BIOT 203 Fall 2023 Immunology Updates PDF

BIOT 203 UPDATES 1) Update to the Critical Path (revised update is available on Blackboard) 1) 2) 3) 4) Lectures – weeks 8, 9, 10, & 11 (Units 7-10) Case Study – Nov 29 (Week 12) Final Exam - Dec 6 (Week 13) Presentations of Group Project (Week 14) 2) Midterms - will be available for review next T...

BIOT 203 UPDATES 1) Update to the Critical Path (revised update is available on Blackboard) 1) 2) 3) 4) Lectures – weeks 8, 9, 10, & 11 (Units 7-10) Case Study – Nov 29 (Week 12) Final Exam - Dec 6 (Week 13) Presentations of Group Project (Week 14) 2) Midterms - will be available for review next Tuesday during drop-in office hours (11:00am-2:00pm) 1) The test will NOT be posted on blackboard for review, and this will be the only time to view your exam. 3) Midterm Grades will be posted to myHumber on Friday. 4) Group Presentation Assignment DUE: • Dec 12, 2023 (11:59PM) • the evening before in-class presentations • Must work in groups • 3-5 students per group • Must enroll in a group on Blackboard by Nov 8 at 11:59PM • Find an academic, peer-reviewed research paper from the Humber library on an immune disease or disorder, and emerging treatment Overview • Create a 5 minute educational video • 11% • Generate a written Report • 7% • Submit a Self and Peer evaluation • 2% 20% of final grade 4) Group Presentation Assignment Video • 5 minutes, presenting the paper of your choice • Identify immune disorder, disease, dysfunction, and an emerging therapy • Explain HOW the immune system is compromised or impacted • Ask yourself: What is going wrong? What is not functioning properly? • Examine how the emerging treatment paradigm aims to correct or support immune system • Interpret how the application of biotechnology in immunology has been used in the paper • ex: ELISA, FACS, PCR, etc. Report • Abstract • 250 words (MAX) summarizes the content of the video. Can NOT be the same as the abstract from the paper you are presenting • Video link • do NOT post the video directly to Blackboard • Transcript • Translate all audio from the video to text • APA style reference list • Must include the paper that you are presenting and any other papers that you may use to help prepare the video Professionalism • Submit a Self and Peer Evaluation form • This is an individual submission • Application & Assessment #1 feedback • Group Projects Immune Dysfunction IMMU N OL OGY | B IOT 203 FA L L 2 0 2 3 | W E E K 8 D R . N IC H OLA S L E B L ON D Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 4 Unit 7: Immune Dysfunction TOPICS LEARNING OBJECTIVES Hypersensitivity Describe tolerance and self-tolerance, as it relates to immune response ◦ I, II, III, IV ◦ Mechanism ◦ Examples Autoimmune Disease Immunodeficiency Atherosclerosis and Cardiovascular Disease Fall 2023 | J.Memme Define and describe the four classes of hypersensitivity. Differentiate between allergies and autoimmune disease. Differentiate amongst various disorders related to immune system dysfunction. IMMUNOLOGY | BIOT 203 5 Immune Dysfunction Dysfunction of the Immune System gives rise to a variety of autoimmune diseases or immune disorders Normally due to the functional defect in one or more cells of the immune system Hypersensitivity Autoimmune Immunodificiency Hyperactive or hypoactive Acquired or congenital Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 6 Hypersensitivity Immune system DAMAGES the body instead of PROTECTING Type I ◦ IgE Mediated ◦ Allergies Type II ◦ IgG Mediated Cytotoxic ◦ Blood Group Incompatibility Type III ◦ Immune Complex ◦ Systemic Lupus Erythematosus By OpenStax College - Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013., CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=30148349 Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 Type IV ◦ Cell Mediated ◦ Type I Diabetes 7 Type I Hypersensitivity IgE-mediated degranulation of basophils and mast cells and release of vasoactive amines mast cell ◦ Smooth muscle contraction: Bronchospasm - (constriction of the muscles in the walls of the bronchioles) leads to breathing difficulties ◦ Blood vessel dilation: Vasodilation - leads to decreased blood pressure ◦ Accelerated heart rate: increased circulation ◦ Edema: Swelling, vasodilation of capillary endothelium ◦ Rapid: occurring within minutes