As I was studying for the USMLE, I learned something interesting and this is a concept tested in the USMLE Step 1. You will also encounter a situation like this when practicing medicine since Americans love their unhealthy burgers and fries. As you know cholesterol cannot be broken down by the body like other molecules. Fats, carbohydrates, amino acids can all be burned by our bodies but cholesterol cannot and this is why cholesterol is a big health concern. Too much cholesterol in our bodies can lead to atherosclerosis which can lead to heart attack. So as I was studying, this system in getting rid of cholesterol is so interesting that I had to type it up from the top of my head and I know I will remember this for my long term memory because it’s so interesting.
Glucose from sugars such as carbohydrates converts to Acetyl CoA which then converts to Cholesterol and finally converts to Bile Acid. Bile acid is released from the liver to the intestines and it’s used to emulsify all the fat we consume for digestion in the intestines. However, bile acid is recycled back to the liver by albumin and so there is no reason for cholesterol to be essential. Too much cholesterol does not get used to make bile acid and it stays in the blood stream and it causes many problems such as atherosclerosis because cholesterol is not needed. So to help someone with cholesterol the individual is given Cholestyramine, which will bind with bile acid to be excreted out of the body and so the body will need floating cholesterol to create more bile. In order to create more bile it will pull cholesterol from the blood stream and make use of it which will lower the cholesterol concentration.
Another natural way to rid the body of cholesterol is eating a high fiber diet. So when your mom told you to eat your vegetables, she was telling you that for your own good. A high fiber diet also works in a similar fashion to wash out the cholesterol. However, one must do so before the cholesterol becomes plaque in the arteries of the heart, because after that happens then it’s not possible to reverse the problem without a risky open-heart surgery.
There are other methods to help individuals with high cholesterol level but it comes with side effects such as using statin drugs which inhibit HMG-CoA reductase which is the key enzyme in synthesizing cholesterol. However, HMG CoA reductase also creates Farnesyl PPi which is a key component in synthesizing CoQ enzyme. If you stop CoQ enzyme from synthesizing then you stop the Electron Transport Chain, which is a major pathway in the mitochondria. The liver and the muscles have a lot of mitochondria which works continuously in metabolism. To counteract the CoQ enzyme deficiency when using statin drugs, CoQ 10 supplement can be used to provide the body with the necessary CoQ enzyme.
I hope this post gave you an idea of how you will need to think after the 16 months in Bonaire. If you didn’t know don’t panic just take your time and study till you fully understand the concept.
The contributors of the innate immunity includes the epithelial surface or barrier, neutrophils, macrophages, natural killer cells, blood proteins, and cytokines (which is also a protein).
In adaptive immune response, lymphocytes and cytokines are directly involved in the immune response against antigens. In adaptive immune response the contributors of the innate immunity are utilized such as neutrophils, macrophages, and natural killer cells.
Adaptive immunity has two types of responses, the first is an antibody-mediated response called humoral immunity; the second one is phagocytosis of the pathogen so it’s a cell-mediated response. In the humoral response the antibodies which mediates the immune response are produced by plasma cells. In humoral response antibodies and memory cells are constantly being produced. The second immune response is not antibody mediated but cell-mediated response. In cell-mediated response the antibodies are not there and B lymphocytes, T lymphocytes, and anti-presenting cells are involved. Anti-presenting cells include macrophages and dendritic cells. Adaptive immunity develops when a person has a second encounter with a pathogen, so the immune response targets that pathogen; this is called specific immunity.
There are two types of immunities; they include active and passive immunities. Active immunity is when the individual is exposed to the pathogen, it’s also known as “post disease”. And the second immunity is passive immunity, which is when the immunity is passed on to an individual such as a mother to a fetus, or when an individual or an animal is getting immunization. Passive immunity is a humoral immunity type.
