Clinical Immunology and serology Practice MLIS-201 Prof. Dr. Ezzat M Hassan Immunology Dept., Med. Res. Inst., Alex. Univ. Outcomes By the end of the lecture the students will be able to • Recognize Structure of the immune system. • Enumerate the Cell Frequency of Different Leukocytes in Blood of Healthy Individuals Structure of the immune system Immune system Cells Organs 1-Cells of the Immune System Cells of the Immune System Myeloid cells lymphoid cells Granulocytic Monocytic T-cells B-cells Neutrophils Basophils Eosinophils Macrophages Langerhans & Kupffer cells Dendritic cells? Helper Cytotoxic Suppressor Plasma cells Dendritic cells? Cell Frequency of Different Leukocytes in Blood of Healthy Individuals ~ 60% neutrophils (50% - 70%) ~ 3% eosinophils (>0% - 5%) ~ 0.5% basophils (>0% - 2%) ~ 5% monocytes (1% - 9%) ~ 30% lymphocytes (20% - 40%) Myeloid Lineage Granulocytes Neutrophils Eosinophils Basophils Monocytes Macrophages Megakaryocytes Platelets Erythrocytes (RBC) Dendritic cells (APC) Neutrophils 60-70% of WBCs Multi-lobed nucleus Granulated cytoplasm Life span is 2-3days Prominent in inflammatory response Leukocytosis is marker for infectious process Dead neutrophils make up a large proportion of pus. Actively phagocytic Eosinophils ~2% of WBCs Bi-lobed nucleus Granulated cytoplasm Stains red with acid dye (eosin) Prominent in response to parasitic infections Phagocytic Basophils <1% of WBCs Lobed nucleus Heavily granulated cytoplasm Stains blue with basic dye Prominent in allergic responses Non-phagocytic Secrete allergic & inflammatory mediators Monocytes and Macrophages Monocytes: Large WBCs Monocytes are circulating precursors of Macrophages. Macrophages Found in the organs, not the blood. Made in bone marrow as monocytes Called macrophages once they reach organs. Long lived Phagocytic Initiate immune responses as they display antigens to the lymphocytes (APC). Activated by cytokines and gamma interferon Secretes numerous immune response factors Phagocytosis Macrophages Bifunctional Antigen presentation Liver Skin Kuppfer cells CNS Spleen,lung Denteritic cells Microglia Macrophages Mast Cells Found in many different tissues Contains granules which release histamine Play role in allergic reactions Dendritic Cells Have long “dendrites” Major role as APC Stimulated by innate response Have constitutive MHC II expression Phagocytic APC T cell APC INTERACTING WITH T CELL Lymphoid Lineage Lymphoid cells NK (Natural killer cells) T-cells B-cells Lymphocyte Production Lymphocytes are produced in: lymphoid tissues (e.g., tonsils) lymphoid organs (e.g., spleen, thymus) Bone marrow Make up 20–30% of circulating leukocytes Majority are stored in lymphoid organs, not circulating (remember that only about 1% of your WBCs are in the blood) Classes of Circulating Lymphocytes T cells: thymus-dependent Make up 80% of circulating lymphocytes B cells: bone–marrow derived Make up 10–15% of circulating lymphocytes NK cells: natural killer cells Make up 5–10% of circulating lymphocytes Lymphocytes 1-T Lymphocytes Mature in thymus Have T cell receptors (TCRs) Recognize Ag on cells only CELL-MEDIATED IMMUNE RESPONSE T cell subclasses: 1. Cytotoxic T cells Helper T cells 2. Stimulate function of T cells and B cells Suppressor T cells 3. Inhibit function of T cells and B cells Regulatory T cells 4. 