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Review
. 2014;39(1):109-15.
doi: 10.5114/ceji.2014.42135. Epub 2014 Apr 17.

Perforin: an important player in immune response

Iwona Osińska  1 , Katarzyna Popko  2 , Urszula Demkow  2
Affiliations
Review

Perforin: an important player in immune response

Iwona Osińska et al. Cent Eur J Immunol. 2014.

Abstract

Perforin is a glycoprotein responsible for pore formation in cell membranes of target cells. Perforin is able to polymerize and form a channel in target cell membrane. Many research groups focus on the role of perforin in various diseases, immune response to bacterial and viral infections, immune surveillance and immunopathology. In addition, perforin is involved in the pathogenesis of autoimmune diseases and allogeneic transplant rejection. Natural killer (NK) cells and CD8-positive T-cells are the main source of perforin. However, CD4-positive T-cells are also able to express a low amount of perforin, when classic cytotoxicity is ineffective or disturbed. Polymerized perforin molecules form channels enabling free, non-selective, passive transport of ions, water, small-molecule substances and enzymes. In consequence, the channels disrupt protective barrier of cell membrane and destroy integrity of the target cell. This review will focus on mechanisms of action and structure of perforin. Also, in this review we discuss the problem of abnormal perforin production in diseases such as: hemophagocytic lymphohistiocytosis (HLH), leukemias and lymphomas, infectious diseases and autoimmune diseases. Better understanding of the role of these molecules in health and disease will open a new field of research with possible therapeutic implications.

Keywords: HLH; Hashimoto's disease; SLE; autoimmune diseases; cytolytic granules; granzyme; type 1 diabetes.

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Figures

Fig. 1
Fig. 1
Formation of channel in a target cell membrane (according to [8, 9] – modified)
Fig. 2
Fig. 2
Mechanism of action of cytotoxic effector cell (cytolytic granules) (according to [8, 13] – modified)
Fig. 3
Fig. 3
Immune response (according to [18] – modified): A) Normal immune response to viral infection, B) Pathologic immune response in HLH
Fig. 4
Fig. 4
The mechanisms of pancreatic β-cell destruction (according to [28] – modified): A) perforin and granzyme-dependent pathway; B) Fas/FasL interaction-dependent pathway (in case of perforin deficiency, CTLs use this method of apoptosis induction); C) cell survival (no perforin or Fas deficiency on β cells) – in vitro conditions
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