a. Sexual transmission: > 75% of cases
(1) Homosexual transmission (anal intercourse between men): most common in the United States
(2) Heterosexual transmission: most common in developing countries
b. Intravenous drug abuse c. Other modes of transmission
(1) Vertical transmission: transplacental route, blood contamination, breastfeeding
(2) Accidental needlestick: risk per accident is 0.3%.
(3) Blood products: risk per unit of blood
< 0.0002%
d. Body fluids containing HIV: blood, semen, breast milk; the virus cannot enter intact skin or mucosa.
2. Etiology: RNA retrovirus
a. HIV-1: most common cause in the United States b. HIV-2: most common cause in developing countries 3. Pathogenesis
a. HIV envelope protein (gp120) attaches to the CD4 molecule of T cells.
b. HIV infects CD4 T cells, causing direct cytotoxicity and loss of cell-mediated immunity.
c. Reverse transcriptase converts viral RNA into provi- ral double-stranded DNA, which is integrated into the host DNA.
4. HIV and AIDS testing (Table 3-6) 5. Clinical findings
a. Acute phase: mononucleosis-like syndrome 3-6 weeks after infection
b. Latent (chronic) phase: asymptomatic period 2-10 years after infection
(1) CD4 T-cell count > 500 cells/4
(2) Viral replication in follicular dendritic cells (reservoir cells)
c. Early symptomatic phase
(1) CD4 T-cell count 200-500 cells/4
(2) Generalized lymphadenopathy; non-AIDS- defining infections, including hairy leukopla- kia, or Epstein-Barr virus (EBV)-caused glossitis;
fever, weight loss, diarrhea d. AIDS (Table 3-7)
(1) Criteria: HIV-positive with CD4 T-cell count 200 cells/4 or with an AIDS-defining condition
Most common ac- quired immunodefi- ciency disease worldwide: AIDS
Most common CNS fungal infection in AIDS:
cryptococcosis
Chapter 3 Immunopathology 35 TABLE 3-6 Laboratory Tests Used in HIV and AIDS
Test Use Comments
ELISA Screening test Detects anti-gp120 antibodies Sensitivity - 100%
Positive within 6-10 weeks
Western blot Confirmatory test Used if ELISA is positive or indeterminate -- 100% specificity
p24 Antigen Indicator of active viral Positive prior to seroconversion and when replication AIDS is diagnosed (two distinct peaks) CD4 T-cell count Monitoring immune Useful in determining when to initiate
status HIV treatment and when to administer prophylaxis against opportunistic infections
HIV viral load Detection of actively Most sensitive test for diagnosis of acute dividing virus HIV before seroconversion
ELISA, enzyme-linked immunoabsorbent assay
TABLE 3-7 Organ Systems Affected by AIDS
Organ System Condition Comments
Central nervous system (CNS)
AIDS-dementia complex Primary CNS lymphoma Cryptococcosis
Toxoplasmosis CMV retinitis Esophagitis Colitis
Biliary tract infection Focal segmental
glomerulosclerosis Pneumonia
Kaposi's sarcoma Bacillary angiomatosis
Caused by HIV Caused by EBV
Cause of CNS fungal infection Cause of space-occupying lesions Cause of blindness
Caused by Candida, herpes, CMV Caused by Cryptosporidium Caused by CMV
Causes hypertension and nephrotic syndrome
Caused by Pneumocystis carinii and Streptococcus pneumoniae Caused by HSV-8
Caused by Bartonella henselae Gastrointestinal
Hepatobiliary Renal Respiratory Skin
CMV, cytomegalovirus EBV, Epstein-Barr virus; HSV-8, herpes simplex virus type 8
(2) Most common AIDS-defining infections:
Pneumocystis carinii pneumonia, systemic can- didiasis
(3) AIDS-defining malignancies: Kaposi's sarcoma (Figure 3-3), Burkitt's lymphoma (EBV), primary CNS lymphoma (EBV)
(4) Causes of death: disseminated infections (cyto- megalovirus, Mycobacterium a yilun complex) 6. Immunologic abnormalities: Iymphopenia (low CD4
T-cell count), cutaneous anergy (defect in cell-mediated
Most common ma- lignancy in AIDS:
Kaposi's sarcoma
36 Pathology
Figure 3-3 Kaposi's sarcoma in HIV. Skin lesions are raised, red, and nonpruritic.
TABLE 3-8 Complement Disorders Disorder Comments Hereditary
angioedema
C6–C9 deficiency
Deficiency of Cl esterase inhibitor; continued Cl activation decreases C2 and C4 and increases their cleavage products, which have anaphylatoxic activity
Normal C3
Swelling of face and oropharynx
Increased susceptibility to disseminated Neisseria gonorrhoeae or N. meningitidis infections
immunity), hypergammaglobulinemia (due to poly- clonal B-cell stimulation by EBV), CD4:CD8 ratio < 1 7. Pregnant women with AIDS: treatment with a reverse
transcriptase inhibitor reduces transmission to newborns to less than 8%.
C. Complement system disorders (Table 3-8)
1. Complement pathways: classic and alternative a. Cl esterase inhibitor inactivates the protease activ-
ity of Cl in the classic pathway.
b. Membrane attack complex (C5–C9) is the final common pathway for both the classic and alternative pathways.
2. Testing of the complement system
a. A decrease in C4 or C2 indicates activation of the classic pathway.
b. A decrease in factor B indicates activation of the al- ternative pathway.
c. A decrease in C3 indicates activation of either system.
VII. Amyloidosis
A. Amyloid: fibrillar protein that forms deposits in interstitial tissue, resulting in organ dysfunction
1. Characteristics
a. Linear, nonbranching filaments in a (3-pleated sheet
Chapter 3 Immunopathology 37
TABLE 3-9 Common Types of Amyloidosis and Associated Clinical Findings Type of
Amyloidosis Clinical Findings Primary and
secondary
Senile cerebral
Nephrotic syndrome, renal failure (common cause of death) Arrhythmia, heart failure
Macroglossia, malabsorption Hepatosplenomegaly Carpal tunnel syndrome
Dementia (Alzheimer's type) caused by toxic AP deposits in neurons Amyloid precursor protein coded by chromosome 21
Associated with Down syndrome
b. Apple-green—colored birefringence in polarized light with Congo red stain of tissue
c. Eosinophilic staining with H&E stain 2. Types: derived from different proteins
a. Amyloid light chains (AL) b. Amyloid-associated (AA)
c. (3-Amyloid (A(): derived from amyloid precursor protein
B. Types of amyloidosis (Table 3-9)
1. Systemic: similar tissue involvement in both types a. Primary: AL amyloid; associated with multiple
myeloma (30% of cases)
b. Secondary (reactive): AA amyloid; associated with chronic inflammation (e.g., rheumatoid arthritis, tuberculosis)
2. Localized: confined to a single organ (e.g., brain) 3. Hereditary: autosomal recessive disorder involving AA