Lymphocytes and Their Receptors - Ross University

Lymphocytes and their receptors George Nadăș,Professor of Immunology, [email protected] Key Points Lymphocytes Lymphocytes are the cells that can recognize and respond to foreign antigens Lymphocytes all look the same but can be differentiated by their characteristic cell surface molecules These c...

Lymphocytes and their receptors George Nadăș,Professor of Immunology, [email protected] Key Points Lymphocytes Lymphocytes are the cells that can recognize and respond to foreign antigens Lymphocytes all look the same but can be differentiated by their characteristic cell surface molecules These cell surface molecules are classified by the CD (cluster of differentiation) system Lymphocytes possess antigen receptors plus the signal transducing molecules required to activate the cell They also possess receptors for cytokines, immunoglobulins, and complement In domestic animal species, some cell surface molecules are unique to each species. These are classified by the WC (workshop cluster) system The collection of cell surface molecules on a lymphocyte is called its immunophenotype 2 Lymphocytes Introduction Lymphocytes are central to the adaptive immune system and the defense of the body There are three major types of lymphocyte: 1. Natural killer (NK) cells that play a role in innate immunity; 2. T cells that regulate adaptive immunity and are responsible for cell-mediated immune responses; 3. B cells that are responsible for antibody production Within these major types are many subpopulations, each with different characteristics and functions 3 Lymphocytes Lymphocyte structure Lymphocytes are small, round cells, 7 to 15 µm in diameter Each contains a large, round nucleus that stains intensely and evenly with hematoxylin 4 Lymphocyte structure Lymphocytes The nucleus is surrounded by a thin rim of cytoplasm containing some mitochondria, free ribosomes, and a small Golgi apparatus Scanning electron microscopy shows that some lymphocytes are smooth surfaced, whereas others are covered by many small projections NK cells are usually larger than T or B cells and may contain obvious cytoplasmic granules 5 Lymphocytes Lymphocyte populations Lymphocytes are found throughout the body in lymphoid organs, in blood, and scattered under mucosal surfaces Despite their uniform appearance, they are a diverse mixture of subpopulations Although these subpopulations cannot be identified by their structure, they can be identified by their characteristic cell surface molecules and by their behavior 6 Lymphocytes Identifying features of T and B cells 7 Lymphocytes Lymphocyte subpopulations – T cells The loss of cell-mediated immunity as a result of neonatal demonstrated thymectomy the existence of first T lymphocytes After T cells leave the thymus, they accumulate in the paracortex of lymph nodes, the PALS - spleen, and the interfollicular areas of the Peyer’s patches. T cells also account for 60% to 80% of the lymphocytes in blood 8 Lymphocytes Lymphocyte subpopulations – B cells Similar experiments involving bursectomy in chickens FYI pointed to the existence of B lymphocytes In mammals, B cells originate in the bone marrow but mature within Peyer’s patches or in the bone marrow before migrating to the secondary lymphoid organs B cells predominate in the cortex of lymph nodes, in follicles within the Peyer’s patches and spleen, and in the marginal zone of the white pulp of the spleen B cells account for 10% to 40% of blood lymphocytes 9 Lymphocyte receptors Lymphocyte surface molecules All cells express thousands of different protein molecules on their surface Hundreds of these molecules have been characterized and associated with a functional or chemical name, as a cluster of differentiation (CD) designation Currently, the CD nomenclature system gives sequential numbers to each molecule: CD1, CD2, CD3, CD4, CD8, CD16, and so on, up to CD371 10 Lymphocyte receptors CD nomenclature CD4 is found only on the T cells that recognize processed exogenous antigen, the T helper cells CD4 is a receptor for MHC class II molecules CD8, in contrast, is found only on T cells that attack and kill abnormal cells – cytotoxic T cells CD8 is a receptor for