Scanning electron micrograph of Staphylococcus aureus bound to the surface of a human neutrophil. “Granulocytic Phagocytes,” by Frank R. DeLeo and William M. Nauseef.
Companion reading, audio, and video
1. Kishiyama JL. Ch. 3 Disorders of the Immune System, AIDS Pgs. 53-57 In: Hammer GD and McPhee Eds. JS.
Pathophysiology of Disease : An Introduction to Clinical Medicine, 7th Ed. New York: McGraw-Hill Education, 2014
2. Diseases of the Immune System, Ch.6. Immunodeficiency Syndromes, Acquired Immunodeficiency Syndrome (AIDS).
Pgs.441-463 In: Kumar V and Abbas AK. Robbins and Cotran Pathologic Basis of Disease 8th ed. Philadelphia:
Saunders, 2014
3. Robbins and Cotran Pathologic Basis of Disease 8th ed. Audio Ch. 6 -Immunodeficiency Syndromes, Acquired
Immunodeficiency Syndrome (AIDS) section.
Important Epidemiology Note: “The Pandemic of HIV continues to be a serious international problem
As of 2005, there were about 38.6 million people worldwide living with HIV/AIDS, with 2.8 million
deaths in 2005 and 4 million people newly infected with HIV.”
U.S. CDC (Centers for Disease Control and Prevention) http://www.cdc.gov/HIV/
Marc Imhotep Cray, M.D. 3
Prevalence of human immunodeficiency virus (HIV) infection among the adult population worldwide.
World Health Organization (WHO) figures from 2006 demonstrate the extent of the HIV pandemic throughout the world.
Rubin R and Strayer DS Eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine, 2012
Marc Imhotep Cray, M.D. 4
Acquired immunodeficiency syndrome (AIDS)
AIDS is an infectious disease caused by human immunodeficiency viruses
(HIV)
AIDS is characterized by a profound suppression of immune system and
susceptibility to infections, neurologic disorders, and malignancies
Ireland KA. Visualizing Human Biology, 3rd ed. New Jersey: Wiley & Sons, 2011
HIV test results are often falsely positive in newborns born to HIV-infected
mothers because these antibodies can cross placenta but are also often
falsely negative within first few months of infection
An effective vaccine remains an elusive goal, in part due to rapid mutation rate of virus
during reverse transcription
There are four (five) classes of antiretroviral drugs, each of which targets one of four viral
processes
1. Reverse transcriptase inhibitors
nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs),
nonnucleoside reverse transcriptase inhibitors (NNRTIs),
2. Protease inhibitors (PIs),
3. Entry (fusion) inhibitors, and
4. Integrase inhibitors
Preferred initial therapy is a combination of two NRTIs with a PI, a NNRTI, or an integrase
inhibitor
Marc Imhotep Cray, M.D. 14
Human immunodeficiency virus and its life cycle
After attachment to CD4 and a chemokine
co-receptor (usually CCR5), virus membrane
fuses with cellular membrane to allow entry
into cell
Following uncoating, reverse transcription
of viral RNA results in production of double-
stranded DNA (dsDNA)
This is inserted into host genome as HIV
provirus, by a virally coded integrase
enzyme
Cell activation leads to transcription and
production of viral mRNAs
Structural proteins are produced and
assembled
Free HIV viruses are produced by viral
budding from host cell, after which further
internal assembly occurs with cleavage of a
large precursor core protein into small core
protein components by a virally coded
protease enzyme, producing mature virus
particles, which are released and can go on
to infect additional cells bearing CD4 and Male D etal. Immunology, 8th Ed. Philadelphia, PA: Elsevier-Saunders, 2014
chemokine co-receptor 15
Highly Active AntiRetroviral Therapy (HAART) cont.
