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

1-Cells of the Immune System

Cells of the Immune System Basophils Neutrophils Eosinophils Granulocytic Langerhans & Macrophages Kupffer cells Dendritic cells? Monocytic Cytotoxic Helper Suppressor T-cells Plasma cells B-cells Dendritic cells? lymphoid cells Myeloid cells

~ 60% neutrophils (50% - 70%) ~ 3% eosinophils (>0% - 5%) ~ 0.5% basophils (>0% - 2%) ~ 5% monocytes (1% - 9%) ~ 30% lymphocytes (20% - 40%) Cell Frequency of Different Leukocytes in Blood of Healthy Individuals

Myeloid Lineage Granulocytes  Neutrophils  Eosinophils  Basophils Monocytes Megakaryocytes Erythrocytes (RBC) Dendritic cells (APC) Macrophages Platelets

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

Macrophages Liver Kuppfer cells Skin Denteritic cells CNS Microglia Spleen,lung Macrophages Bifunctional Phagocytosis Antigen presentation

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 INTERACTING WITH T CELL T cell APC

Lymphoid Lineage

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 Attack cells infected by viruses & malignant cells 2. Helper T cells Stimulate function of T cells and B cells 3. Suppressor T cells Inhibit function of T cells and B cells 4. Regulatory T cells Regulate the functions other T cells 5. 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

Immunoglobulins-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

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

Spleen Structure Gross Largest single collection of lymphoid tissue in the body Ovoid organ in upper left quadrant of abdomen Microscopic Compartmentalized Red pulp White pulp Periarticualr lymphoid sheath 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 1 st 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.