The Immune System

The immune system was presumably evolved by animals during evolution as a means of self-preservation in a world teeming with microorganisms. It is not selective and immune responses ensue against foreign substances regardless of whether they are bacterial products or not.

Therefore the immune system has become exquisitely specialized and highly complex, to protect the host from potentially noxious environmental agents (antigens). The introduction of foreign substances into the host may have an adverse effect on a variety of cells; hence this system synthesizes highly specialized molecules (antibodies), also generating selected cells, called cytokines, adhesion molecules, chemokines, and the like.

Related cells and cell products are consequently a defense system designed to interact with foreign agents to protect the host from any external injury.

  • Immunity is the complex of cellular and/or humoral events following the entry of foreign substances (nonself) into the host. These events are overall free of adverse effects for the majority of subjects, therefore defined as normal.
  • Immunology is the study of the ways used by the host to maintain homeostasis in the internal environment when confronted with non-self.
  • Allergy currently implies all forms of hypersensitivity with detrimental consequences for the host and type I, IgE-mediated or cell-mediated reactions.
  • Atopy is a term underlining the personal or familial hereditary aspects of allergic reactions and is associated usually in childhood or adolescence with increased production of IgE antibodies and/or altered specific reactivity in response to ongoing exposures to allergens, usually proteins.

A thoroughly functioning immune system serves three main functions:

  1. defense against invasion of microorganisms and foreign substances, ingested, inhaled or achieved by mucosal contact, or by parenteral injection;
  2. homeostasis fulfilling universal requirements of multicellular organisms to preserve uniformity of a given cell type, as well removing worn-out “self” components; and
  3. surveillance devoted to perception and destruction of mutant cells.

Therefore, inability to relate to unum is intrinsic to atopic diseases that depend on hyperproduction of IgE antibodies being IgE-mediated. This is a genetic characteristic, although the mode of transmission is still a matter of debate, and the fact of being atopic does not result automatically in the development of clinical manifestations.

Atopy is also polymorphous, manifesting in various forms, starting out as AD or food allergy (FA), to further develop into allergic rhinitis (AR) and/or asthma.

According to the classic theory of clonal selection, the crucial function of the immune system from the first days of life is to distinguish self from nonself, for example, between what belongs to or is closely correlated to the organism (tolerance to self antigens) and what is foreign,with the goal of eliminating the latter, independent of its potential pathogenicity.

This is the quintessential dichotomy of immunology: the self versus non-self discrimination. We shall see that theories regarding self/non-self are still valid (as long as they are not interpreted literally), with the exception of some recent studies that have clarified how the so-called neonatal window period represents an ontogenetic window only as far as tolerance induction is concerned.

Immunity is acquired at the first contact with non-self (antigen recognition), it is specific for a given foreign substance and acquired, since it is able to respond to molecules not encountered before. Following an initial antigen stimulus, finally familiar with self and non-self, a series of reactions results, sometimes as if it were reacting to invaders.

In virtue of such events, the integrity of the organism, which becomes protected from successive entries of potentially pathogenic substances, is maintained. This is put into practice by the immune memory enabling the immune system to memorize previous exposures to a particular antigen, in a way analogous to natural memory that recalls past experiences.

Amongst all defense mechanisms put into action by the host against any external aggressor, we find a network of organs, tissues, cells and molecules responsible for immunity: the integrated immune system. The interconnected and coordinated responses following the entry of foreign substances are globally known as immune reactions.

Relatively small modifications in the delicate and complex molecular and cellular structures of the immune system may cause a functional disequilibrium that is responsible for a cascade of organic perturbations that may become evident alterations, such as atopic diseases varying in nature and severity and primary immune deficiency (PID).

Ideally, the immune reactions determine schematically ordered responses articulated on six levels: processing, presentation and recognition of non-self, cellular activation, elaboration of biologically active chemical substances,mediators, and cellular cooperation.

The final outcome of the encounter between host and a foreign invader is now recognized as dependent upon an integrated network of multidirectional communication pathways and signaling, where the mechanisms of memory, effector responses and consequent regulation of secretory proteins and soluble molecules such as the interleukins (ILs) are clarified.

Antigen contact starts to form those elements necessary for its recognition, including the cells emitting signals, ILs transducing such signals and target cells receiving them by binding to appropriate receptors; following transduction and amplification of signaling, a detectable physiological response occurs.

Thus, immune responses usually culminate in the elimination of provoking agents. The specificity of antigen recognition, as defined in molecular terms, is entrusted to three structures: the variable (V) region of Igs (immunoglobulins), MHC (major histocompatibility complex) V regions and TcR (T-cell receptor) chains.

A fourth component of molecular recognition, the cluster of differentiation (CD) markers, differentiates subsets of T from B lymphocytes (from lympha, water) and other cell populations.