Immunology lec
Download as PPT, PDF31 likes4,492 views
This document provides an introduction to immunology and the immune system. It discusses the study of immunology and defines the immune system. It also describes the innate and adaptive immune responses, natural and artificial immunity, the roles of antibodies and lymphocytes in humoral and cell-mediated immunity, and the functions of the lymphatic system. Key cell types like phagocytes, B cells, T cells, and antigens are also introduced.
Immunology lec
- 2. IMMUNOLOGY AND THE IMMUNE SYSTEM * Immunology * Study of the components and function of the immune system * Immune System * Molecules, cells, tissues and organs which provide non-specific and specific protection against * Microorganisms * Microbial toxins * Tumor cells * Crucial to human survival
- 3. THE IMMUNE RESPONSE AND IMMUNITY * Immune response * Innate (non-specific) * Adaptive (specific) * Primary * Secondary * Immunity * State of non-specific and specific protection * Acquisition of Immunity * Natural * Artificial
- 4. NATURALLY ACQUIRED IMMUNITY * Active * Antigens enter body naturally with response of * Innate and adaptive immune systems * Provides long term protection * Passive * Antibodies pass from mother to * Fetus across placenta * Infant in breast milk * Provides immediate short term protection
- 5. ARTIFICIALLY ACQUIRED IMMUNITY * Active * Antigens enter body through vaccination with response of * Innate and adaptive immune systems * Provides long term protection * Passive * Antibodies from immune individuals injected into body * Referred to as * Immune serum globulins (ISG) * Immune globulins (IG) * Gamma globulins * Provides immediate short term protection
- 6. PRINCIPAL FUNCTION OF THE IMMUNE SYSTEM * To protect humans from pathogenic microorganisms * Pathogenic microorganisms (Pathogens) * Microorganisms capable of causing infection and/or disease * Infection * Ability of pathogen to enter host, multiply and stimulate an immune response * Disease * Clinical manifestations associated with infection
- 7. BACTERIA, VIRUSES, FUNGI, PARASITES—OH MY! * Streptococcus pyogenes (Group A Streptococcus) * Klebsiella pneumoniae * Mycobacterium tuberculosis * Ebola virus * Human Immunodeficiency Virus (HIV) * Aspergillus fumigatus * Candida albicans * Cryptococcus neoformans * Cryptosporidium parvum * Stronglyoides stercoralis * Ascaris lumbricoides * Plasmodium falciparum
- 8. DEFENSE MECHANISMS OF THE HUMAN HOST * Innate Mechanisms (Innate immunity) * First line of defense * Non-specific * Adaptive Mechanisms (Adaptive immunity) * Second line of defense * Highly specific with memory * Cooperation between mechanisms
- 9. THE CLUSTER OF DIFFERENTIATION (CD) * A protocol for identification and investigation of cell surface molecules * CD number assigned on basis of 1 cell surface molecule recognized by 2 specific monoclonal antibodies * CD nomenclature established in 1982 * 1st International Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA)
- 10. THE CLUSTER OF DIFFERENTIATION (CD) * CD markers on leukocytes Granulocyte CD45+, CD15+ Monocyte CD45+, CD14+ T lymphocyte CD45+, CD3+ T helper lymphocyte CD45+, CD3+, CD4+ T cytotoxic lymphocyte CD45+, CD3+, CD8+ B lymphocyte CD45+, CD19+ Natural killer cell CD45+, CD16+, CD56+, CD3-
- 11. THE LYMPHATIC SYSTEM * Lymph * Fluid and cells in lymphatic vessels * Lymphatic vessels * Collect and return interstitial fluid to blood * Transport immune cells throughout body * Transport lipid from intestine to blood * Lymph nodes * Kidney shaped organs at intervals along lymphatic vessels * Other secondary lymphatic tissues and organs
- 13. LYMPHOCYTES AND THE LYMPH NODES * Naïve lymphocytes circulate between blood, lymph and secondary lymph nodes * Pathogens from infected tissue sites are picked up by lymphatic vessels and arrive at closest lymph node * T and B cells congregate at specific regions of nodes * Architecture and size of nodes change in response to activation of lymphocytes
- 16. LYMPHOCYTES AND THE SPLEEN * Spleen * Lymphoid organ in upper left abdomen * Functions * Remove damaged or old erythrocytes * Activation of lymphocytes from blood borne pathogens * Architecture of Spleen * Red pulp * Erythrocytes removed * White pulp * Lymphocytes stimulated
- 18. SECONDARY LYMPHOID TISSUES ASSOCIATED WITH MUCOUS MEMBRANES * Primary portals of entry for pathogens * Respiratory tract * Gastrointestinal tract * Secondary lymphoid tissues * Bronchial-associated lymphoid tissue (BALT) * Gut-associated lymphoid tissues (GALT) * Tonsils, adenoids, appendix, Peyer’s patches * Pathogens are directly transferred across mucosa by “M” cells