of exposure to an antigen Mast cell releases granules à inflammation By OpenStax College - Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013., CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=30148349 Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 8 Type I | IgE-Mediated Tendency to have type I hypersensitivities is inherited ◦ Reactions occur in at least 20% to 30% of population IgE causes immediate hypersensitivities ◦ Immediate reaction of the sensitized individual - within minutes of exposure ◦ Sensitization occurs when antigen contacts some part of body and induces response IgE antibodies bind to receptors on mast cells and basophiles ◦ Antigen readily binds IgE antibodies ◦ Within seconds, mast cells degranulate releasing mediators that initiate immune reaction Localized or systemic (anaphylactic shock) Examples: Allergies to pollen, pet dander, insect venoms, fungal spores, dust mites, peanuts, penicillin Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 9 Type I | IgE Mediated Mechanism First exposure IgE antibodies are produced in response to an antigen (allergen) https://www.onlinebiologynotes.com/wpcontent/uploads/2018/03/hypersensitivitytype-I-sensitizing-dose.png Re-exposure Antigen is detected by mast cell or basophil ◦ Receptors have the same specificity as IgE antibodies Cell undergoes degranulation ◦ Releases inflammatory mediators produced ◦ i.e. histamine, leukotrienes Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 10 Type I | Local Anaphylaxis Most allergic reactions are LOCAL anaphylaxis Hives ◦ Allergic skin condition characterized by formation of wheal and flare rash Hay fever ◦ Allergic condition caused by inhaled antigen ◦ Condition marked by itching teary eyes, sneezing, and runny nose Asthma ◦ Respiratory allergy ◦ Allergic mediators attracted to inflamed respiratory tract ◦ Results in increased mucous secretion and bronchi spasm By BruceBlaus - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=61465356 Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 11 Diphenhydramine Active ingredient in Benadryl Type I | Allergies Vasoactive amine: histamine ◦ Constricts bronchial muscles, vasodilation, etc. Treatment Loratadine ◦ Antihistamine: competitively blocks histamine receptors By Harbin - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=7674614 Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 12 Type I | Systemic anaphylaxis Vasodilation throughout body BP drops capillaries become porous Edema (swelling) Constricts brachioles Systemic anaphylaxis ◦ SEVERE allergic reaction ◦ RAPID, may cause death Antigen enters bloodstream and becomes widespread ◦ Massive release of mediators causes extensive blood vessel dilation and ◦ Reactions affect almost entire body ◦ Can induce shock ◦ Can result in fluid loss ◦ Causes fall in pressure leading to blood flow insufficiency By Mikael Häggström - Own work, CC0, https://commons.wikimedia.org/w/index.php?curid=17700404 Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 13 Type I | Systemic anaphylaxis Treatment ◦ Epinephrine autoinjector (i.e. EpiPen) ◦ Relaxes muscles in airway, stomach, intestines, bladder ◦ Increase blood pressure Immunotherapy ◦ Desensitization or hypo-sensitization ◦ Inject individual with extremely dilute suspension of allergen ◦ Concentration of allergen gradually increased over time ◦ Individual gradually becomes less sensitive ◦ Injection of antibodies to bind IgE ◦ Most IgE are bound to mast cells and basophiles ◦ Essentially anti-IgE antibodies ◦ Engineered anti-IgE: rhuMab = recombinant human Monoclonal antibody By Tokyogirl79 - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=50838162 Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 14 Type II Hypersensitivity Humoral autoimmune disease Tissue-specific antibody-mediated destruction of healthy cells Antibody-dependent cellular toxicity – binding of antibody (IgG, IgM) to cell membrane or the extracellular matrix) Activated self-reactive B cells produce IgM or IgG (w/help of Th) ◦ Antibodies attach to antigen on HOST cells *bound antigen ◦ Intrinsic antigen: normally present in host ◦ Extrinsic antigen: antigen formed as a result of an infection or medication (penicillin) that attaches to the host cell (penicillin) ◦ Antibody-Antigen complex on HOST cells Compliment