Adaptive Immune System (Immunology: PHT-321) PDF

The Adaptive Immune System Introduction, Cells, Organs and Molecules of Adaptive Immune System Immunology: PHT-321 Dr. Amnah Alalmaie [email protected] Dr. Mohammad Khali...

The Adaptive Immune System Introduction, Cells, Organs and Molecules of Adaptive Immune System Immunology: PHT-321 Dr. Amnah Alalmaie [email protected] Dr. Mohammad Khalid [email protected]  1.1 Adaptive Immunity: Second Line of Response Depend upon having previous contact with a particular microorganism Relies on genetic events and cellular growth Responds more slowly, over few days Is specific Each cell responds to a single epitope on an antigen Has anamnestic memory Repeated exposure leads to faster, stronger response Leads to clonal expansion Microorganisms come in contact with cells of the immune system (macrophages and lymphocytes) to initiate the acquired specific immunity which may be:- -Humoral (through antibodies) -Cellular (cytotoxic effects).  Specific and Adaptive Immunity Specific defense mechanisms (immunity) – use specific receptors to recognize specific antigens Adaptive defense mechanisms adapt to what ever antigens are presented. There are billions of T cell and B cell receptors – poised on naïve lymphocytes, i.e. cells borne with receptors that are untested (never been used) – just waiting for their specific antigen B Cells: Provide antibody-mediated immunity (humoral immunity) Defend against antigens and pathogens in body fluids (‘humors’) T Cells: Provide cell-mediated immunity (cells must interact) Defend against abnormal cells and pathogens that enter a cell and present the ‘foreign parts’ = antigens on the cell surface  Properties of Specific Immunity Specificity: Each T or B cell responds only to a specific antigen and since there are so many different lymphocytes this ‘army’ can respond to 1011 possible antigens Versatility: The body produces several types of lymphocytes, but billions of different receptors: each recognizes a different type of antigen and a bacterium has many antigens so a bacterium is attacked by many different lymphocytes. Memory: Activated lymphocytes make memory cells = exact copies or clones: these clones are distributed throughout the body – and if the same antigen reenters the system these clones are ready to react, very fast! Tolerance: Immune system ignores “normal” (self) antigens, BUT if the selection process in the bone marrow and thymus fails, self antigens are recognized = autoimmunity.  1.2 Antigens (Immunogens) Antigens "Ags" are substances capable of acting as specific stimulants for the specific immune response. 1) Foreignness: the immune system somehow discriminates (recognize) between "self" and "non-self“. 2) Molecular size : small molecules while proteins and polysaccharides are immunogenic. 3) Specificity : only restricted portions of them are involved in the actual binding with the antibody combining sites. Such areas determine the specificity of the antigen and are designated as antigenic determinants (epitopes). 4) Chemical complexity : a molecule must possess certain degree of chemical complexity in order to be immunogenic.  1.3 Anatomy of the Immune System ❑Thymus – glandular organ near the heart – where T cells learn their jobs ❑Bone marrow – blood-producing tissue located inside certain bones blood stem cells give rise to all of the different types of blood cells ❑Spleen – serves as a filter for the blood ✓Removes old and damaged red blood cells ✓Removes infectious agents and uses them to activate cells called lymphocytes ❑Lymph nodes – small organs that filter out dead cells, antigens, and other “stuff” to present to lymphocytes ❑Lymphatic vessels – collect fluid (lymph) that has “leaked” out from the blood into the tissues and returns it to circulation  Organs, cells and molecules of Immune System The immune system is localized in several parts Tonsils and adenoids of the body Thymus Lymph nodes Immune cells develop in the primary organs - Spleen bone marrow and Payer’s patches thymus (yellow) Appendix Immune responses occur in the secondary Lymphatic vessels organs (blue) Bone marrow  Lymphoid tissues Lymphoid tissues contain a characteristic cell the lymphocyte, which also occurs in lymph and is one of the blood leukocytes Lymphoid tissues contain leukocytes and also non-leukocyte as stromal cells. 