Despite impressive advances in our understanding and treatment of HIV infection, the long-term prognosis of patients with AIDS remains a concern. Although with effective drug therapy the mortality rate has declined in the United States, the treated patients still carry viral DNA in their lymphoid tissues. Truly curative therapy remains elusive. Similarly, although considerable effort has been mounted to develop a protective vaccine, many hurdles remain before this becomes a reality. Molecular analyses have revealed an alarming degree of variation in viral isolates from patients; this renders the task of producing a vaccine extremely difficult. Recent efforts have focused on producing broadly neutralizing antibodies against relatively invariant portions of HIV proteins. At present, therefore, prevention, public health measures, and anti-retroviral drugs remain the mainstays in the fight against AIDS.
Progression of disease. HIVinfectionprogressesthroughphases.
Acute HIV infection. Manifestationsofacuteviralillness
Chronic (latent) phase. Disseminationofvirus,hostimmuneresponse,progressivedestructionofimmunecells.
AIDS. Severeimmunedeficiency.
Clinical features. Full-blownAIDSmanifestswithseveralcomplications,mostlyresultingfromimmunedeficiency.
Tumors,especiallytumorscausedbyoncogenicviruses
Antiretroviraltherapyhasgreatlydecreasedtheincidenceofopportunisticinfectionsandtumorsbutalsohasnumerouscomplications.
Amyloidosis is a condition associated with a number of disorders in which extracellular deposits of fibrillar proteins are responsible for tissue damage and functional compromise. These abnormal fibrils are produced by the aggregation of improperly folded proteins (which are soluble in their normal folded configuration). The fibrillar deposits bind a wide variety of proteoglycans and glycosaminoglycans, which contain charged sugar groups that give the deposits staining characteristics thought to resemble those of starch (amylose). Therefore, the deposits were called amyloid, a name that is firmly entrenched despite the realization that the deposits are unrelated to starch.
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Amyloid deposits can occur in a variety of conditions, in each of which the protein composition is different. Although amyloid always has the same morphologic appearance, it is biochemically heterogeneous. In fact, at least 30 different proteins can aggregate to form fibrils with the appearance of amyloid. Regardless of their derivation, all amyloid deposits are composed of nonbranching fibrils, each formed of intertwined polypeptides in a β pleated sheet conformation (
Fig. 5.41 ). Approximately 95% of the amyloid material consists of fibril proteins, the remaining 5% being various glycoproteins.
The three most common forms of amyloid are the following:
AL (amyloid light chain) amyloid is made up of complete immunoglobulin light chains, the amino-terminal fragments of light chains, or both.
AA (amyloid-associated) amyloid is composed of an 8500dalton protein derived by proteolysis from a larger precursor in the blood called SAA (serum amyloidassociated) protein, which is synthesized in the liver.
β-amyloid protein (Aβ) is a 4000-dalton peptide that is derived by proteolysis from a much larger transmembrane glycoprotein, called amyloid precursor protein.