Lec 12 - Immune System PDF

© 2013 Pearson Education, Inc. Anatomy 10B: Introduction to Human Physiology Fall 2024 Mt. San Antonio College Lecture: Immune System Anatomy...

© 2013 Pearson Education, Inc. Anatomy 10B: Introduction to Human Physiology Fall 2024 Mt. San Antonio College Lecture: Immune System Anatomy 10B: Introduction to Human Physiology Fall 2020 Overview of the Immune System The role of the IMMUNE SYSTEM is to recognize “self” from “non-self”. The body’s ability to protect itself is known as IMMUNITY The immune system has the following general functions: Recognizes abnormal cells Removes damaged or dead cells Protects from foreign invaders PATHOGENS: disease-causing invaders that can trigger an immune response ANTIGENS are molecules or “pieces” of the pathogen that induces an immune response Cytotoxic T cell attacking cancer  Players yers The of the Players Players of ofof the the Immune theImmune System Immune Immune System Players of the Immune System System System Cells of the immune system are called LEUKOCYTES Unlike other blood cells, leukocytes have the ability to leave the of the immune circulation andsystem are called LEUKOCYTES enter tissues Cells of e other the cells, blood immune system are leukocytes the have various the abilitytypes of WBCs to leave the collectively known as LEUKOCYTES Cells Unlike ation of thetissues immuneleukocytes anderythrocytes, enter system arehave called theLEUKOCYTES ability to leave the circulation and enter tissue where they Unlike f exert the other their immune blood cells, effects system are leukocytes the varioushave the of types ability WBCs to leave the circulation collectively known and enter tissue where as LEUKOCYTES they perform their function Lymphoid Tissue BONE MARROW: Site of white blood cell production LYMPHATIC VESSELS: Carry lymph from tissues to lymph nodes and lymph organs before returning to blood circulation LYMPH NODES, TONSILS, GALT: Collection of white blood cells for immune responses SPLEEN: Replaces damaged blood cells, collection of white blood cells for immune responses THYMUS: Site of T-lymphocyte (T-cells) maturation Cells Cellsofof Cells the of theImmune the ImmuneSystem Immune System System Cells of the Immune System (Overview) NEUTROPHILS: Phagocytic cells; engulf bacteria and destroy bacteria Release chemicals involved in inflammation (vasodilators and chemotaxins) BASOPHILS (MAST CELLS): Involved in allergic reactions by secreting histamine and other chemicals involved in inflammation Involved in preventing blood clots by secreting heparin MONOCYTES (MACROPHAGES): Phagocytic cells and major antigen-presenting cell Release chemicals involved in inflammation EOSINOPHILS: Involved in allergic reactions Attach and kill parasites DENDRITIC CELLS: Phagocytic cells Antigen-presentation Cells of the Immune System LYMPHOCYTES: Cells that are involved in specific immune responses Lymphocytes include the following cell types: B-lymphocytes, T-lymphocytes, and NK Cells The Immune ImmuneResponse Response The Immune Response The human body has THREE LINES OF DEFENSES against invasion of various pathogens The second and third line of defenses utilize chemical signals to carry out specific immune responses CYTOKINES are peptide messengers that are released from cells and influence the growth of the host cell ANTIBODIES are proteins that are secreted by specific immune cells - bing to antigens and make them visible to the immune system INNATE DEFENSE SYSTEM: FIRST LINE OF DEFENSE: Skin, mucous, gastric secretions and ciliary cells SECOND LINE OF DEFENSE: Internal cell populations that respond when our first line of defense mechanisms have failed ADAPTIVE DENENSE SYSTEM: THIRD LINE OF DEFENSE: Specific resistance and relies on antigens te Immunity: Nonspecific Innate hapter 21 TheDefenses: Non-Specific Immune System: Innate Immunity765 and Adaptive Body Defenses onses an elite o attack Surface barriers Skin esponse, Mucous membranes onsider- ponse. Innate defenses Internal defenses d adap- Phagocytes Natural killer cells of these Inflammation of this Antimicrobial proteins u know Fever hoid or- INNATE DEFENSES is part of the immune system that is always present and defends against the ATE im- DEFENSE DEFENSES pathogens SYSTEM iswithout part is part ofrecognition