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Immunology NOTES.docx

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Department
Physiology
Course Code
PHGY 209
Professor
Ian Gold

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Dw too much about viral infection and complement Two immune response discussed: -innate immune response was thought useless -adaptive immune response  was thought important but it was discovered opposite to have borrowed from the innate response to make us more efficient. Immunity can apply to bacteriahumoral immune response -antibodies are humoral material.. SCIDsevere combined immune deficiency They have neither humoral antibody, nor the ability to generate a cell-mediated immune response… The analyses of these children after death, shows us a lot of the immune system.. They have no Thymus-gland.. bone marrow are hypo-cellular, no lymphocytes or lymph nodes … ------------------------------------------------------------------------------------ AIDS Started by Gay-related immune deficiency then was called-->acquired immune deficiency syndrome(AIDS)viral infectionHuman immunodeficiency Virus (HIV) CAUSE: A particular cell that is missing or rapidly drops off and when it drops below a certain level, the person is so sick that they die… Missing cell is TH4-helper cell—a lymphocyte ORGANS of the Immune System • Primary Organs – (Stem cells from the Yolk Sac and Fetal Liver)EXAM !!!(prior to birth) (these cells are passed on first to the Bone Marrow then the Thymus Gland) – Bone Marrow – Thymus Gland • Secondary Organs(before birth these secondary organs are populated with B-cells and T-cells from the primary ) – Lymph nodes – Spleen – Mucosa-Associated Lymphoid Tissue (MALT)(occurs in the Gut, under the endoderm of the Bowel, and under the bronchiole tissue of the tubes leading to the lungs note: CD4+ are all T-helper cells[not cytotoxic] Development of the immunoglobulin takes place in parallel with B-cell maturation. B-cell maturation occurs in the absence of antigen, Dw too much about viral infection and complement -First observation of the immune response in the west took place because of the Smallpox disease.(NOT CHICKEN POX) Dr. Edward Jenner discovered cure: -This disease killed so many people, EXCEPT milkmaids…these milkmaids were however still had the chance to catch other diseases(e.g. chicken pox) -These milkmaids had Cow Pox(AKA Vaccinia), from the cows.. which made them resistant to Smallpox!!(Cow pox gave the person resistance to Small pox) -People were vaccinated by Vaccinia in order to be saved from smallpox… The disease was then gone after a certain point.. ANTIGEN • 1. Immunogen(refers to Antigen)(a material that can evoke an immune response..humoral antibody in the serum or cellular lymphocytes in blood) • 2. Hapten (+ Carrier = Immunogen)(is a foreign material that is too small to induce a immune response by itself(e.g. Dinitrophenol)… a Hapten requires a carrier molecule(the protein) which together makes it an immunogen.. A HAPTEN IS WHAT IS TARGETED BY THE ANTIBODY… • 3. Allergen (are antigen that cause allergy..e.g. from ragweed pollen) Most allergens are completely harmless.. it is the immune response directed towards them is what causes the damage. A person must be first exposed to an allergen(e.g.breath in), which then evokes the immune system to recognize the allergen and cause the damage. NOT immunogenic to everyone, but whoever’s immune system has the genetic ability to react to the allergen, will be affected by the allergy.. An offspring’s immune system is susceptible to different types of allergys compared to the parent (not all allergic to same shit… not really passed down exactly!) • 4. Tolerogen: leaves someone tolerant to somethings that others are not • 5. Ligand: Antigen binds to antibody.. so both are considered a ligand EVERY CELL IN THE BODY contains the SAME GENOME (e.g. the brain and the Liver have the same genome) why the liver cell is liver cell and not brain, is because the brain cell information is suppressed…different stem cells have their own purpose.. note: CD4+ are all T-helper cells[not cytotoxic] Development of the immunoglobulin takes place in parallel with B-cell maturation. B-cell maturation occurs in the absence of antigen, Dw too much about viral infection and complement -Hematopoietic stem cells: give rise to ALL BLOOD CELLS… Monocyte: as it comes out of the bone