Cells and Organs of the Immune System PDF

CELLS AND ORGANS OF THE IMMUNE SYSTEM hematopoiesis ________________________: the formation and development of red and white blood cells from stem cells stem -every specialized mature blood cell is derived from a common _____________...

CELLS AND ORGANS OF THE IMMUNE SYSTEM hematopoiesis ________________________: the formation and development of red and white blood cells from stem cells stem -every specialized mature blood cell is derived from a common ________________ cell multipotent -this cell is called _____________________________ (i.e. able to differentiate along a number of different pathways to generate different cells) -early in hematopoiesis, the stem cell differentiates along one of two lines, giving rise to lymphoid a ______________________ myeloid stem cell or a _________________________ stem cell -these stem cells differentiate into progenitor cells (capable of self-renewal) -lymphoid stem cell generates T and B progenitor lymphocytes -myeloid stem cell generates progenitor cells for red blood cells (erythrocytes), platelets and various WBC (leucocytes) including neutrophils, eosinophils, basophils, monocytes, mast cells Lymphoid Cells white blood cells -lymphocytes constitute 20-40% of body’s _________________________________ function -can be broadly subdivided on the basis of _________________ and cell-membrane __________________ components: -B cells -T cells -null cells B lymphocytes antibodies can block bacterial adhesion/invasion binding of antigen causes clonal selection - particular cell begins dividing -major site of maturation is the Bone marrow membrane-bound -distinguished from other lymphocytes by the presence of ________________________ immunoglobulin ______________________ (antibody) molecule (serves as a receptor for antigen) B-Cell Receptor =_____________________________________________ antigen -a B cell is activated when it binds an _____________________ specific for its membrane-bound antibody differentiate -this activation causes the B cell to _______________________________ into memory B cells and effector (plasma) B cells memory -memory cells: long life; give immunologic ______________________ -effector cells: do not express membrane bound Ab, but a secreted form not made specifically against an antigen, b cells are random T Lymphocytes -site of maturation is in the Thymus T-Cell Receptor (TCR) -have an antigen binding receptor = __________________________________________  -unlike B cells that can recognize soluble antigen, the TCR recognizes antigen only when cell membrane protein the antigen is associated with a _____________________________________ -encoded by gene within the major histocompatibility complex associated with the antigen-presenting cell (macrophage) - links with antigen and is bound in membrane - antigen is presented in MHC receptor -thus, when a T cell encounters antigen associated with an MHC molecule on a cell, T cell proliferates and differentiates into memory T cells and various effector T cells -there are 2 subpopulations of T cells: T Helper 1. __________________________________ (TH) T cytotoxic 2. __________________________________ (TC) -display different membrane glycoproteins CD4 - TH display ________________________ CD8 -Tc display ________________________ -after TH cell recognizes and interacts with an antigen-MHC II molecule complex, cell is cytokines activated and releases various growth factors known collectively as _________________ -cytokines play and important role in activating B cells, Tc cells, macrophages, and other cells professional antigen presenting cell carries MHC class 2 molecule with antigen -under the influence of TH -derived cytokines, a Tc cell that recognizes an antigen-MHC I molecule complex proliferates and differentiates into an effector cell called a cytotoxic T lymphocyte (CTL) -CTL does not secrete cytokines; it exhibits cytotoxic activity ie. monitors cells of the body and eliminates any that display antigen, such as virus-infected cell, tumour cells (altered self cells) t helper - mhc class ii - dendritic, macrophages, etc t cytotoxic - mhc class i - any cell of the body Null Cells -one functional population of null cells is called natural killer cells (NK) granulated -NK cells are large __________________________ lymphocytes tumour -they play an important role in host defence against _________________________ cells - play a role in both innate and adaptive immune responses - surveil body for cancerous cells Myeloid Cells Mononuclear Cells monocytes -consist of circulating ________________________ macrophages in blood and ___________________ in the tissue (monocytes that enter tissue differentiate into tissue specific macrophages) phagocytic -macrophages are actively ______________________ cells capable of ingesting and digesting exogenous antigens such as whole microorganisms, insoluble particle, injured and dead host cells, cellular debris etc amoeboid -move by ____________________________ movement and form pseudopodia to extend around material to be ingested Granulocytic Cells -three types: neutrophils, eosinophils, basophils Neutrophils -produced in the bone marrow -are released in greater numbers in response to many infections first -are generally the ___________________ cells to arrive at the site of inflammation phagocytic -are active _________________________________ cells Eosinophils -phagocytic cells that can migrate from the blood into tissue spaces parasitic -play a major role in the defence against ___________________________ organisms Basophils non-phagocytic -__________________________________ granulocytes -function by releasing pharmacologically active substances contained within their cytoplasmic granules allergic -this release of the contents plays a major role in certain _____________________ responses Mast Cells -mast cell precursors circulate in the blood as undifferentiated cells—they differentiate only when they enter tissue -found in a variety of tissues including skin, connective tissues, mucosal epithelial tissue of the respiratory, genitourinary and digestive tracts histamine -have a large number of granules containing _______________________________ allergies -play an important role in the development of _________________________________ Dendritic Cells process -__________________ present and _____________________ antigen to TH cells class II MHC molecules -constitutively express high levels of ________________________________….this makes them potent antigen-presenting cells ORGANS AND TISSUES -can divide organs involved in the development of the immune response into primary and secondary lymphoid organs Primary lymphoid organs -are where immature lymphocytes mature and differentiate into antigen-sensitive mature B and T cells thymus -the ___________________________ is a primary lymphoid organ -located above the heart -precursor cells of T cells migrate here, proliferate, mature bone marrow -the ___________________________ is a primary lymphoid tissue Secondary lymphoid organs antigens -are where lymphocytes may encounter and bind _____________________, proliferate whereupon they ______________________ and differentiate into fully mature antigen-specific effector cells spleen -__________________________ is a secondary lymphoid organ -filters blood and traps blood-borne microorganisms and antigens lymph -________________________ nodes -lie at junctions of lymphatic vessels where they filter out harmful mircoorganisms and antigens from the lymph -B cells proliferate here mucosal associate tissues -______________________________________ (ie gut associated lymphoid tissue, skin associated lymphoid tissue) are secondary lymphoid tissues provide defense of vulnerable membrane surfaces tonsils and appendix etc., Using the body’s immune system as a defence against cancer: a paradigm shifting approach to cancer treatment Traditional treatments for cancer, including surgery, radiation and chemotherapy, are now being joined by cancer immunotherapy. Cancer immunotherapy is a form of treatment that enhances a particular aspect _____________________________ of the immune system in order to fight or control malignant cells. Many types of immunotherapy are being researched. Some early results have been very encouraging. Three new immune system-boosting strategies 1. Checkpoint Inhibitors 2. Dendritic Cell Vaccine 3. CAR-T cells 1. Checkpoint Inhibitors antibodies These are new drugs (often ____________________!) that disrupt the ability of cancer cells to evade the immune system. How does this work? T cells By preventing tumour cells from interacting with _________________ (and thereby fooling them into thinking that they are “normal” cells), checkpoint inhibitors allow T cells to identify and attack cancer cells. Three checkpoint inhibitors have been approved by Health Canada (ipilimumab, pembrolizumab, and nivolumab). Nivolumab has been approved just recently (March 1, 2016). It is an anti-PD1 agent. Challenges 1. Not all patients react the same way to the same drugs. The reasons for this are unknown. multiple 2. Sometimes ______________________ inhibitors are required. 2. Dendritic Cell Therapy This therapy attempts to boost the immune system by identifying cancerous antigen and dendritic exposing _____________________________ cells to them. How is this done? Healthy cells, cancer cells and immature dendritic cells are isolated from the patient antigens Scientists identify __________________ unique to the cancerous cells by comparing them to the healthy cells antigen Expose dendritic cells to ___________________ Allow dendritic cells to mature Reintroduce dendritic cells to patient Mature dendritic cells now present the cancer-specific antigen to ____________________________ T cells, thereby triggering an effective response against the cancer cells. Early work done in melanoma patients has yielded positive results, but these patients have also received other therapies in addition immunotherapy. slow ____________________ process long term work is still in its early days so the _________________________ effects are unknown 3. CAR-T Cells (Chimeric Antigen Receptor) recognizes b cell and t cell receptor This immune therapy creates T cells that express a surface B cell receptor _______________________________. How is this done? T cells extracted from patient Using a retrovirus, genetic information is transferred to the T cells allowing them to make cancer and express a __________________-specific antibody as a surface receptor T cells are grown in the lab Cells are re-introduced into the patient Modified T cells can now seek out, directly identify and destroy cancer cells that express target the ______________________________ antigen. early results have shown this to be an extremely potent therapy especially effective against “liquid” cancers, such as leukemia and lymphoma Challenges: potent immune response must be modulated: it can be life-threatening custom must be __________________-designed for each patient making it time- consuming and expensive does not work well with solid tumours