The I/I response is the reaction of the vascularized connective tissue, characterized by the accumulation of fluid and leukocytes in extravacular tissues. It is considered to be a protective mechanism aiming to rid the organism of both the initial cause of cell injury (such as micro-organisms, toxins, antigens) and the consequences of such injury (e.g. necrotic cells and tissues). In this process cellural and extra-cellular elements participate in a complex co-operative network. The cellular components of the I/I response include leukocytes such as monocytes-macrophages, polymorphonuclear neutrophils, eosinophils and basophils, platelets, dentritic cells, mast cells, epithelial and endothelial cells and fibroblasts (innate immune system) as well as lymphocytes T, B, NK (adaptive immune system). These cells co-operate using molecular signals, including cytokines [Interleukines (ILs), colony-stimulating factors (CSFs), interferons (IFNs), tumor necrosis factors (TNFs), transforming growth factor (TGF), chemokines], vasoactive amines (histamine, serotonine), plasma proteases (kinine system, complement system), arachidonic acid metabolites (prostaglandins, leukotrienes, lipoxins), platelet-activating factor (PAF), nitric oxide (NO) and neuropeptides. The first step in the initiation of the I/I response is the activation of the innate immune system. This nonspecific response serves to locate the injurious agent, restrict the tissue damage and eliminate the harmful agent, initiate the adaptive immune system and determine the path that will be followed (cellular / humoral response).

In this procedure mast cells play an initiative role, early affecting the microvascular response. Mast cells consist of two populations, distinguished by their enzyme content. The T (tissue) mast cells contain trypsine alone and are also termed mucosal mast cells due to their location near mucosal surfaces. The TC (connective tissue) mast cells contain both trypsin and chymotrypsin. Rapidly responding to any foreign stimulus substance mast cells are activated leading to their degranulation, releasing several pro-inflammatory mediators. The activation and degranulation of mast cells is regulated by several mediators such as IL-3 and stem cell factor (SCF). TNF-α seems to be an important mast cell survival factor whereas IFN-γ is a potential inducer of mast cell apoptosis (41, 42). Finally, CRH can induce secretion of vascular endothelial growth factor (VEGF) selectively (43).

Subseqently, the adaptive immune system is activated by the innate immune responses. As lymphocytes arrive to the inflammatory area, antigen-presenting cells (APCs) such as plasmacytoid dentritic cells, interstitial and Langerhans dentritic cells and astrocytes present infectious agent antigens of macrophages to T cells. This is the ignition signal for the activation of the adaptive immunity, consisting of cellular (T4, T8, NK lymphocytes) and humoral (B lymphocytes, plasmacells, antibodies) immunity. CD4 helper T cells are the regulators of this antigen-specific response. These cells can be subdivided on the basis of cytokines produced in Th1 T cells which promote primarily the cellular/inflammatory immunity and Th2 cells which have a primary role in the regulation of humoral immunity. The balance between Th1 and Th2 is important for the homeostasis within the immune system. Glucocorticoids (GCs) and catecholamines, the hormones released during stress, have a significant effect on this balance. Glucocorticoids suppress the production of IL-12, the main inducer of Th-1 responses (44, 45) and thus, they affect the Th-1/Th-2 balance leading to a Th-2 shift. In contrast to catecholamines, glucocorticoids also have a direct effect on Th-2 cells by up-regulating their IL-4, IL-10 and IL-13 production (45, 46). On the other hand, the two major catecholamines, norepinephrine (NE) and epinephrine, potently inhibit the production by APCs of IL-12 thus suppressing the development of Th1 type cells (44, 47, 48).