These are often of prolonged duration in recipients of HSC transplants. Among the many reasons for this impairment is the slow reconstitution of the adaptive immune system (derived from donor HSC), after the recipient’s immune system is destroyed or suppressed to allow the graft to take. During the many months that may be needed for immune reconstitution, recipients are susceptible to a variety of infections, mostly with viruses, such as CMV and EBV.
RejectionofsolidorgantransplantsisinitiatedmainlybyhostTcellsthatrecognizetheforeignHLAantigensofthegraft,eitherdirectly(onAPCsinthegraft)orindirectly(afteruptakeandpresentationbyhostAPCs).
Typesandmechanismsofrejectionofsolidorgangraftsareasfollows:
Hyperacute rejection: Preformedanti-donorantibodiesbindtograftendotheliumimmediatelyaftertransplantation,leadingtothrombosis,ischemicdamage,andrapidgraftfailure.
Acute cellular rejection: Tcellsdestroygraftparenchyma(andvessels)bycytotoxicityandinflammatoryreactions.
Acute antibody-mediated (humoral) rejection:Antibodiesdamagegraftvasculature.
Chronic rejection: Dominatedbyarteriosclerosis,thistypeiscausedbyTcellactivationandantibodies.TheTcellsmaysecretecytokinesthatinduceproliferationofvascularsmoothmusclecells,andtheantibodiescauseendothelialinjury.ThevascularlesionsandTcellreactionscauseparenchymalfibrosis.
Treatmentofgraftrejectionreliesonimmunosuppressivedrugs,whichinhibitimmuneresponsesagainstthegraft.
Transplantationofhematopoieticstemcells(HSCs)requirescarefulmatchingofdonorandrecipientandisoftencomplicatedbygraft-vs-hostdisease(GVHD)andimmunedeficiency.
Immune deficiencies can be divided into primary (or congenital) immunodeficiency disorders, which are genetically determined, and secondary (or acquired) immunodeficiencies, which may arise as complications of cancers, infections, malnutrition, or side effects of immunosuppression, irradiation, or chemotherapy for cancer and other diseases.
Immunodeficiencies are manifested clinically by increased infections, which may be newly acquired or reactivation of latent infections. The primary immunodeficiency syndromes are accidents of nature that provide valuable insights into some of the molecules critical in the development of the immune system. Paradoxically, several immunodeficiencies also are associated with autoimmune disorders, perhaps because the deficiency results in loss of regulatory mechanisms or persistence of infections that promote autoimmunity. Here we briefly discuss the more important and best-defined primary immunodeficiencies, to be followed by a more detailed description of acquired immunodeficiency syndrome (AIDS), the most devastating example of secondary immunodeficiency.
Primary immunodeficiency diseases are inherited genetic disorders that impair mechanisms of innate immunity (phagocytes, NK cells, or complement) or the humoral and/or cellular arms of adaptive immunity (mediated by B lymphocytes and T lymphocytes, respectively). These immunodeficiencies are usually detected in infancy, between 6 months and 2 years of age, the telltale signs being susceptibility to recurrent infections. With advances in genetic analyses, the mutations responsible for many of these diseases are now known (
Fig. 5.36). Here we present selected examples of immunodeficiencies, beginning with the more common defects in the maturation and activation of B lymphocytes and T lymphocytes, followed by disorders of innate immunity.