Mechanisms of immunotherapy: a historical perspective.

OBJECTIVE: To provide a historical review of mechanisms proposed during the last century to explain the efficacy of immunotherapy. DATA SOURCES: We retrieved review articles and original research from MEDLINE, OVID, and PubMed that addressed our topic of interest. STUDY SELECTION: Articles were selected for their relevance to immunotherapy and mechanisms. RESULTS: Early studies focused on the production of blocking antibodies induced by immunotherapy, with mechanistic explanations aimed at understanding a relationship between blocking antibodies and clinical response. This was followed by a period when the effects of immunotherapy on levels and function of effector cells in the allergic response were studied. Aiding in characterization of this response was the discovery of IgE and its role in allergic sensitization, which brought a renewed focus on the antibody-mediated effects of immunotherapy. In an attempt to create a unifying hypothesis to explain humoral and cellular mechanisms of immunotherapy, recent approaches have been focused on the role of the T cell and, specifically, regulatory T cells. CONCLUSIONS: Although the clinical practice of immunotherapy has been refined since its introduction 100 years ago, our understanding of the mechanisms that underlie this success has awaited discoveries in basic immunology.

Acquired Chiari malformation Type I associated with a supratentorial arteriovenous malformation. Case report and review of the literature.

Chiari malformation Type I (CM-I), a condition defined by caudal descent of the cerebellar tonsils through the foramen magnum, is generally considered a congenital lesion. Several authors, however, have described an acquired form that appears identical to the congenital lesion on neuroimages. The most commonly reported cause of an acquired CM-I is cerebrospinal fluid diversion through a lumboperitoneal shunt. In this paper, the authors report the case of a patient in whom an acquired CM-I developed in association with a supratentorial arteriovenous malformation (AVM) of the brain. Development of the acquired CM was documented on serial magnetic resonance images. Moreover, the CM was seen to originate and worsen in concert with the clinicoradiological progression of the AVM. The underlying mechanism responsible for the acquired CM in this case is thought to be a high-flow venopathy of the transverse and sigmoid sinuses causing occlusion on the right and redirection of venous outflow into posterior fossa veins, with consequent venous congestion and swelling of the posterior fossa structures.