Introduction Immunotherapy

The mammalian adoptive immune system is divided into two key branches; humoral and cellular, according to the type of pathogen the immune system recognize and can respond to. In humoral immunity, antibodies, which are soluble molecules produced by B-lymphocytes, patrol the blood stream and eliminate extracellular pathogens. In cellular immunity, T lymphocytes, in particular CD4+ T cells Helper T cells (CD4+) are white blood cells that act as "initiators or primers" in the immune response. When they get activated, they proliferate and secrete molecules called cytokines that regulate or 'help' other lymphocyte cells function and CD8+ T cells Cytotoxic T cells (CD8+) (CTL) are white blood cells that destroy infected cells. These cells function as 'killer' or cytotoxic cells because they are able to destroy target cells which express specific epitopes that they recognize. are designed to eliminate foreign intracellular pathogens and transform (cancerous) cells. T cells recognize their target epitopeEpitope is a fragment of an antigen that is recognised by the immune system and targeted by antibodies, cytotoxic T cells or both on the cell surface in association with two types of self MHCOriginally recognized as antigens responsible for graft rejection after transplantation. These are molecules that bind processed antigens and display them on the surface of cells for controlling their recognition by the immune system. MHC class I molecules are displayed on most cells in the body while MHC class II, only by subset of immune cells. molecules. The first type, MHC class II, is expressed by subsets of the immune system, recognized by CD4+ T cells and is responsible for immune response priming. The second type, MHC class I, is expressed by all cells in the body and is recognized by  CD8+ T cells, is responsible for eliminating any cell expressing MHC class I/foreign epitope complexes (Figure 1).

Figure 1: Activation of T cells by Dendritic Cells

An efficient T cell vaccine needs to incorporate sufficient number of antigenic A substance that is recognized by the immune system and triggers an immune reaction (usually protein). A given antigen will commonly contain many different epitopes. sequences with immunogenic properties i.e. having binding properties to MHC Class I and MHC II molecules. This is not trivial, since in a given antigen, only small fragments can actually bind MHC molecules. Furthermore, each individual has a different set of 3-6 MHC class I and MHC II molecules, out of a potential pool of several hundred molecules. Lastly, each MHC class I and class II molecule has different binding restrictions. In addition, most vaccines require an Adjuvant, which is an external non-specific sequence for elevating a specific immunity to the vaccines (Figure 2).

Figure 2: The different requirements form B and T cell vaccines

Currently, there are two main approaches to overcome these challenges;

> Mixed non-purified targets: these are vaccines that comprise a non-purified mixture of selected antigen/s from a given pathogen's genome or the entire pathogen. In this approach, the vaccines are composed of a mixture, at various levels of purity, of immunogenic and non-immunogenic MHC class I and or II-restricted epitopes of a given antigen or the entire pathogen with the rational that larger sequences contain more epitopes which statistically can bind more combinations of MHC molecules. However, the mixture of specific and mon-specific epitopes reduces the specificity of the response, which may reduce efficacy and lead to side-effects.

> Selected MHC I or II epitope/s: these are vaccines which comprise selected MHC class I or class II restricted epitopes derived from a certain pathogenic-derived antigen. These vaccines consist of high purity sequence/s resembling only the immunogenic epitopes of a given antigen/s. This approach leads to a specific but weak immune response, which is applicable only to small part of the population with a given MHC repertoire.

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