Bms 545 Immunology Past Paper PDF

WELCOME- BMS 545 IMMUNOLOGY NOVEMBER 20, 2024  THE REST OF THE SEMESTER (ALL MODULE 4)  11/20- Transplantation & Begin Cancer  11/22- Cancer & Tumor Immunity  11/25- Hypersensitivity (Asynchronous- Enjoy Thanksgiving break!!!!!)  11/27-11/29- Thanksgiving break...

WELCOME- BMS 545 IMMUNOLOGY NOVEMBER 20, 2024  THE REST OF THE SEMESTER (ALL MODULE 4)  11/20- Transplantation & Begin Cancer  11/22- Cancer & Tumor Immunity  11/25- Hypersensitivity (Asynchronous- Enjoy Thanksgiving break!!!!!)  11/27-11/29- Thanksgiving break Because we have  12/2- Autoimmune Disorders this one PPT over  12/4- “What’s Wrong with Me?” Case Study 11/20 & 11/22, don’t  12/6- Final Immunology debrief: The Well Patient forget DITKI due Friday & Monday!!!!  LEARNING OBJECTIVES  Define common cancer terminology & identify how tumors are classified  Describe what oncogenes and oncoviruses are and how they play a role in tumor development  List seven key features of all cancer-causing cells  Identify malignant transformation, tumor antigens and the theory of immune surveillance  Compare & contrast tumor antigens, tumor-specific antigens, & tumor-associated antigens  Diagnose different types of blood cancers based on lab tests, signs & symptoms, e.g. leukemiaS, lymphomaS, & multiple myeloma  Compare & contrast the leukemias & lymphomas (e.g. acute vs. chronic)  Define immunosurveillance  Describe how mAbs can be used for both diagnosis & treatment of cancers  Monoclonal antibodies against cell-surface antigens are increasingly used in cancer immunotherapy (e.g. to diagnose via staining, target toxins, target radiation, & make NK cells kill tumor cells)  What is ADCC? Figure 17.5 Causes of death in the United States in 2019 Figure 17.1 Pie charts showing the incidence and mortality in 2018 for the 10 most common cancers worldwide  The evolution of cancer from healthy human cells 17-1 Cancer results from mutations that cause uncontrolled cell growth Cancer- an umbrella term for a wide variety of diseases caused by abnormal & invasive cell proliferation Figure 17.2 Benign and malignant tumors can arise from the same type of tissue  Tumor- a growth arising from uncontrolled cell proliferation. It may be benign & self-limiting OR malignant & invasive  Benign- cellular growth, i.e. wart, which is caused by an abnormal proliferation of cells but is localized & contained by epithelial barriers  Malignant- tumor that is capable of uncontrolled & invasive growth Illustration of tumors of the breast  Adenoma- general name given to a benign tumor of glandular tissue  Adenocarcinomas- malignant tumors of glandular tissues Figure 17.8 Growth and life span of a common human tumor  The evolution of cancer from healthy human cells 17-2 Cancer arises from a cell that has accumulated multiple mutations A typical series of mutations acquired by a cell while progressing to malignant transformation- the changes that occur in a cell to make it cancerous  After malignant transformation when tumor becomes invasive, tumor cells rapidly acquire additional mutations- Some make cells more invasive, others are random & have no deleterious affect on growth & proliferation of malignant cells  Oncogene- mutant or unregulated form of a gene that can cause cells to proliferate abnormally & form a tumor; most derived from genes controlling growth & proliferation  Tumor suppressor gene- gene encoding a cellular protein that normally functions to prevent cells from becoming cancerous  Lead to tumor cells becoming genetically diverse- Natural selection favors cells that are most effective at both invasion & proliferation  This accumulation of mutations would typically occur over ~10–20 years  Metastasis- spread of tumor from its origin site to other tissues. Some cells from primary tumor invade other tissues & grow & divide to become secondary tumors  The evolution of cancer from healthy human cells 17-3 Exposure to chemicals, radiation, & viruses facilitates progression to cancer  Oncogenic virus- a virus that contributes to causing cancer  Only a minority of people infected with an oncogenic virus progress to develop cancer  Viruses MUST act in conjunction with other factors  Some