MHC class I molecules and is required for the recognition of processed endogenous antigen 11 Lymphocyte receptors Antigen receptor complexes – B cells Each B cell is covered with about 200,000 to 500,000 identical antigen receptors (BCRs) – many more than the 30,000 TCRs expressed on each T cell Unlike the TCR, the BCR can bind antigens when released from the B cell surface Antibodies are simply soluble forms of BCR secreted into body fluids, belonging to the class of proteins called immunoglobulins (α, γ, δ, ɛ, µ = IgA, IgG, IgD, IgE and IgM) B cell receptors 12 Lymphocyte receptors Antigen receptor complexes – T cells Exogenous antigen trapped and processed by dendritic cells is presented to T helper cells in secondary lymphoid organs Each T helper cell has about 30,000 antigen receptors (TCRs) on its surface – identical The 2 populations of T cells are differentiated by their TCR binding chains One uses paired α and ß peptide chains (TCR α/ß) and the other uses paired γ and δ chains (TCR γ/δ) T cell receptors 13 Lymphocyte receptors Molecules that regulate lymphocyte function Proteins on cell surface serve a physiological function Some are enzymes, some are transport proteins, and many are receptors All cells use receptor molecules to communicate with their environment or with other cells They need receptors for antigen-presenting cells as well as receptors for many molecules that regulate lymphocyte responses including receptors for cytokines, antibodies and for complement components 14 Lymphocyte receptors Molecules that regulate lymphocyte function Antibody receptors Lymphocytes have receptors for antibodies Since these receptors binds to the Fc region of antibody molecules, they are called Fc receptors (FcR) The FcR for IgG are designed FcγR since they bind the γ chain of IgG Likewise those for IgA are designated FcαR and those for IgE are FcεR Receptors for IgM have been described on both T and B cells, but receptors for IgD have not been identified 15 Lymphocyte receptors Molecules that regulate lymphocyte function Cytokine receptors Lymphocytes have receptors for many different cytokines Examples of CD molecules that are cytokine receptors include CD25, part of IL-2 receptor CD118 - an interferon receptor CD 124 - IL-4 receptor CD 125 – IL-5 receptor CD120 - tumor necrosis factor (TNF) receptor CD210 - IL-10 receptor 16 Lymphocyte receptors Molecules that regulate lymphocyte function Complement receptors 4 major complement receptors on lymphocytes (CR1-CR4) B cells and activated T cells: express - CR1 (CD35) which binds to C3b and C4b - CR2 (CD21) which binds C3d and C3bi NK cells express CR3 and CR4 17 Lymphocyte receptors Adherence molecules Integrins Integrins are heterodimeric proteins formed by α and ß chains The ß1-integrins consist of a ß1 chain (CD29) paired with one or several different α chains (CD49) They bind cells to extracellular matrix proteins such as fibronectin, laminin, and collagen The ß2-integrins consist of a ß2 chain (CD18) paired with one of several α chains (CD11) They control the binding of leukocytes to vascular endotelium and bind T cells to APCs 18 Lymphocyte receptors Adherence molecules Selectins The emigration of lymphocytes from the bloodstream into tissues is regulated by P-selectin (CD62P), L- selectin (CD62L), and E-selectin (CD62E) P and E selectins are found on vascular endothelial cells When these cells are activated by inflammation, they express selectins that bind neutrophils, T cells, and monocytes L-selectin binds lymphocytes to high endothelial venules in lymphoid organs 19 Lymphocyte receptors Adherence molecules Immunoglobulin superfamily (IgSF) Some members of the IgSF are lymphocyte adhesion molecules – ICAM-1 (CD54) binds to the integrin, CD11a/CD18 ICAM-1 is normally expressed on DCs and B cells Inflammation induces ICAM-1 expression on vascular endothelium and permits phagocytic cells to bind and move to into inflammed tissues Immunoglobulin superfamily (IgSF) ICAM-1 is also responsible for the migration of T cells into areas of inflammation (Type 4 hypersensitivity) 19 Lymphocytes and their receptors ©2024 Ross University School of Veterinary Medicine. 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