Response

The principal role of the immune system is to confer protection on the organism against foreign invading pathogens, which can gain access to the body by different routes. The targeted (specific) immune response is generated by the combined interaction of the cellular and humoral responses, both coordinated by the production of active substances—the cytokines. Cellular immunity refers to the immune mechanisms mediated by T lymphocytes, regardless of immunoglobulin molecules, whereas humoral immunity denotes secretion of antibodies by B lymphocytes. The humoral and cellular arms of the immune system should be viewed, not as two independent mechanisms of self defense, but rather as acting in an orchestrated and synergistic manner to accomplish protection [2],

2.1. Humoral Immune Response

B-cells stem from bone marrow precursors and later localize in the circulation as well as in follicles of peripheral lymphoid tissues. They are responsible for the production of antibodies, once they have differentiated into plasma cells [3], B-lymphocytes are also involved in antigen presentation to T-cells, secretion of immunoregulating cytokines and establishment of 'memory' towards antigenic determinants [4].

Direct activation of B-cells by distinct antigens is facilitated by binding to antigen receptors located within the membrane of the B-lymphocytes and under the influence of cytokines. This complex interac tion activates B-cells after which they proliferate and produce the appropriate antibody.

The final function of the B-cell (i.e., memory cell, plasma cell or cytokine secreting cell) is determined by the profile of the cytokines present, and the mechanisms of activation (through B-cell receptors for the Fc region of IgG, or for complement components) [4], The end product following antigenic stimulation is a population of B-cells producing and secreting one specific antibody against the introduced antigen.

Immunoglobulins are glycoproteins forming 9 classes of isotypes: IgG, divided to 4 subclasses (IgG 1-4), IgM, IgA comprising 2 subclasses (IgAl-2), IgD and IgE (Tables 1) [5]. The basic structure of immunoglobulins (similar in all five isotypes) consists of two identical heavy chains (MW 50,000-75,000)combined with two identical light chains (MW 25,000). Antigen specificity is determined by variable areas containing the antigen binding site, whereas the constant region (as can be inferred from its name), is common to all immunoglobulins of a certain class. The hypervariable region is located in the variable region, representing the closest relationship to the epitope (its corresponding site on the antigen). The idiotypes, located in the variable region are the antigenic determinants (defining antigen binding) of the immunoglobulins themselves.

The diversity of antibody response is formulated due to encoding of the heavy and light chains by multiple genetic elements. As such, light chains are generated following pairing of VK and JK genes, whereas heavy chains exhibit greater diversity since they are created following the assembly of three germline genes (VH, DH, JH).

2.2. Cellular Immune Response

A T-cell cycle is initiated in hematopoietic stem cells, differentiating in the thymus and subsequently wandering to the lymphoid tissue in the periphery [2, 6]. T-cells are heterogeneous by virtue of their different functions (lysis of foreign cells, modulation of the interaction between B and T cells, regulation of monocyte functions). The peripheral T-cells are discerned by their expression of antigenic markers. As such, T-cells carrying CD4 molecules (T-helpers) interact with antigen associated with MHC class II on the surface of the antigen presenting cell, and T-cells expressing

CD8 molecules (cytotoxic T-cells) engage in suppression of the immune response. The T-cell receptor is a molecule present on the surface of the T-cell, responsible for recognition of the complex antigen-MHC II molecule [7], The variety of T-cell receptors is immense, thus accounting for its ability to recognize diverse antigens.

The immune response is mounted following presentation of the antigen to the lymphocytes by antigen presenting cells, examples of which are: macrophages, Langerhans cells and dendritic cells. The process of presentation requires the participation of MHC class II molecules on the surface of the antigen presenting cell. The antigen, prior to its presentation to the T-cell is processed and degraded and later associated with the MHC class II molecule to form a complex reacting with the T-cell receptor. It should be outlined that the APCs are capable of secreting cytokines that act to facilitate the interaction described above.

2.3. Coordination of the Immune Response

Several intrinsic factors belonging to the immune system itself are responsible for the modulation and regulation of the immune response.

Cytokines are small proteins (MW 8000-30,000) produced and secreted by a diverse population of cells (i.e., macrophages, monocytes, T and B cells, as well as nonlymphoid cells) [8]. Cytokines elicit different actions (Table 2) including proinflammatory (TNF, IL-1, IL-2) and anti-inflammatory (TGF, IL-4, IL-6, IL-10) functions and stimulation of lymphocyte proliferation (IL-2, IL-7).

The regulation of cytokines is under the supervision of genetic factors (capable of generating corresponding inhibitors) and by the liberation of soluble forms of cytokine receptors.

The complement system consists of circulating glycoprotein constituents that can be triggered and activated in two major patterns to initiate a cascadic chain of events, the consequence of which leads to diverse influences on the progression and perpetuation of the immune response [9]. This cascade can, therefore, be activated by the classical pathway (immune complexes comprising IgM and IgG) or by the alternative pathway—independent of antibodies (by bacterial LPS).

The idiotypic system—will later be reviewed in detail.

Table 1. Characteristics of human immunoglobulin subclasses

Characteristic

IgG

IgM

IgA

IgD

IgE

Molecular form

Monomer

Pentamer, hexamer

Monemer, dimer

Monomer

Monomer

Molecular weight

160,000

900,000

170,000

180,000

190,000

Subclasses

1,2,3,4

None

1,2

None

None

Serum half life(days)

How To Bolster Your Immune System

How To Bolster Your Immune System

All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.

Get My Free Audio Book


Post a comment