Cell-mediated deficiency:
Viruses
  • Cytomegalovirus
    • A group of viruses in the family Herpesviridae infecting humans and other animals, many of the viruses having special affinity for salivary glands, and causing enlargement of cells of various organs and development of characteristic inclusions (owl eye) in the cytoplasm or nucleus. Infection of embryo in utero may result in malformation and fetal death. They are all species- specific and include salivary virus, inclusion body rhinitis virus of pigs, and others. Syn: visceral disease virus.
  • Herpesviridae
    • A heterogeneous family of morphologically similar viruses, all of which contain double- stranded DNA and which infect man and a wide variety of other vertebrates. Infections produce type A inclusion bodies; in many instances, infection may remain latent for many years, even in the presence of specific circulating antibodies. Virions are enveloped, ether- sensitive, and vary up to 200 nm in diameter; the nucleocapsids are 100 nm in diameter and of icosahedral symmetry, with 162 capsomeres. The family is subdivided into 3 subfamilies Alphaherpesvirinae, Betaherpesvirinae, and Gammaherpesvirinae, and includes herpes simplex virus, varicella-zoster virus, cytomegalovirus, and EB virus (all of which infect humans), pseudorabies virus of swine, equine rhinopneumonitis virus, infectious bovine rhinotracheitis virus, canine herpesvirus, B virus of Old World monkeys, several viruses of New World monkeys, virus III of rabbits, infectious laryngotracheitis virus of fowl, Marek disease virus of chickens, Lucké tumor virus of frogs, and many others.
  • Measles
    • An acute exanthematous disease, caused by measles virus (genus Morbillivirus), a member of the family Paramyxoviridae, and marked by fever and other constitutional disturbances, a catarrhal inflammation of the respiratory mucous membranes, and a generalized maculopapular eruption of a dusky red color; the eruption occurs early on the buccal mucous membrane in the form of Koplik spots, a manifestation utilized in early diagnosis; average incubation period is from 10–12 days. Recovery is usually rapid but respiratory complications and otitis media caused by secondary bacterial infections are common. Encephalitis occurs rarely. Subacute sclerosing parencephalitis may occur later and is associated with chronic infection. Syn: morbilli.
  • Human papilloma virus
    • An icosahedral DNA virus, 55 nm in diameter, of the genus Papillomavirus, family Papovaviridae; certain types cause cutaneous and genital warts; other types are associated with severe cervical intraepithelial neoplasia and anogenital and laryngeal carcinomas. Over 70 types have been characterized on the basis of DNA relatedness. Syn: infectious papilloma virus.
    • Human papillomavirus infection is the most common sexually transmitted viral disease. The interval between exposure and clinical evidence of disease ranges from 3 weeks to 8 months. A single unprotected contact with an infected person carries a 60% risk of infection. At least 80% of cervical cancers are attributable to HPV infection, and 25% of all irregularities seen on Pap smears are believed to result from the presence of the virus, which is often otherwise asymptomatic. HPV typing in women with atypical squamous cells of undetermined significance (ASCUS) on cervical Pap smear helps to identify those in whom more intensive surveillance for premalignant change is warranted. Invasive cervical cancer is associated with types 16, 18, 31, 33, and others. Some 40% of HIV- positive women develop severe cervical dysplasia caused by HPV, which in many cases proceeds to fatal cancer with an aggressiveness not commonly seen among non–HIV- positive women. External genital warts (condylomata acuminata) are usually due to HPV type 6 or 11. Women with external genital warts are not at increased risk of cervical cancer and do not need colposcopy or other special surveillance if routine Pap smears are negative. About 20–30% of HPV infections regress spontaneously. Diagnosis of HPV infection is based on visual inspection (including colposcopy with application of acetic acid to the cervix), Pap smear, and biopsy, with detection of viral DNA in tissue. Treatment options include surgical excision, cryosurgery, laser ablation, loop electrosurgical excision, and intralesional injection of interferon. External genital warts usually respond to topical treatment of podofilox gel or to imiquimod (a cytokine- inducing agent), which can be applied by the patient. Subclinical HPV infection, detectable only by Pap smear or other laboratory methods, may prove impossible to eradicate. The virus cannot be cultured, and there is no test to confirm cure.
    • HIV (Human Immunodeficiency Virus)
HIV/AIDS
graphic
Fig. 5-36 Schematic illustration of the human immunodeficiency virus (HIV)-1 virion. The viral particle is covered by a lipid bilayer derived from the host cell and studded with viral glycoproteins gp41 and gp120.
  • Human T-cell lymphotropic virus type III; a cytopathic retrovirus (genus Lentvirus, family Retroviridae) that is 100–120 nm in diameter, has a lipid envelope, and has a characteristic dense cylindrical nucleoid containing core proteins and genomic RNA. There are currently two types: HIV-1 infects only human and chimpanzees and is more virulent than HIV-2, which is more closely related to Simian or monkey viruses. HIV- 2 is found primarily in West Africa and is not as widespread as HIV-1. In addition to the usual gene associated with retroviruses, this virus has at least 6 genes that regulate its replication. It is the etiologic agent of acquired immunodeficiency syndrome (AIDS). Formerly or also known as the lymphadenopathy virus (LAV) or the human T- cell lymphotropic virus type III (HTLV-III). Identified in 1984 by Luc Montagnier and colleagues. Syn: lymphadenopathy-associated virus.