marrow, goes into the tissue and becomes the fixed tissue macrophage(described later) monocyte or macrophage depend on where they sit The Three Lines of Defenses of the Host 1- The Coverings of the Body (Skin and Mucous Membranes, which BOTH need to be present to keep you from being affected and evoking a immune response) -skin and mucous membranes: provide unpleasant living conditions for microorganismsepidermis, Mucus, pH, Enymes 2 – The Innate Immune Response came early in evolution! Bone fish bla bla..stimulated by danger signals(PAMP)  comprise of cellular material: -Phagocytic cells [eats microorganisms (neutrophils[has granulosidic cytoplasm], macrophages[reaches out to ingest bacteria], interdigitating dendritic cells[ingest bacteria[keep inside] and carry them as whole bug on the surface.. have bacteria inside & outside])….also Natural killer cells… -Cells with inflammatory mediators (basophils, mast cells[not emphasized much...], eosinophils) comprise of humoral factors: Acute phase reactant(e.g. C-reactive protein[used by doctors to see if inflammatory reaction is shown, Complement[a sequence of molecules..talk in details later.. also present in adaptive immune response?], interleukin,etc.) & Cytokinins (interferon-alpha) note: CD4+ are all T-helper cells[not cytotoxic] Development of the immunoglobulin takes place in parallel with B-cell maturation. B-cell maturation occurs in the absence of antigen, Dw too much about viral infection and complement NO MEMORY repetitive.. if you step on glass..everytime will be same reaction.. sees danger signalPAMP - the first cell to be involved in the innate immune response (OR AN IMMUNITY in general) is called: fixed tissue Macrophage (its sitting in the tissue right through all your body, under the skin `, under the bronchiole tree, under the gut mucosa.. toll-like receptors(TLR) are on he surface of these macrophages, found on all hematological cells, toll-like got its name because the TLR was first found in fruit-flies. -TLR, recognize PAMPs(pathogen associated molecular patterns) which are patterns on microorganisms that are not present on mammalian and human tissues. When a TLR sees a PAMP, it attacks in because its not part of the mammal…PAMP shows where the bacteria and since the TLRs binds onto it…(PAMP=lipopolysacchide,& peptidoglycan) PAMPthese are not present in human or mammels -Lipopolysacchide(LPS) of gram-negative bacteria -Peptidoglycan(PGN) of gram-positive bacteria TLRtarget those foreign to humans&mammal , evoke immediate immune response When the fixed tissue macrophage takes up a bacteria’s PAMP.. it emits a signal : MDNCF[Monocyte derived neutrophil cytotactic factor[recall: Monocytebecome the fixed tissue macrophage] -monocytes secrete : Monocyte derived neutrophil (chemotactic[in the neutrophil])?? factor, which brings in neutrophils.. this will happen AGAIN at the END of the immune response for totally different reasons.. these same cells that are there at the beginning, wind up there at the end with the adaptive immune response, borrowing from the innate immune response. Signal comes from the fixed tissue macrophage[from monocyte?] to call in the neutrophils…to call in neutrophil there are steps: For neutrophils to get there, 1)theres a signal(MDNCF), that says to neutrophil that it needs help! 2)neutrophils are in blood and are rolling in the capillary and need to get out of the capillary and go where the bacteria is.. 3)so the neutrophil’s receptors and the endotherial cells of the capillary’s receptor have to change..dont need to know details of the receptor names and shit right now.. but the receptors change allowing the neutrophils to adhere to the inside wall of the capillary… 4)the neutrophils keeps rolling until it can squeeze itself out of the capillarys and through cells and into the tissue… through a process called Diapedesis… 5)After entering the tissue the neutrophil goes to the site of the bacteria to get rid of the bacteria through phagocytosis note: CD4+ are all T-helper cells[not cytotoxic] Development of the immunoglobulin takes place in parallel with B-cell maturation. B-cell maturation occurs in the absence of antigen, Dw too much about viral infection and complement 6)There are many ways of phagocytosis, but one of the forms the neutrophil sacrifices itself… takes in the bacteria and digests it and excretes it and DIES…before this death occurs, the neutrophil throws out