Immunology I - Ross University - PDF

PID: Immunology I George Nadăș ,Professor of Immunology, [email protected] Learning Objectives Recognize the different types of immune response Recognize the cells & components of the immune system and understand their respective roles Understand how pathogens are recognized by the im...

PID: Immunology I George Nadăș ,Professor of Immunology, [email protected] Learning Objectives Recognize the different types of immune response Recognize the cells & components of the immune system and understand their respective roles Understand how pathogens are recognized by the immune system Understand the basic mechanisms of innate immunity, its activation and effector mechanisms Inflammation, Phagocytosis, Complement, NK cells 3 Definitions Immune system Collection of cells, tissues, and molecules that mediate resistance to foreign elements (antigens) Immune response Coordinated reaction of these cells and molecules to antigens Immunology Study of the immune system, including its responses to microbial pathogens and damaged tissues and its role in disease 4 Definitions Antigen Antibody generator Molecules that induce an immune response when introduced into the body Epitope or antigenic determinant Part of an antigen that is actually responsible for inducing the immune response and binding to the products of the immune response (lymphocyte receptors and antibodies) 5 THE IMMUNE SYSTEM Self vs Non-self whatispartomy f body The immune system must be able to discriminate foreign elements from components of its own organism Failure results in Autoimmunity Immune responses should be generated only when components of the immune system come into contact with non-self elements 6 THE IMMUNE SYSTEM Two types of defense Innate Immunity Adaptive Immunity (Non-specific) (Specific) Physical barriers skin Humoral Immunity Inflammation Cellular Immunity Complement 7  THE IMMUNE SYSTEM Innate Immunity vs Adaptive Immunity Innate Immunity Adaptive Immunity Activation Always active* Only when in contact with antigens Main cells Macrophages, Neutrophils, NK cells T cells & B cells Response time Fast (minutes to hours) Slow (days to weeks) Structures common to several Specific epitope, typically unique to a Specificity pathogens pathogen Memory Absent Present 8 THE IMMUNE SYSTEM Cells of the Immune System Neutrophils Basophils Eosinophils Mast cells Monocytes/Macrophages Dendritic cells NK cells lacksomeofftis oflymphocyte Lymphocytes (T and B cells) 12 THE IMMUNE SYSTEM Cells of the Immune System Neutrophils Role: Antimicrobial effectors, particularly in acute bacterial infection/inflammation Mechanism: Phagocytosis; Degranulation; Neutrophil extracellular trap formation relin Insaf t Faith'athem Eosinophils Role: Antiparasitic effectors, particularly in helminthic infection; Some antiviral action; Roles in allergy Mechanism: Degranulation; Limited phagocytosis whateosinophilsdobest 13 THE IMMUNE SYSTEM Cells of the Immune System theyareveryuncommon 1 Basophils moresimilartoneutrophils eosinophils Role: Mediator of inflammation Mechanism: Degranulation Mast cells seeinLNCTSKIN NeverinBII Role: Immune surveillance, mediator and amplifier of inflammation and allergy Mechanism: Detection of threats and release of inflammatory mediators via degranulation (vasoactive amines) or synthesis of lipid mediators and cytokines toallowotherproteinscellstoassistw inflammation flow basicallycauseincr inblood 14 THE IMMUNE SYSTEM Cells of the Immune System monocytes in blood macrophage intissues Macrophages diverse f x s Primary function: Immune surveillance, moderate antimicrobial capacity, limited antigen presentation Mechanism of action: Detection of threats and release of inflammatory mediators; Phagocytosis helpw transitiontoadaptive bc oftheirsmallroleinpresentingantigens Dendritic cells capturemicrobesbreakdowninsmallerpiecesto present APC Primary function: Immune surveillance, antigen processing and presentation Mechanism of action: Detection of threats and release of inflammatory mediators; Endocytosis and phagocytosis 15 THE IMMUNE SYSTEM Cells of the Immune System LYMPHOCYTES theydon'tneedactivationunlikeotherlymphocytes NK (Natural Killer) cells lackantigenreceptors don'trecognizeantigens Role: Destruction of virally infected or abnormal host cells (including tumor cells) Mechanism: Recognition of virally infected or abnormal host cells and targeted release of cytotoxic granules 16 THE IMMUNE SYSTEM Cells of the Immune System LYMPHOCYTES T cells and B cells mainft Antigenreceptor allowsrecognitionofepitote Role: adaptive immunity; recognition of specific antigens/ epitopes - T cell Receptor (TCR) & B Cell Receptor (BCR) Mechanism: activation and regulation of cell-mediated and antibody responses; memory cells 17 THE IMMUNE SYSTEM Cell Communication in the Immune System Cell-to-cell contact Receptors Expressed