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ACQUIRED IMMUNITY RECOGNITION. ORGANIZATION OF IMMUNE CELLS UNDER EPITHELIAL SURFACES. Ag-specific B-cell. Th1. B. NK cell. Th2. Eosinophil granulocyte. NKT cell. Th17. Neutrofil granulocyte. Granulocyte. Macrophage activation. Macrophage. Cellular killing. CTL. Treg.
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ACQUIRED IMMUNITY RECOGNITION
ORGANIZATION OF IMMUNE CELLS UNDER EPITHELIAL SURFACES Ag-specific B-cell Th1 B NK cell Th2 Eosinophil granulocyte NKT cell Th17 Neutrofil granulocyte Granulocyte Macrophage activation Macrophage Cellular killing CTL Treg Epithelial cells Stroma cells DC CELL – TO – CELL COMMUNICATION NETWORKS PERIPHERAL TISSUES PERIPHERAL LYMPHOID TISSUES
ACQUIRED IMMUNITY Cells Receptors SENSING RECOGNITION SENSING RECOGNITION Signaling pathways Cell-to-cell collaboration SIGNAL TRANSDUCTION SIGNAL TRANSDUCTION Effector mechanisms RESPONSE RESPONSE DEFENCE SYSTEMS INNATE IMMUNITY
ADAPTIVE (ACQUIRED) IMMUNITY Antigen recognizing receptors Fishes 450 millon years Helper T cell Cytotoxic T cell B cell Lamprey LYMPHOCYTES
9-13various Toll-receptors TLR family Several millions antigen receptors Acquired immunity Innate immunity 450 million years Ancient WHAT IS RECOGNIZED BY INNATE AND ACQUIRED IMMUNITY?HOW DO THEY RECOGNIZE PATHOGENS? RECEPTORS Common pattern of groups of pathogens Pathogen Associated Molecular Pattern PAMP Recognition by receptors Pattern Recognition Receptor PRR Unique structural elements Antigenic determinant Recognition by highly specific antigen receptors B cell receptor BCR (sIg) T cell receptor TCR
WHAT CELL TYPES MEDIATE ACQUIRED IMMUNITY INNATE/NATURAL IMMUNITY ACQUIRED/ADAPTIVE IMMUNITY Phagocytes (monocyte/macrophage, neutrophil, dendritic cell) Killer cells (NK cell, δ T cell) B1 lymphocytes (CD5+) B lymphocytes (B2) T lymphocytes helper T cell cytotoxic T cell CELLS HUMORAL FACTORS Enzymes (lysozyme,transferrin, lactoferrin, spermin, trypsin) Antibacterial peptides Complement system Cytokines, chemokines Antibodies Produced by B-cell derived plasma cells
Macfarlane Burnet (1956 - 1960)CLONAL SELECTION THEORY Antibodies are natural products that appear on the cell surface as receptors and selectively react with the antigen Lymphocyte receptors are variable and carry various antigen-recognizing receptors ‘Non-self’ antigens/pathogens encounter the existing lymphocyte pool (repertoire) Antigens select their matching receptors from the available lymphocyte pool, induce clonal proliferation of specific clones and these clones differentiate to antibody secreting plasma cells The clonally distributed antigen-recognizing receptors represent about ~107 – 109 distinct antigenic specificities
1012 lymphocytes in our body ( B and T lymphocytes) How many SPECIFICITIES ? DIVERSITY OF LYMPHOCYTES Assumption 2 The receptor can be activated by many different antigens Assumption 1 All lymphocytes have a different receptor Cc. (minimum) 10 million various (107) B lymphocyte clones with different antigen-recognizing receptors Cc. (minimum) 10 – 1000 million various (107 - 9) T lymphocyte clones with different antigen-recognizing receptors
Ag Plasma cell ACTIVATION Clonal expansion Differentiation Antibody (immunoglobulin Ig) secretion MEMORY B CELLS BINDING OF ANTIGEN TO THE SELECTED B-LYMPHOCYTES RESULTS IN CLONAL EXPANSION B cell B Cell Receptor (BCR)
No. of cells with useful specificity Threshold of protective effector function No. of cell divisions Clonal selection induces proliferation and increases effector cell frequency
Circulation Restricted life span Homeostasis Apoptosis Activation Clonal expansion/proliferation Differentiation Plasma cell Antibody production Memory cell POSSIBLE FATES OF B-LIMPHOCYTE CLONES Transient, not final differentiation state
THE B-CELL ANTIGEN RECOGNIZING RECEPTOR AND ANTIBODIES PRODUCED BY PLASMA CELLS HAVE THE SAME PROTEIN STRUCTURE = IMMUNOGLOBULIN B CELL Antigen recognizing receptor BCR Immunoglobulin (Ig) Antibody
a a Antigen binding L L L L H H H H b a signalling B CELL TWO FORMS OF IMMUNOGLOBULINS Membrane-bound Ig Antigen-specific receptor Secreted Ig Antigen-specific soluble protein EFFECTOR MOLECULE PLASMA CELL
IMMUNOGLOBULIN IgG VH FV= VH+ VL VL Antigen binding site
Primary response Secondary response Antibody g/ml serum MEMORY Antigen A Lag Recognition Activation AFFERENT Primary Response toantigen B Antigen A Antigen B Days A antigén TIME COURSE OF THE ADAPTIVE IMMUNE RESPONSE Cell interactions CENTRAL Effector/execution Regulation EFFECTOR Response to antigen A
9-13various Toll-receptors TLR family Several millions antigen receptors Acquired immunity Innate immunity 450 million years Ancient WHAT IS RECOGNIZED BY INNATE AND ACQUIRED IMMUNITY?HOW DO THEY RECOGNIZE PATHOGENS? RECEPTORS Common pattern of groups of pathogens Pathogen Associated Molecular Pattern PAMP Recognition by receptors Pattern Recognition Receptor PRR Unique structural elements Antigenic determinant Recognition by highly specific antigen receptors B cell receptor BCR (sIg) T cell receptor TCR
CHARACTERISTICS OF INNATE AND ACQUIRED IMMUNITY NATURAL/INNATE • Rapid, prompt response (hours) • No variable receptors • Limited number of specificities • No improvement during the response • No memory • Not transferable • Can be exhausted, saturated COMMON EFFECTOR MECHANISMS FOR THE ELIMINATION OF PATHOGENS ADAPTIVE/ACQUIRED • Time consuming • Variable antigen receptors • Many very selective specificities • Efficacy is improving during the response • Memory • Can be transferred • Regulated, limited • Protects self tissues
TOW LEVELS OF DEFENSE TWO TYPES OF THE IMMUNE RESPONSE AQUIRED/ADAPTIVE IMMUNITY Protects after activation and clonal expansion against pathogens INNTE/NATURAL IMMUNITY Protects without prior activation or multiplication against pathogens First line of defense Inrerited Persistant presence Rapid response Short term protection Second line of defense Acquired Slow response Self and non-self specificity Long term protection (memory)
