ANP1115 Lecture 6: Immune System Part 1 PDF

ANP1115 Lecture 6: Immune System – Part 1 Chapter 17: pp. 651-656 Chapter 21: pp. 783-814 2.3 list the 5 different types of leucocytes and give a brief description of the structure and function of each Leukocytes only formed elements that are complete cells...

ANP1115 Lecture 6: Immune System – Part 1 Chapter 17: pp. 651-656 Chapter 21: pp. 783-814 2.3 list the 5 different types of leucocytes and give a brief description of the structure and function of each Leukocytes only formed elements that are complete cells Fig. 17.9 11,000/l) - body’s response to bacterial or viral invasion - number can double within hours granulocytes & See also Table 17.2 agranulocytes Never Let Monkeys Eat J. Carnegie, B1. Granulocytes neutrophils, basophils, eosinophils spherical, larger than RBCs, lobed nuclei, cytoplasmic granules visible when stained with Wright’s stain (i) Neutrophils: > 50% leukocytes; cytoplasm contains 2 types of granules that take up both acidic & basic dyes - granules contain hydrolytic enzymes & some antibiotic-like proteins (defensins) = polymorphic leukocytes phagocytes: ingest & destroy bacteria; (eg: acute infections such as meningitis, appendicitis) (ii) Eosinophils: 2-4% all leukocytes; blue-red nucleus (often with 2 lobes) + coarse, red granules > ***parasitic worms; cannot be phagocytized, but surround & release digestive enzymes > modulate immune response allergies, asthma (iii) Basophils: rarest WBCs (0.5% of leukocytes); cytoplasmic granules contain histamine (vasodilator, makes blood vessels leaky & attracts other WBCs); S- or U-shaped dark purple nucleus Fig. 17.10 B2. Agranulocytes: includes lymphocytes, monocytes no visible granules; nuclei spherical or kidney-shaped (i) Lymphocytes: 2nd most common leukocyte; large, dark purple nucleus + rim of pale blue cytoplasm; some in bloodstream, but most are in lymphoid tissue (lymph nodes, spleen, etc) T lymphocytes (T cells): act directly against virus-infected cells, tumor cells B lymphocytes (B cells): give rise to plasma cells that produce antibodies (ii) Monocytes: largest leukocytes; gray-blue cytoplasm + U- or kidney-shaped nucleus; in tissue, differentiate into macrophages > phagocytic in chronic infections (eg: TB) > also against viruses, some bacteria J. Carnegie, UofO The main steps of leukopoiesis leukopoiesis is hormonally regulated according to body’s situation interleukins and colony-stimulating factors: hormones that regulate production of leukocytes, as needed Hemocytoblast Stem cells myeloid stem cell lymphoid stem cell Committed myeloblast monoblast lymphoblast cells eosinophil neutrophil basophil monocyte lymphocyte Products bone marrow stores mature granulocytes (not erythrocytes); usually contains ~10X more granulocytes than found in blood lifespan of granulocytes = 0.25-9.0 days (most die in line of duty) J. Carnegie, UofO Fig. 17.11 Leukocyte Disorders (i) Leukemia: cancer of WBCs - usually descendants of a single cell remain unspecialized & mitotic > acute if derives from blast-type cell; chronic if from cells at later stages bone marrow taken over by cancerous cells → severe anemia, clotting problems (also fever, weight loss, bone pain) > NB: WBCs numerous but non-functional - death usually from internal bleeding & overwhelming infections > Treatment: irradiation & administration of anti-leukemic drugs; bone marrow transplant https://medicalxpress.com/news/2016-06-aggressiveness-acu te-myeloid-leukemia-elucidated.html J. Carnegie, UofO (ii) Infectious mononucleosis: caused by Epstein-Barr virus; excessive numbers of enlarged and abnormally-shaped lymphocytes (initially mistaken as monocytes), many abnormal (tired, achy, chronic sore throat, low-grade fever) (iii) Leukopenia: abnormally low WBC count - usually due to drugs, especially glucocorticoids & chemotherapy drugs Infectious mononucleosis & production of atypical lymphocytes; eduserv.hscer.washington.edu/.../  THE IMMUNE SYSTEM Innate (nonspecific) defenses: protect against foreign substances/abnormal cells without having to specifically identify them (generalized carbohydrate/lipid cell surface markers) Adaptive (specific) defenses: (acquired immunity) – subpopulations of lymphocytes that recognize the specific target (usually specific cell surface proteins), subclone themselves and carry out a targeted immune response in two different ways Fig. 21.1 (11th edition) So how does the innate immune get informed/activated? The innate immune system can be triggered by microorganisms entering the body from outside (PAMPs) or by tissue damage without any externally-derived infection (DAMPs; e.g. a sprained ankle, a pulled muscle, a broken bone) What are PAMPs and DAMPs? PAMPs (Pathogen-Associated Molecular Patterns) are molecular patterns associated with molecules not normally present in the body (e.g. bacterial cell wall) – some of these are recognized by Toll-like receptors present on the surface of phagocytic cells – end results are phagocytosis but also triggering of inflammatory response & notification of adaptive immune system DAMPs (Damage-Associated Molecular Patterns) are patterns of molecules in the wrong place in our body (e.g. DNA in the cytoplasm or outside the cell). PAMPs and DAMPs notify the innate immune system that something is wrong with no need to recognize a specific microorganism or to clone subpopulations of cells