6_2019_03_02!01_10_37_AM(2) adaptive immunity, facts and functions.ppt
- 1. Immunology • The Study Of Immune System • Latin Word immunis=“exempt” • Earliest Written Reference was Thucydides 430 BC • Pasteur Was First To Successfully Apply Vaccination
- 2. 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
- 3. Innate (Non-Specific) Immunity • Innate Immunity Made Up Of 4 Forms • Anatomical, physiological, phagocytic and inflammatory • Anatomical: skin, epidermis (densely packed dead cells) • Flow of Mucus Prevents Bacterial Entry By Washing Them Away • Normal Flora Colonize Epithelial Cells Of Mucosal Surfaces, Pathogens Compete With Them For Attachment Sites
- 4. • Physiologic Barriers – pH (stomach) – Temperature (fever) – Soluble Factors (interferons, lysozyme) • Phagocytic Barriers – Specialized Cells Perform Most Of Phagocytosis (macrophages, neutrophils) Innate (Non-Specific) Immunity
- 5. • Inflammatory Barriers – Vasodilation – Cappillary permeability – Leukocyte Infiltration • Chemotactic means • Increased Adherence • Leaky capillaries Innate (Non-Specific) Immunity
- 6. • C-Reactive Protein (liver) • Histamine (vasodilation, increased permeability • Kinins – Small peptides normally inactive in blood – Ex. Bradykinin (causes pain) Chemical Mediators Of Inflammation
- 7. • Close collaboration – Macrophages can secret cytokines that affect the type of adaptive immunity • Macrophages/DCs Present Antigen • Lymphocytes Increase Effectiveness of Macrophages Innate and Adaptive Immunity
- 8. 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
- 9. 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 – Provides immediate short term protection
- 10. 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
- 11. • 4 Characteristics – Memory – Diversity – Antigenic Specificity – Self/non self recognition Adaptive Immunity
- 12. ~ 60% neutrophils (50% - 70%) ~ 3% eosinophils (>0% - 5%) ~ 0.5% basophils (>0% - 2%) ~ 5% monocytes (1% - 9%) ~ 30% lymphocytes (20% - 40%) Frequency of Different Leukocytes in Healthy Individuals
- 15. ORIGIN OF THE IMMUNE SYSTEM CELLS • Derived from progenitor cell in bone marrow – Pluripotent hematopoietic stem cell • Progenitor Stem Cells – Erythroid lineage • Erythrocytes and Megakaryocytes – Myeloid lineage • Monocyte/macrophage, dendritic cells, PMN’s, mast cells – Lymphoid lineage • Small and large lymphocytes
- 17. • Lymphocytes – B cells, mature in Bone Marrow (CD19, CD20) • in periphery they express a unique surface antibody • Plasma cells differentiated B cell, short lifespan, antibody factory • Memory B cell (CD45RO), long life span Cells Of The Immune System
- 18. 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)
- 19. 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-
- 20. • T cells, mature in Thymus (CD3, CD4, CD8) • Two Major subsets, TH (CD4) and TC (CD8) • Third type TS not as clear • Mature T cell expresses TCR • TCR cannot recognize antigen on its own • MHC I (all nucleated cells) or MHC II (APCs) is required • TH cells secrete cytokines • TC less cytokines, more cytotoxic (virus and tumor survailance) Cells Of Immune System
- 21. • Antigen Presenting Cells • Number of Cells capable of Antigen Presentation • Dendritic Cell (DC) professional APC • Macrophages, B cells • Besides Antigen They Provide Co- stimulation • APCs are a safeguard against autoimmunity Cells Of Immune System
- 23. • B cells are specific, 100,000 identical antibodies on 1 B cell • 108 different B Cells in Bone Marrow, Enormous Diversity • Reduction To Avoid Auto-antibodies • Same for T Cells, Elimination in Thymus Specificity and Diversity
- 24. • Genetic Complex With Multiple Loci • MHC I - CTLs • MHC II - TH • MHC I+2-microglobulin – 3 classes A, B, C (human) – 2 classes K and D (mouse) • MHC II – 3 classes DP, DQ, DR (human) – 2 classes IA, IE (mouse) • Highly Polymorphic in Humans Major Histocompatibility Complex (MHC)
- 26. • First Protein Antigens Must Be Broken Down • Form Complexes With MHC I or II • Exogenous Antigens – Antigens Processed Throw Endocytic Pathway – Binding of Ags To MHC II – Expression of MHC II+Ags On Surface – CD4 T Cells Recognize Ag Throw Class II MHC • Endogenous Antigens – Antigens Processed Throw Cytosolic Pathway – Produced Within Cell, Ex. Virus Ag, Cancer Ag – MHC I Molecules Bind Ag in ER – CD8 T Cells Recognize Ag Throw MHC I Processing and Presentation of Antigens
- 27. Processing and Presentation of Antigens
- 28. • Ag Reactivity Determines Clonal Expansion • Immunologic Memory is By-product of Clonal Expansion • Humoral Primary Response – 7 Days Before Antibody Levels Rise – Antibody Titer is Low Compared to Secondary • Humoral Secondary Response – 1-2 Days Antibodies Are Detected – Antibody Titer Higher (100-1000 fold higher) – Lasts Longer Clonal Selection of Lymphocytes and Memory
- 30. • Cell Mediated Response (TH or CTL) is Similar – Primary Response 10-14 Days For Skin Rejection – Secondary Response Starts Immediately Clonal Selection of Lymphocytes and Memory
- 31. Aberrant Respones – Allergy, Asthma, Anaphylaxis Asthma/Allergies Attacks Are Very Common Mediated Thru IgE IgE Binds Mast Cells, Basophils Re-exposure Cross Links IgE Causes Degranulation, Histamine, prostanoids
- 32. 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)
- 33. 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
- 34. 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
- 35. 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)
- 36. 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
- 37. 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)
- 39. 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
- 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
- 42. LYMPHOCYTES, LYMPHOID TISSUES AND ORGANS • Lymphocytes originate in bone marrow • Lymphoid tissues and organs – Primary • Development and maturation of lymphocytes • Bone Marrow (B cells) and thymus gland (T cells) – Secondary • Mature lymphocytes meet pathogens • Spleen, adenoids, tonsils, appendix, lymph nodes, Peyer’s patches, mucosa-associated lymphoid tissue (MALT)
- 44. 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
- 45. 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
- 46. 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
- 47. 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