- 20. THE INNATE IMMUNE RESPONSE * Mediated (initiated) by phagocytes, NK cells and soluble proteins * Phagocytes * Cells specialized in the process of phagocytosis * Macrophages * Reside in tissues and recruit neutrophils * Neutrophils * Enter infected tissues in large numbers * Recognize common molecules of bacterial cell surface using a few surface receptors * Phagocytosis * Capture, engulfment and breakdown of bacterial pathogen
- 22. THE INNATE IMMUNE RESPONSE * Inflammatory response enhances phagocytosis through acute phase proteins * Mannose-binding lectin (MBL) * Binds to bacterial surface with particular spatial arrangement of mannose or fucose * C-reactive protein (CRP) * Binds to phosphorylcholine on bacterial surface * Complement * Set of proteins which bind to bacterial surface * Inflammatory response * Accumulation of fluid and cells at infection site (swelling, redness, heat and pain)
- 24. THE ADAPTIVE IMMUNE RESPONSE * Creates millions of different B and T cells for specific antibody-mediated and cell-mediated immunity * Antibody-Mediated Immunity (AMI) * Involves B lymphocytes, plasma cells and antibodies * Humoral immunity * Name derives from antibodies found in body fluids (humors - old medical term) * Cell-Mediated Immunity (CMI) * Involves T lymphocytes, antigen-presenting cells and MHC (major histocompatibility complex) molecules * Cellular immunity
- 25. ANTIBODY-MEDIATED (HUMORAL) IMMUNITY * Directed against extracellular microorganisms and toxins * B-lymphocytes (B cells) * Differentiate into plasma cells which produce antibodies * Function as antigen-presenting cells (APC’s) * Classification of Antibodies (Immunoglobulins) * Immunoglobulin M (IgM) * Immunoglobulin G (IgG) * Immunoglobulin A (IgA) * Immunoglobulin D (IgD) * Immunoglobulin E (IgE)
- 26. CELL-MEDIATED IMMUNITY (CMI) * Directed against intracellular microorganisms * Non-phagocytic cells and phagocytic cells * T-lymphocytes (T cells) * Differentiate into effector cells following antigen presentation by antigen presenting cells (APC’s) * Functional types of T cells * Helper (CD4 T cells) * TH1 and TH2 cells * Cytotoxic (CD8 T cells) * Regulatory * CD4 and CD8 Tregs
- 27. THE NATURE OF ANTIGENS * Historically named as antibody generators * Molecule which stimulates production of and binds specifically to an antibody * Contemporary view distinguishes between * Antigen * Molecule which can bind to specific antibody but cannot elicit adaptive immune response * Immunogen * Molecule which can stimulate adaptive immune response * Best immunogens are proteins with MW > 10,000
- 28. THE NATURE OF ANTIGENS * Carbohydrates, nucleic acids and lipids are also potential antigens / immunogens * Hapten * Small (low MW) molecule unable to elicit immune response * Combines with larger carrier molecule which together function as immunogen * Antibody may react independently with hapten following hapten/carrier adaptive immune response * Example * Penicillin G (MW of 372) * Albumin (MW of 66,000)
- 29. THE NATURE OF ANTIBODIES * Antibodies are glycoproteins * Exist as monomers, dimers or pentamers of basic structure * Basic antibody structure has 4 polypeptide chains * 2 identical light chains * 2 identical heavy chains * Regions of heavy and light chains * Variable * Constant
- 31. THE NATURE OF ANTIBODIES * Also referred to as * Immune globulins / Immunoglobulins (IG) * Immune serum globulins (ISG) * Gamma globulins * Contemporary immunology * Antibody * Secreted form of IG made by plasma cells * Immunoglobulin * Antigen binding molecules of B cells * (B cell antigen receptors)
- 32. CLASSIFICATION OF ANTIBODIES (IMMUNOGLOBULINS) * Five (5) classes (isotypes) * Immunoglobulin A (IgA) * Immunoglobulin G (IgG) * Immunoglobulin M (IgM) * Immunoglobulin D (IgD) * Immunoglobulin E (IgE) * Based on structural differences in constant regions of heavy chains * Classes have specialized effector functions
- 34. B LYMPHOCYTES AND HUMORAL IMMUNITY * Originate from stem cells in bone marrow * Maturation in bone marrow followed by migration to secondary lymphoid tissue * Antigen exposure in secondary lymphoid tissue * Following exposure to antigen, differentiation into plasma cells and memory cells * Plasma cells produce antibodies of all IG classes
- 35. ACTIVATION OF ANTIBODY PRODUCING CELLS BY CLONAL SELECTION * B lymphocytes recognize intact pathogenic microorganisms and toxins * B lymphocytes possess specific surface receptors for recognition of specific antigen * IgM and IgD * Binding of specific antigen results in proliferation of a clonal population of cells * Antigen determines clonal proliferation