proteins, NK cell, Tc cell à destroys cells Antibody-mediated dysfunction à disrupts cellular activity By OpenStax College - Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013., CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=30148349 Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 15 Type II | IgG Mediated Mechanism Cells can be destroyed in type II reactions through complement fixation and antibody-dependent cellular cytotoxicity (ADCC) Complement-fixing antibodies react with cell surface antigens causing cell injury or death ADCC ◦ Natural killer cell recognizes FC of antibody, releasing granules, apoptosis Antibody mediated cellular dysfunction ◦ Block, interfere, or activate receptors Image: https://image.slidesharecdn.com/3-immunology-csbrp151030105114-lva1-app6892/95/3-immunologycsbrp-3 638.jpg?cb=1446202395 Examples of type II hypersensitivities are ◦ Transfusion reactions ◦ Hemolytic disease of the newborn https://www.youtube.com/watch?v=kLaUz58CBMc Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 16 Type II | Blood Group Incompatibility Mismatched blood transfusion ◦ Blood samples are tested against donor samples that contain A, B, O, and RhD antigen Rhesus disease ◦ Mother is RhD-, but child inherits RhD+ from father ◦ First pregnancy: mother is exposed to RhD+ from baby ◦ Second pregnancy: antibodies produced destroy RhD+ blood cells Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 17 Type II | Mismatch Blood Transfusion IgG and IgM antibodies bind to foreign antigens on the surface of otherwise healthy human blood cell types Results in activation of the complement cascade (classic pathway) ◦ Cell lysis ◦ opsonization and enhanced phagocytosis by phagocytes of the blood cells with the foreign antigen Patient Receives blood transfusion Result? Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 18 Type II Hemolytic Disease Basis of disease: incompatibility of Rh factor between mother and child Rh+ father Anti-Rh antibodies form in Rh negative mother pregnant with Rh positive fetus ◦ First Rh-positive fetus unharmed ◦ Second Rh-positive fetus provokes strong secondary immune response ◦ IgG antibodies of secondary response cross placenta causing extensive damage to fetal red blood cells Rh- mother carrying first Rh+ fetus During delivery, Rh antigens develop in mother blood Mother produces antibodies against Rh (anti-Rh antibodies) Rh- mother carrying second Rh+ fetus Mother’s antiRh antibodies cross the placenta, damaging fetal RBCs Prevention: Anti-IgD injection during first pregnancy Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 19 Type III Hypersensitivity Humoral autoimmune disease Antigen-antibody complex deposit in blood vessel walls Interaction of antibodies with soluble antigens ◦ Results in soluble antigen-antibody complexes deposited in tissues ◦ Localized inflammation and tissue damage Complexes in tissues à damages tissues By OpenStax College - Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013., CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=30148349 Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 20 Type III | Immune Complex-Mediated Immune complexes consist of antigen and antibody bound together Usually adhere to Fc receptors on cells ◦ Complexes are destroyed and removed Certain instances complexes persist in circulation or at sites of formation ◦ Initiate blood clotting mechanism ◦ Activate complement contributing to inflammation Complexes commonly deposited in skin, joints, and kidney Complexes also cause disseminated intravascular coagulation (DIC) ◦ Large number of Clots formed in the blood vessels ◦ Leads to system failure Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 21 Type III | Systemic Lupus Erythematosus Disorder associated with autoantibodies against fragments of nucleic acids and chromosomal proteins IgG-antigen complexes form and circulate Complex deposits end up in the membrane of blood vessels Produces inflammation that affects many organs and tissues Compliment system is activated Antibody-antigen complex deposited in blood vessels Increase vascular permeability, Frustrated phagocytosis by neutrophils, Inflammation f blood vessel ◦ Antibody: IgG ◦ Antigen: DNA, nucleoproteins Cell damage, DNA release