Table 1 Types of cell death and their immunological consequence

Apoptosis (type 1 cell death). This is accompanied by a rounding up of the cell, retraction of pseudopods, reduction of cellular volume, chromatin condensation, nuclear fragmentation, few or no ultrastructural modifications of cytoplasmic organelles, and plasma membrane blebbing, but the integrity of the cell is maintained until the final stages of the process.

Some forms of apoptosis are non-immunologic, while others are immunogenic. The pre-apoptotic surface exposure of CRT and HSP70/HSP90 may have a profound impact on the immune response. In addition, the release of HMGB1 during late apoptosis promotes antigen processing by DCs and hence contributes to cytotoxic T-cell activation.

Autophagic cell death (ACD; type 2 cell death). Occurs without chromatin condensation but is accompanied by massive autophagic vacuolization of the cytoplasm. The term ACD simply describes cell death with autophagy.

High. It may release DAMPs (HMGB1, ATP, and others) and elicit substantial inflammation.

Necrosis (type 3 cell death). Characterized by a gain in cell volume, swelling of organelles and rupture of plasma membrane, and subsequent loss of intracellular contents, including HMGB1, ATP, etc.

High. This causes release of DAMPs and elicits substantial inflammation and affects local environment.

Pyroptosis (or caspase 1-dependent cell death). It is a highly inflammatory form of cell death mediated by the inflammasome and caspase-1 activation, and triggered by various pathological stimuli, such as microbial infection, or stroke, heart attack and cancer.

High. It is a highly inflammatory form of cell death due to cytokine release and escape of cytoplasmic contents (DAMPs). However, some pathogens encode immunosuppressive proteins.

Secondary necrosis. This is the dissolution of the cell following apoptosis. Some remaining cellular contents are released.

High. It is quite immunogenic due to necrosis occurring in apoptotic cells at the late stage.