chromatin DNA and proteases.. and forms to hold in and contain the bacteria in a NET[neutrophil extracellular trap] so it doesn’t spread.. and neutrophils dies JUST KNOW THAT the neutrophil DIGESTS bacteria, contains the bacteria in a NET[neutrophil extracellular trap] goes through oxidative electron transfer, and DIES -dead bugs(bacterias) and dead neutrophil which sit under the skin MAKE UP PUSS, After neutrophils come into the area of infection.. they digest bacteria and die.. fixed tissue macrophage is not needed anymore… NEXT CELL INVOLVEDDendritic Cells[discovered by ralph minor…] -Dendritic cells take in the remaining bacterias.. and go up the lymphatic system and into the lymph node of the GROIN[the regional lymph node for bacteria from your foot] Other cells part of the innate immune response : Natural killer Cells There are number of natural killer cells…given later but not really important to know the different types.. NK cells kill your own cells unless they are turned off.. -Cells have a NK cell activating Ligand which bind to NK cells, also, there is a molecule called [Major Histocompatibility complex] MHC class I molecule which Why not make a substance that specifically removes MHC molecules of Cancer cells… -however, if the MHC class I molecule is not present, the NK cell will not be turned off and will kill that cell, even if it is its own… -However the NK cell activating Ligand MUST be present for the NK cell to recognize the cell that is to be killed. -The MHC class I molecule that turns off the NK cell is the present on all nucleated cells.. This occurs in auto-immune diseases and even cancer.. many cancers patients modify or lose MHC class I molecules, so it cant turn off the NK cells.. virus’ can alter the MHC class I molecules, so the NK cells kill the virally infected cells.. ------------- COMPLEMENT pathway (humoral factor)[ also part of adaptive immune system [will get more details during adaptive immune system] -Has three(3) possible activation sites.. three different activating pathways to activate the Complement 1)Classical Pathway:Antigen/Antibody complexes[talked about later] note: CD4+ are all T-helper cells[not cytotoxic] Development of the immunoglobulin takes place in parallel with B-cell maturation. B-cell maturation occurs in the absence of antigen, Dw too much about viral infection and complement 2)Alternative Pathway: PAMPs on the pathogen surfaces 3)MB-lectin pathway(dw about this..) Alternative vs. Classical pathway
 - The means by which the two pathways are activated is different, but they eventually converge on the same complement proteins Know that PAMPS can activate complement for the innate immune response, which leads to the killing of pathogens ------------- 3 -The Adaptive (Acquired) Immune Response – Humoral (Immunoglobulin/antibody mediated) – Cell-mediated (T cell/lymphocyte effector) – UNLIKE innate response.. IT HAS MEMORY • Antigen (and epitope) specific • Antigen presenting cells (APC) –> ( MHC class II+peptide )this is where the T-cells bind onto..(after a T-cell finds its specificity, it will clone and undergo many division creating daughter cells that will also divide which will build up an army of cells that recognize the same antigen (clonal expansion) • [THERE ARE ONLY 3 APC in the body (THE ONLY MHC class II )! – Interdigitating dendritic cell – Macrophage – B lymphocyte (B cell) These are the only 3 cells in the body that can present antigen MHC is the type of molecule against which a tissue rejection response takes place.. it’s a MHC antigen which is transplanted… transplantation occurs by chance not naturally...MHC is unique to almost each person.. maybe 6 people in the world have same MHC… There are Two types of MHC molecules.. CLASS I( present on ALL nucleated cells of the body.. and they turns off NK cells), and CLASS II[present on ONLY 3 cellsDendritic cell, Macrophage, and B lymphocyte(B cell)] MHC class II are antigen-presenting moleculespresent the peptides of the bug after the bug(bacteria)[antigen] is destroyed and broken down into pieces.. the peptides from that bug are flipped into MHC class II molecule on the surface of the dendritic cell [the dendritic cell that starts life as part of the innate immune response is what links the innate immune response to the adaptive immune response… ] MHC’s have no specificity to the peptide they receive.. note: CD4+ are all T-helper cells[not