Nada Mohamed Ahmed, MD, MT (ASCP)i

Nada Mohamed Ahmed, MD, MT (ASCP)i

Objectives Organs Of Immune System Primary Secondary Lymphoid Organs Cells of the immune system: phagocytes Non-specific killer cells Cells of the immune system Cells of the adaptive immune system Specificity of adaptive immune response Lymphocyte recirculation

Organs Of Immune System Primary Lymphoid Organs – Bone Marrow and Thymus Maturation Site Secondary Lymphoid Organs – Spleen, lymph nodes, – MALT (mucosal associated lymph tissue) – GALT (gut associated lymph tissue) Trap antigen, APC, Lymphocyte Proliferation

Primary and Secondary Lymphoid Organs Primary Lymphoid Organs Also called “central lymphoid organs” It is where immature lymphocytes develop Organs where differentiation, proliferation and maturation of stem cells into immuncompetent cells take place. Includes:  Thymus  Bone Marrow Secondary Lymphoid Organs It is where antigen is localized so that it can be effectively exposed to mature lymphocytes. initiate adaptive immune response. Includes:  Spleen  Lymph Nodes  Tonsils  Appendix  Peyer’s patches

Primary Lymphoid Organs BONE MARROW  The site of B cell maturation and hematopoiesis Function: Responsible for the production of important immune system cells like B cells, granulocytes, natural killer cells and immature thymocytes. Also produces platelets and RBC.

SPLEEN  Organ of the immune system composed of T-cells, B-cells, natural killer cells, macrophages, dendritic cells and red blood cell.  It is a production site of antibodies and activated lymphocytes, which are delivered to the blood. Function: Filters the blood and entraps foreign materials (antigen). Provides defense against blood-borne antigens. Secondary Lymphoid Organs

TONSILS  Two masses of soft glandular tissue on either side or the back of the mouth. Function: Traps bacteria and viruses from inhaled air.

Secondary Lymphoid Organs APPENDIX  Thin, dead-end tube measuring about three-to-four inches in length and it hangs from the cecum. Functions: Help tell the lymphocytes exactly where they have to head over to attack infection and it also enhances the massive intestine's defenses to a range of drugs and foods.

Cells of the immune system Immune system Myeloid cells Granulocytic Neutrophils Basophils Eosinophils Monocytic Macrophages Kupffer cells Dendritic cells Lymphoid cells T cells Helper cells Suppressor cells Cytotoxic cells B cells Plasma cells NK cells

Development of the immune system NK cell Stem cell Macrophage Lymphoid progenitor Myeloid progenitor T cell B cell Plasma Cell Granulocyte Monocyte Mast cell Dendritic cell

Cells of the immune system GranularAgranular (35% in circulation) Basophil Eosinophil Plasma cell Lymphocyte (T, B, NK) NeutrophilDendritic cell Monocyte

Phagocytosis and Intracellular killing Neutrophils and Macrophages

Phagocytes – neutrophils (PMNs)  Neutrophils defend against bacterial or fungal infection They are commonly referred to as polymorphonuclear (PMN) leukocytes  Neutrophils are very active in phagocytosing bacteria and are present in large amount in the pus of wounds. Characteristic nucleus, cytoplasm Granules CD66 membrane marker protein Geimsa stain Neutrophil

Characteristics of neutrophil granules Primary granulesSecondary granules Azurophilic; young neutrophilsSpecific for mature neutrophils Contain: cationic proteins, lysozyme, defensins, elastase and Contain: Lysozyme, NADPH oxidase components and myeloperoxidaseLactoferrin and B12-binding protein

Phagocytes – macrophages Characteristic nucleus lysosomes CD14 membrane marker protein Macrophage Monocytes eventually leave the bloodstream to become tissue macrophages, which remove dead cell debris as well as attacking microorganisms

Non-specific killer cells NK cells Eosinophils

Natural killer (NK) cells Also known as large granular lymphocytes (LGL). Kill virus-infected or transformed cells.

Eosinophils Eosinophils primarily deal with parasitic infections. Eosinophils are also the predominant inflammatory cells in allergic reactions.

Basophils Basophils are chiefly responsible for allergic and antigen response by releasing the chemical histamine causing vasodilationvasodilation

Mast cells Characteristic cytoplasmic granules Responsible for burst release of preformed cytokines, chemokines, histamine. Role in immunity against parasites. Mast cell: a cell filled with basophil granules, found in numbers in connective tissue and releasing histamine and other substances during inflammatory and allergic reactions.

Cells of the immune system: innate Phagocytes – Monocytes/macrophages – PMNs/neutrophils NK cells. Basophils and mast cells. Eosinophils.

Cells of the immune system: Cells that link the innate and adaptive arms – Antigen presenting cells (APCs) Heterogenous population with role in innate immunity and activation of Th cells Rich in MHC class II molecules. – Examples Dendritic cells Macrophages B cells Others (Mast cells)

Cells of adaptive immune response T cells and B cells

Cells of the immune system: adaptive Lymphocytes – B cells Plasma cells (Ab producing) – T cells Cytotoxic (CTL) Helper (Th) – Th1 – Th2

Major distinguishing markers MarkerB cellCTLT-helper Antigen RBCR (surface Ig)TCR CD3--++ CD4-- + CD8--+ CD19/ CD20+-- CD40+--

Specificity of adaptive immune response TCR and BCR – both specific for only ONE antigenic determinant TCR is monovalent BCR is divalent T cell TCR Ag B cell BCR Ag Each B and T cell has receptor that is unique for a particular antigenic determinant on Ag

Development of the immune system NK cell Stem cell Macrophage Lymphoid progenitor Myeloid progenitor T cell B cell Plasma Cell Granulocyte Monocyte Mast cell Dendritic cell Bone Marrow Thymus Tissues 2° Lymphoid

Lymphocyte recirculation Lymphocytes enter 2° lymphoid organs via high endothelial venules (HEVs) Ag is transported to lymph nodes via APC Upon activation, lymphocytes travel to tissues. T cell B cell MonocyteDC APC T cell B cell T cell Bone marrow Thymus Tissues Virgin lymphocytes Spleen and lymph nodes Primed lymphocytes

Lymphocyte recirculation After activation, new receptors (homing R ) are expressed to direct to tissues R on lymphocytes recognize CAMs on endothelial cells Chemokines at infection help attract activated lymphocytes T cellB cell MonocyteDC APC T cell B cell T cell Bone marrow Thymus Tissues Virgin lymphocytes Spleen and lymph nodes Primed lymphocytes

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