http://www.lupusimages.com/browser/fancybox/2505/Chart%20of%20Type%20III%20hypersensitivity%20(allergic)%20reactions%20in%20SLE Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 22 Type IV hypersensitivity Cell-mediated autoimmune disease ◦ absence of antibodies Delayed response (48 to 72 hour) Cells of the immune system promote chronic inflammation (Th1, TH17) or indirectly attack host cells (Tc) causing organ/tissue damage Cytokines à activates Tc and macrophages By OpenStax College - Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013., CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=30148349 Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 23 Type IV | Delayed Cell-Mediated Delayed hypersensitivities caused by cell-mediated immunity ◦ Slowly developing response to antigen ◦ Reactions peak in 2 to 3 days instead of minutes T cells are responsible for reactions ◦ Reactions can occur nearly anywhere in the body Delayed hypersensitivity reactions responsible for contact dermatitis, tissue damage, rejection of tissue grafts and some autoimmune diseases Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 24 Type IV | Diabetes & Arthritis TYPE I DIABETES MELLITUS RHEUMATOID ARTHRITIS Tc attack the insulin producing pancreas islet cells Th1 cells cause chronic, multisystem, inflammatory autoimmune disease that affects synovia and cartilages of small and large joints as well as other organs Not enough or complete loss of insulin production Why is insulin production important? ◦ Glucose à energy ◦ Glucose à storage as glycogen How does osteoarthritis differ? ◦ mechanical wear and tear on joints Recall: Type II Diabetes (Unit 6) Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 25 Type IV | Tuberculin (TB) Screening Test involves introduction of small quantities of protein antigens from tubercle bacillus into skin ◦ In positive skin test injection site reddens and gradually thickens ◦ Reaction reaches peak in 2 to 3 days Reactions result from sensitized T cells (new vs previous exposure to the bacteria) ◦ T cells release of cytokines to promote influx of macrophages Positive results based on combination of ◦ Size of inflamed area plus medical risk factors By BruceBlaus - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=61444951 By BruceBlaus - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=61444952 Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 26 Type IV | Contact hypersensitivities (CHS) T cell-mediated, Ag-specific skin inflammation induced by skin exposure to haptens in sensitized individuals ◦ Haptens: small molecules that can elicit an immune response when attached to a carrier protein. ◦ Haptens + Carrier = Hapten-carrier adducts Urushiol is found in poison ivy Urshiol is absorbed through the skin T-cell mediated ◦ Cytokines initiate inflammation that attracts macrophages ◦ Macrophages release mediators to add to inflammation Once oxidized in skin cells, the reactive quinone-type molecule is produced (the hapten) Hapten reacts with skin proteins to create hapten carrier adduct Common contact allergies ◦ Poison ivy and poison oak, nickel in metal jewelry, chromium salts in leather, latex products By Stilfehler - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=7965367 Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 27 Hypersensitivity Type I ◦ Allergic Anaphylaxis Type II ◦ Bound antiBody Type III ◦ soluble immune Complex Type IV ◦ Delayed By OpenStax College - Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013., CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=30148349 Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 28 Pathophysiology of Autoimmune Diseases How does this happen? Autoimmune disease ◦ Can be single organ or multi-system in nature ◦ Results in damage or destruction of cells, tissues, organs ◦ Alters the function and/or growth of cells, tissues, and organs Gender bias ◦ Women more affected than men Fall 2023 | J.Memme Adaptive Immune System produces cells that fail negative selection Consequence of failing negative selection ◦ Reservoir of self-reactive cells than mount an immune response against the host ◦ Self-reactive T-cells ◦ Auto-antibody producing plasma cells IMMUNOLOGY | BIOT 203 29 Recall: T-Cell Differentiation T-cell progenitor Expresses CD4 & CD8 T-cell receptor recognizes Signal received Result Selection Fall 2023 | J.Memme