of viruses may even act indirectly, e.g. Kaposi’s sarcoma is restricted to people who are immunosuppressed by infection with HIV or by immunosuppressive drugs administered during organ transplantation Human immune responses to cancer 17-10 Vaccination against human papillomavirus antigens prevents the occurrence of genital cancers Figure 17.16 Components of the papilloma vaccines (you do not need to memorize)  The evolution of cancer from healthy human cells 17-4 Common features of cancer cells distinguish them from normal cells  All cancer-causing cells have seven key features in common →  Additionally, cancer cells can be identified by tumor-specific antigens & tumor-associated antigens  Tumor-specific antigens- antigen that is characteristic of tumor cells & is not expressed by healthy normal cells  Mutations acquired by somatic cells during oncogenesis give rise to tumor-specific antigens  Tumor-associated antigens- antigen characteristic of certain types of tumor cells, and which is also present on some types of normal cells Figure 17.9 Proteins that are tumor-specific antigens contain tumor-specific mutations  For example, shown here are tumor antigens discovered while studying T-cell response to different types of cancer:  5 are peptide antigens containing a point mutation (red)  3 are peptides derived from novel protein produced by fusion of BCR & ABL genes that characterizes chronic myelogenous leukemia  ABL is an oncogene & BCR encodes a kinase (gene, NOT B- cell receptor) You do NOT need to memorize these   Accumulation of dysfunctional cells & loss of mitosis regulation. LEUKEMIAS:  Uncontrolled production of abnormal cells overtakes/replaces production of CANCER OF normal cells with time. BLOOD-FORMING  Proliferation of cancerous WBCs cells in bone marrow limits space for CELLS development of other cells, (mechanical effect, not enough space)  Decrease RBCs: anemia  Decrease platelets: easy bruising/bleeding  LEUKEMIAS CLASSIFIED BASED UPON: 1. Cell lineage:  Lymphoid  Myeloid 2. Speed of cancer progression:  Acute  Chronic *Myelogenous=Myeloid *Lymphocytic= Lymphoid Neutrophils most common myeloid leukemia!  Speed: Acute vs. Chronic Acute: Develop from progenitor cells in earlier stage Immature/nonfunctional cells (blasts) spill into blood from bone marrow. Fast-growing and aggressive with short life expectancy (weeks to months). Immediate treatment critical. Chronic: Develops from later stages of blood cells. Production of more mature cells (unlike acute) but still not normal functioning No blasts in the blood. Slower growing with longer survival (years) Watch and wait!  Hodgkin & Non-Hodgkin Lymphoma Differences Hodgkin Non-Hodgkin Reed-Sternberg Cells NO Reed-Sternberg Cells Upper body tumors (usually) Tumors in L.N. all over body (Usually) Highestrates in young adults (15- 24) & adults over 60 All ages, but increases with age Lymphoma is a cancer of the LYMPH NODES Reed-Sternberg Cell (Malignant B-cell) Large, multiple nuclei  Multiple Myeloma Malignancy of PLASMA CELLS in bone marrow More common in males More common in people of African- Caribbean descent Median age 70 years old Abnormal antibodies produced by myeloma cells: M-protein Myeloma cells secrete mediators that stimulate osteoclasts: Bone loss Skeletal pain Multiple Myeloma: Signs/Symptoms CRAB [C]alcium: elevated calcium [R]enal Insufficiency [A]nemia [B](Lytic) Bone lesions  Human immune responses to cancer 17-5 Immune responses to cancer have similarities to those made against virus-infected cells Immunosurveillance- the capacity of the immune system to recognize cancer cells at an early stage and eliminate them before they cause disease 17-8 Control of cancer by the immune system does not require elimination of all the tumor cells 17-9 Successful tumors are ones that evade and manipulate the immune response  Controlling cancer with immunotherapy 17-11 Monoclonal antibodies are valuable tools for the diagnosis of cancer The next few slides show specific examples, but do NOT need to be memorized- merely examples that if we know unique markers of the different cancers, we can use mAbs to stain for these markers and diagnose cancer  Light micrograph of a tumor section