Infection with the human immunodeficiency virus (HIV) is the cause of acquired immune deficiency syndrome (AIDS). Although substantial gains in curbing the rate of spread of HIV have been made, this worldwide epidemic continues to spread, especially through heterosexual contact in lessdeveloped countries. HIV is an enveloped retrovirus that replicates in cells of the immune system. Viral entry requires the presence of CD4 and a particular chemokine receptor, and the viral cycle is dependent on transcription factors found in activated T cells. Infection with HIV causes a loss of CD4 T cells and an acute viremia that rapidly subsides as cytotoxic Tcell responses develop, but HIV infection is not eliminated by this immune response. HIV establishes a state of persistent infection in which the virus is continually replicating in newly infected cells. Current treatment consists of combinations of antiviral drugs that block viral replication and cause a rapid decrease in virus levels and a slow increase in CD4 Tcell counts. The main effect of HIV infection is the destruction of CD4 T cells, which occurs through the direct cytopathic effects of HIV infection and through killing by CD8 cytotoxic T cells. As CD4 Tcell counts wane, the body becomes progressively more susceptible to opportunistic infection. Eventually, most untreated HIVinfected individuals develop AIDS and die; however, a small minority, socalled longterm nonprogressors, remain healthy for many years with no apparent ill effects of infection. We hope to be able to learn from these people how infection with HIV can be controlled. The existence of these people, and of others who seem to have been naturally immunized against infection, gives hope that it will be possible to develop effective vaccines against HIV.
Summary to Chapter 13.
Whereas most infections elicit protective immunity, successful pathogens have developed some means of at least partly resisting the immune response and can cause serious, sometimes persistent, disease. Some individuals have inherited deficiencies in different components of the immune system, making them highly susceptible to certain classes of infectious agents. Persistent infections and inherited immunodeficiency diseases illustrate the importance of innate and adaptive immunity in effective host defense, and present ongoing challenges for immunological research. The human immunodeficiency virus (HIV), which leads to acquired immune deficiency syndrome (AIDS), combines the characteristics of a persistent infectious agent with the ability to create immunodeficiency in its human host, a combination that is usually slowly lethal to the patient. The key to fighting new pathogens such as HIV is to increase our understanding of the basic properties of the immune system and its role in combating infection.
Questions.
13.1 Matching: Match the following gene defects with the associated primary immunodeficiency.
13.2 True or False: individuals with mutations in the genes encoding the il-12 p40 subunit are susceptible not only to pathogens such as M. tuberculosis that require a tH1 response, but type 3 (tH17) responses are also affected.
13.3 Short Answer: name two genetic defects that lead to the absence of CD8+ t cells with CD4+ t cells preserved, and one genetic defect that leads to the absence of CD4+ t cells with CD8+ t cells preserved.
13.4 Short Answer: Both CD40l deficiency and aiD deficiency cause hyper-igM syndrome, but t-cell function is severely impaired in CD40l deficiency and preserved in aiD deficiency. Why?
13.5 True or False: Common variable immunodeficiency (CViD) severely impairs both t-cell and antibody responses.
13.6 Multiple Choice: Which of the following hereditary immune disorders does not have an autoimmune or autoinflammatory phenotype?
A. autoimmune polyendocrinopathy-candidiasisectodermal dystrophy (aPeCeD), caused by defects in
B. Familial Mediterranean fever (FMF), caused by pyrin mutations
C. Ommen syndrome, caused by RAG1 or RAG2 hypomorphic mutations