the ofofthe immune immune system that a specific system thatpresent is always antigen is alwaysand present and against defends defendspathogens against wit ells/materials system without recognition of identity nhe INNATE First line of DEFENSE defenses SYSTEM include: chemical and is part of the Humoral physical immune - if thosedefense immunity barriers that fail, the second is linealways of of defense – surface barriers – if invaders get past those, second line of defense provides B cells of entmol- defense of defenses provides and responds immunity relatively include chemical quickly and physical to protect barriers from - if those fail,foreign the secondsubstances line of defense provide face InnateBarriers: Physical Defenses: Surface and Barriers mical Barriers ACE BARRIERS include both physical and SURFACE BARRIERS include both physical and al barriers and are part of the first line of chemical barriers and are part of the first line of e defense Skin us Membranes Physical barrier oil/sweat glands Keratinized us membranes epidermis that surround impermeableand gastrointestinal to most substances ourinary tracts Dendritic cells can recognize pathogens and ntain enzymes and antibodies alert immune system ed Cells Mucous Membranes ted cells that surround Mucus the respiratory membranes tract that surround ic secretionsgastrointestinal and urogenital tracts Ciliated Cells lowed pathogens can be killed in hostile acidic onment Ciliated cells that surround the respiratory tract Gastric secretions Swallowed pathogens can be killed in hostile acidic environment  of the innate defenses is the process of PHAGOCYTOSIS - Innate Defenses: Phagocytosis lood cells recognize unique “pieces” of microorganisms, these HOGEN-ASSOCIATED MOLECULAR PATTERNS (PAMS) ocytosis A key element of the innate defenses is the process of capable of doing phagocytosis are called PHAGOCYTES PHAGOCYTOSIS - specific white blood cells recognize unique “pieces” of microorganisms, these are called PATHOGEN- e attracted to infected ASSOCIATED area by CHEMOTAXINS MOLECULAR PATTERNS (PAMS)- chemical ments from an invader Carbohydrates or lipoproteins OSIS s the Cells is process that PHAGOCYTES a in receptor-mediated arewhich phagocytes capable squeeze of phagocytosis through blood are called er tissue a particular unwanted Phagocytes are attracted to infected area by CHEMOTAXIS - chemical signals or fragments from an invader DIAPEDESIS is the process in which phagocytes squeeze GES and NEUTROPHILS are through blood vessels and enter tissue phagocytes Phagocytosis Antigen Presenting Cells ANTIGEN PRESENTING CELLS are cells that present fragments of a pathogen on their cell membranes - fragments are loaded onto platforms called MAJOR HISTOCOMPATIBILITY COMPLEXES (MHC) Professional antigen presenting cells: Dendritic cells, Macrophages, Langerhans cells and B- lymphocytes Non-professional antigen presenting cells: All nucleated cells other than white blood cells Turn Turn To ToYour YourPartner….. Partner…. Turn To Your Question –1 Partner… Q: Which of the following best describes an Antigen- Presenting Cell? a) A cell that has the capability to undergo Phagocytosis b) A cell that presents pieces of the cell itself on the cell membrane c) A cell that presents pieces of the pathogen on the cell membrane d) A cell that cannot undergo Phagocytosis  Innate Immunity: Macrophages Macrophages MACROPHAGES are present in nearly every tissue (stationary) or traveling in blood. ophages Macrophages MACROPHAGES macrophages originate fromindifferentiated are present (stationary) or -traveling MONOCYTES nearly every tissue once in inthe tissue, monocytes become blood. Macrophages originate from differentiated MONOCYTES - once in the tissue, monocytes become macrophages Alveolar Macrophages of the lung - Alveolar Macrophages of the lung - picture pictureshows showsthe pathology the of aof a pathology smokers smoker’slung. lung. Darkening Darkening ofof lung tissue lung is created tissue by is created macrophages that have by macrophages thatengulfed have engulfed impurities impuritiespresents presentsin cigarettes in cigarettes nate Immunity: Natural Killer Cells nate Immunity: Natural Killer Cells Innate nate Immunity: Immunity: NaturalKiller Natural KillerCells Cells IMMUNE