Cell Death Mechanisms and the Immune System

Abstract

The immune system provides good models for cell death, a phenomenon now recognized to be of fundamental importance in many fields of biology. Cell death is strikingly polymorphic: it can proceed via necrosis (as in complement-mediated cell death) or apoptosis, but the latter displays different patterns (in the receptor-mediated death of some thymocytes, in cell death mediated by TNF alpha or by cytotoxic T cells), perhaps reflecting different pathways of control of a common core mechanism. Even though there are differences in the morphological and metabolic changes associated with the different patterns of apoptosis, some recurrent sequences of events are observed in almost all dying cells. The metabolic state of a cell often seems to play a major role in determining if and how this cell will die in given external circumstances. The nature of molecules causally involved in the dying cell can now be approached in some systems.

Met‐enkephalin induces cytolytic processes of apoptotic type in K562 human erythroid leukemia cells

“…2 le, Lding to the formation of 200 bp DNA fragments. As desc~'ibed by Golstein et al [7], the presence of internucleosomal D XlA fragmentation has been used as a major marker for cell death of this type [7,8] and we may thus conclude that Meten kephalin induces the apoptotic mechanism of cell death in K ~62 tumor cells. Several aspects of the results obtained require further cornmint and explanation.…”

Patterns of cell death: the significance of apoptosis for dermatology

“…Apoptosis is a "programtned" fortn of death in a dual sense: it occurs at genetically pre-deterrnined points in titne during the life-span of an individual, and it follows a pre-programmed pattern of molecular events (4,5).…”

“…There is considerable debate on how tnany distinct forms of apoptosis exist and how they differ biochetnically and in their regulation (5)(6)(7)(8). Todate, at least two broad categories should be distinguished: one receptor-mediated, genetically controlled fortn of apoptosis that requires active protein synthesis and classically occurs in thymocytes, and another, less-understood fortn that tnay repiesent a tnore general cellular iesponse pattern to injury, as seen in cell-mediated cytotoxicity (5)(6)(7)(8).…”

“…Todate, at least two broad categories should be distinguished: one receptor-mediated, genetically controlled fortn of apoptosis that requires active protein synthesis and classically occurs in thymocytes, and another, less-understood fortn that tnay repiesent a tnore general cellular iesponse pattern to injury, as seen in cell-mediated cytotoxicity (5)(6)(7)(8). Given that there is no generally aeccpted tnodel for all subtypes of progratntned cell death and for all the various cell populations undergoing apoptosis, we lean in this review on data from the thymocyte model (5) since it is the best-studied one.…”

Fas involvement in Ca(2+)-independent T cell-mediated cytotoxicity.

“…p rogrammed ceU death, often called apoptosis (1), massively occurs within the immune system as a component of its normal development (2)(3)(4). Part of this process seems to involve the Fas cell surface molecule (5)(6)(7)(8), which can transduce a ceU death signal (5,6) and is not or is abnormally expressed (9) in the Ipr mutant mouse (for review, see reference 10) exhibiting a lymphoproliferative disorder.…”