Physiological immune regulatory mechanisms

The immune system is regulated at several levels.

Antigen regulation
The antigen is the primary regulator. It determines the affinity maturation of B-lymphocytes. Antigenic competition means that peptides from different antigens compete for binding sites on MHC. It also depends on the density of MHC II complexes. class on the surface of APCs co-decides what the answer will be. To achieve a response, certain threshold antigen densities are required on APCs. TH2-ly requires higher concentrations than TH1-ly. The automatic termination of the immune response is due to the short lifespan of the effector lymphocytes. Activated T-lymphocytes carry the apoptotic receptor Fas and its ligand FasL (interaction interacts with apoptosis).

Antagonistic peptides
The immune response is efficiently regulated by peptide variants that are structurally similar to antigenic peptides. These peptides are partial agonists. Their reaction with TCR is weaker or significantly stronger. Instead of stimulation, there is attenuation (anergy), T-cells perform only some functions. The T-cell response then differs both quantitatively and qualitatively. This is due to the complexity of the TCR, which transmits various stimuli.

Antibody regulation
Secreted antibodies compete with BCR for antigen. It acts as a negative regulator of stimulation of other B-cells. Immunocomplexes containing antigen and IgG class antibodies block lymphocyte activation. Regulation using an idiotype network is not entirely clear.

Cytokine regulation and intercellular contact
Regulatory and signaling molecules between leukocytes mediate cytokines. This can be prevented by endocytosis of receptors or their rejection, resp. by binding inhibitors to receptors. For example, CTLA-4 (CD152) is an inhibitory receptor that prevents too easy activation. Nevertheless, it is structurally similar to T-cell costimulatory receptors (CD28). KIR works in NK cells similarly. Self-destructive interactions of the apoptotic Fas receptor with the FasL ligand lead to complete apoptosis of the cell.

T-cell mediated suppression
The cytokine-mediated negative interaction of TH1 and TH2 cells is an important factor in the regulation of inflammation. TH2-lymphocytes (produce IL-4, IL-10) suppress inflammation and transplant reactions. They have a suppressive effect. Soluble antigen-specific suppressor factors produce some CD8 + cells as a form of soluble TCR that competes with and blocks TCR on the surface of other T-cells of similar specificity. The main form of negative regulation of T-lymphocytes is clonal elimination, functional silencing (anergization) after contact with antigen on the surface of cells other than professional APCs, which do not provide the necessary costimulatory signals. This is crucial in the development of tolerance to autoantigens and allergens.

Neuroendocrine regulation
Physiologically, there is a very important relationship between the immune, nervous and endocrine systems. Some neurotransmitters act directly on leukocytes, which have the appropriate receptors for them, such as norepinephrine. Direct contact of mast cells and nerve endings leads to mast cell degranulation. Corticosteroids, growth hormones, thyroxine, endorphins, etc. also act on leukocytes. They are able to produce hormones: endorphins, ACTH, TSH, growth hormone, vitamin D3. Many cytokines act on the nervous system. IL-1, IL-6, LIF and TNFα increase temperature (fever). Emotions and stress (corticosteroids) also have an effect.

Factors influencing the outcome of the immune response
The result of the organism's response depends on:
 * immune system status: embryonic, neonatal, attenuated, or immunosuppressive, susceptible to a tolerogenic response,
 * antigen properties: molecular size, monomer or polymer, aggregation state,
 * antigen dose: very low or high doses tend to be tolerogenic,
 * route of administration: orally, intradermally.