stained with hematoxylin & eosin (H&E) showing typical ‘starry sky’ appearance, with lymphoma cells forming the sky & tumor-eating macrophages the stars Figure 17.17 Diagnosis of Burkitt’s lymphoma  Left: fluorescence imaging of six lymphoma-cell nuclei (blue), where chromosomes have been probed for presence of MYC gene translocation diagnostic of Burkitt’s lymphoma  Red & green fluorescence-tagged DNA probes are specific for sites on either side of breakpoint in MYC proto-oncogene on chromosome 8. Both hybridize to normal chromosome 8, giving it a yellow spot  Only red probe hybridizes to translocated chromosome 8, which has lost that part of MYC containing ‘green’ site  Green spot indicates chromosome that has received the translocated piece of MYC  So, each tumor cell has a red, a green, & a yellow spot  Right: light micrograph of tumor section stained with antibody specific for Myc oncoprotein  Intensive staining (brown) of tumor cells & no macrophage staining Figure 17.18 Hodgkin’s lymphoma is caused by B cells that have lost B-cell characteristics  In Hodgkin’s lymphoma, malignant B cells comprise a small minority of the cells 1. Light micrograph of a Reed–Sternberg tumor cell with characteristic ‘owl’s eyes’ morphology 2. Treatment with an anti-Pax-5 antibody shows absence of Pax-5 characteristic of Hodgkin’s lymphoma- Absence of this defining B-cell transcription factor stops signaling from B-cell receptor 3. Expression of CD30- antibody-mediated immunotherapy target 4. Expression of CD15- antibody-mediated immunotherapy target Figure 17.19 Diagnosis of anaplastic large-cell lymphoma Light micrographs of tumor sections:  Left: tumor cells are large & shaped like horseshoes  Center: tumor cells express CD30 at cell surface (brown staining using anti-CD30)  Right: tumor cells have characteristic translocation between anaplastic lymphoma kinase (ALK) gene & nucleophosmin (NPM) gene forming oncogenic fusion protein & accumulates in nucleus & cytoplasm (dark staining using an anti-NPM– ALK)  Controlling cancer with immunotherapy 17-12 Monoclonal antibodies against cell-surface antigens are increasingly used in cancer immunotherapy Other examples of mAbs used in treating various types of other cancers: Figure 17.20 Antibodies are used to target toxins to tumor cells  We can also use antibodies to treat cancer cells by targeting them with toxins to destroy just those cancer cells!  For example:  Anti-CD30 antibody brentuximab is coupled to cytotoxic drug auristatin by a cathepsin-cleavable linker = called brentuximab–vedotin  After antibody has attached the conjugate to surface of tumor cell, the conjugate is internalized into endosomes, where cathepsin cleaves the linker & releases the auristatin  Potent anti-mitotic drug passes to nucleus, where it binds to microtubules & prevents them from forming a mitotic spindle  Prevents mitosis & induces tumor cell to die by apoptosis Figure 17.22 Antibodies can target radioactive isotopes to the tumor-cell surface  Conjugates of anti-CD20 antibodies with radioactive isotopes are used to irradiate & kill non-Hodgkin’s B- cell lymphoma cells Figure 17.23 Many therapeutic monoclonal antibodies work by delivering tumor cells to be killed by NK cells  Therapeutic antibodies are specific for a protein on surface of tumor cells, e.g. rituximab to CD20  Antibodies coat a tumor cell with their Fc regions pointing away from cell  Fc regions can then engage FcγRIII receptors on an NK cell  Signals from receptors activate NK cell to kill tumor cell  This is an example of antibody dependent cell-mediated cytotoxicity (ADCC)- the killing of antibody-coated target cells by NK cells having the receptor FcγRIII, which recognizes the Fc region of the bound antibody; a function of NK cells Also a Scientist Professor Quarraisha Abdool Karim -Born in Tongaat, South Africa -She is known as a symbol of hope for young women pursuing careers in sciences -Epidemiologist specializing in HIV in South Africa -Recently recognized for her groundbreaking work on the CAPRISA-004 project -Her contributions to the CAPRISA-004 project provided evidence that a microbicide added to HIV treatment decreased a woman’s chances of contracting HIV by 54%