2 main lymphoid organs & tissues: PRIMARY - where cells of the immune system develop; bone marrow and thymus SECONDARY - where the immune response develops; spleen, lymph nodes and tonsils All lymphoid organs are interconnected by the lymphatic and blood circulatory systems through which cells of the immune system circulate and access non-lymphoid tissues. Leukocytes are not found in significant numbers in other tissues EXCEPT when there is inflammation; In case of inflammation, very large numbers of leukocytes will be present, and may form organised collections of cells resembling 2ndry lymphoid tissues. Leukocytes: LYMPHOID - lymphocytes of different types; B-cells, T-cells, NK-cells MYELOID - dendritic cells, monocytes/macrophages and granulocytes  1.4 Cellular Components of the Innate and adaptive Immunity All formed elements (except T-lymphocytes) leave the bone marrow and directly enter Erythrocyte and circulate in the blood. Platelets WBCs Neutrophil Red bone Eosinophil marrow = site of origin Basophil Monocyte Macrophage Pr e-T-lymphocyte B-lymphocyte Plasma cell T-lymphocytes mature in the Thymus thymus prior to circulating in T-lymphocyte T-lymphocyte the blood. maturation All cells of the immune system and RBCs arise from haemopoietic stem cells B-Cell  B-cells see the world via receptors on their surface B cells or B lymphocytes use BCRs = immunoglobulins (Ig) or antibodies (Ab) B-lymphocyte: cell of humoral immunity  B-Cell Overview: Percentage of Circulating Lymphocytes: 10–15% Functions: Produce antibodies (Ab/Ig) on their surface and secrete them outside the cell. Each B-cell has many identical antibodies. Different B-cells produce different antibodies. Development: B-cells are born in the red bone marrow. Selection Process: Naïve B-cells are challenged to recognize self-antigens (not non-self antigens). Outcome of Recognition: Recognition of self-antigens leads to the death of B-cells. Only B-cells that do not recognize self-antigens and can recognize foreign (non-self) antigens survive.  When activated B cells recognize their specific antigen, they differentiate into plasma cells and memory cells. Plasma cells are just clones of activated B cells and are hyperactive. Plasma cells synthesize and secrete antibodies/immunoglobulin Memory cells are positioned around the body – ready to respond to antigen  B cell Recognizes Antigen by Producing Antibody Fab = variable regions = 2 antigen- binding sites Immunoglobulin (Ig) = protein 2 variable (aa) regions 1 constant (Fc) region Secreted or attached to B-cells Antigen binding activates B-cell and make them divide Fc region = constant region  Fab = variable regions = 2 antigen- binding sites Fc region = constant region  B Cell Receptors: The antibody Molecule Antibody molecule composed of two heavy chains and two light chains Both the heavy and light chains comprise a variable (V) and constant (C) region The variable regions are responsible for binding of a specific protein called as antigen First 100 amino acid of amino terminal of both H and L chains are variable The specificity of an antibody is determined by the shape of its variable region A particular antibody will bind to a protein that has a region with a complementary structure to the antibody’s own variable region Antibodies can be grouped in 5 classes;  or IgA,  or IgG,  or IgD,  or IgE, and  or IgM. These classes are called as Isotype The Specificity of An Antibody Is Determined By The Shape of Its Variable Region Antibody Isotypes  Function of Antibody Isotype IgG Most abundant immunoglobin 80% of serum Ig ~10mg/mL Sub Class of IgG; IgG1, IgG2, IgG3, IgG4 IgG1, IgG3 and IgG4 cross placenta IgG3 Most effective complement activator IgG1 and IgG3 High affinity for FcR on phagocytic cells, good for opsonization  IgM 5-10% of serum immunoglobulin 1.5 mg/mL mIgM (also IgD) expressed on B-cells as BCR Pentameric version is secreted First Ig of humoral immune response High valence Ig (10 theoretical) More efficient than IgG in complement activation  IgA 10-15% of