The G class is considered prototypical and is formed by two heavy chains (H) with variable weight between 50 and 70 kDa and two light chains (L) weighing around 20–25 kDa (Fig. 3.2). Electrostatic bonds and bisulphurate bridges keep the single chains together.

Both chains have a variable (V) region which interacts with the antigen and a constant one (C) which activates the immune system functions like the complement system, the phagocytosis, the cell’s mediated lysis, etc.

The interconnection region between V and C components undergoes three-dimensional arrangements in order to adapt its structure to the Ag surface. Each variable region is formed by other three hypervariable subregions where their shape defines the specificity of the molecule. Both variable and fixed regions on the chains L and H are arranged on of Fab region, which binds the Ag.

In general terms, the Ig molecules can be considered biochemical transducers able to (Table 3.1):

Then, it appears that the Ig can modulate the inflammatory response, and this capability can be useful in the different phases of sepsis, which are characterized by a different arrangement of the immune response. Actually, sepsis and its related conditions as severe sepsis and septic shock can be considered as a complex and articulated response to an infection, which is characterized by (at least) two different phases. In the first one, whose features are the classical signs of fever, leucocytosis, hemodynamic instability, metabolic acidosis, etc., there is a predominant secretion of proinflammatory mediators (TNF, various interleukins, etc.) that can cause the derangement of organs different from the one in which the infective process and immunity response have started. This reaction is mainly determined by the action of the indicated proinflammatory mediators, whose qualitative and quantitative properties are genetically determined and thus vary from an individual to another; the subsiding of this initial response is determined either by reduction of the production of proinflammatory substances and by the contemporaneal release of mediators with anti-inflammatory capabilities [3].

If the patient survive the initial insult, a second phase ensues, which is characterized by the reduction and progressive disappearance of the above described proinflammatory response due to the overwhelming action of anti-inflammatory mediators ultimately leading to a state of immunoparalysis; this condition is characterized by a profound alteration of both natural and adaptive immunity mechanism, and the consequent immunitary state can be compared to that present in advanced neoplastic conditions [4, 5]. This state, which is difficult to diagnose due to the lack of suitable biological markers, is particularly frequent in patients affected by multiple chronic conditions, who can survive the infection and/or its related conditions causing the intensive care unit admission (surgery, lung infection, etc.) but who cannot be weaned from the mechanical ventilation and are prone to multiple infections, thus becoming critically ill chronic patients.

The above described clinical aspects can justify the use of IvIg both in the early phase of sepsis, in which they can modulate an excessive systemic inflammatory response, and in the more advanced phase, during which their antibacterial action can restore the adaptive immune response. These actions are only partly shared by other immunomodulatory substances recommended by the SSC guidelines, like steroids with glucocorticoid activity: indeed, if their use has a rationale in the early inflammatory phase, in the later one, their use can contribute at the occurrence of immunoparalysis. Anyhow, the use of IvIg does not replace the other therapies indicated by the SSC, including the early administration of appropriate antibiotics and the surgical drainage of infective sources. Even if it is probable that in the next future some other immunomodulatory and immunostimolatory molecules can be introduced in clinical practice, actually their application has to be considered only experimental.