Antigens are cells that is recognized and act upon by the immune system. Antigens can be molecules or whole cells. The immune system cells do not act on the entire antigen, but instead the immune cells act on the epitopes or other words antigenic determinants, which is antigen present regions on the molecules and pathogen cells. Antigens vary, they can be polysaccharides, lipids, proteins, nuceloproteins, bacteria, protozoa, tumor cells, or virus-infected cells.
Antibodies are glycoproteins and they are a type of the immunoglobin. Antibodies interact with antigen determinants by recognizing their receptors and binding to epitopes. Antibodies either circulate in plasma in the blood vessels or they migrate to tissues or in gland secretions such as in mammary glands or salivary glands.
Antibodies have many classes but basically they have two light chains and two heavy chains. The heavy chains are connected by disulfide bonds. Antibodies have a “Y” shape with the bottom region to be the FC receptor and the top to be antigen-bonding regions.
The classes of antibodies include IgG, IgM, IgA, IgD, IgE. The antibody classes of IgG along with IgD and IgE are monomers in shape. And IgM is a pentamer and IgA can be a dimer or trimer.
Remember that IgG is the most numerous antibody class compromising of at least 75% of the immunoglobulin serum. IgG is the only antibody that passes from the placenta to the fetus.
MEMORIZE THE ANTIBODIES CLASSES CHART.
IgA antibodies are located in secretions such as vaginal fluid, tears, and saliva. As mentioned earlier it is in the form of a dimer or trimer united by a polypeptide chain called protein J and a secretory or transport protein. An important note about this antibody is that it is resistant to several enzyme and so inhibits growth of microorganisms.
IgM is the antibody that exists as a pentamer but on the surface of a B lymphocyte they exist as a monomer with IgD. IgM exist as 10% maximum of the immunoglobulin serum. They can be membrane-bound or circulating-bound. IgM, once bound to the B lymphocyte, helps proliferate the B lymphocytes to differentiate into antibody-secreting plasma cell.
IgE antibody exist as a monomer in the smallest amount out of all the antibodies and it’s located on the surfaces of mast cells and basophils. Once the IgE is bounded to mast cells and basophils and after the cells encounter the antigens it triggers a the liberation of granules; this in general characterizes an allergic reaction.
Antibodies agglutinate cells, they glue cells with each other, and precipitate antigens, causing neutralization of antigens. Opsonization is a term when antibodies cover the microorganism which triggers it to be phagocytosed. Opsonization activates the compliment system. For the compliment system, remember that 20 different types of plasma proteins are produced in the liver.
The compliment system has a very important protein called C3. In order to defend the body C3 it stimulates phagocytosis due to opsonization and it induces lysis of microorganisms.
Cytokines are proteins or glycoproteins with low molecular masses. Cytokines influence both humoral and cell –mediated immune responses. They are produced by cells of the immune system such as lymphocytes, macrophages, and leukocytes and other cells such as endothelial cells and fibroblasts. A cytokine such as chemotaxins or chemokines attract leukocytes to sites of inflammation.
Interferons are proteins which are produced in response to viruses. They are very specific and they are active against virus infected cells. Interferons refrain viruses from reproducing and they activate natural killer cells; they also increase MHC Class I levels.
Lymphocytes are a type of cells of the immune system. Lymphocytes include B, T, an Natural killer cells. B and T cells are the only cells that can selectively recognize epitopes. B and T cells are not easily distinguishable. However, since they have different surface markers they can be distinguished by immunocytochemicle methods.
For lymphocytes the primary lymph organs are thymus and the bone marrow. The secondary lymph organs include spleen, lymph nodes, the tonsils, and aggregates of lymphocytes.
Lymphocyte precursors all originate from the bone marrow. B lymphocytes and Natural killer cells mature and leave the bone marrow and migrate to the blood circulation to colonize in connective tissue, epithelia, and the secondary lymphoid organs. T lymphocytes on the other hand mature in the bone marrow but instead of colonizing to the connective tissue after migrating to the blood, they go to the thymus. At the thymus they undergo proliferation and differentiation and then they leave the thymus to colonize to the connective tissues and lymphoid organs.