cytotoxic] Development of the immunoglobulin takes place in parallel with B-cell maturation. B-cell maturation occurs in the absence of antigen, Dw too much about viral infection and complement The Major Histocompatibility Complex CLASS I [ those present on all cells] each species MHC are different.. and are categorized as followed: terms Complex & System intercolate.. EACH MHC in a person is UNIQUE!!! It defines you!!! • Mouse: H2 complex • Human: HLA complex (Human Leukocyte Antigens) • HLA System • Two (2) molecular classes – MHC I (HLA-A, HLA-B, HLA-C) [have 20 alleles per site.. so this leave most humans with unique MHC] – MHC II (HLA-DP, HLA-DQ, HLA-DR)[also have 20 alleles per site] In each class, molecules have 2 chains – (alpha) and – (beta) • In MHC (HLA) Class I molecules, the chains are of markedly different molecular masses: A large alpha chain, and a small beta-2 microglobulin chain. • In MHC (HLA) Class II molecules, the alpha and beta chains are almost of the same size. ANOTHER(like neutrophils) way of phagocytosis can be done by Dendritic, macrophage, or B-lymphocyte(B-cll) 1) Antigen gets ingested and breaks down 2) There is a synthesis of the MHC Class II protein which hold a and antigen peptide fragment.. 3) Comes to the surface of the dendritic cell This process happens because the cell wants the auto immune system to recognize the foreign antigen.. the immune system wont recognize the MHC, because it is part of the person, therefore the MHC is to hold out the ‘foreign’ antigen protein fragment. note: CD4+ are all T-helper cells[not cytotoxic] Development of the immunoglobulin takes place in parallel with B-cell maturation. B-cell maturation occurs in the absence of antigen, Dw too much about viral infection and complement Dendritic cells grab the remaining bacterias and goes to the T-Helper cell (which is what was missing in HIV AIDS patients) -ALL T-Lymphocyte Helpers are CD4-positive This cell[T-helper cells] is the first specific reactionCD4+ [cluster differentiation]is the marker for ALL T-Helper cells.. ALL T-Helper cells have CD4+ on their surfaces.. Dendritic cells link the innate immune system with the adaptive immune system…FIRST SPECIFIC REACTION! With the T-helper cells. Glic & Cheng -wanted to show why we should immunize cows n chicken in a farm.. -Main interest was the Bursa of Fabricius…no one knew what this part did…this part sits in chicken at the CLOECA(the main exit point of the Urinary and Digestive system) -he removed the Bursa to try an immunize the chicken… nothing happened… -if you immunize a serum and add it to the antigenic material..a white precipitate should form in between the antibody and the antigen… the ligands precipitate…. NOTHING happened when cheng added serum to antigenic material… -CHENG did an error..he used eggs that Glic had bersectimized ..paper was publishd -Another scientist realized that the Bursa is the place, where the cells that make antibody, come from… the Bursa contained Lymphoid cells and epithelial cells.. -these Lymphoid cells were then called B-Lymphocytes [b=bursa~ for human its bone marrow] -At this time.. another scientist tried removing the thymus in mice during birth or immediately after birth.. -These animals where kept safe from infection until they were adults.. -They made antibodies… but they made it poorly.. -they could not reject grafts.. and could not effectively protect themselves against viruses -The Thymus ALSO consists of Lymphoid and epithelial cells.. -this led to think that T-lymphocyte cells, T-cells (T=thymus), help B-cells(the B lymphocyte cells) make humoral antibody and also take part in cell-mediated immune reactions AKA T-helper cells T-cells help the B-cells and are critically involved in cell-mediated immune response (graft protection[foreign shit coming in] , viral protection, etc) Human don’t have Bursa, the B-cell come from the Bone marrow instead! note: CD4+ are all T-helper cells[not cytotoxic] Development of the immunoglobulin takes place in parallel with B-cell maturation. B-cell maturation occurs in the absence of antigen, Dw too much about viral infection and complement -Stem cells originate[before birth] from the Yolk sac & Fetal Liver -stem cells are then passed to the Bone marrow -Bcells and Tcells start of as Stem lymphocytes -Stem lymphocytes are sent into the Thymus BEFORE being differentiate
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