Immuno2 Cells PDF

LECOM-Pharmacy School BMS-PDA II Immun 2 Cells, Tissues & Organs of the Immune System Dr. Saber Hussein  Objectives 1. B and T lymphocytes and NK cells 2. T cells Subpopulations: Helper, cytotoxic and suppressor 3. Antigen presenting cells 4....

LECOM-Pharmacy School BMS-PDA II Immun 2 Cells, Tissues & Organs of the Immune System Dr. Saber Hussein  Objectives 1. B and T lymphocytes and NK cells 2. T cells Subpopulations: Helper, cytotoxic and suppressor 3. Antigen presenting cells 4. Phagocytes: Monocytes (macrophages) & granulocytes (eosinophil, neutrophil, basophil & mast cells) 5. granulocyte and platelet role in inflammatory response 6. Primary tissues of the Immune System: 1. Bone marrow & 2. Thymus 7. Secondary tissues: 1. Lymph nodes, 2. spleen, 3. Payer patches  Cells of the Immune System Lymphoid Lineage – T helper cells (TH) – Cytotoxic T cells (Tc or CTL) – B cells – Natural Killer Myeloid Lineage – Polymorphonuclear granulocytes Neutrophil Basophil & Mast cells Eosinophil – Mononuclear phagocytes Dendritic cells & Macrophages – Megakaryocytic Lineage Platelets  Hematopoiesis Hematopoiesis is the process of blood cell maturation from the stem cell to the active, functional blood cell (red or white) Red blood cells and white blood cells are formed in the bone marrow Stem cells are totipotent or pluripotent – Totipotency - The ability of a cell, such as an egg, to give rise to unlike cells [differentiate] and thus to develop into or generate a new organism or part. – Pluripotency - The potential of a cell to develop into more than one type of mature cell, depending on environment Myeloid cells and lymphoid cells are pluripotent cells with a common ancestor, a totipotent cell  Hematopoiesis Myeloid cell Erythrocyte; Neutrophil, Monocyte → Macrophage; Eosinophil; Basophil & Mast cell; Megakaryocyte → Platelet Lymphoid cell Lymphocytes: T cell B cell → Plasma cell NK cell Cells involved in the immune response  Polymorphonuclear Granulocytes PMNs include – Mainly neutrophils – Eosinophils – Basophil & mast cells From bone marrow at 7 million/minute Short lived (2-3 days) About 60-70% of WBCs (Extravasation):  Extravasation (Diapedesis) PMNs leave the circulation by adhering to the endothelium & squeezing out It is promoted by chemokines IL-1  Neutrophil Subject to chemotactic stimulation by: – Complement fragments (C5a) – Products of platelets & leukocytes – Bacterial products – Protein products of fibrinolysis Lysosomes contain i. Primary granules contain Hydrolases Peroxidases Lysozyme ii. Secondary (specific) granules contain: Lactoferrin Lysozyme  Neutrophils Have multilobed nuclei Their primary function is – Phagocytosis enhanced by opsonization with complement and Abs Important secondary function – promote inflammation Neutrophils kill by producing – reactive oxygen metabolites – hydrolytic enzymes (Granules) – nitric oxide – antibiotic proteins such as defensins bacterial permeability inducing protein  Basophils are in circulation Basophils & – Have S-shaped nucleus Mast cells – Are round Mast cells are stationary: 1. Mucosal mast cells (MMC) 2. Connective tissue mast cells (CTMC) Granules’ contents are called mediators such as: – Heparin – Histamine – SRS-A (slow-reacting substance of anaphylaxis) – ECF-A (eosinophil chemotactic factor A)  Basophils and mast cells are Basophils and mast the least prevalent of the leukocytes cells They possess high affinity Fc receptors for IgE They release the chemical mediators of immediate hypersensitivity, including: – Histamine – Prostaglandins – Thromboxanes – Leukotrienes – Heparin They also produce eosinophil chemotactic factor (ECF) – which causes eosinophils to enter the area of worm infestation or allergen localization  Eosinophils Bilobed nucleus Granules stain with acid dyes- eosin Capable of phagocytosing & killing microorganisms