Someofthemorecommondisordersaffectinglymphocytesandtheadaptiveimmuneresponseare:
X-SCID: FailureofTcellandBcellmaturation;mutationinthecommonγ chainofacytokinereceptor,leadingtofailureofIL-7signalinganddefectivelymphopoiesis
Autosomal recessive SCID: FailureofTcelldevelopment;secondarydefectinantibodyresponses;approximately50%ofcasescausedbymutationinthegeneencodingADA,leadingtoaccumulationoftoxicmetabolitesduringlymphocytematurationandproliferation
X-linked agammaglobulinemia (XLA): FailureofB-cellmaturation,absenceofantibodies;causedbymutationsintheBTK gene,whichencodesB-celltyrosinekinase,requiredformaturationsignalsfromthepre–B-cellandB-cellreceptors
Di George syndrome: Failureofdevelopmentofthymus,withTcelldeficiency
X-linked hyper-IgM syndrome: Failuretoproduceisotypeswitchedhigh-affinityantibodies(IgG,IgA,IgE);mutationsingenesencodingCD40Loractivation-inducedcytosinedeaminase
Common variable immunodeficiency: Defectsinantibodyproduction;causeunknowninmostcases.
Selective IgA deficiency: FailureofIgAproduction;causeunknown
Deficienciesininnateimmunityincludedefectsofleukocytefunction,complement,andinnateimmunereceptors.
Thesediseasespresentclinicallywithincreasedsusceptibilitytoinfectionsinearlylife.
Secondary (acquired) immune deficiencies may be encountered in individuals with cancer, diabetes and other metabolic diseases, malnutrition, chronic infection, and in patients receiving chemotherapy or radiation therapy for cancer, or immunosuppressive drugs to prevent graft rejection or to treat autoimmune diseases (
Table 5.14).
As a group, the secondary immune deficiencies are more common than the disorders of primary genetic origin. Discussed next is perhaps the most important secondary immune deficiency disease, AIDS, which has become one of the great scourges of humankind.
AIDS is a disease caused by the retrovirus human immunodeficiency virus (HIV) and is characterized by profound immunosuppression that leads to opportunistic
Table 5.14 Causes of Secondary (Acquired) Immunodeficiencies infections, secondary neoplasms, and neurologic manifestations. Although AIDS was first recognized as a distinct entity as recently as the 1980s, it has become one of the most devastating afflictions in history. Of the estimated 36 million HIV-infected individuals worldwide, about 70% are in Africa and 20% in Asia. More than 25 million deaths are attributable to HIV/AIDS, with 1 to 2 million deaths annually. Effective anti-retroviral drugs have been developed, but the infection continues to spread in parts of the world where these therapies are not widely available, and in some African countries, more than 30% of the population is HIV infected. Despite the remarkable progress in drug therapy of AIDS, cure is still a distant goal. The advent of these drugs also raises its own tragic concern; because more individuals are living with HIV, the risk of spreading the infection will increase if vigilance is relaxed.
The enormous medical and social burden of AIDS has led to an explosion of research aimed at understanding this modern plague and its remarkable ability to cripple host defenses. The literature on HIV and AIDS is vast. Here we summarize the currently available data on the epidemiology, pathogenesis, and clinical features of HIV infection.
Epidemiologic studies in the United States have identified five groups of adults at high risk for developing AIDS.