- 37. ACTIVATION OF ANTIBODY PROCDUCING CELLS BY CLONAL SELECTION * Proliferation of activated cells is followed by differentiation into * Plasma cells * Life span of * 4 to 5 days * 1 to 2 months * Produce 2,000 antibody molecules / second * Memory cells * Life span of years to decades * Differentiate into plasma cells following stimulation by same antigen
- 38. PRIMARY AND SECONDARY ANTIBODY RESPONSE * Primary Response * Following exposure to an antigen, there is a slow rise in IgM followed by a slow rise in IgG * Secondary Response * Following exposure to previously encountered antigen, there is a rapid rise in IgG and slow or no rise in IgM * Memory or anamnestic response
- 40. T LYMPHOCYTES AND CELL-MEDIATED IMMUNITY * Originate from stem cells in bone marrow followed by migration to thymus gland * Maturation takes place in thymus gland followed by migration to secondary lymphoid tissue * Respond to antigens on the surface of antigen presenting cells (APC’s) * Antigen presenting cells (APC’s) * Macrophages * Dendritic cells * B lymphocytes
- 41. T LYMPHOCYTES AND CELL-MEDIATED IMMUNITY * Antigen presenting cells (APC’s) * Ingest and process antigens then display fragments (short peptides) on their surface in association with molecules of major histocompatibility complex (MHC) * Major histocompatibility (MHC) molecules * MHC class I molecules * Present antigens to CD8 T cells * MHC class II molecules * Present antigens to CD4 T cells * T cells which encounter antigen differentiate into effector T cells
- 43. ROLES OF EFFECTOR T CELLS IN IMMUNE RESPONSE * CD8 cytotoxic T cells * Enter bloodstream and travel to infection site * Kill cells infected with viruses and other intracellular microorganisms * CD4 TH1 helper T cells * Enter blood stream and travel to infection site * Help activate macrophages * CD4 TH2 helper T cells * Work within secondary lymphoid tissues * Help activate B cells
- 46. DISORDERS OF THE IMMUNE SYSTEM * Hypersensitivity Reactions * Over-reaction of adaptive immune response to harmless antigens * Four Types of reactions (I- IV) * Autoimmunity * Misdirected adaptive immune response * Results from a loss of self-tolerance * Three Types (II, III, IV) of reactions * Immunodeficiencies * Components of immune system either absent or defective * Genetic or acquired etiology
- 47. IMMUNOLOGY FOR DIAGNOSIS OF DISEASES * Analytical methods using either antibody or antigen with an indicator system for detecting specific * Antibodies * Detected using antigens or antibody * Antigens * Detected using antibody * Indicator systems * Latex particles (colored) * Microspheres (colored) conjugated with antibody * Enzymes conjugated to antibody * Fluorochromes conjugated to antibody * Nitrocellulose membranes fixed with antigen or antibody
- 48. METHODS IN DIAGNOSTIC IMMUNOLOGY * Latex agglutination (LA) * Latex particles (dyed) coated with antigen, antibody or? * Read visually for clumping of latex particles * Staphyloslide (Becton Dickinson) * Identification of Staphylococcus aureus * Staphylococcus aureus produces * Coagulase (bound and free) * Protein A * Blue latex particles coated and not coated with * Fibrinogen * IgG
- 49. METHODS IN DIAGNOSTIC IMMUNOLOGY * Immunochromatographic assay (ICA) * Antibody or antigen immobilized (Test line) * Antibody immobilized (Control line) * Membranes * Nitrocellulose, cellulose acetate * Read visually for colored test and control lines * Examples * Group A Streptococcus (GAS) antigen * Influenza A and B antigens * Respiratory syncytial virus (RSV) antigen * Rotavirus antigen * HIV-1/2 antibody
- 50. PRINCIPLES OF OraQuick RAPID HIV-1/2 ICA ANTIBODY TEST * Antigens and antibody immobilized onto nitrocellulose membrane in T and C zones * Test (T) Zone * Synthetic peptides from HIV envelope region * Control (C) Zone * Goat anti-human IgG * Developer solution * Facilitates flow of specimen onto test strip * Rehydrates protein-A gold colorimetric reagent
- 51. IMMUNOLOGY FOR PREVENTION OF DISEASE * Hepatitis B * Pre-exposure prophylaxis * Vaccination with hepatitis B surface antigen (HBsAg) * Post-exposure prophylaxis * Administration of * Hepatitis B Immune Globulin (HBIG) Human * Purified IgG antibody from plasma of donors with high titer of antibody to the hepatitis B surface antigen (anti-HBs)
- 52. IMMUNOLOGY FOR TREATMENT OF DISEASE * Rheumatoid Arthritis * Remicade (Infliximab) * IgG kappa monoclonal antibody against tumor necrosis factor – alpha (TNF-alpha) * Breast Cancer * Herceptin (Trastuzumab) * IgG kappa monoclonal antibody against human epidermal growth factor receptor 2 (HER2)