SURVEILLANCE: normal monitoring of normal tissue by NATURAL KILLER MMUNE CELLSSURVEILLANCE (NK CELLS) - constant monitoring of normal tissues by NATURAL KILLER (NK) UNE SURVEILLANCE: normal monitoring of normal tissue by NATURAL KILLER CELLS (NK CELLS) MUNE LLS NK SURVEILLANCE: Cell recognize constant bacteria, monitoring foreign cells, of normal cells virus-infected tissues andby NATURAL tumor cells KILLER (NK CELLS ll recognize bacteria, foreign cells, virus-infected cells and tumor cells KCELLS CELLS recognizes Normal cells bacteria, recognizes are bacteria, foreign generally cells, ignored foreign virus-infected byvirus-infected cells, the cells immune system cells and and cancer cancer cells cells mal cells are generally ignored by the immune system Normal Normal cells Cancer cells are are cells generally often generally contain ignoredignored by the by tumor-specificthe antigens immune immunethat system system are recognized by NK Cells  Innate tivates NK Immunity: cells Natural Killer Cells atural Killer Cells NK CELLS have a variety of different functions: snnate Immunity: Natural Killer Cells Killer Cells Can induce apoptosis at target cells Release small granules that contain PERFORIN and GRANZYMES munity: target cellNatural Killer Cells Release INTERFERONS that inhibit viral replication at virus-infected cells aining perforins sells which e pores in their r arrive at the NK CELLS have a variety of different functions: mbrane Can induce apoptosis at target cells Interferons INTERFERONS are proteins that can induce a non-specific response to viral infection by a variety of different mechanisms Nearly all cells have the ability to secrete interferons Inhibit viral protein synthesis Inactivation of viral RNA Enhances phagocytic and cytotoxic mechanisms carried out by other white blood cells  Inflammation Inflammation lammation ! INFLAMMATION is the body’s response to injury and a vital part o NFLAMMATION MMATION is the local is the localtoresponse response infection ortoinjury infection and/or – function of theinjury. The inflammatory respons inflammatory se is system; INFLAMMATION to body’s is the destroy foreign invaders attempt local and toresponseto heal set stage to itself forinfection after injury and/or injury. The inflammatory tissue repair ection and sets the stage for tissue repair ! Inflammation r signsresponse of tissue injurywith deals is and and inflammation infection triggered – local sets the stage Physical by: swelling, redness, for tissue trauma, heat, and painirritating chemicals, in repair llmark signs of inflammation: Local redness, swelling, heat, and pain Hallmarkmicroorganisms signs of inflammation:- viruses, fungi,swelling, Local redness, and bacteria heat, and pain mmatory ammatory Response Inflammation Response Flowchart Inflammation Inflammatory Response 768 Flowchart UNIT 4 Maintenance of the Body We will use HISTAMINE for our example… We will use HISTAMINE 768 tory UNIT 4 Maintenance of the Body We will use HISTAMINE for our exam matory Innatedefenses Innate defenses Internal Internal defenses defenses e Initial stimulus Physiological response Initial stimulus Signs of inflammation Tissue injury Physiological response Result Signs of inflammation Tissue injury Result Release of inflammatory chemicals Release of leukocytosis- (histamine, complement, inducing factor kinins, prostaglandins, etc.) Leukocytosis Release of inflammatory chemicals (increased numbers of whiteRelease of leukocytosis- (histamine, complement, blood cells in bloodstream) inducing factor kinins, prostaglandins, etc.) Arterioles Increased capillary Attract neutrophils, dilate permeability monocytes, and lymphocytes to Leukocytes migrate to area (chemotaxis) injured area Leukocytosis Local hyperemia Capillaries (increased numbers of white (increased blood leak fluid Margination blood cells in bloodstream) flow to area) (exudate formation) (leukocytes cling to capillary walls) Arterioles Increased capillary Attract neutrophils, dilate permeability monocytes, and Diapedesis Leukocytes migrate to Leaked protein-rich Leaked clotting lymphocytes to (leukocytes pass through fluid in tissue spaces area (chemotaxis) proteins form interstitial capillary walls) injured area clots that wall off area to prevent injury to surrounding tissue