serum Ig Predominant Ig in secretions Milk, saliva, tears, mucus 5-15 g of IgA released in secretions! Transcytosis Subclass of IgA; IgA1, IgA2 Serum mainly monomeric Secretions as dimer or tetramer, polymers are not common though Transcytosis  IgE Very low serum concentration, 0.3g/mL Participate in immediate hypersensitivities reactions. Ex. Asthma, anaphylaxis, hives Binds Mast cells and blood Basophils through FcR Binding causes degranulation (Histamine release)  IgD Expressed on B-cell Surface IgM and IgD, Expressed on B-cell Surface Low serum concentrations, ~30g/mL  Role of Antibodies 1) Opsonize the Microorganisms i.e. combine with surface antigens and enhance the phagocytosis (IgG). 2) Agglutinate the Microorganisms, so become easily phagocyted (IgM). 3) Direct bactericidal or lytic effect with complement (IgG & IgM). 4) Block the infective ability of the Microorganisms or virus (IgG & IgA). 5) Neutralize toxin or cellular product (IgG & IgA). 6) Precipitate toxin or cellular product (IgG & IgA). Antibody Recognizes Immunogen  Isotypic Determinants on Antibodies Isotype Isotypic Determinants: Specific regions of antibodies that differ between species but are consistent within a species. Function: Trigger production of anti-isotype antibodies when introduced between different species. No immune response within the same species, preventing attack on host antibodies  Allotype Allotype Determinants: Specific regions of antibodies that differ among individuals within the same species. Function: Can trigger an immune response when antibodies from one individual are introduced into another individual within the same species. Important in understanding genetic variations and immune response among individuals of the same species.  Idiotype Idiotypic Determinants: Unique regions of antibodies that vary even among antibodies of the same class and species. Function: Represent the specific antigen- binding sites, giving each antibody its unique specificity. Can trigger an immune response against the idiotype itself, potentially playing a role in immune regulation and autoimmunity. T-Cell  T-cells see the world via receptors on their surface T cells or T lymphocytes use TCRs = T cell receptors = CD3 complex T-lymphocytes: cells of cell-mediated immunity  T cells Overview: T-Cell Receptor (TCR): One T-cell has a single type of TCR with a wholly unique specificity. Each T-cell has as many as 100,000 identical TCRs. TCR is also known as the CD3 complex. Structure: T-cell receptor is a heterodimer. Heterodimers can be: αβ (alpha beta) γδ (gamma delta)  T-Cell Characteristics Make up 80% of circulating lymphocytes. Recognize antigens only when they are processed and displayed on a cell, typically on Antigen-Presenting Cells (APCs).  Main Types of T Cells: Helper T cells: Stimulate function of T and B cells and macrophages; TH cells, CD4+ Cytotoxic T cells: Attack cells infected by viruses and produce cell-mediated immunity; TC cells, CD8+ Memory T cells: respond to a previously encountered Antigen Suppressor T cells: Inhibit function of T and B cells  Differentiation of T-Cell Subsets by Surface Glycoproteins CD4 Cells: Characterized by having CD molecules numbered from 1 to 8, except CD8. T-helper (TH): Produce interleukins (lymphokines or cytokines). Stimulate other T-cells, B-cells, and phagocytes. CD8 Cells: Characterized by having CD molecules numbered from 1 to 8, except CD4. T-cytotoxic (TC): Capable of killing virus-infected cells, tumor cells, and foreign grafts. T-regulatory (T regs or TS): Modulate immune response by inhibiting excessive immune activity.  The Major Histocompatibility Complex (MHC) Major Histocompatibility Complex (MHC): Surface glycoprotein molecules also known as human leukocyte antigens (HLA). Found on the surface of white blood cells (WBCs) and provide cell uniqueness to an individual. MHC Classes: 1.Class I MHC: Composed of two polypeptide chains. Found on the surface of all nucleated cells. Recognized by TC (CD8) cells. 2.Class II MHC: Composed of two polypeptide chains. Found on the surface of B-cells, dendritic cells, and macrophages (antigen- presenting cells or APCs). Recognized by TH (CD4) cells. Thank You