Organ transplant recipients are susceptible to infection due to their generalized immunosuppressed state. Furthermore, the allograft lung has increased susceptibility due to its direct communication with the environment. The lung transplant recipient experiences on average 3 episodes of infectious complications and the type of infection depends on the clinical setting of the transplanted patient (e.g. harvest injury, complication from primary disease, airflow obstruction from chronic airway rejection). Therefore, awareness of the clinical setting enhances diagnostic accuracy. This discussion will cover the general mechanisms of infection, factors leading to increased susceptibility in the allograft, types of infections, and the histologic differential diagnoses.

II. General Mechanisms of infection compared to other immunologic processes

A. Infection

In the respiratory tract, microorganisms either exist in symbiosis with the airway tissue without causing disease (colonization) OR produce disease by breaking through the defense barriers and invading into the parenchyma. The balance between the host's immune system and the virulence of the microorganism depends on a number of factors which evolve over the life of the allograft.

Airway Defense Barriers: Ciliated respiratory epithelium, cough reflex, mucociliary clearance, reflex bronchoconstriction, immune effector cells.

Alveolar Defense: Alveolar fluid contains surfactant, phospholipids, enzymes, albumin, transferrin, alpha-1-antitrypsin, immunoglobulins, and complement. Alveolar cells consist of macrophages (85%), lymphocytes (10%), neutrophils (2%), eosinophils (<1%).

B. Rejection

The same cell mediated immunologic process which participates in defense against microorganisms also targets the donor histocompatibility antigens. Acute cellular rejection involves CD4+ T-cells infiltrating the allograft, predominantly in the perivascular and peribronchiolar regions. The hallmark of chronic rejection is the development of irreversible scarring, compromising the lumen of the small airways and the vessels. Interestingly, during the active phase of chronic rejection, the predominant mononuclear cell type shifts to CD8+ T-cells. In very active ACR and CR, there may be extensive tissue damage with neutrophilic infiltration as a response to the necrosis. With prolonged luminal compromise, the airways are colonized by microorganisms, which may later become invasive. In such cases, the distinction from infection becomes difficult and may be impossible at times.

C. Post Transplant Lymphoproliferative Disorder

PTLD is thought to be a lymphoproliferation of EBV infected B-cells arising in the setting of over immunosuppression. The patients at risk are those who encounter EBV as a primary infection during the post-transplant course. The proliferation may be seen anywhere lymphoid tissue presides, although in lung transplant recipients, presentation in the allograft is relatively common. Histopathological manifestation appears as nodular sheets of atypical lymphoid cell which are not dissimilar to Non-Hodgkins lymphomas. Some cases are similiar to lymphomatoid granulomatosis or T-cell rich B-cell lymphomas with a large subset of reactive T-cells. Reduction in immunosuppression often results in regression of PTLD.