Phagocytosis of pathogens Local hyperemia Heat Redness Pain Capillaries Swelling and dead tissue cells (increased blood leak fluid (by neutrophils, short-term; Margination by macrophages, long-term) (leukocytes cling to flow to area) (exudate formation) 21 Pus may form capillary walls) Locally increased Possible temporary Temporary fibrin temperature increases impairment of patch forms metabolic rate of cells function scaffolding for repair Area cleared of debris Diapedesis Leaked protein-rich Leaked clotting (leukocytes pass through fluid in tissue spaces proteins form interstitial capillary walls) Healing clots that wall off area to prevent injury to The Inflammatory nflammation Response Flowchart The Inflammatory Response 768 UNIT 4 Maintenance of the Body Innate defenses Internal defenses MAST CELLS (BASOPHILS) release HISTAMINE , which causes: MAST CELLS (BASOPHILS) release HISTAMINE, which causes: Initial stimulus Physiological response Tissue injury Signs of inflammation Result Vasodilation Vasodilation Increase Increase whitewhite bloodtocells blood cells to infected/injured area infected/injured area Release of inflammatory chemicals Release of leukocytosis- (histamine, complement, inducing factor Increase bloodblood flow causes heat andheat and kinins, prostaglandins, etc.) Increase flow causes redness redness Leukocytosis (increased numbers of white blood cells in bloodstream) Increase capillary permeability Arterioles Increased capillary Attract neutrophils, dilate permeability monocytes, and Increase Capillaries capillary permeability lymphocytes to Leukocytes migrate to become more porous - allowing white area (chemotaxis) injured area Local hyperemia (increased blood flow to area) Capillaries leak fluid (exudate formation) Margination (leukocytes cling to Capillaries blood become cells to squeeze moreblood between porous - allowing vessels white blood cells to squeeze between capillary walls) (DIAPEDESIS) Fluidblood leaks vessels (DIAPEDESIS) out causes pain and swelling Diapedesis Leaked protein-rich Leaked clotting (leukocytes pass through fluid in tissue spaces proteins form interstitial capillary walls) Fluid leaks out causes pain and swelling clots that wall off area to prevent injury to surrounding tissue Phagocytosis of pathogens Heat Redness Pain Swelling and dead tissue cells (by neutrophils, short-term; Margination by macrophages, long-term) 21 Locally increased Possible temporary Temporary fibrin Pus may form Chemotaxis Certain whiteasblood cells begin to temperature increases impairment of patch forms scaffolding for repair Histamine serves a chemotaxin - attract metabolic rate of cells function Area cleared of debris whiteexpress adhesion blood cells molecules that to infected/injured area bind to Healing surface of endothelial cells pical signals of inflammation are: Heat, Redness, Pain & Swelling Figure 21.3 Inflammation: flowchart of events. The four cardinal signs of acute inflammation are shown in red boxes, as is impaired function, which in some cases constitutes The Inflammatory nflammation Response Flowchart The Inflammatory Response 768 UNIT 4 Maintenance of the Body Innate defenses Internal defenses MASTCELLS MAST CELLS (BASOPHILS) (BASOPHILS) release release HISTAMINE, HISTAMINE which causes: , which causes: Initial stimulus Physiological response Vasodilation Signs of inflammation Tissue injury Result Chemotaxis Increase white blood cells to infected/injured Release of inflammatory chemicals (histamine, complement, kinins, prostaglandins, etc.) Release of leukocytosis- inducing factor Histamine serves as a chemotaxin - area Leukocytosis attract Increase white blood blood cells flow causes to redness heat and (increased numbers of white blood cells in bloodstream) infected/injured area Increase capillary permeability Arterioles Increased capillary Attract neutrophils, dilate permeability monocytes, and lymphocytes to Leukocytes migrate to Different Capillaries becomecells moresecrete porous -specific allowing white area (chemotaxis) injured area bloodchemotaxins for particular bloodleukocytes Local hyperemia Capillaries (increased blood flow to area) leak fluid (exudate formation) Margination (leukocytes cling to capillary walls) cells to squeeze between vessels (DIAPEDESIS) Fluid leaks out