Transplant-related immunosuppression: a review of immunosuppression and pulmonary infections

Abstract

Solid organ and hematopoietic stem cell transplantation are definitive therapies for a variety of end-stage diseases. Immunosuppression has improved graft survival but leaves the patient susceptible to infectious complications. Of these, pulmonary infections are the leading cause of morbidity and mortality in the transplant recipient. Allograft rejection is mediated primarily by T cells, with B cells playing a role via antibody production. Depending on the transplant type, rejection can be hyperacute, acute, or chronic. Hyperacute rejection occurs as an immediate response to preformed antibodies to donor human leukocyte antigens. Acute cellular rejection involves recipient T-cell recognition of human leukocyte antigen molecules expressed on donor-derived, antigen-presenting cells (direct allorecognition) or presentation of donor-derived peptides by recipient antigen-presenting cells to recipient T cells (indirect allorecognition). Once the alloantigens are recognized as foreign, the activation, proliferation, and production of cytokines by T lymphocytes and other immune cells lead to the amplification of the alloimmune response. This complex process involves the generation of effector T cells, antibody production by activated B cells, and macrophage activation. Alloimmunity is facilitated by the production of many cytokines, chemokines, and other effector molecules, such as complement. The immunosuppressants involve many classes of drugs, including antibody therapies that eliminate specific groups of cells or alter signaling pathways used by effector cells. The article reviews the agents and associated infections.

Figure 1.

Infection timeline for recipients of solid organ transplants and HSCT. Data represent the traditional time to onset of infection and may not account for the effect induced by the use of antimicrobial prophylaxis. Adapted with permission from Reference .

Figure 2.

Proposed infection timeline based on the use of common prophylactic antimicrobials such as sulfa, azoles, and antivirals in recipients of solid organ transplants. Dotted lines denote onset of infection that would occur without prophylaxis, as reported in Figure 1. Solid lines indicate the most common times to onset of infection for each pathogen. Asp = Aspergillus; Blasto = Blastomyces; CAP = community-acquired pneumonia; CMV = cytomegalovirus; Cocci = Coccidioides; Crypto = Cryptococcus; EBV = Ebstein-Barr virus; Histo = Histoplasma; HSV = herpes simplex virus; MTb = Mycobacteria tuberculosis; PCP = Pneumocystis carinii; Toxo = Toxoplasmosis; VZV = Varicella zoster virus. Zero denotes the time of transplantation.

Figure 3.

Proposed infection timeline based on the use of common prophylactic antimicrobials such as sulfa, azoles, and antivirals in recipients of HSCT. Dotted lines denote onset of infection that would occur without prophylaxis, as reported in Figure 1. Solid lines indicate the most common times to onset of infection for each pathogen. Asp = Aspergillus; CAP = community-acquired pneumonia; CMV = cytomegalovirus; EBV = Ebstein-Barr virus; GVHD = graft versus host disease; HHV 6 = human herpes virus 6; HSV = herpes simplex virus; MTb = Mycobacteria tuberculosis; PCP = Pneumocystis carinii; VZV = Varicella zoster virus. Zero denotes the time of transplantation.