MHC I MHC II Survival and Maturation Survival and Expresses CD8 Expresses CD4 Positive CD8+ Positive CD4+ different Maturation Stops expressing CD4 Stops expressing CD8 IMMUNOLOGY | BIOT 203 Neither MHC I or MHC II MHC I or MHC II high affinity Strong Signal Respond to self-peptide antigens Apoptosis Apoptosis Negative Negative 30 Tolerance and Self-Tolerance Tolerance Self Tolerance Fall 2023 | J.Memme Central tolerance Peripheral tolerance IMMUNOLOGY | BIOT 203 Anergy Suppression 31 Tolerance and Self-Tolerance Tolerance Failure of the immune system to respond to an epitope in an aggressive way Do not attack self-antigens (proteins, etc.) Self Tolerance Inactivation or destruction of lymphocytes expressing BCR or TCR that recognize and bind self-epitopes Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 32 Tolerance and Self-Tolerance Central tolerance Apoptosis of lymphocytes expressing BCR or TCR that recognize and bind self-epitopes in primary lymphoid tissues (bone marrow and thymus) during early development of B or T cells Peripheral tolerance Inactivation (anergy or suppression) of circulatory B or T cells expressing BCR or TCR that recognize and bind selfepitopes Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 33 Tolerance and Self-Tolerance Normal immune response to antigen does not occur Anergy Inactivation of B and T cells when naïve lymphocytes bind via their BCR or TCR (“first signal”) Fail to receive the second signal provided by T cells (for B-cells) and APCs (for T-cells) that are necessary for activation Suppression Fall 2023 | J.Memme Suppressor T-cells / Regulatory T-cells inhibit of auto-reactive T-cells (Tc and Th cells) via cytokine release and/or cell-cell contact IMMUNOLOGY | BIOT 203 34 Loss of Self-tolerance Molecular Mimicry Epitope Spreading Loss of Suppression Sequestered Antigens • Response to microbial epitopes that may cross-react with the host epitope that are structurally similar to the microbial one • Response to an epitope leads to generation of responses to multiple epitopes, including host epitope • Loss of Treg activity, usually with aging • Sequestration of selfantigens in anatomical sites, immunologically privileged sites Fall 2023 | J.Memme • Brain, corena, uterus during pregnancy… (sites normally protected from immune system) IMMUNOLOGY | BIOT 203 Neoantigens • Self-antigens that have been modified by some extrinsic factor so that they appear foreign to the immune system 35 Autoimmune Diseases Body usually recognizes self antigens Destroys lymphocytes that would destroy self Fall 2023 | J.Memme Malfunction in immune recognition basis for autoimmunity IMMUNOLOGY | BIOT 203 Autoimmune diseases may result From reactions to antigens that are similar to self antigens or after tissue injury • Self antigens released from injured organ • Autoantibodies form and interact with injured tissues and cause further damage 36 Autoimmune Disorders Lymphocytes attack the body’s own cells (antigens) Self-tolerance of lymphocytes is lost ◦ B cells produce antibodies and Tc cells activate their cytotoxicity Causes: ◦ ◦ ◦ ◦ Similarities between viral and self antigens (Hepatitis C autoimmunity) Cell malfunction due to antibody binding (Grave’s Disease; thyroid gland) Immune complex forms (rheumatoid arthritis; joints) Cell-mediated destruction of specific cell types (insulin-dependent diabetes mellitus; insulinsecreting cells of pancreas) ◦ Genetically predisposed (higher risk) due to specific human leukocyte antigen (HLA) gene alleles Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 37 Spectrum of Autoimmune Diseases Reactions occur over spectrum ◦ Organ-specific to widespread responses Organ-specific • Thyroid disease: Only thyroid is affected Fall 2023 | J.Memme Widespread response • Lupus: Autoantibodies made against nuclear constituents of all body cells • Rheumatoid arthritis: Immune response made against collagen in connective tissue IMMUNOLOGY | BIOT 203 38 Treatment of autoimmune diseases Kill dividing cells Control T cell signaling Anti-inflammatory medications Replacement therapy Immunosuppressant Cyclosporin Cortisone-like steroids Insulin Inhibits transcription of IL2 Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 39 Immunodeficiency Disorders Immunodeficiency disorders are marked by the body’s inability to