causes pain and swelling Diapedesis Leaked protein-rich Leaked clotting (leukocytes pass through fluid in tissue spaces proteins form interstitial capillary walls) clots that wall off area to prevent injury to surrounding tissue Phagocytosis of pathogens Heat Redness Pain Swelling and dead tissue cells (by neutrophils, short-term; by macrophages, long-term) 21 Locally increased temperature increases Possible temporary impairment of Temporary fibrin patch forms Pus may form Chemotaxis scaffolding for repair Histamine serves as a chemotaxin - attract metabolic rate of cells function Area cleared of debris Healing white blood cells to infected/injured area pical signals of inflammation are: Heat, Redness, Pain & Swelling Figure 21.3 Inflammation: flowchart of events. The four cardinal signs of acute inflammation are shown in red boxes, as is impaired function, which in some cases constitutes Complement System The COMPLEMENT SYSTEM (“complements” or helps the immune system) consists of a series of proteins that are released that ultimately kills infected cells by attacking cell membranes Formation of MEMBRANE ATTACK COMPLEX that forms a large channel in the membrane that disrupts osmotic balance causing target cells to swell and burst Fever A FEVER occurs when your body temperature is higher than normal – in adults, a fever is considered anything about 100.4F (38C) PYROGENS are produced by body tissues and many types of pathogens Pyrogens trigger the hypothalamus – site of thermoregulation. Tells the body to generate and retain more heat Increasing temperatures increase the immune response and makes it harder for viruses to multiply in the body Too high fever can be a problem…..high temperatures can become a physical modulator to proteins that require tertiary structures for their function edaptive Defense Immunity: Antigen-Specific System Adaptive Defenses: Antigen-Specific Responses es Humoral immunity B cells Adaptive defenses Cellular immunity T cells ADAPTIVE IMMUNITY are antigen-specific responses - body needs to come into contact and are two major Figure IVE recognize IMMUNITY21.1typeOverview of LYMPHOCYTES a specific of innate and antigen are antigen-specific – Badaptive CELLS & responses T CELLS defenses. - bodyaneeds to come intoincontact and recognize a sp UNITY: antigen-specific responses. Body recognizes specific antigen a foreign LS mature in immunity the THYMUS & Binvolving (primarily production of antibodies CELLSBmature in the and lymphocytes) BONE MARROW HUMORAL IMMUNITY: Also referred to as antibody-mediated immunity; involve the Humoral cellular the innate IMMUNITY: ORAL system, IMMUNITY: CELLULAR immunity the Tadaptive Also referred Also IMMUNITY: (involving system referred Also lymphocytes) are must toreferred “meet” the intruder toasasantibody-mediated antibody-mediated directly immunity; to as cell-mediated immunity; distinct but overlapping immunity areas antibodies involve ; involves are the production cytotoxic cells of antib humoral ULAR and immunity activationAlso IMMUNITY: of other WBCs to as cell-mediated immunity; involves cytotoxic cells and activatio referred exposure to a specific foreign substance – an ANTIGEN Immunocompetent Lymphocytes Maturation of lymphocytes (B cells and T cells) involves becoming immunocompetent – cells can recognize, by binding a specific molecule or antigen B-lymphocytes: Maturation ”bootcamp” occurs in the bone marrow T-lymphocytes: Maturation “bootcamp” occurs in the thymus During maturation: Lymphocytes that bind too strongly to the body’s own cells are destroyed – avoid autoimmunity Lymphocytes that bind and react weakly to body’s own cells remain Maturation of lymphocytes is initiated at fetal development and continues throughout life Mature into fully functional antigen-activated cells upon binding with a specific recognized antigen Adaptive Immunity: Active Immunity NATURALLY AQUIRED ACTIVE IMMUNITY develops after natural exposure to antigens in the environment or nature Ex: Contracting the measles gives immunity against future infection by the measles Ex: Exposure to COVID possibly provides immunity against future infection by COVID ARTIFICALLY INDUCED ACTIVE IMMUNITY develops after administration of an antigen Ex: Immunization by vaccination – vaccines contain dead