Immune System Part II

B cells have surface receptors also but the receptors are IgM and IgD. One B cells may have 10,000 of the AB. Each one of the AB are pre programmed to recognize and bind to specific AG. There is a huge diversity of B cells due to their variable region. Until activated, these are virgin B cells. Vast array of virgin B cells and virgin T cells- very few like one another are waiting to go into action in secondary lymphoid tissue.

Specific Immune response has two parts I.Cell mediated response-Involves T-cells killing infected cells II.Humoral response-Involves Helper T-cells and B-cells which produce AB to eliminate pathogens. This process is called clonal selection works because it involves the specific selection of AG specific T cells and B cells. Virgin B and T cells will be called into action by the primary immune response in a process called clonal selection- It is call the clonal selection because it involves the rapid selection of single lines or clones selected from vast lymphocyte armies-

Acquired or Specific Immune response has two parts Cell Mediated and Humoral responses I. Cell mediated response 1. Macrophages (have both MHC I and MCH II proteins) 2. Macrophage goes to the site of infection as part of the nonspecific or innate response 3. The macrophage devours virus, AG, or bacteria and the macrophage. Bits and pieces of invader now combine with MHCI and MHCII proteins. These MHC proteins and AG now are moved to the plasma membrane. The macrophage (or an infected cell) is called and antigen presenting cell APC. Infected cells will also combine bits and pieces of the pathogen with MHC I proteins and become an APC cell.

4.The macrophage is now APC. 5. Now the APC (macrophage) goes to the virgin T cells looking for a match between the TCR (T cell receptor) receptor and the MCH protein and antigen on the APC (macrophage).

When the APC binds with virgin T-cell a substance called interleukin(IL1). IL1 is a cytokine. Interleukin (IL1) causes T-cells to reproduce making either cytotoxic T-cells, T-memory cells, or helper T-cells depending whether the match is with a MHC I and MHCII protein. In this diagram, it is with MHC I proteins and cytotoxic T cells and memory cells are made.

Meanwhile if a MHC II protein and antigen makes a match with a TCR on a T cell, then the T cell becomes a helper T cell. In this diagram the match is with a MCH II protein. More on helper T cells later on. Notes about CD proteins-The proteins holding the two cells together are called cluster differentiation proteins (CD). CD proteins are found on lymphocytes. There is a variety of CD proteins and different lymphocytes will contain different CD proteins. Some

CD proteins are used for adhesion and other CD proteins are used for as receptors to initiate cell signaling. This is magnified diagram shows the role of CD proteins on helper T (CD4) and cytotoxic (CD8) cells. Their function is for adhesion.

While this is happening, pathogens are infecting body cells. Bits and pieces of the pathogens are inserted into the MHC I protein. Either by the intracellular MHC or surface MHC. This is identified as one that is infected.

The perforin forms pores on the infected cell. Granzymes cause the cell to undergo apoptosis and death of the cell. The cytotoxic cell can go on it merry way to get rid of other infected cells. *Cytotoxic cells also kill cancer cells because cancer cells change and have new proteins. Some of these new proteins combine with MHC I proteins and appear on the surface of the cancer cell. Cytotoxic cells will combine with cancer cell and kill it. Every once in a while the cells will escape the cytotoxic-T-cell because the MHCI protein has also changed *There is no longer a dual match and cells replicate or metastasize

This is another’s rendition of how a cytotoxic cell kills in infected cell. Below is a cytotoxic cell (orange) killing a cancer cell (purple)

II. Humoral Response involves the arousal of B cells and antibody formation. Activated helper-T- cells act much like the macrophages did in activating virgin T cells. 1. Virgin B cells has AB on surface. It captures free floating AG which is taken into the cell. 2. The AG combines with a MCH II protein and is taken to the surface of the plasma membrane. 3. Helper-T-cell with its MCH II recognition site and antigen recognition site finds B-cell with AG and MHCII protein.

4. The two join and the helper-T-cell secretes interleukin 2 (IL2) which is a cytokine. This causes the B-cell to reproduce. 5. The B-cells fall into 2 types a. Memory-B-cells for the secondary immune response b. Plasma cells which will produce copious amounts of AG specific AB Any given humoral response stimulates a variety of different B cells, each giving rise to a clone of thousands of plasma cells.

