Immunological Cytotoxic Factors

Abstract

The host immune system has evolved a variety of strategies to control pathogens and tumour development. The beneficial outcome is the death of the offending cell (transformed or pathogen‐infected) and consequently the demise of the invading pathogen. However, if uncontrolled, these mechanisms will also contribute to host immunopathology. Many of the mechanisms used by the immune system to eliminate intracellular and extracellular pathogens and transformed cells include not only death mediators associated with cytotoxic lymphocytes, but also soluble proteins such as the complement system and the defensins, which are designed to eliminate extracellular pathogens. Recent evidences suggest that the major cytotoxic mediators of host cell‐mediated immunity may possess noncytotoxic functions such as induction of proinflammatory cytokines or inactivation of proteins involved in the pathogen life cycle. Key Concepts: The host immune system can kill transformed and infected cells by apoptosis. The pleiotropism of host immune system‐induced cell death is a consequence of evolutionary pressure of tumour/pathogens. Host cell‐mediated immunity use cytotoxic granule exocytosis, death receptors and the release of soluble cytokines to combat cancer and infection. Death receptors are involved in the regulation of cell homoeostasis and prevention of autoimmune disorders. Granule exocytosis possesses noncytotoxic functions like regulation or proinflammatory processes, cardiovascular diseases or inactivation of viruses. Cytotoxic function of granule exocytosis critically depends on perforin. Interferons regulate cell cycle and apoptosis susceptibiltiy of pathogen‐infected or cancer cells. Complement system induces lysis of pathogen or tumour cells and helps to clear apoptotic cells. Antimicrobial peptides eliminate extracellular and intracellular pathogens and induce apoptosis in some tumour cells. Selectivity of antimicrobial peptides for pathogens is based on the lipid composition of membranes.