BiondVax - Universal Influenza (Flu) Vaccine

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A Brief Summary: MHC and Lymphocyte Functions
Both B and T lymphocytes are able to recognize antigens. B cells are responsible for humoral (serum) immunity by producing antibodies (Ab). These Ab also called immunoglobulins (Ig) are divided into five chief classes: IgG, IgM, IgA, IgD, and IgE each with special properties. T lymphocytes, making up about 70% of all lymphocytes, are responsible for cellular immunity, meaning they attack and kill infected cells. T cells also help to regulate the production of Ab by the B cells. There are four types of T lymphocytes: helper, cytotoxic, delayed hypersensitivity (associated with allergies) and suppressor.

Differentiation of B and T cells into a vast variety of clones, each responding to a specific antigen, involves two phases: the primary or antigen-independent phase and the secondary or antigen-dependent phase. During the primary phase, stem cells proceed through stages of differentiation to generate vast amounts of B or T cell clones, each with unique antigen receptors. The antigen-binding proteins of B cells (Ig) and T cells (T cell receptor or TCR) consist of similar polypeptide chains with distinct antigenic specificities. The immune system generates an incredibly diverse range of gene sequences, or antigen-binding specificities for antibodies.

In the secondary phase, cells can recognize an infinite number of antigens (but each individual cell recognizes only one antigen). When a particular antigen binds to the antigen receptors on the appropriate lymphocyte, that cell is triggered to proliferate into a large clone of cells, all responsive to the specific antigen. In this clonal selection process, some of the lymphocytes become long-lived memory cells and others differentiate into plasma cells secreting antibodies.

Another type of immune cell was discovered in 1975: the natural killer (NK) cell, which looks like a lymphocyte but contains granules. NK cells recognize some feature of the target cells, either directly or via receptors that attach to the tails of antibodies on the target cell's surface. As a result, NK cells act by releasing the contents of their granules to kill the target cells or by influencing other immune cells.

Differences in antigens between individual animals of the same species are called alloantigens; these are the major factors in the rejection of allogeneic tissue grafts, called histocompatibility antigens. A group of closely linked genes producing gene products prominently displayed on cell surfaces comprises the Major Histocompatibility Complex (MHC). MHC antigens play a major role in immunity and in self-recognition in the differentiation of cells and tissues and they are therefore a critical factor for protection against invading foreign antigens such as pathogens and grafts. In humans, the MHC is called HLA, for human leukocyte group A antigens.

Three classes of gene products are encoded in the MHC. Class I molecules are expressed on nearly all cell surfaces. Class II molecules are expressed only on B-lymphocytes, some monocytes, and activated T lymphocytes. Class III molecules are components of complement proteins, which act in concert with Ab to direct the immune response. Self versus non-self discrimination in the immune response is controlled by MHC class I and II molecules.

Antigen processing:

The first step in the recognition of a foreign antigen is their processing by Antigen Presenting Cells (APC). APCs are phagocytic cells that ingest particulate material, infectious agents and cellular debris.
This non-specific ingestion phagocytosis results in the APC’s activation and the release of soluble mediators called cytokines that assist the immune response. This phase of the immune response is termed innate immunity, and differs from the exogenous and endogenous adaptive immune paths described below.
Proteins from these sources are then cut into small pieces, called peptides, and the pieces are combined with MHC II proteins.
The MHC-peptide complex is then pushed out to the cell surface.
If the peptide comes from an exogenous antigen like bacteria, then the MHC-peptide is able to interact with certain classes of lymphocytes such as helper T-cells that induce proliferation of stimulated B-cells and the production of antibodies directed against the presented peptides and the cells that express them. This system is called the exogenous pathway.
The endogenous pathway is active against most viral infections and cancer cells. Certain viral or cancerous proteins are broken up into peptides in the cytoplasm and directed into the endoplasmic reticulum, where it is incorporated into an MHC-I proteins and traffics to the cell surface.
This signal calls the cellular immune system, especially cytotoxic T-lymphocytes, to come and kill the infected or cancerous cell resulting in their destruction.

During influenza infection, the body recognizes the infected cells as carrying foreign Ag and a cellular immune response destroys them, preventing further spread of the virus. BiondVax's technology enhances the body’s ability to recognize virus-associated antigens by exposing these epitopes during vaccination so that when infection occurs, the body is ready to confront it by inducing the memory responses. The body fights the viral infection more effectively by combining elements of all immune pathways including the stimulation of innate and adaptive immunity.

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