Another drawing of B cell selection and activation of plasma cells. Each plasma cell is estimated to secrete about 2,000 antibody molecules per second over the cell’s 4-5- day life span. REMEMBER WHAT ANTIBODIES CAN DO!!!!!!!!!!!!!!!!!!!!!!!!!! They are AG specific. -AB can bind to several AG -AB can trigger complement holes in the cell -Opsonization

Suppressor-T-cells- helps to stop the immune response 1. Do not know how they are activated- possibly down AG 2. Thought to stop any further virgin B or T cells from being activated. So *immune response stops because plasma cells and cytotoxic cells only have a short life.

Secondary immune response Memory cells live for many years If AG comes back the memory cells( B and T) immediately recognize it. They divide quickly and get rid of invasion. The graph shows that it may take two weeks from the initial exposure to when plasma cells are producing the greatest amount of antibodies but upon second exposure it only take two days to produce the same number of antibodies that the initial exposure caused. In only seven days the number of antibodies in the blood stream is 100 times the amount produced by the primary response. This is because of memory cells B cell and memory helper-T cells

Vaccines- used of killed or inactivated viruses that no longer causes the disease but provides AG which will cause the immune response making memory cells so that when exposed to the pathogen, there is a quick secondary immune response

Natural active immunity- (mumps) Exposed to the actual pathogen and caused the disease. Memory cells were made. Subsequent exposure to the disease does not cause the disease. Artificial active immunity- (vaccine) Given inactive parts of the pathogen so that memory cells were made. Subsequent exposure to the disease does not cause the disease. Natural passive immunity- AB in breast milk and the IgG antibodies of a pregnant woman cross the placenta to her fetus. Lasts a few weeks to a few months Artificial passive immunity- shot with AB in the antiserum from an animal that has already had the disease. Passive immunity can be transferred artificially by injecting antibodies from an animal that is already immune to a disease into another animal. For example, a person bitten by a rabid animal is injected with antibodies against rabies virus because rabies may progress rapidly, and the response to an active immunization could take too long to save the life of the victim.

Lymphocyte diversity and B cells- There are not enough genes to provide for the diversity of millions of lymphocytes. There are app. 300 DNA segments during development the 300 segments are rearranged to produce # different proteins for variable region of AC (18 billion). Also AB can be modified once made T cells- less is known but think may be similar to B cells. Next slide is an example of how genes are rearranged to form different AB. The slide after that shows how clonal selection works in the immune system.

ABO blood groups and the immune system On the surface of red blood cells there are polysaccharide chains attached to proteins. The immune system considers them as antigens unless the person contains that gene. A person with type A blood contains A antigen whereas a person with type B blood contains B antigen. A person with type AB blood has both A and B antigens and a person with type O blood has neither. During the process of lymphocyte maturation, lymphocytes recognize self and will not make antibodies against the antigens on its own red blood cells. For example, if one has type A blood, then one would not make antibodies against the A antigen but would make antibodies against the B antigen. There are bacteria in the environment that has proteins similar to the A and B antigens. When these bacteria enters a person’s body, the body will make antibodies for any A or B antigen that is not found on one’s own blood type. Now the person has circulating “ preformed” antibodies for blood types that the person does not possess. For example a person with type A blood will have type B antibodies even though

ABO blood groups and the immune system a person with type A blood will have type B antibodies even though they have not been exposed to type B blood. This makes blood typing important in transfusions. The antibody for these antigens are IgM and do not cross the placenta. The Rh antigen is another antigen found on red blood cells. There are several variations of this antigen. It is a protein. If one has it, then they are Rh+ and if one does not then they are Rh-. There is a problem for a pregnant women who is Rh- and if her fetus is Rh+. During the first pregnancy, when birthing the child, some of the baby’s blood will mix with the mother’s. She will make AB against the Rh antigen. Now the second pregnancy, if any the blood mixes, her Rh antibodies will cross the placenta and agglutinate the babies red blood cells called erythroblastosis fetalis. To prevent this, the mother is injected with anti- Rh antibodies. This will eliminate any fetal blood cells that should cross into her body and prevent her from making AB against the Rh factor.

AIDS-Acquired immunodeficiency syndrome Is caused by a RNA virus. The virus attaches to CD4 protein and gains entry into the helper T cell. (macrophages and brain cells also have CD4 proteins) Once inside, the RNA is reverse-transcribed into DNA. This piece of DNA integrates itself into the genome of the helper T -cell. Now it can direct the production of more viruses. The helper T cell dies because of the damaging effects of the virus. The destruction of the helper T cell effects both the humoral response and the cell mediated response. Usually people with AIDS die of secondary infections from opportunistic pathogens like a pneumonia caused by a fungi or Kaposi’s sarcoma, a rare cancer. There is no cure for AIDS only a combination of drugs that slows down the progress of the disease.

A T-cell being infected by the aids virus (blue particles)