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Immune systemImmune system

The immune system is the body's way of protecting itself from foreign and potentially harmful microbes such as viruses and bacteria. When an unknown substance enters the body the immune system responds with a cascade of reactions which begin with identification of the microbe and hopefully ends with the neutralization of the pathogen. The identification and recognition of a pathogen however is a tricky process as the immune system must be able to differentiate between its own cells and foreign ones. The inability of the immune system to differentiate between foreign and native cells is potentially dangerous as it could lead to autoimmune diseases which can vary in severity from eczema to lupus. The responsibility of identifying pathogens is put on small glycoproteins called antibodies.

AntibodiesAntibodies

There are 5 main isotopes of antibodies in mammals which allows the immune system to differentiate between the varying types of invasions which in turn ensures that the situation is handled properly and efficiently. The 5 antibody isotopes are IgG, IgM, IgA, IgE, and IgD. IgG is the most common isotope which constitutes about 80% of the total antibodies circulating in the blood. IgM antibodies are found on the surface of B cells, and are usually the first antibodies at the site of an infection. IgA antibodies are found in mucus, tears, sweat, and breast milk where it prevents colonization by pathogens. IgE antibodies are the least abundant isotope however they play an important role in allergic reactions and inflammatory response. IgD antibodies are predominantly found on the surface of B-lymphocytes where they are thought to activate B cells.

Antibodies are made up of 2 pairs of light and heavy chains. The heavy chains of antibodies are specific to each isotope with: α, δ, ε, γ, and μ corresponding to: IgA, IgD, IgE, IgG, and IgM respectively. The light chain of the antibody is separated into two categories for mammals: lambda (λ) and kappa (κ). Antibodies are further differentiated into two regions: the constant region and the variable region. Like their names suggest, the constant region stays the same for its specific isotope however the variable region changes to accommodate many different antigens. The two ends of the variable region contain sites called Fabs which stands for fragment antigen binding region. This region is the area where the beta sheets of the antibody bind specifically to antigens. The constant region of the antibody is made up of 2 heavy chains specific to each isotope. This region is also called the Fc region or the fragment, crystallizable region. This end of the antibody mediates the next step of immune response for the given isotope which in turn allows for different types of responses.

Type I HypersensitivityType I Hypersensitivity

Hypersensitivity diseases, such as food allergy, affect 25% of the world's population. These diseases, which can lead to death, are due to reactions within a person's own immune system. in such cases, specific triggers called antigens, such as proteins in bee venom or grass allergens, bind to IgE antibodies which in turn leads to the degranulation of mast cells. Once mast cells degranulate, an inflammatory response is triggered. Inflammatory responses occur normally within the immune system, however in hypersensitivity diseases, antigens which are typically seen as harmless can lead to massive reactions and can cause anaphylactic shock where the person's blood pressure drops dramatically and their airways swell inhibiting respiration.

Hypersensitivity mechanismHypersensitivity mechanism

When the immune system is first exposed to an allergen plasma cells differentiate to produce many IgE antibodies specific to the present allergen. These IgE antibodies then bind to Fc epsilon R1 receptors on mast cells with their constant heavy chain region which is also called the Fc region. The binding between mast cells and IgE antibodies is highly favored as the Fc region has an immense affinity for Fc epsilon R1 receptors on the mast cells with a KD of 10^-9M.

When the immune system is exposed to the allergen a second time, the antigens bind to the IgE antibodies on mast cells which causes them to degranulate. When mast cells degranulate they release histamine, proteoglycans, and serine proteases which make up the inflammatory response. Since mast cells are prepared with so many IgE antibodies, the reaction of the inflammatory response is pretty severe for a normally harmless antigen.

Mechanism of the first and second response to allergen exposure.

Phl p 2 and huMab2Phl p 2 and huMab2