Immune deficiency
  • Profound T-cell mediated immunodeficiency
  • Lymphopenia
  • Selective loss of CD4+ T-cells
  • Reversal of CD4-CD8 ratio
  • Altered monocyte/macrophage functions
  • Preferential loss of memory T-cells
  • Polyclonal B-cell activation
Complications
  • Wasting
  • Secondary neoplasms
  • Hypergammaglobulinemia and circulating immune complexes (glomerulonephritis)
  • CNS involvement
  • via monocytes
  • Toxic cytokines
  • Aseptic meningitis
  • Vascular myelopathy
  • Peripheral neuropathy
  • Encephalopathy:  AIDS dementia
  • Opportunistic Infections
Opportunistic infections
  • Bacterial
    • Mycobacterium tuberculosis
    • Nocardia
    • Atypical mycobacteria
  • Protozoal
    • Toxoplasma
    • Pneumocystis
    • Cryptosporidia
  • Fungal
    • Candida
    • Cryptococcus
  • Viral
    • CMV
    • Herpes simplex
    • Herpes zoster
Risk groups
  • Homosexual/bisexual men
  • Intravenous drug users
  • Hemophiliacs and blood or blood component recipients
  • Heterosexual contact with high risk groups
  • 6% of cases have no risk factors identified
Increased risk for neoplasms
  • Lymphoma
  • Kaposi sarcoma
Natural history
Early acute phase
  • Transient viremia
  • Self-limited sore throat
  • Myalgia (muscle pain)
  • Temporary fall in CD4+ T-cells
  • Viral load at end of acute phase reflects balance between HIV production and loss
  • Higher the viral load- the more rapid the progression
Middle phase
  • Clinical latency
  • Rapid viral replication
  • Gradual decline of CD4+ T-cells
  • Lymphadenopathy
  • Fever, rash & fatigue @ end of this phase
  • May last 7-10 years
Final crisis phase
  • Rapid decline in host defenses
  • Low CD4+ counts<200
Full-blown AIDS
  • Infections
  • Wasting
  • Secondary neoplasms
HIV infection
graphic
Fig. 5-39 Pathogenesis of HIV-1 infection. HIV-1 initially infects T cells and macrophages directly or is carried to these cells by dendritic cells. Viral replication in the regional lymph nodes leads to viremia and widespread seeding of lymphoid tissue. The viremia is controlled by the host immune response (not shown), and the patient then enters a phase of clinical latency. During this phase, viral replication in both T cells and macrophages continues unabated, but there is some immune containment of virus (not illustrated). There continues a gradual erosion of CD4+ cells by productive infection (or other mechanisms; see text). When the CD4+ cells that are destroyed cannot be replenished, CD4+ cell numbers decline and the patient develops clinical symptoms of full-blown AIDS. Macrophages are also parasitized by the virus early; they are not lysed by HIV-1, and they can transport the virus to various tissues, particularly the brain.
Non-transforming type C cytopathic retrovirus
Viral envelope gp 120 binds to receptors on (helper/CD4) T-cells
Reverse transcriptase allows virus to integrate into host cell genome
Transmission
  • Sexual contact
  • Parenteral inoculation
  • Genital ulcers
  • Heterosexual transmission increasing
Fungi
  • Candida
    • A genus of yeastlike fungi commonly found in nature; a few species are isolated from the skin, feces, and vaginal and pharyngeal tissue, but the gastrointestinal tract is the source of the single most important species, Candida albicans.
  • Aspergillus
    • A genus of fungi (class Ascomycetes) that contains many species, a number of them with black, brown, or green spores. A few species are pathogenic for humans, avians, and other animals. There are about 300 species in this genus.
  • Pneumocystis
    • The eukaryotic microorganism responsible for interstitial pneumonia in immunocompromised patients. The exact taxonomic position remains unclear, as the organism has morphologic similarities to protozoa but shares substantial 16S ribosomal RNA and mitochondrial DNA with some species of the Ascomycetes. P. carinii fails to grow on fungal culture media but takes up fungal stains, and infections from it respond to antiprotozoal as well as to some antifungal drugs.
Bacteria
  • Mycobacteria
    • A genus of aerobic, nonmotile bacteria (family Mycobacteriaceae) containing Gram-positive, acid-fast, slender, straight or slightly curved rods; slender filaments occasionally occur, but branched forms rarely are produced. Parasitic and saprophytic species occur. A number of species are associated with infections in immunocompromised people, especially those with AIDS. The type species is Mycobacterium tuberculosis. It is the type genus of the family Mycobacteriaceae.
  • Listeria
  • A genus of aerobic to microaerophilic, motile, peritrichous bacteria containing small, coccoid, Gram- positive rods; these organisms tend to produce chains of 3–5 cells and, in the rough state, elongated and filamentous forms. Cells 18–24 hours old may show a palisade arrangement with a few V or Y forms; the bacteria produce acid but no gas from glucose and are found in the feces of humans and other animals, on vegetation, and in silage and are parasitic on poikilothermic and warm- blooded animals, including humans. The type species is Listeria monocytogenes.
Protozoa (cryptosporidia)
A genus of coccidian sporozoans (family Cryptosporiidae, suborder Eimeriina) that are important pathogens of calves and other domestic animals, and common opportunistic parasites of humans that flourish under conditions of compromised immune function; can cause self- limiting diarrhea in immunocompetent persons.
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