Immunology Lecture 1 2024 PDF

Is the immune system important and what exactly does it do? 12th November 2024 Introduction to the immune system  Learning objectives Learn about the importance of immune system Start to describe its anatomy and organisation Begin to name and understand immune cells...

Is the immune system important and what exactly does it do? 12th November 2024 Introduction to the immune system  Learning objectives Learn about the importance of immune system Start to describe its anatomy and organisation Begin to name and understand immune cells-in fact quite a few!! State and introduce some immunology concepts  The Immune System Prevent / limit infection Is that it? Do all of these organisms have an immune system?  The immune system-3 questions to ponder? Can you live without an immune system? What happens when you take the immune system away? Why don’t we just try to live in a sterile environment? What is foreign?  How many of you have done aqua/water zorbing? How many of you have heard of the bubble boy? Severe combined immunodeficiency disease (SCID) Lethal irradiation of mice and humans Immune cells are known to be vulnerable to radiation: – apoptosis (programmed cell death) in mature T and B lymphocytes (long-lived white blood cells responsible for adaptive immunity) – by lethal damage in bone marrow stem cell precursors of monocytes and granulocytes (short- lived white blood cells responsible for innate immunity) as well as natural killer cells (lymphocytes responsible for innate immunity). Doses of A-bomb radiation, both mature lymphocytes and bone marrow stem cells were severely damaged Immune cell depletion As a result, many people died from active infections Radiation effects research foundation. http://www.rerf.jp/radefx/late_e/ Extreme immune deficiency leads to recurrent infections Why don’t we just try to live in a sterile environment? Gnotobiotic (Germ-free) mice  Gnotobiotic mice-no microbes in the gut Reduced size of lymphoid organs Reduced serum IgG Payer’s patches do not develop properly Isolated lymphoid follicles are absent Reduced T cells in lamina propria and epithelium Defective production of cytokines and AMP  The clean/sterile environment in humans Hygiene hypothesis Vaginal birth vs Caesarean section Early exposure to certain antigens / bacteria can protect against infections in the future.  Immune system-anatomy and organisation Immune System 1st line 2nd line 3rd line Intact skin and Innate Immunity Acquired Immunity mucous membranes (Natural) (Adaptive) Barrier Non-Specific Specific B-lymphocytes Complement T-lymphocytes Neutrophils Memory T cells Monocytes / macrophages Cytotoxic T cells Natural Killer Cells Antibodies  Immune System-the functional units and layers Organs Cells Messengers – Intracellular – Intercelluar Macromolecules and Molecules  Cells of the immune system All functional immune cells are derived from the ‘hematopoietic stem cell’ (HSC) < 1 in 50,000 cells in BM HEMATOPOIESIS – The differentiation of HSC into mature blood cells Hematopoiesis-progenitor cells Granulocy te/ Monocyte Eosinophil Myeloid progenito Basophil r Megakaryocyte HSC Erythrocyt e T-cell Lymphoid progenito B-cell r NK cells  Hematopoiesis-site Granulocy te/ Monocyte Eosinophil Myeloid Bone progenito Basophil r Marrow Megakaryocyte HSC Erythrocyt e Lymphoid T-cell Thymus progenito B-cell r NK cells mages in Kuby Immunology p51 and 53  Primary lymphoid organs Where immune cells develop Thymus – SELECTION and maturation of T-cells Bone Marrow – MANUFACTURER – Supports self renewal of HSC – Supports differentiation of HSC to mature blood cells  Secondary lymphoid organs Where the immune response is generated and organised: Spleen Lymph nodes Mucosal associated lymphoid tissue (MALT) – BALT – NALT – GALT (tonsils, adenoids, appendix, Peyer’s Patches Intracellular signal transduction Cell surface receptor Transmembrane domains Adapter molecules Signaling molecules Nuclear localisation Gene transcription  Intercellular signalling Communication between cells Autocrine-secreted and acts on the same cell Paracrine-secreted and acts on another cell Endocrine-secreted into the circulation for action at a different site in the body Messengers are called CYTOKINES  What is foreign? Pathogens Disease Colds Organ transplants Prosthetic joints and medical devices BUT  What about? Food Commensal bacteria-skin and gut – More bacteria than human cells – Gnotobiotic mice Sperm / vagina Babies in the uterus Antibodies in breast milk  Self and nonself Self-Nonself theory (Burnett 1965) ‘only non-self entities activate the immune system’ Infectious nonself theory (Janeway 1989) ‘only entities that express conserved pathogen associated molecular patterns activate the immune system’ Danger hypothesis (Matzinger 2002) ‘The immune response is triggered by danger signals from damaged tissues’  The concept of ‘tolerance’ In health the immune system does not attack itself (SELF- TOLERANCE) Producing the correct response against the correct antigen Resistance against self antigens The ability to discriminate between pathogens and commensals Immune cells with high affinity for ‘self’ are destroyed in the thymus  The concept of immune ‘privilege’ Some sites are more tolerant of ‘foreign or non-self antigens’. Brain, Eye, Testis, Fetus and Uterus unit Here there is a COST/BENEFIT ratio Damage to a sensitive organ vs an advantage to the host – The GUT  The concept of immune ‘memory’ The ability of the immune system to respond: – More swiftly – More efficiently – During a second response to the same pathogen Suggests a ‘learned’ ability Suggests an ability to ‘store’ information  The Immune System Prevent / limit infection – detecting microorganisms – Killing microorganisms – Differentiating pathogens from non-pathogens – Removing debris – Returning the body to a state of ‘Homeostasis’ – Generate ‘Memory’ – Normal organ development  Next lectures Beginners guides to: Innate Immunity: Later Adaptive Immunity: Tomorrow