REGULATION OF IMMUNE RESPONSES

Types of Immunoregulation

Adaptive immune responses are well-regulated processes. The regulation counts for much to achieve a specificity of antibodies and TCRs on effector T cells, and immune memory, restrict the effector activity by protective goals and avoid overactivation of the immune system. Naturally, such events as a "cytokine storm," autoimmune disorders, and allergic conditions are undesirable. At least, there are five levels of regulation:

   – Immune system-derived regulatory mechanisms
   – Hepatic control
   – Neuroendocrine regulation (control due to neurons and endocrine glands)
   – Epigenetic regulation
   – Genetic regulation


Immune system-derived mechanisms include the negative feedback model, idiotype/anti-idiotype network, and regulation by natural and induced immunoregulatory lymphocytes and adaptive helper T cells, which exploit cytokines and costimulatory/coinhibitory molecules (ergotypes).

Idiotype/anti-idiotype network is idiotype-anti-idiotype interactions between antigen-directed molecules (TCR or BCR), which are called idiotypes, and constituted due to anti-idiotypic responses. Anti-idiotypes structurally correspond to idiotypes forming the so-called "internal shape of antigen."

Natural immunoregulatory cells (nTreg and Breg) are constantly present in the immune system regardless of adaptive immune responses.

Adaptive (induced) immunoregulatory T cells (pTreg, Tr1, and Th3) matter much for the completion of immune responses, immunosuppression and immune tolerance.

Adaptive helper T cells are formed in the course of adaptive immune responses. Type 1 helper T (Th1) cells, type 2 helper T (Th2) cells, follicular helper T (Tfh) cells, T follicular regulatory (Tfr) cells, type 9 helper T (Th9) cells, type 17 helper T (Th17) cells, and type 22 helper T (Th22) cells are the different types of adaptive helper T cells, which specifically upregulate or downregulate adaptive immune responses and memory cell shaping.

Hepatic regulation includes metabolic processes important for the functioning of the immune system.

Neurotransmitters and neuropeptides taken together are called neuromediators, which transmit signals between neurons, muscle cells, endocrine gland cells, and cells of the immune system. In addition, cytokines provide the same cells and organs with back-signals making the bidirectional neuroimmune network.

Epigenetic regulation involves mechanisms by which the body reads our genes without their alteration: DNA methylation, posttranslational histone modifications linked to a chromatin remodeling and micro-RNA-mediated gene silencing.

V genes rearrangement is a type of the rearrangement of B-cell and T-cell V genes to achieve a required specificity of effector molecules at the end of adaptive responses because the initial antigen may not be entirely complementary to BCR or TCR of appropriate lymphocyte clones.

Somatic hypermutations represent molecular changes in the V genes of immunoglobulins in the course of B-cell-mediated responses that lead to the increase in an antibody's affinity and specificity.

Immune response power is a type of gene regulation based on that grooves of different Class I and Class II HLA molecules upload antigens with different efficacy on which the response power depends.

©V.V.Klimov