or inactive pathogens or antigens derived from those pathogens Ex: With COVID…vaccine injects mRNA to produce viral spike protein Adaptive Immunity: Passive Immunity NATURALLY AQUIRED PASSIVE IMMUNITY develops after transfer of antibodies from mother to child Ex: Transfer of maternal antibodies across the placenta or breast milk ARTIFICALLY INDUCED PASSIVE IMMUNITY develops upon administration of antibodies Ex: Administration of rabies vaccine or antivenom Adaptive Defenses: B-Lymphocytes Adaptive Defenses: B-Lymphocytes B-LYMPHOCYTES (B-CELLS) are key players of humoral immunity of the adaptive defenses B-LYMPHOCYTES B-cells are characterized(B-CELLS) are key functionally players by their ofsurface cell humoralreceptors immunity that of the adaptive bind defenses to a specific antigen B-cells At birth, are characterized presence of NAIVE functionally LYMPHOCYTES by their cell that surface are few inreceptors numbers, that bind to a specific but differentiate when exposed to an antigen ntigen At birth, presence of NAIVE LYMPHOCYTES that are few in numbers, but differentiate when cytes Mediate the Adaptive exposed to an antigen e Response YTES can be characterized functionally by their surface receptors – each binds  Primary ry Immune Primary Immune Response Response Immune Response PRIMARY IMMUN PRIMARY IMMUNE RESPONSERESPONSE represents represents initial exposure exposureto toforeign foreign an antigen…Ex: Measles or COVI Ex: Measles or COVID- 19 Uponactivation, ymphocytes Upon activation, CLONAL differentiate CLONAL into EFFECTOR creates EXPANSION EXPANSION CELLS creates more and lymphocytes MEMORY more thatthat CELLS lymphocytes differentiate into EFFECTOR differentiate CELLSCE into EFFECTOR and MEMORY cells CELLS can carry CELLS out immediate response or become PLASMA CELLS and MEMORY Effector cells remain aftercells carry out exposure immediate – allow response “memory” by becoming PLASMA CELLS (secrete plasma antibodies) of antigen Effector cells Memory carry cells out after remain immediate response exposure - allow or becomeofPLASMA antigen CELLS (secrete plasma antibodies) MUNE RESPONSE represent initial exposure to “memory” foreign antigen Memory cells remain after exposure - allow “memory” of antigen Turn TurnToToYour CheckToFor Turn YourPartner…. Partner… Understanding…. Your Partner… Q: Which of the following is correct regarding B-lymphocytes? a) Plasma cells are B-lymphocytes that produce antibodies that circulate in the bloodstream b) Memory call are B-lymphocytes that produce antibodies that circulate in the bloodstream c) Memory cell are B-lymphocytes that remain in the body for long periods of time d) Plasma cells are B-lymphocytes that produce antibodies and are in the body for long periods of time  ondary Immune Secondary Response Immune Response Secondary Immune Response SECONDARY NDARY IMMUNEIMMUNE RESPONSE RESPONSE takesafter takes place place subsequent after subsequent exposure exposure to antigen to antigen - quicker - quicker and more robus § SECONDARY IMMUNE RESPONSE takes place after subsequent exposure to antigen; quicker and more robust response due to memory cells - cells have “memory” for specific antigen e due tomore and memory Ex: cells Ifrobust - cells comeshave response COVID-19 due “memory” to for specific memory cells back….. antigen for specific antigen – have “memory”  Antibody Anatomy TIBODIES or IMMUNOGLOBULINS (Ig) are Y-shaped proteins that contain 4 polypeptide chains Antibody Anatomy B REGIONS: ANTIBODIES Contain antigen binding site or IMMUNOGLOBULINS (Ig) are Y-shaped proteins that contain 4 polypeptide chains thatStem REGIONS: recognize specific region bindsantigens to cell surface of immune cell FAB REGIONS: Contain antigen binding site FC REGIONS: Stem region binds to cell surface of immune cell Antibody-Mediated Responses Antibodies do not directly destroy pathogens, but create physical barriers or mediate responses that lead to the destruction of pathogens NEUTRALIZATION: Antibodies can combine with pathogen and can physically prevent them from interacting with other cells AGGLUTINATION: Antibodies can cause clumping of pathogens TAGGING FOR DESTRUCTION: Antibodies can ”tag” pathogens that lead to the destruction by other white blood cells – Phagocytes, Natural Killer