8 Chapter 1 Burn injury is a prevalent cause of disability and mortality throughout the world and its consequences affect patients both physically and mentally [1,2]. Depending on the severity of the injury and condition of the victim, healing of burns can be problematic, leading to secondary medical complications [3–5]. Health issues that often occur relatively early after burn injury are systemic inflammatory response syndrome (SIRS), hyper-metabolism, wound deepening, bacterial infection and hypovolemia due to a massive loss of fluids [6–9]. These extreme reactions in the body are likely to hinder and delay the wound healing process and have a major impact on morbidity and mortality of burn survivors [10,11]. Treatment of burn injuries is an intensive and time-consuming process. Complications of burn injury are generally present for the long-term or permanent and even years later new symptoms might occur, especially when patients are growing or when vital organs are irreversibly damaged [8,12]. Among long-term complications of burn injury are (hypertrophic) scar formation, loss of skin elasticity, contractions or diseases related to vital organs. Next to that, problems with mental well-being and reduced quality of life impact patients’ overall health [13,14]. Over the years, it has become more and more evident that the immune system plays an indispensable role in most (patho-) physiological responses to burn injury [15,16]. It remains, however, largely unclear how specific immune reactions lead to burn-related diseases. IMMUNE CELLS AND INFLAMMATORY FACTORS IN WOUND HEALING Next to being a protective, physical barrier to the outside, the skin is an important regulator of homeostasis [17]. Cells in the skin continuously carry out immune surveillance to ensure early and effective defense mechanisms against both internal (e.g. oncogenesis) and external threats (e.g. bacteria or viruses) [18]. The immune system consists of two arms: the innate and the adaptive immune system. The innate immune system reacts in a generic, rapid and nonspecific way, while the adaptive arm is more specialized, organized and takes more time to develop [19]. Granulocytes, mast cells, monocytes, macrophages, dendritic cells and natural killers cells (NK cells) are cells of the innate immune system and react through stimulation of pathogen-recognition receptors (PRRs). Upon interaction with pathogens, they activate cascades and recruit other immune cells via cytokine release and antigen presentation [20]. The adaptive immune system consists of T cells and B cells which are lymphocyte subtypes with a unique repertoire of immune receptors to discriminate auto-antigens from allo-antigens. These cells can react strongly to pathogen antigens by secreting antibodies, toxins and cytokines and are able to build immunological memory that will establish a stronger and more rapid response after subsequent re-encounter [19,21]. Beside fibroblasts and
RkJQdWJsaXNoZXIy MTk4NDMw