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Chapter 24 The Immune System

Chapter 24 The Immune System - Ch 24 The Immune System Ch...

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Unformatted text preview: Ch 24: The Immune System Ch 24: The Immune System 3 Major Functions Major 1. 2. 3. Protection from disease causing invaders (= ?) Removal of dead /damaged tissues & cells Recognition & removal of abnormal cells Immunologic “mistakes:” 1.Incorrect responses: autoimmunity 2.Overactive responses: allergy 3.Lack of response: immune deficiency History: First effective immunization Terminology Terminology • • • • • Pathogen, allergen Antigen, antigenic determinant Antibody (Ab), immuno­globulin, γ­globulin Allergen Opsonins: proteins that coat pathogens that make them targets for immune cells • May be complement, Ab, others • Nonspecific (innate) vs. specific (acquired) • • Immunity Active vs. passive Immunity Cellular vs. humoral Immunity Pathogens: Pathogens: • • • • • Bacteria (Staph, Strep) Viruses (Herpes) Fungi, yeasts (Coccidioidomycosis) Parasites (malaria, trypanosomiasis) Toxins (EtOH) Bacteria Bacteria • True cells – Cell wall (usually) – Capsule • Selfreplicate • – Most can reproduce outside host cells Susceptible to AB Escherichia coli Viruses Viruses • Not a true cell – DNA or RNA with capsule of protein • Intracellular replication only – Grow in tissue culture • Not susceptible to AB – There are a few antiviral drugs HIV (see Emerging Concept, p 779) Immune System Functions Immune System Functions 1. Scavenge dead, dying or abnormal (cancerous) body cells 2. Protect from pathogens 1. Bacteria 2. Viruses 3. Protozoa (malaria), fungi (histoplasmosis) multicellular parasites (filaria) 3. Foreign Molecules The Immune Response, introduction The Immune Response, • If physical and chemical barriers fail, the Immune System responds with detection, identification, destruction. – Sometimes overwhelmed • Antibodies (Ab) recognize and then bind to • antigens (Ag) Lots of cytokine communication The Immune Response: Keep pathogens out & destroy those that break defense 1. Innate (= nonspecific): 1. – – – – Present at Birth Nonspecific hinders pathogen and toxin entry and dispersion through body. • E.g. skin. strengthens specific immune system 1. Acquired (= specific): – – – inactivation of a specific pathogen Requires previous exposure Humoral vs. CMI Anatomy of Anatomy Immune System Immune Lymph system Lymph + Immune cells Immune Immune Cells Immune Cells Fig 24-4 6 basic groups of Leukocytes: 1. 2. 3. 4. 5. 6. Eosinophils Basophils (blood); Mast cells (tissue) Neutrophils Monocytes (blood), macrophages (tissue) Dendritic cells Lymphocytes (plasma, helper, cytotoxic & NK) APCs Antigen Presenting Cells Antigen Presenting Cells (APCs) • Note foreign protein on their surfaces • Macrophages, dendritic cells, lymphocytes 1) Innate Immunity – Barriers, 1) Innate Immunity – Phagocytosis & Inflammation • Physical & chemical barriers keep pathogens out – skin, mm – stomach acid, lysozyme • Phagocytosis: Patrolling & stationary leukocytes (macrophages, neutrophils, NK cells) attack and destroy pathogens/foreign molecules nonspecifically – Phagocytes may be aided by opsonins (Usually an Ab) – NK cells use antiviral interferons • Inflammatory response initiated via secretion of cytokines (e.g. histamine) Fig 24-6 Inflammation Inflammation • An innate protective mechanism activated by • cytokines in response to tissue damage Acute Phase: Release of several proteins – Prevent further damage – Mast Cell degranulation • Histamine (from mast cells) is vasodilator • Other cytokines: – – – Interleukin: for MP Bradykinin: pain mediation Complement: Damages invaders Uterine inflammation Some factors in Inflammation Some factors in Inflammation •Acute Phase Proteins •Prevent further damage •Histamine •Present in mast cells •Vasodilation •Interleukins •Cytokines •Complement •Cascade of proteins •Chemotaxins, cytokines, etc. Complement Proteins – The Complement Proteins – The Complement System Consists of ∼ 30 proteins circulating in blood plasma Inactive until cleaved by a protease which, in turn, converts them into a protease ⇒ Expanding cascade of activity (reminiscent of clotting cascade) ⇒ Induction of inflammatory response, phagocyte chemotaxis, opsonization, and cell lysis ⇒ “Complement fixation” is the process MAC MAC 2) Acquired (Specific) Immunity 2) Acquired (Specific) Immunity p 787 Antigen (pathogen) specific Overlaps with innate immunity 1o cell type involved: lymphocyte Is systemic (= whole body involved) Has memory Two branches: Humoral Cell­mediated Active vs. Passive Immunity Active vs. Passive Immunity Active: protection via introduction of antigen into responsive host naturally acquired via infection “unnaturally” acquired via ? Passive: protection via transfer of antibodies or immune cells into non­immune host Naturally: fetus receives mothers antibodies via placenta “unnaturally” via injection of immune serum after exposure (snake bite, Rh­ mother with Rh+ child) 2 Branches of Acquired 2 Branches of Acquired Immune System: 1. Humoral or antibody mediated (B­cells) 2. Cellular or cell mediated (T­cells) Three major types of lymphocytes: B, T & NK Lymphocytes Lymphocytes Antigen­Specific Responses B lymphocytes activated ⇒ become: – Plasma cells: antibodies – attack that antigen – Memory cells: 20 immune response to same antigen T lymphocytes activated ⇒ direct attack NK (Natural Killer) cells attack virus­ infected cells and tumor cells 1o cell: Naive Lymphocyte Memory cells Compare to