Cells, Compliment System ction ntibody Function Antibody – Mediated Responses PENDENT CELL OXICITY nction of antibodies g” pathogen, allowingisimmune to “tag” pathogen, allowing immune em recognition. at occurs n the cell:next? ….Depends on the cell: Degranulation hagocytosis -Lymphocyte Adaptive Development Defenses: T-Lymphocytes Adaptive Defenses: T-Lymphocytes LYMPHOCYTES travel from the bone marrow to the thymus where they mature T-LYMPHOCYTES T-LYMPHOCYTES ture (T-CELLS) T-cells develop travel (T-CELLS) T-CELL fromfrom travel RECEPTORS the into bone marrow the bone their to membranes marrow cell the tothymus where the thymus they mature – TCwhere they mature receptors bind to Mature AJOR T-cells Mature express T-cells T-CELL express HISTOCOMPATIBILITY RECEPTORS T-CELL RECEPTORS COMPLEXES that that recognizeonMAJOR recognize (MHC) HISTOCOMPATIBILITY MAJOR cells that foreign antigensCOMPLEX HISTOCOMPATIBILITY have MHC) on APCs. (MHC) on APCs. COMPLEXES esent T-Lymphocytes T-Lymphocytes HELPER HELPER T-CELLS (CD4+ T-CELLS CELLS) (CD4+ recognize CELLS) professional recognize APCs:APCs: professional B-lymphocytes, macrophages, B-lymphocytes, and dendritic macrophages, cells and dendritic Professional cells APCs present MHCII complexes T-Lymphocyte Development Professional CYTOTOXIC CYTOTOXIC Nucleated T-CELLSAPCs T-CELLS APCs present present (CD8+ (CD8+ MHCI MHCII CELLS) complexes recognize complexes all nucleated cells that present antigen CELLS) recognize all nucleated cells that present antigen Nucleated APCs present MHCI complexes § T-LYMPHOCYTES travel from the bone marrow to the thymus where they mature  Helper T-Cell Activation s white blood cell production …hence, “helper” cells. e specific cytokines that increase the production of: macrophages, b-cells, and cytotoxic t- white blood HELPER cells…..more T-CELLS robustcells, are not cytotoxic immune rather response they enhance the immune response by secreting cytokines that increases white blood cell production …hence, “helper” cells. T-Lymphocyte Activation Release specific cytokines that increase the production of: macrophages, b-cells, and cytotoxic t-cells More white blood cells…..more robust immune response § MHI: Presented on all nucleated cells Cytotoxic T-Cell Activation CYTOTOXIC T-CELLS are cytotoxic cells - they destroy APCs and avoids reproduction of bacteria, Cytotoxic T-Cell Activation viruses, parasites that are in the host cell Cytotoxicity occurs by the means of: CYTOTOXIC T-CELL GRANULES: Release secretory granules that contain PERFORIN and CYTOTOXIC T-CELLS GRANZYMES are cytotoxic – both ultimately cells leads to- apoptosis they destroyatAPCs and avoids infected cell reproduction of bacteria, viruses, parasites that are ACTIVATION OFin FAS the host cell “DEATH RECEPTOR” – signal transduction pathway that leads to Cytotoxicity occurs by the means of: T-Lymphocyte Activation apoptosis Release enzymes CYTOKINE that causeEnhance SECRETION: cells to undergo other apoptosis white blood cell production (Ex: Macrophages)  HIV: Human SHuman & HIV Scien&fic(Teaching(Framework( Immunodeficiency Virus (HIV) Immunodeficiency Virus Assessment) Equity) Ac&ve) and) Learning) Diversity) Collec&ng)Classroom)Evidence) HUMAN § HIV directlyIMMUNODEFICIENCY infects the HELPER T-CELLSVIRUS– (HIV) is a virus The immune that does system primarily infects HELPER T-CELLS The get ridvirus can HIV, be transmitted throughto contact with infected blood, vaginal fluids and semen D IMMUNE DEFICIENCY of some but someSYNDROME manages (AIDS) survive is caused by the HUMAN IMMUNODEFICIEN HIV surface proteins bind to receptors on Helper T cells and take over the host by: § Survival HIV) – whichleadscompromises to the creation of newimmune the viruses and destruction of many system IMMUNODEFICIENCY Integrating the viral genome (RNA) into the a VIRUS (HIV) is virusT that Helper primarily cells genome (DNA)infects HELPER and replicates T-CELLS more copies of helper T-cells ace canproteins be the bind to receptors virus transmitted through on T-helper contact with cells; affects infected its host blood, by: fluids and semen vaginal grating its genome Induces into the Cytotoxic host T-cells and to kill replicates infected more cells and copies other healthy white blood cells  Acquired Immune Deficiency