HAART is often initiated at time of HIV diagnosis
Although not curative, antiretroviral pharmacotherapy can significantly
reduce viral replication, restore immune function, lead to clinical
recovery, and markedly extend life expectancy
Resistance to nnRTIs and PIs usually occurs through mutations that alter
binding sites for these drugs
Marc Imhotep Cray, M.D. 23
HIV modes of transmission
HIV is transmitted by exposure to infected body fluids or
sexual or perinatal contact , and also through breast-feeding
Kumar V and Abbas AK. Robbins and Cotran Pathologic Basis of Disease 8th ed. Philadelphia:
Marc Imhotep Cray, M.D. Saunders, 2014 25
Pathogenesis of AIDS
Primary targets for HIV are CD4+ T cells but viruses also invade
macrophages and dendritic cells
Rubin R and Strayer DS Eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine, 2012
3. Minor infections
P. jiroveci pneumonia
C. albicans infections of the mouth, esophagus, vagina, and
lungs
Cytomegalovirus enteritis and pneumonitis
Atypical mycobacterial infection (M. avium-intracellulare) of GIT
Cryptococcus neoformans meningitis
Cryptosporidium enteritis
CD4 count less than 200 cells/mL: obtain baseline ophthalmologic examination, start
Pneumocystis jiroveci pneumonia (PCP) prophylaxis with
trimethoprim-sulfamethoxazole (TMP-SMX), 1 double-strength tablet daily (preferred regimen);
or dapsone, 100 mg orally once daily (check baseline G6PD); or atovaquone, 1500 mg daily.
CD4 count less than 100 cells/mL: if toxoplasma IgG positive, start either TMP/SMX double-
strength daily or dapsone, 50 mg daily, and pyrimethamine, 50 mg once weekly, with folinic
acid, 25 mg once weekly.
CD4 count less than 50 cells/mL: ophthalmologist examination every 3 months, prophylaxis
against Mycobacterium avium complex (MAC) with azithromycin, 1200 mg weekly, or
clarithromycin, 500 mg orally twice daily.
From: Runge MS and Greganti MA. Netter's Internal Medicine 2nd Ed. Saunders, 2008
HIV, with gp120 and gp41, infects T cells that express CD4 and either CXCR4
or CCR5
HIV can also infect phagocytic cells (e.g., macrophages, dendritic cells,
microglial cells). Microglia infected with HIV forms multinucleated giant
cells in the central nervous system (CNS)
CDC. Centers for Disease Control and Prevention: 1993 revised classification system and expanded surveillance
definition for AIDS among adolescents and adults. MMWR 41(RR-17):1, 1992.
Studdiford, JS and Tully AS. USMLE Images for the Boards: Philadelphia. Saunders ,2013
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. 2015
74
Sources and further study:
Sources:
Damjanov I, Pathology Secrets 3rd ed. Philadelphia: Mosby, 2009
Diseases of the Immune System, Ch. 6. . Immunodeficiency Syndromes, Acquired Immunodeficiency
Syndrome (AIDS). Pgs.441-463 In: Kumar V and Abbas AK. Robbins and Cotran Pathologic Basis of
Disease 8th ed. Philadelphia: Saunders, 2014
Kishiyama JL. Ch. 3 Disorders of the Immune System, AIDS Pgs. 53-57 In: Hammer GD and McPhee JS.
Eds. Pathophysiology of Disease : An Introduction to Clinical Medicine, 7th Ed. New York: McGraw-Hill
Education, 2014
Longo DL, Fauci AS, Kasper DL, et al (editors). Harrison’s Principles of Internal Medicine, 18th ed.
McGraw-Hill, 2012
Rubin R and Strayer DS Eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine, 6th Ed.
Baltimore: Lippincott Williams & Wilkins, 2012
Klatt EC. Robbins and Cotran Atlas of Pathology, 3rd Ed. Philadelphia: Saunders, 2015
Runge MS and Greganti MA. Netter's Internal Medicine 2nd Ed. Saunders, 2008
Studdiford, JS and Tully AS. USMLE Images for the Boards: Philadelphia. Saunders, 2013
eLearning (IVMS Cloud)
Infectious Disease
Microbial biology & Immune System
Rural Medicine Global Health (Focus on Ethiopia)
Marc Imhotep Cray, M.D. 75