Lecture 7 The Immune System and Cancer Dr William Coley Developed a cancer treatment that relied on boosting immune response by exposing the body to bacteria What IS the Immune System and tissue A vast communication network of cells and chemical signals distributed in blood First line of defense is the mucus membrane in lungs GI Tract is full of bacteria that help protect is Our microbiom Lymphatic System Bone marrow and lymph nodes they hold cells such as B and T cells and the spleen housing lymphocytes and is where antigens and white blood cells meet and figure out a way to fight the foreign invader Evidence for Immune Reactivity to Tumors Certain tumors regress spontaneously melanomas and neuroblastomas There is an increased incidence of primary and secondary malignancies in Antibodies and immune T lymphocytes have been detected in patients with immunodeficient patients tumors The young and the very old have an increased occurrence of tumors We can be immunized against tumors Cells of the Immune System Innate Immunity There components are ALWAYS ON and are not antigen specific Adaptive Immunity These components are TURNED ON in response to specific antigens Ex B and T cells Leukocytes WBCs white blood cells They come from two different types of stem cells Myeloid Stem cells Lymphoid stem cells Adaptive Immune System Cells Innate Immune System Cells Lymphoid cells become Adaptive Immune System Cell Functions T Cells that mature in the Thymus there are multiple types of T cells such as This involves many steps including exposing nascent T cells to self anitgens killer helper and inhibitor the antigens inside your body Any T cell which recognizes self is destroyed Autoimmune diseases arise when this system fails to detect self recognizing T B cells mature in the bone marrow They become plasma cells and memory cells cells Both produce antibodies An antibody is a protein produced in response to antigen invasion Antibodies are antigen specific meaning that antibody A only recognizes antigen A and antibody B only recognizes antigen B Antigen Foreign protein Recognize by immune system as a threat Induces antibody production How the Immune System Works Antigen Infected cell displays antigen T cells activated memory cytotoxic and or matures cytotoxic T cells Antigen macrophage presents antigen higher T cells activated memory helper T cells nonspecific killers Antigen B cells activated can also activate helper T cells that will activated memory helper T cells Plasma cells memory cells antibodies B cells grow in the bone marrow B and T cells circulate in our fluids looking for invaders The Immune System B cell encounters an antigen that fits its receptors B cell gets T cell help and is activated B cell expands clonally differentiating into plasma and memory cells Plasma cells produce antibodies that bind to neutralizing them phagocytes prefer invaders that have been coated with antibodies and readily eat them up Memory cells will be activated to act faster in producing antibodies if the same invader returns Tumor Host Interactions Endothelial Cells Provide blood supply Angiogenesis stimulators Angiogenesis inhibitors Immune Cells Antibodies lymphocyte attack Tumor antigens Immune inhibitors degradation Barrier to movement Other normal cells lack of adhesion Growth stimulators and inhibitors Motility stimulators and inhibitors How Does Cancer Escape Detection On the outside tumor cells look like normal host cells self Extracellular matrix and basal lamina Adhesion molecules proteolytic How The immune system does not recognize self recall T cell maturation If a cancer cell expresses a protein that resembles non self the immune system will recognize it and destroy it It follows that natural selection favors cancer cells that do not induce strong immune response because strongly immunogenic cells are killed off Weakly or non immunogenic cells survive and proliferate However sometimes strongly immunogenic cells can survive and proliferate Some cancers divide so quickly that they overwhelm the immune system Cancer cells also surround themselves with dense connective tissue that shields them from immune attack Some cancer cells produce molecules that destroy T cells Some cancers escape via immunoediting Elimintation Innate and adaptive immunity kill off all dangerous cells Equilibrium Genetic instability immune selection push back and then regrowth of dangerous cells Escape Cells that can escape the immune system Presentation of Cancer Antigens 1 Antigen is taken up by an antigen presenting cell 2 Antigen is broken down into small fragments 3 Antigen fragments are bound to MHC molecules 4 MHC presents the antigen fragment to lymphocytes which are stimulated to attack that antigen Once we get cancer can we make our immune system better at fighting it There are Several Things that can be done Cancer cells rely on proteins from nearby healthy cells to hide them from the immune system Engineered antibodies can strip away disguises Cancer cells produce proteins that suppress the immune system New drugs that can suppress the suppressors are being tested We can take T cells and genetically engineer them to recognize proteins unique to the cancer cells Cancer Vaccines A few cancer cells are removed from the patient And a few immune system cells are also removed The cancer and immune cells are cultured together The immune cells will take antigens from the cancer cells so they can now recognize the cancer These immune cells are put back in the patient so they can recognize the tumor and alter the rest of the immune system We can also produce anticancer antibodies in the lab Antibodies that Stimulate Cell Killing These antibodies function by targeting proteins on the surface of cancer cells These antibodies themselves mark the cancer cell for destruction by the immune system Ex Rituxan Binds the CD 20 protein on normal and cancerous B cells It then recruits cells of the immune system to destroy B cells Normal B cells regrow after the body has been cleared Immunotherapy Treating the patient instead of the disease APCs catches tumor antigens and B and T cells come and fight the antigens B cells mark the cancer cells with antigens and then T cells fight all cells that have that mark In an equilibrium event tumors will mutate and overpower the immune system Conjugated Antibodies This approach utilizes antibodies to target toxic molecules to the cancer cells Radiolabeled Small radioactive particles attached
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