make and sustain an adequate immune response Primary or congenital Secondary or acquired Fall 2023 | J.Memme • Inborn as a result of genetic defect or developmental abnormality • Can be acquired as result of infection or other stressor IMMUNOLOGY | BIOT 203 40 Primary Immunodeficiencies Generally rare Few or no antibodies produced ◦ Agammaglobulinemia ◦ 1 in 50,000 people Neither B nor T lymphocytes are functional ◦ Severe combined immunodeficiency disorder (SCID) ◦ 1 in 500,000 live births Little or no IgA produced ◦ Selective IgA deficiency ◦ 1 in 333-700 people Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 41 Secondary Immunodeficiencies Result from environmental factors, rather than genetic Often results from depletion of certain cells of the immune system ◦ Syphilis, leprosy and malaria affect T-cell population and macrophage function ◦ Malignancies of lymphoid system decrease antibodymediated immunity Most serious widespread immunodeficiency is HIV (AIDS) ◦ Destroys helper T cells ◦ Inhibits initiation of cellular and antibody-mediated immunity Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 42 Atherosclerosis and Cardiovascular Disease Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 43 44 Atherosclerosis and Cholesterol Nikolai Anichkov (1885-1964) 45 (Kenneth, 2021) Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 46 (Kenneth, 2021) Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 47 (Kenneth, 2021) Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 48 Atherosclerosis: General Overview (Tabas, 2010) 49 Reverse Cholesterol Transport (RCT) (Heinecke, 2012) 50 (Eshghjoo et al., 2022) Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 51 AMP-activated Protein Kinase (AMPK) Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 52 Chronic systemic AMPK activation therapy is protective against atherogenesis Modified from (Wang, et al. 2017) 53 The role of Myeloid AMPK in Atherosclerosis; Mixed Results (Coa et al., 2016) Fall 2023 | J.Memme (Zhang et al., 2017) IMMUNOLOGY | BIOT 203 54 Investigating the role of myeloid AMPK signaling and A-769662 intervention therapy in the progression of atherosclerosis P C S K 9 -A A V (D 3 7 7 Y ) WT MF a 1a 2 6w W e s te rn 0 .2 % W T PBS W T A -7 6 9 6 6 2 M F a1a2 M F a1a2 12w D ie t (W D ) W e s te rn D ie t ± A -7 6 9 6 6 2 (3 0 m g /k g ) C h o le s t e r o l PBS A -7 6 9 6 6 2 * 60 % W e ig h t G a in G ra m s 40 35 30 WD 25 40 20 W D + T h e ra p y 0 0 2 4 6 W eeks 8 10 12 A -7 6 9 6 6 2 : - + W T - + MF a 1a 2 (LeBlond et al., 2020) 55 Myeloid AMPK and A-769662-intervention therapy role in atherogenesis F e m a le 2 A v e r a g e n e u tr a l A v e ra g e M a le 0 .4 2 le s io n a r e a (m m ) F e m a le lip id -r ic h a r e a (m m ) M a le 0 .4 0 .3 0 .2 0 .1 0 .0 A -7 6 9 6 6 2 : - + WT - + M acK O - + WT - + M acK O 0 .3 0 .2 0 .1 0 .0 A -7 6 9 6 6 2 : - + WT - + M acK O - + WT - + M acK O (LeBlond et al., 2020) 56 Myeloid AMPK and A-769662-intervention therapy do not alter myeloid content within lesions in male mice M a le 80 M acKO C D 6 8 + P la q u e A r e a % A -7 6 9 6 6 2 V e h ic le W T 60 40 20 0 A -7 6 9 6 6 2 : - + WT - + M acK O (LeBlond et al., 2020) 57 Autophagy marker p62 is unaffected by myeloid AMPK or A-769662-intervention therapy in male mice M a le 40 1 .5 30 1 .0 0 .5 0 .0 A -7 6 9 6 6 2 : - + WT - + M acK O P la q u e A r e a 2 .0 % p62+CD68+ M acKO R e la tiv e le s io n p 6 2 M F I A -7 6 9 6 6 2 V e h ic le W T 20 10 0 A -7 6 9 6 6 2 : - + WT - + M acK O (LeBlond et al., 2020) 58 Progress Tracking Assessment #7 Available on Blackboard in Unit Learning Materials ◦ You are in encouraged to collaborate with your peers but must submit your own individual product. ◦ Submit via Blackboard using the assignment submission link before the end of the day. IMMUNOLOGY | BIOT 203 FallBY-SA 2023 | J.Memme By 7mike5000 - Own work, CC 3.0, https://commons.wikimedia.org/w/index.php?curid=24912116 59 Transfer of …. Antigen-specific IgE bound to donor mast cell Antigen-specific IgE, which binds to host mast cell Donor antigenspecific IgE Antigen-specific bound IgE allergen Allergen crosslinked to bound IgE Antigen-specific bound IgE allergen Donor mast cell (transferred to host) Degranulation of inflammatory mediators Fall 2023 | J.Memme IMMUNOLOGY | BIOT 203 Host mast cell 60