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DGfI Day of basic immunology An Evolutionary Arms Race Infection Immune system Viruses and other infectious agents have developed many ways to escape the immune system, but the immune system also has a lot of clever strategies Credits: Ahmed Sheriff, Deniz Zeisig, Susanne Bürgis, Alexandros Theodoridis, Tobias Strapatsas, Hans-Martin Jäck, Aaron Marshall Day of Day of Pandemic: Spanish Flu 1918/1919 Estimated 40 Million dead Day of Infectious microbes are everywhere: Bacteria, viruses, fungi, parasites Influenza virus Salmonella bacterium How does the body defend itself against these invaders? With the help of the Immune system Day of Our Immune System can also defend us against cancer arising in the body A T cell (orange) killing a cancer cell (mauve) Day of When the immune system errs... ALLERGY Allergy happens when the immune system mistakenly “defends” against a microbe that’s not really a microbe: pollen, house dust, cat hair, specific foods… A very widespread problem, and rising: up to 30% of the population in some developed countries Why do some people´s immune systems give allergic reactions, but not others? Day of When the immune system errs... Autoimmunity Rheumatoid arthritis (joints) Inflammatory bowel disease (intestine) Type I diabetes (pancreas) Multiple sclerosis (brain and spinal cord) Systemic lupus erythrematosus (multiple tissues) It is also important to know how we can turn an over-active immune system OFF! Day of Know your immune system! What is it really? Consists of certain substances and cells in the body, that each provide different kinds of defenses against pathogens The armed forces of the body: • White Blood Cells such as B-cells and T-cells (Lymphocytes) • Phagocytes • Blood proteins • Antibodies Day of Defence mechanisms against infections (I) Innate Immunity Barriers Blood proteins Phagocytes (II) Acquired immunity B- and T-Cells Day of (I) Innate Immunity - Barriers Skin Saliva Stomach acid Intestinal flora Pathogens find ways to penetrate body barriers! Day of (I) Innate Immunity = immediate defence reactions Proteins from the blood attach to microbes marking of the microbes for phagocytes (eat me!) direct destruction of microbes Phagocytes, also known as macrophages Microbes become food! HELP Attract more phagocytes Release messenger molecules that affect the whole body (Interleukins) Fever, new formation of phagocytes, opening of local blood vessels Day of A wound = a call to arms! Inflammation brings rapid assistance Characteristics of inflammation: Redness, swelling, pain, heat The fight begins against growth and spreading of the pathogens : phagocytes are called in, wound healing is started Day of Defence mechanisms against infections (I) Innate Immunity (II) Acquired immunity Barriers Blood proteins Phagocytes Ready to fight many pathogens Activation of specific immune cells: B- and T-Cells Need to learn how to fight each new pathogen (and can remember afterwards!) Day of (II) Aquired immunity - the Lymph System Adenoids Tonsils Lymph nodes Kidney Thymus Heart Spleen Peyers Patches Appendix • Thymus • Bone Marrow • Lymph nodes • Spleen • Tonsils Lymph nodes Bone Marrow • Appendix Day of (II) Aquired immunity = a custom-tailored defensive strategy Initiation Phagocytes and dendritic cells alert B and T cells Z Z Z Z Z T Who needs my help? ZZ Z Activation! Day of T-cells get into the action T-cell Killer T-cell Destruction of the infected cells Asta la vista, baby! Helper T-cell Activation of B cell Antibody production Day of B-cells get into the action Interaction of B-cell and T-Helper cell in lymph node T Here comes help! Finally you‘re here! B cell becomes a plasma cell Antibodes are produced to neutralize the invader! Day of Influenza Virus Antibodies bind to surface projections neutralizing the virus Day of Lock-and-Key Principle Day of The immune system has a memory ! The immune system can learn ! Memory B- and T-cells can remember the invading microbe for years. Therefore next time the same microbe is encountered, one can fight it off faster and more effectively. Think vaccination!!! T B Day of BUT - Viruses routinely use small variations to evade immune memory! Small variations in the Virus genes Small variations in the virus surface structure Y Reduced protection by Antibody Day of OR RARELY - Large change to completely escape immunity: Large variations in the Virus genes occur in another species Completely different virus surface structures NO protection by Antibody - Bird flu pandemic! Bird cell Day of Defence mechanisms against infections (I) Innate Immunity (II) Acquired immunity Barriers Blood proteins Phagocytes Activation of specific immune cells: B- and T-Cells Fast Takes time to develop Specific for type of microbe Specific for exact microbe Constant level of protection Memory for strong protection in the future Day of What causes allergy? Pollen B cell meets an Allergen and produces antibodies -> WHY do B cells sometimes mistake Allergens for Pathogens? Day of Mast cells bind these antibodies on their surface Day of When the loaded mast cells come into contact with allergen they are activated and produce histamine Histamine Allergy symptoms Why do some people‘s immune systems give allergic reactions, but not others? Genes Environmental exposure to allergens Air pollution Smoking ??? Day of Questions How can we reverse immune responses to allergens? How do we turn off autoimmunity without completely destroying the immune system? Can we mobilize the immune system to fight off cancer? How can we quickly mobilize the immune system to fight new emerging infectious diseases? SARS, bird flu How to develop vaccines for chronic infections such as HIV? Day of We’re working on it! Day of Your Questions?