The Lymphoid System Part 1

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.

Is a Caribbean Medical School Right For You?

Doctors are always needed in America and with the baby boomers retiring in the next decade, there will be a shortage of 80,000 doctors. Currently there is less an a million physicians in America so, that leaves 1 doctor for 3 patients on average. The medical field is the most competitive professional field. Medical schools can only take so many and that’s why they choose the best of the best. So if you get rejected what’s the alternative? The alternative is an off-shore medical school, in the Caribbean.

Caribbean medical schools have become a big destination for Americans and Canadians who seek a medical degree and could not get admitted to an American or Canadian medical school. In my opinion these off-shore medical schools are a second chance for the ultimate goal, and that is the chance to practice medicine in the United States or Canada. Most students prefer practicing in America so, for the rest of the article we’ll stay with American requirements with little mention of Canada.

The types of students who go to Caribbean schools have their personal reasons of why they don’t have good GPAs as undergrads, but basically they want a second chance to prove themselves. In a Caribbean school, their passion of becoming a doctor is tested rigorously; they have to go through many challenges in order to reach their goal of being an MD. Since they go to a Caribbean school, they have to study harder than US medical students because the Caribbean school teachers in will not spoon feed them.

The off-shore medical schools include the big three schools: St. George School of Medicine, Ross University School of Medicine, and American Caribbean University School of Medicine. Other smaller medical schools include: St. Mathews University School of Medicine, St. James School of Medicine, University of Medicine and Health Sciences. There are many more schools but too many to name. Some of the schools listed have multiple campuses in more than one country. The big three are the most expensive medical schools with tuition as much as $49,000 per semester, which is the same as a private US medical school. The higher the tuition the more accreditation the school has. But some schools have all the accreditations and their tuition fees are not that high. Sometimes it’s cheaper to go to a Caribbean medical school than to go to a US medical school because there will be less amount of loans to pay.

Anyone who goes to an off-shore medical school can get a descent residency in the United States. An IMG (international medical graduate) takes the USMLE tests and does rotations side-by-side with students from US medical schools.

Over the recent years Caribbean medical schools has become popular for lower standards to admit students; lower standards include lower minimum GPA requirements, MCAT scores, no research, and less hours of volunteering. Some medical schools don’t even require an MCAT score to admit a student to their school if they have a high number of volunteering hours or a descent GPA. However students are required to take the pre-medical pre-requisites classes in order to start the MD program. The pre-requisite classes are also required for admissions to US medical schools.

The pre-requisite pre-medical classes include:
General Chemistry (1 Year with Lab)
General Biology (1 Year with Lab)
Organic Chemistry (1 Year with Lab)
Physics (1 Year with Lab)
English (at least 6 credit hours)
Math (Calculus I)
Biochemistry (optional)

The process of gaining a medical degree is the same in all off-shore schools in the Caribbean, but they are slightly different from US medical schools. The student takes 16 months doing basic science courses off-shore and then he/she will go back to the US and study for the USMLE Step 1. Some schools make it mandatory for students to take their 5th semester/Kaplan course to prepare for the USMLE. And other schools give their students choices of taking Kaplan/Falcon courses or studying without taking the courses. After passing the Step 1, the students are assigned to a US hospital affiliated with the school the students are from. Canadian students can do their rotations in Canada but they can only do 14-weeks rotations in each province. Canada is not the best place for IMGs, according to what I read, but I can be wrong. At the end of the 3rd year or at the beginning of the 4th year, students are advised to begin to apply for residency in their field of interest. All students have to first choose between family medicine and internal medicine. Internal Medicine has more choices of specialties than family practice; therefore, most medical graduates from Caribbean and US medical schools go into internal medicine. After 2 years of rotations in an affiliated hospital, the medical student sits for the USMLE Step 2. USMLE Step 2 has two parts now, the CS and CK, which are taken separately. After passing the Step 2, the Caribbean medical school gives the student his/her MD degree. The entire MD program takes about 3.5 years to 4 years to complete.

So do you want to save at least $100,000? Do you want avoid the long wait to get into medical school? Do you want to a second chance? If all the answers to these questions are yes then I suggest you get into a Caribbean school to fulfill your dream of becoming a doctor.