Syndrome (AIDS) Transition from HIV to AIDS occurs when an individual has a higher ratio of infected Helper T- romcell HIVthan healthy T-cell to AIDS occurs when an individual has a higher ratio of infected Helper T-cell than he In the clinic, HIV patients measure their T-cell count AIDS patient mortality occurs by the means of a compromised immune system c, HIV patients measure Pneumonia, their infections, andT-cell count cancers Harmful Immune Responses: Allergy ALLERGY (HYPERSENSITIVITY) - conditions in which immune responses to environmental antigens cause inflammation and damage to the body Agents that cause allergy are called ALLERGENS and include certain foods, pet dander, and pollen Ex: Anaphylactic Shock - Hypersensitivity to an allergen resulting in hypotension and bronchoconstriction EXCESSIVE INFLAMMATORY RESPONSE - excessive production of chemicals involved in inflammation may damage healthy tissues Ex: Asthma Ex: Septic Shock  Harmful Immune Responses: Autoimmunity oimmunity UNE DISEASE - Inappropriate attack of healthy tissue triggered by auto-antibodi mmunity oimmunity munity When When Immune Immune SystemSystem oimmunity AUTOIMMUNE DISEASE: Inappropriate attack of healthy tissue triggered by the production of auto-antibodies and cytotoxic T-cells. ple sclerosis, Rheumatoid arthritis, Lupus, Type-1 Diabetes Mellitus Malfunctions Ex: Multiple sclerosis, Rheumatoid arthritis, Lupus, Diabetes Mellitus Type I Malfunctions Possible causes: Still unclear…..Autoimmune conditions are MULTIFACTORIAL in their cause - meaning the diseased state is possibly caused by a mixture of genetic and environmental factors utoimmunity: Diabetes Mellitus Type Autoimmunity: Diabetes Mellitus Type -1 -1 PE 1TYPE DIABETES MELLITUS is suggested to be caused by caused an autoimmune reaction thatreaction destroysthat the insulin ucing Case Study: Insulin Signaling 1 DIABETES beta cells destroys of insulin the MELLITUS the pancreas is suggested (produces producing little of beta cells to be to the no insulin) by an autoimmune pancreas (produces little to no insulin) e 1 diabetes is typically Type 1 diabetes is diagnosed in childrenin typically diagnosed and young adults, children but itadults, and young can develop but itatcan anydevelop age at any age Harmful Immune Response: Transfusion Reactions ABO Blood typing – erythrocytes do not have MHC, but do have antibodies Blood type A individual contains: A surface antigens and produce Anti-B antibodies Rh (Rhesus) factor: No one has Rh antibodies unless exposed to Rh positive from another person Hemolytic Disease Hemolytic of Disease the of Newborn the Newborn Hemolytic Disease of the Newborn What Occurs When you get the COVID Vaccine? The COVID vaccine is an mRNA vaccination Minutes after the COVID vaccination: Muscle cells take up mRNA and undergo extensive protein synthesis of the spike protein – spike protein attaches to the ACE2 receptors in human cells 15-30 minutes after the COVID vaccination: Patients are asked to wait for an observation period to watch for allergic reaction 12-14hrs to days later: Patients may feel soar and experience fatigue – this is caused by local inflammation and the infiltration of white blood cells to the local area White blood cells called by cytokines and chemokines: dendritic cells, B-lymphocytes and T- lymphocytes Signs that your immune system is working!  How COVID-19 Kills A VIRUS DISEASE - 2019) kills through on mmune system COVID-19 (CORONA VIRUS DISEASE - 2019) kills through on overreaction of the immune system okines cause over proliferation of leukocytes - Overproduction of cytokines cause over proliferation of involved in inflammation leukocytes - specifically key players involved in inflammation cytes into lung tissue Infiltration causesinto of leukocytes lung lunginjury tissue causes lung injury ion causes sepsis (hypotension and low blood Excessive inflammation causes sepsis (hypotension and low nary edema blood perfusion) and pulmonary edema MOST DEATHS DUE TO COVID-19 ARE DUE TO RESPIRATORY UE TO COVID-19FAILURE ARE DUE TO RESPIRATORY What Does ‘Return to Normal’ Mean For the Immunocompromised? Many Americans are foregoing masks in public places with COVID restrictions easing, but for the immunocompromised the risk of doing so is much higher