lymphocytes have a CD8 glycoprotein determinant.

Interleukin 1 (IL-1) is produced by a variety of cells. Primarily, it is produced by activated macrophages or monocytes, although it can also be produced by activated B cells, keratinocytes, skin-layer hairy cells, and natural killer cells. IL-1 acts synergistically with IL-6 to stimulate production of IL-2. Human IL-1 consists of α and β forms, or two different proteins. They have limited similarity of amino acid sequence, and the β form is more abundant as a serum protein.

Each secretory IgA molecule has a molecular weight of 400,000 and consists of two H2L2 units and one molecule each of J chain and secretory component. Some IgA exists in serum as a monomer H2L2 with a molecular weight of 160,000. Some bacteria, such as Neisseria, can destroy IgA1 by producing protease. It is the major immunoglobulin in milk, saliva, tears, and colostrum. IgA does not fix complement, so one would anticipate that a complement fixation test would not be useful for IgA antibody.

Both IgG and IgM activate complement by the classic pathway, while IgA activates it by the alternative pathway. Neither IgD nor IgE can activate complement. Complement is a system of several proteins that is activated by either an immune or a nonimmune pathway. Both of these pathways result in the production of many biologically active components that cause cell lysis and death.

IgD antibody consists of two light chains and two heavy chains. Its role is not known but can be found on the surface of lymphocytes where it may act as a surface receptor.

IgA antibody is involved in local immunity at the level of the mucous membrane. IgA antibody also arises early in disease. IgA antibody is shortlived and will disappear similarly to IgM.

IgG antibody persists in most people and indicates the antigens to which they have been exposed. IgG is not formed early in infection but is a secondary response arising weeks to months after antigenic challenge. IgG also has a built-in memory. Even people with very low levels of specific IgG will respond to an antigen challenge with an IgG response

Borrelia burgdorferi, the causative agent of Lyme disease, elicits an acute antibody response. IgM appears within days to a few weeks following tick bite, and IgG appears a few weeks later. IgG persists, IgM does not.

Fifth disease is a viral exanthem commonly seen in children 8 to 12 years old. Children are ill for a few days but recover without incident. Unfortunately, if a pregnant female acquires the disease in the first trimester of pregnancy, the fetus is at risk. The causative agent is thought to be a parvovirus (parvovirus B19).

Delta agent is a recently discovered antigen associated with HBsAg. Its presence usually correlates with HBsAg chronic carriers who have chronic 248 Microbiology 8279_Tilton_07.f.qxd 11/14/01 5:03 PM Page 248 active hepatitis. EIA and radioimmunoassay (RIA) tests are available to detect antibodies to delta agent.