Immune System Response
Figure 1: This diagram from Alberts et al. shows the development of T and B-cell from the thymus and bone marrow and the response created by both.
Figure 2: This diagram from Alberts et al. shows the central (yellow) and peripheral (blue) lymph organs that makeup the immune system.
Figure 3: This diagram (from Hendry et al) shows the various cells involved in the immune system.
Types of Immune Response/Antibodies:
Now that we have an idea of what cells and areas of the body are involved in the immune system, lets discuss the response created by the immune system. There are two types of response, the innate (non-specific) and adaptive (specific) responses. We will focus on the adaptive or specific to make a better connection to the immune system's role in MG. The adaptive immune response involves antibodies, T-cells and B-cells.[8] The antibodies are broken into 5 classes, the IgA, IgD, IgE, IgG and IgM.[7] The antibodies have their own unique heavy chains and tails with light chains that affect what it will bind to and its specificity for certain antigens. Helper T cells (HTCs) can identify antigens and induce B-cells to create specific antibodies for that antigen. This immune response leads to the detruction of the antigen. As you can see in Figure 4, different effector helper T cells can activate macrophages and cytotoxic (cell killing) T cells (CTCs).[6] To differentiate between the HTCs and CTCs, you can look to the co-receptors. HTCs have CD4 whereas CTCs have CD8. There is another class of T cell that regulate the other T cells, ensuring proper function and the HTCs and CTCs are not targeting normal self cells. These regulatory T-cells have CD4 receptors like the HTCs. Figure 5 shows the binding to the different T cells using the two receptors.[6] The receptors bind in this case to proteins called major histocompatibility complex (MHC) proteins. MHC proteins are split into 2 classes (I and II) based on presentation of the foreign peptide or antigen that the respective T cell will bind to. The balance of these three T cell types are important to successful immune regulation and response.[8]
With the knowledge of what T-cells are out there and what they activate, let's take a closer look at how CTCs and HTCs can recognize foreign substances using figures 6 and 7. Figure 6 represents an immune response to a virus. The idea is for the cell take in and process the virus to extract the viral protein. Proteasomes can then break that protein down into smaller peptide units that bind with the MHC complex to the cell surface to be presented to the CTC. Figure 7 shows an antigen response through a similar process of breaking down the protein antigen into peptides that bind to the MHC complex and are presented in this case to HTCs because the activated MHC is of class II.[6]
So far we have discussed where the immune systems, the cells that are involved and how the adaptive immune system becomes aware of antigens and viruses. That is all important, but what happens next? We will continue with a focus on normal system function related to MG. With that in mind, we will explain how antibodies play a role in antigen response once the HTCs activate the B-cells.
As explained above there are five classes of antibodies and as the name suggests they are "anti"-"body". In most scenarios the antibodies tag or inhibit the antigen that they are associated with. The B-cells continue to differentiate and form memory (remembers for future reference) and plasma cells that secrete 2,000 or so antibodies per second.[6] These antibodies then travel through the lymph or blood to reach the infected site. Antibodies can attach to multiple antigens and gather them for destruction. They can also bind to proteins and block pathways or speed up reactions. All of these activities allow easy identification and destruction of the pathogen by the immune system through many processes, one of which is complement. Antibodies also have different affinities. See Figure 8 below for the various antibodies and the affinity mechanism and cell expression. [8]
There are other portions of the immune system, but the normal physiology of the above topics relate directly to MG and are the focus for this site. If you would like more information on the immune system, feel free to check out our references or the articles listed on the side of this page.
This video gives a great review of T and B cells. https://www.youtube.com/watch?v=xaz5ftvZCyI
This video gives a review of how the immune system differentiates between self and non-self.
Figure 7: Adapted from Alberts et al. This figure shows the cellular response cycle to an antigen and how it processes for presentation to the helper T cell, which stimulates B cells to form antibodies against the antigen.
Figure 6: Adapted from Alberts et al. This figure shows the cellular response cycle to a viral infection and how it processes the virus for presentation to the cytotoxic T cell.
Figure 4: From Alberts et al., this depicts the different effector helper T cells formed through differentiation.
Figure 5: From Alberts et al. this shows CD4, CD8 and T cell type differences.
Figure 8: This figure is adapted from Williams et al. It shows the various antibodies, their affinities, cell expression and mechanisms.
Cells and Organs:
The human immune system is essential for protection against infection and disease. The cells for the immune system are primarily created in the bone marrow and thymus. The bone marrow cells are known as B-cell and the thymus cells are T-cells. Figure 1 depicts the creation of these cells. These cells travel to various tissues (peripheral lymphoid organs shown in Figure 2) in the body and mature. These organs include the gut, lymph nodes, spleen and others.[6] The T-cells provide an immune response and B-cells provide antibody response. Other cells included in the immune system are shown in Figure 3.[7]