Compare Fig 24-10 Fig Effector (plasma) cells Immune Memory Immune Memory •From B­Lymphocyte clones •Plasma Cells manufacture Ab •Memory Cells wait for the next exposure Antibodies = Immunoglobulins = Ig = Antibodies = Immunoglobulins = Ig γ γ λοβυλινσ (origin of name) Fig 24-12 Heterogenous group of molecules: 5 subclasses 5 subclasses of Igs: 5 1. IgG: main Ab (75%) in serum; + main Ab during 2o response 2. IgA: main Ab is external secretions 3. IgE: main Ab in allergic reactions 4. IgM: Ab on virgin B­cells; + main Ab during 1o response 5. IgD: Ab on virgin B­cells Compare to Compare Fig 24 –11 Fig IgM IgG 2° immune response: stronger & more rapid Importance of Immunizations!! <2h Antibody = Antibody = Antibody = “work against foreign body” “work against foreign body” 1o Ab function: bind Ag to B lymphocyte and initiate production of additional antibodies (usually IgM) Other Ab functions: bind to pathogens and target them for destruction (via several different mechanisms!) Study Fig 24-13 Antibody Functions ­ Mechanisms of Antibody Action Antibody Functions ­ Mechanisms of Antibody Action N.B. All extracellular! Fig 24­13 p 791 Humoral Immunity Humoral Immunity virgin B cells antibody secretion activated B cells The Complement The System System = 1o humoral humoral mediator of Ag-Ab mediator reaction reaction Involves ∼ 30 plasma & Involves cell membrane proteins recognition, activation, attack Leads to: ? Review: cellular vs. humoral immunity cellular vs. humoral immunity T lymphocytes 1. 2. 3. 4. cytotoxic (killer) helper Memory Direct attack of infected cells necessary B lymphocytes 1. 2. Become plasma cells 1. Make Ab memory cells T cells ­ CTLs T cells ­ CTLs Have specific receptors on cell membrane (TCR) TCR cannot bind free Ag. Ag must be presented by APC Ag presentation together with APC form the Major Histocompatibility Complex (MHC) Fig 24-15 Importance of MHC molecules Importance of MHC molecules • MHC class I: found on surface of all nucleated cells – used to present peptides from intracellular invaders – E.g., viruses – Cytotoxic T­cells kill the cell • MHC class II: found on surface of macrophages, dendritic cells, and B­cells – The APC • High number of MHC alleles in population (Transplant rejection in case of incompatible MHC) Cytotoxic T­ Cytotoxic T­ lymphocytes (CTLs) Attack and destroy cells with MHC I – Ag complex 2 mechanisms of destruction: – Perforins and granzymes – Fas (death) receptor activation Apoptosis Cytotoxic T cell Action Destruction of cells Destruction displaying MHC class Idisplaying antigen complexes antigen Perforin molecules create protein channels in target cell membrane granzymes enter and trigger apoptosis in target cell different mech. from MAC !! Immune Response Pathways Immune Response Pathways 1) Defense against extracellular 2) 3) 4) bacteria Defense against Viral Infections Allergic Response Organ & Tissue Transplants Fig 24-17 Immune Response Pathways Immune Response Pathways 1) Defense against extracellular bacteria: • Complement activation – Mast cell degranulation and inflammation – Chemotaxins – Opsonins • Phagocytes ingest bacteria – Enhanced by opsonization • Inflammation ⇒ recruitment of phagocytes, B & T lymphocytes • Acquired response ⇒ antibodies (opsonins and neutralization), CTLs … if needed Fig 24-17 2) Defense against Viral Infections 2) Defense against Viral Infections Remember: virus replication is intracellular and thus not exposed to circulating Ab 1. Circulating antibodies inactivate or target extracellular virus (opsonization, neutralization) 2. Intracellular defense mechanisms needed once virus has entered cell: CTL major defender (also some NK cells) 3. Activated MΦ ⇒ inflammatory cytokines; α ­ interferons (induce host cells to produce antiviral proteins) Fig 24-18 Fig 24-19 3) Allergic Response p 797 3) Allergic Response Inflammatory immune responses to non­ pathogenic antigens Symptoms range from mild tissue damage to fatal 1. Immediate Hypersensitivity (ITH): Hay fever, cat allergies . . . Ab mediated (IgE!), may take minutes 2. Delayed Hypersensitivity (DTH): poison oak . . . due to T­cell abnormality, may take days Allergies cont. Allergies cont. • What is an allergen? – May be almost anything: pollen, metals, organic or inorganic, etc., etc. • Strong genetic component • Allergies in response to ingestion, inhalation, injection, skin contact • Sensitization phase (= 1o immune response) followed by 2o immune response on subsequent exposures Anaphylaxis Anaphylaxis Most severe IgE mediated allergic reaction Massive histamine release within minutes ⇒ Hives, bronchoconstriction and widespread vasodilation ⇒ shock 4) Organ & Tissue Transplants 4) Organ & Tissue Transplants • MHC (= HLA (Human leukocyte Ag)) are the 1º tissue antigens – If donor and recipient HLA match, less rejection • Establishment of “self tolerance” during T cell development – Failure = Autoimmunity • ABO (and Rh) blood typing (AA, AO, BB, BO, AB, OO) • Blood transfusion problems due to antibodies in plasma → Transfusion reaction with hemolysis and possible kidney damage Fig 24-20 Autoimmune diseases Autoimmune diseases • Immune surveillance recognizes abnormal cells – Cancer cells • Important function of IS: Self­tolerance through • clonal deletion Failure of self tolerance: autoimmunity Table Table 24 – 4 etc. etc. Immunology is a fast­moving area Immunology is a fast­moving area • PsychoNeuroImmunology Research deals with neuro­endocrine­immune interactions • Stress alters immune system function ...
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