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Natural Killers: The story of Cytotoxic T-cells, Vigilante Warriors of the Immune System
- 1. NATURAL KILLERS: Thestory of CYTOTOXIC T-CELLS, VIGILANTE WARRIORS of the immune system
- 3. But before we getto the Killers…
- 6. Special agent: NaturalKiller DESTRUCTION SPECIALIST PREFERRED WEAPON: CYTOTOXIC GRANULES DISPOSITION: TAKE NO PRISONERS POSSIBLY PSYCHOTIC History: Homicidal excursions targeting virus infected and cancer cells STATUS: AT LARGE Natural Killer
- 13. What happens whenNatural Killers don’t kill? • Immunity is a balance of destruction and restraint • Too much willy-nilly death and destruction and you have autoimmune disease • Not enough killing (which happens naturally as we age) and you get cancer • How do we get the killers to behave?
- 16. “These cells areliving drugs.” - Carl June
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- 19. Thank you foryour attention
Editor's Notes
- #3 It looks like a hairy planet or perhaps a rambutan but NO this is an immune cell in all it’s glory This and many others like it are being pumped through your body as we speak, patrolling for bad guys and prepared for battle.
- #4 But before we get to the killing…. When we say immune system what do we mean? The immune system is made up of a network of cells, tissues, and organs that work together to protect the body from attack by viruses, parasites, bacteria, toxins but also from internal attack as in cancer. Bone marrow, lymphocytes and red blood cells You can think of the immune system as a Complex network of surveillance routes which allow specialized cells to monitor what’s happening and where and to coordinate their efforts to keep you protected.
- #5 Immune responses are mediated by a bunch of different kinds of specialized cells Broadly, there are 2 kinds of responses. : innate and adaptive Each kind of response has it’s special warriors that are dedicated to it The innate immune response functions as the first line of defense against infection. It consists of soluble factors, such as complement proteins, and diverse cellular components including granulocytes (basophils, eosinophils and neutrophils), mast cells, macrophages, dendritic cells and natural killer cells. The adaptive immune response is slower to develop, but is more specific and generates what we call immunological memory. Immunological memory is the basis of why we get vaccinated . Allows us to raise the troops faster and more effectively once we’ve been exposed to something It consists of antibodies, B cells, and CD4+ and CD8+ T lymphocytes. Natural killer T cells and T cells are cytotoxic lymphocytes that straddle the interface of innate and adaptive immunity. Today we’re gonna talk a bit more about natural killers Discuss immunity Memory Vaccination
- #6 So this is actually what is actually going on in your blood Red blood cells…sacks of oxygen And the fuzzy little guys – lymphocytes = white blood cells Survey the environment Patrolling for danger
- #8 Beastmaster vore This is kind of what happens when an NK cell attacks a target
- #9 The natural killer cell (lower left) is locating, binding and attacking a large cancer cell.
- #10 Image shows a scanning electron micrograph of a natural killer (NK) cell (red) embracing a target cell (blue), the surface proteins of which have been biotinylated and stained using streptavidin-conjugated 20 nm gold particles (white dots). Specific experimental details are as described previously105. Ruffled membrane and synaptic filiopodia are clearly evident at the immunological synapse shown, suggesting that membrane morphology could greatly influence the accessibility of proteins for binding, which in turn could influence the duration of intercellular contact. Image was false-coloured by A. Weston, Cancer Research UK, London, UK.
- #11 CREDIT: COURTESY OF BjÖRN ÖNFELT AND DANIEL M. DAVIS(preceding pages) PROTEINS (yellow) cluster at the point where two immune cells meet to trade information. The proteins at this synapse tell a natural killer cell (bottom left) that the B cell (right) is healthy and should be spared. For other cells that fail this test, the natural killer cell has acidic organelles (red) ready to move toward the synapse and deliver a lethal injection.
- #12 The natural killer cell has punctured and destroyed a larger tumor cell.
- #13 The tumor cell's structural matrix is all that remains after its encounter with the natural killer cell.
- #15 a | Following haplo-identical or MHC-matched haematopoietic stem cell transplantation (HSCT), natural killer (NK) cells of donor origin develop in the patient with cancer. b | Alternatively, NK cell populations can be isolated from healthy donors and activated and/or expanded in vitro before infusion into the patient with cancer. In both cases (allogeneic HSCT and NK cell infusion), the aim is to promote the antitumour function of donor NK cells in the patient. Indeed, a fraction of donor NK cells will be not be inhibited by the MHC class I molecules of the patient, as the killer cell immunoglobulin-like receptors (KIRs) expressed by the donor NK cells will not interact with the MHC class I molecules of the patient, and this promotes tumour cell elimination. In contrast to cancer cells, most healthy cells of the patient will not activate donor NK cells, as they lack a sufficient cell-surface density of activating ligands for the donor NK cells. c | An alternative approach is to boost endogenous NK cell activity by treating patients with monoclonal antibodies specific for NK cell-expressed inhibitory receptors. These antibodies are designed to enhance the antitumour activity of the patient's own NK cells without inducing autoimmunity. Download file
- #16 This is what the actual bioproecessing looks like for cellulae immunotherapy So yeah it’s happening…does it work?
- #17 Emma Whitehead’s story Carl June
- #18 These therapies are happening and giving hope to a lot of people who have been fighting these really nasty cancers. Wanna plug LLS for all the good work they do to support scientists to get the research done but also for patients and families.
- #19 Leave with this image Beautiful cells whose sole purpose is to protect us Exciting time for science and medicine The more we understand about how these little cells work the better we can become at harnessing their killer powers to help us develop new therapies for people