on the surface of a cell or in intracellular compartments Ligands Molecules that activate receptors Soluble or membrane-bound canbesynthesizedorreleased mayneedtorewatch 18 THE IMMUNE SYSTEM Cell Communication in the Immune System Cytokines Proteins with diverse functions such as cell growth, activation Interleukins initiallyfoundinleukocyteshencethenamejustacytokine Communication between cells Chemokines Chemotaxis 19  INNATE IMMUNITY Recognition of Pathogens Pathogen-Associated Molecular Patterns or PAMPs receptors innateimmunesystem recognizable by onlyFoundinmicrobesneverinhost Components that are shared between different types pathogens and present a molecular composition that differs from “self” 20 INNATE IMMUNITY Recognition of Damage Damage-Associated Molecular Patterns or DAMPs doesn'tneedmicrobe ex stubbedtoe inflammation cell impo bc theycanrecognizethedamagemicrobeisdoingtohost Released when cells die* (intracellular DAMPs) or generated when connective tissue is damaged (extracellular DAMPs) 21 INNATE IMMUNITY Pattern Recognition Receptors (PRRs) canbefoundindiff locations Receptors of innate immunity that recognize PAMPs & DAMPs Soluble or membrane-bound Signalling or phagocytic activatecytokineproduction orreleaseofgranules 22 INNATE IMMUNITY Sentinel Cells ofwhichwefindinvadersisn'tthesame frequency Recognition of threats Pathogen-Associated Molecular Patterns Damage-Associated Molecular Patterns contain lots of PAMPS DAMPS Sentinel cells Dendritic cells Pro-inflammatory & Macrophages Antimicrobial mediators Mast cells produces 23 24 INNATE IMMUNITY Inflammation Sentinel cell exposed to PAMPs, DAMPs, or pro-inflammatory cytokines Cell activation Upregulation of cellular antimicrobial defenses Release of pro-inflammatory chemokines, lipid mediators, and cytokines. 25 INNATE IMMUNITY Inflammation Mast cells Vasoactive molecules Histamine Serotonine Vasodilation vascular permeability More leukocytes arriving Easier to migrate to tissue needtostrictlyregulated bccouldcause 26 GHHHH INFLAMMATION Systemic Consequences 27 INFLAMMATION Chemokines & Leukocyte Chemotaxis needtotellcellswheretogo followgradientofconcentrationofcytokines 28 INFLAMMATION Leukocyte Kinetics Lymphocytes are present once the adaptive immune system is engaged in the response longertoarriveinhuge s take Monocytes/Macrophages predominate at later stages of inflammation Neutrophils predominate during acute inflammation INNATE IMMUNITY Phagocytosis It is an active process of capturing and ingesting foreign objects/microorganisms by phagocytes Neutrophils and macrophages Destruction of microorganisms, damaged cells and cellular debris, foreign objects theprocessofingestingthemicrotheyareactivatingcytokines Induction of cytokine production Processing and presentation of antigens 30  i INNATE IMMUNITY Phagocytosis 1 1. Phagocytes detect and bind their target 2 2. Surround the captured object with pseudopodia and engulf the object through endocytosis 3 3. The endocytosed object becomes enclosed in the phagosome 4 4. Phagosome fuses with the lysosome to form a phagolysosome 5 5. The contents of the lysosome are released into the phagolysosome PHAGOCYTOSIS Intracellular killing mechanisms Oxidative pathway Use of oxygen and glucose increases several fold “Respiratory burst” Reactive oxygen species (ROS) Reactive nitrogen species (RNS) Toxic to microorganisms PHAGOCYTOSIS m Intracellular killing mechanisms Non-oxidative Dependent on the action of the toxic substances present in lysosomes Cationic proteins – damage the bacterial cell wall Lysozyme – damages the mucopeptides in the bacterial cell wall Lactoferrin – sequestrates iron thus inhibiting bacterial growth Proteolytic and hydrolytic enzymes – digest killed bacteria 33 INNATE IMMUNITY Complement system Collection of circulating and membrane-associated proteins Many complement proteins are proteolytic enzymes Activation occurs in a sequential manner 3 activation pathways: Alternative pathway Classical pathway Lectin pathway 34  activated microbes Lectin Altpath innateimmune by Alternative pathway Complement proteins are activated on microbial surfaces (because complement regulatory proteins are not present on microbes, only on host cells) Lectin pathway Activated when a carbohydrate-binding plasma protein, mannose-binding lectin (MBL), binds to terminal mannose residues on the surface glycoproteins Classical pathway Activated by antibodies that bind to microbes or other antigens reqpresenceofantibodies adtap.fi9te Hart 35  nomatterwhichpathway allend MAC Membrane Attack Complex (MAC) Breaches the cell membrane of the microbe, allowing water to rush into the cell Destruction by osmotic lysis 36 INNATE IMMUNITY rewatch NK cells cancercells virus infectedcells Healthy host cells → MHC I Inhibitory receptors for NK cells Infected or mutated cells: Altered MHC I Activating ligands 37