B lymphocytes have receptors that recognize IgM antibodies. When a B lympgocyte encounters an epitope on an antigen that it recognizes, it leads to proliferation and dedifferentiation. In some cases activation of B lymphocytes are assisted by T-helper lymphocytes. Not all B lymphocytes are activated, some remain as memory cells for a 2nd exposure to the same epitope.
For B lymphocyte development, the antigen-binding specifity is tested before B cells can continue to their maturation process. The binding of IgM and IgD is tested with self-antigens. If the binding of self-antigens to the IgM or IgD receptor molecules is too strong then the B cells will induce apoptosis. If the self-antigen binding to the immunoglobulin receptors is weak then the B cell will love and continue to mature.
T cells make up 65%-75% of the blood lymphocytes so a vast majority of T cells make up the blood lymphocytes. All T cells have T cell receptor or TCR for short. Unlike B cells which recognize antigens, T cells recognize epitopes. T cells are composed of T helper cells and cytotoxic lymphocytes.
T helper cells have many important functions. Their functions are activation of macrophages for phagocytosis, cytokine production, activation of cytotoxic lymphocytes, induction of inflammatory responses, and helping B cells differentiate to plasma cells. T helper cells have CD4 marker on their surfaces so they are called CD4+ T cells.
The second type of T cells are cytotoxic cells. They have the CD8 marker so they are called CD8+ T Cells. They act on foreign cells or virus-infected cells are by two mechanisms. First mechanism is when they attached to cells and release the protein perforin which induce cell lysis. The second mechanism of fighting is by attaching to the cell and activating the program cell death of the cell called apoptosis.
CD4+ and CD8+ cells encounter with a specific epitope which is followed by amplification of that clone. When the T cells populate some of them become effector cells and other become either T helper memory cells or cytotoxic T memory cells.
Natural killer cells don’t have the surface markers like B and T cells and they compromise about 10%-15% of the circulating blood. They act by innate immune response so they don’t need a previous stimulation to kill virus-infected cells or foreign cells, which give their name “natural killer” cells.
AIDS is caused when T helper cells are killed by the infecting retrovirus. When T helper cells die the individual immune system is compromised and the body is open to opportunistic infections.
MHC is short of major histocompatibility complex. There are two type, MHC I and MHC II. MHC is a complex of chromosome loci which encodes proteins. An individual expresses one set of each type of MHC. All cells with a nucleus and platelets have MHC I, while MHC II only exist in only antigen-presenting cells. MHC are integral proteins which are present on cell surface. MHC I class molecule form complexes with peptides. Virus infected cells which produce proteins are degraded by proteasomes which results in production of small peptides. These small peptides join with MHC class I molecules in the surface of the endoplasmic reticulum, and together they migrate to the cell surface (extracellular space).
Peptides that join with MHC II class molecules are by endocytosis and digestion in endolysosomes. Vesicles with these peptides fuse with the Golgi derived vesicles, where the MHC II molecules are, and together they are transported to the cell surface.
On the surface of the cell, MHC molecules present the peptides to the T lymphocytes. T lymphocytes recognize only the small peptides presented by MHC molecules. The T cell will only recognize MHC molecules if it’s from the same individual; if it’s self MHC molecule.
At times grafts can be rejected by the body and it triggers an immune response because of the genetic differences. Cytosolic peptides are presented by MHC class I molecules. Cytosolic peptides are derived from the cell’s own proteins in which T cells see them as self proteins; they are also derived from foreign proteins produced by tumor cells and virus-infected cells. Peptides which are presented by MHC class II molecules are mostly foreign proteins.
In organ transplantations there are four different types of grafts; they are autografts, isografts, homografts or allografts, and heterografts or xenografts.