genetically matched to that microorganism. INNATE DEFENSES Skin & Mucous Membranes  effective, but can be breached ACID: acidity of skin, vaginal and stomach secretions deter growth of bacteria ENZYMES: lysozyme in saliva, respiratory mucus, lacrimal fluid; also, protein-digesting enzymes in stomach MUCIN: digestive and respiratory passageways – sticky, traps microorganisms DEFENSINS: broad-spectrum anti-microbial peptides secreted by mucous membranes and skin OTHER CHEMICALS: some lipids in sebum and dermicidin in http://4.bp.blogspot.com/-x6_92YIWEOA/UKEUN5vk-zI/AAAAAA AAByE/LlHatSUli6k/s1600/first+line+of+defense.jpg eccrine sweat are toxic to bacteria Inflammation a response to any type of injury 4 key signs: redness, heat, swelling, pain (i) prevents spread of microorganisms to nearby tissues (ii) disposes of cell debris & pathogens (iii) sets the stage for repair processes (iv) alerts the adaptive immune system inflammation occurs as part of innate defenses & can be amplified by adaptive immune system responses inflammatory chemicals (e.g. histamine, kinins, prostaglandins, complement) released by injured cells, macrophages, lymphocytes → promote arteriole dilation and capillary leakiness – can also attract other immune cells to the site of injury/infection Fig. 21-1 (rotated)  What causes pain during inflammation? Why is inflammation a helpful response to tissue injury? Define: margination, diapedesis, chemotaxis Fig. 21.2 Fig. 21.3: Summary of Inflammation  Fig. 21.4 Interferon: secreted by virus-infected cells – diffuse to nearby non-infected cells & block protein synthesis, also degrade viral RNA virus not identified or recognized interferon can also activate macrophages & mobilize natural killer cells, allowing for some anti- cancer effects as well Click on image to link to a short news video regarding interferon and COVID 19 Fig. 10-6 (S/W): Another View of the Interferon Mechanism Complement: refers to a group of at least 20 plasma proteins circulating in an inactive state once activated, various components amplify all aspects of inflammatory process C3b functions as an opsonin – what does this mean? J. Carnegie, UofO MAC = membrane attack complex Fig. 21.5 Fever body’s thermostat normally set at ~370C reset by pyrogens released by leukocytes & macrophages exposed to bacteria & other foreign substances high fever is dangerous – why?? moderate fever is helpful: (i) speeds up metabolic rate (ii) causes liver and spleen to sequester iron and zinc J. Carnegie, UofO What are Natural Killer Cells? another type of lymphocyte; NOT specific to a particular antigen so part of the innate immune system and no recognition of a specific antigen MHC 1 (major histocompatibility complex) is expressed by all nucleated cells in our bodies attack virus-infected or cancer cells; two triggers: a combination of expression of a stress marker and a lack of protective MHC 1 cells infected with viruses reduce their expression of MHC 1 (major histocompatibility complex), as do some types of cancer cells Recent studies have shown that natural killer cells also express Toll- like receptors, providing a mechanism for them to be triggered by various PAMPs and/or DAMPS. http://sphweb.bumc.bu.edu/otlt/MPH-Modules/PH/Ph709_Defenses/PH709_Defenses4.html  Adaptive Mechanisms 3 key players: 1) B lymphocytes (humoral immunity) 2) T lymphocytes (cell-mediated immunity) 3) macrophages (antigen-presenting cells) Lymphocytes originate in red bone marrow from hemocytoblasts initially, all lymphocytes are identical – it becomes a B- or T-lymphocyte depending on where it matures (self tolerance, immunocompetence) What is an antigen?? Basically, something capable of mobilizing adaptive defenses (antibody generating) – can have multiple antigenic determinants What is the major histocompatibility complex? – a group of cell surface glycoproteins that mark a cell as “self” – each MHC protein has a groove into which a self-antigen or a foreign antigen can be inserted Fig. 21.6 J. Carnegie, UofO Fig. 21.7. Lymphocyte development, maturation & activation T-cells: migrate to thymus where undergo maturation (2-3 d) under direction of thymic hormones – need to acquire immunocompetence and, equally important, self-tolerance – on average, only 2% success rate! 1. Fig. 21.8. T cell education in the thymus J. Carnegie, UofO 2. B-cells: immature lymphocytes undergo maturation in bone marrow; self reactive “It is our genes, not ones again weeded out antigens, that determine once immunocompetent, display unique what specific foreign receptor on cell surface which makes them substances our immune able to react to one & only one foreign system will be able to antigen recognize and resist.” lymphocytes become immunocompetent before meeting antigens they may later attack B-Cells & the Humoral Immune Response antigen challenge usually in spleen or lymph node if the lymphocyte is a B-cell → a humoral immune response is evoked (i) plasma cells turn out specific antibodies (~2000 molecules/sec); last 4-5 days (ii) antibodies circulate & bind to antigens and mark them for destruction (iii) clone cells that don’t become plasma cells remain as memory cells; can be called upon years later Fig. 21.10 Fig. 11-10 (S & W). A plasma cell is an activated (terminally differentiated) B cell – it is filled with an abundance of RER that is distended because it is filled with antibody molecules.