5. Attack cells infected by viruses & malignant cells Regulate the functions other T cells Memomry T cells For secondary immune responses Lymphocytes 2-B Lymphocytes Mature in bone marrow Have membrane-bound Ab(~10,000 per cell) Go from “naive” to activated. Differentiate into plasma cells, which produce and secrete antibodies (immunoglobins) HUMORAL IMMUNE RESPONSE Plasma cells are Ab secretors ~1-2 week life span B- cells Plasma cells Immunoglobulins B-memory -Long lived -2ry immune response B cells Natural Killer (NK) Cells Also called large granular lymphocytes Responsible for immunological surveillance Lack T and B cell markers Lack Ag receptors Involved with Ab-dependent cell-mediated cytotoxicity (ADCC) Attack: foreign cells virus-infected cells cancer cells Lymphocyte Distribution Tissues maintain different T cell and B cell populations: T Cells: high in blood, thymus, marrow, spleen, others B Cells: high in nodes, spleen, others Lymphocytes wander through tissues, migrating throughout the body to defend peripheral tissues (T cells move faster than B) Have long life span (4 years+, up to 30!) Retain their ability to divide, which is essential to immune system function Hi ! Take short rest!! 2- Organs of the Immune System Organs of Immune System Primary Bone marrow Thymus gland Secondary Spleen Lymph nodes Tertiary MALT Lymphoid Organs & Tissues spleen, thymus gland, Lymph nodes and tonsils Peyer’s patches and bits of lymphatic tissue scattered in connective tissue Figure 20.5 Primary lymphoid organs Thymus Secretes hormones (thymosin and thymopoietin) that cause T lymphocytes to mature It functions strictly in T lymphocyte maturation It does not directly fight antigens Located in mediastinum Deteriorates after puberty Divided into 2 thymic lobes Septa divide lobes into smaller lobules Each lobule contains: a dense outer cortex of dividing T cells a pale central medulla T cells: divide in the cortex migrate into medulla leave thymus by medullary blood vessels Secondary lymphoid organs & tissues Lymphoid Functions Lymphoid tissues and lymph nodes: Distributed throughout body to monitor peripheral infections respond before infections reach vital organs of trunk Lymph nodules in mucosa Lymph nodes monitor plasma/interstitial fluid Spleen Monitor blood Structure Spleen Gross Largest single collection of lymphoid tissue in the body Ovoid organ in upper left quadrant of abdomen Microscopic Compartmentalized Periarticualr lymphoid sheath Red pulp White pulp Site of Ag presentation Major cell types: Lymphocytes Macrophages Dendritic cells RBCs Functions of the Spleen Filters the blood like lymph nodes filter the lymph Phagocytes in the spleen remove abnormal blood cells • • • and other blood components by phagocytosis Storage of iron and other RBC products for later use or elimination Initiation of immune responses by B cells and T cells in response to antigens in circulating blood Site of lymphocyte proliferation Stores RBC’s & platelets Lymph Nodes Structure Gross Bean-shaped structures Drains major segments of lymphatic system Microscopic Major cell types Lymphocytes Macrophages Dendritic cells Cortex/paracortex/medulla Follicles Primary Secondary Peripheral Lymph Node Structure Lymph Nodes Distribution •cervical region • axillary region • inguinal region • pelvic cavity • abdominal cavity • thoracic cavity • supratrochlear region Lymph Nodes Functions: Filter potentially harmful particles from lymph Immune surveillance by macrophages and lymphocytes Areas of lymphocyte production & proliferation 1st line of response to antigens Secondary follicle (Germinal center) is site of B cell proliferation & differentiation After Ag stimualtion lymphocyte numbers increase by 50X in efferent lymphatic vessel (Lymphadenopathy) Tertiary lymphoid tissues Tonsils Follicular structure Contains lymphocytes, macrophages, mast cells Germinal centers appear in response to Ag Protective role in URI Appendix Associated with intestines Responds to Ag Role in GI immune response Mucosa Associated Lymphoid Tissues (MALT) Lymphoid tissues below epithelium (Peyer’s Patches) Presence of B cells Ag presented through unique cell (M cell) Preferentially responds with IgA antibody Next Lecture: Innate immunity Write assay about Mucosa Associated Lymphoid Tissues Lymph Nodes Function of spleen Assignment: Cell Frequency of Different Leukocytes in Blood of Healthy and diseased Individuals.