Degranulation: release of contents in surrounding area Can kill parasites with basic proteins and cationic proteins – Schistosoma mansoni  Monocytes/Macrophages M in the process Monocytes enter circulation from of surrounding bone marrow then migrate into tumor cell various organs and tissues There they mature into: – macrophages – Kupffer cells (liver) – histiocytes (M found in connective tissue) – dendritic cells (lymph nodes, spleen) – glial cells (brain) – Langerhans' cells (skin) Collectively, these cells form a network known as the reticuloendothelial system (RES) or the mononuclear phagocyte system  Differential White Blood Cell Count CELL TYPE % OF WBC'S CELLS/cmm Neutrophil 50 – 60 3000 - 7000 Eosinophil 1–4 50 – 400 Basophil 0.5 – 2 25 – 100 Lymphocyte 20 – 40 1000 – 4000 T cell 80 - 85* B cell 5 - 15* NK cell 5 - 15* Monocyte 2-9 100 - 600 *% of lymphocytes in peripheral blood  Reticuloendothelial System (mononuclear phagocyte System)  Anucleate Platelets Derived from megakaryocytes Contain granules at the ultrastructural level Their major functions are – blood clotting – inflammation Following injury to endothelial cells, platelets adhere to the surface of the damaged tissue, where they release substances that Platelets aggregating – increase vascular permeability, at the site of a wound – activate complement and in a blood vessel – attract leukocytes  Classes of Lymphocytes https://studentconsult.inkling.com/read/basic-immunology-abbas-lichtman-pillai-4th/chapter-1/figure-110 Maturation of Lymphocytes Functions of Lymphocytes NK  B and T lymphocytes T cells develop in the thymus B cells differentiate – in fetal liver & – in postnatal bone marrow Ag recognition via specific receptors NK (natural killer) cells do not express Ag receptor Lymphocytes have – high N:C (nucleus : cytoplasm) ratio LGL (NK; Large granular lymphocytes) have – lower N:C ratio  T Cells Majority of T cells express ab-TCR TC Cell TH Cell CD8 – T-helper cells (TH) CD4 – T-cytotoxic cells (Tc) TCR is an immunoglobulin Carry Gall body (Gb) in the cytoplasm – Gb: A cluster of lysosomes + Lipid droplet MHC-I  Subpopulations of T cells Tc CD8 abT TH1 TH T0 CD4 TH2 gd T  B cells have: Resting B cells have: – MHC I (like all nucleated No Gall bodies cells) & No LGL morphology – MHC II proteins on their surfaces Monoribosomes scattered in MHC proteins are members of the cytoplasm the Ig superfamily that have Ag Activated B cells have rough ER binding capabilities but are not nearly as specific as Ag binding by Ig or T cell antigen receptors B cells function as APCs for induction of immune response B cells have two different receptors for complement: – CR1 (CD35) and MHC-I – CR2 (CD21) that probably have regulatory functions CR2 is the target for Epstein- Barr virus (EBV) binding  NK Cell Have LGL morphology Contain larger number of azurophilic granules than granular T cells Have no specific receptor for Ag recognition Derived from lymphoid cell progenitors in the How can you distinguish NK from T & B? bone marrow 1. No specific receptor 2. NK can lyse certain tumor cell lines in vitro without prior sensitization  Antigen presenting cells APCs – Heterogenous leucocytes – Present Ags to TH or Tc cells – Abel to digest protein Ags – Found primarily in: Skin Spleen Lymph nodes  What cells can serve as APC? 1. Langerhans cells (LC) 2. Dendritic cells 1. Interdigitating dendritic cells (IDC) 2. Follicular dendritic cells (FDC) 3. Germinal center dendritic cells (GCDC) 3. B cells 4. Macrophages  Lymphoid organs Lymphoid organs – Organs of maturation, differentiation and proliferation of lymphocytes Primary (central) lymphoid organs – T and B lymphocytes begin expressing their antigen receptors Secondary lymphoid organs – Site of Ag-dependent proliferation and differentiation  Primary lymphoid organs Bone marrow- where B cells develop Thymus- where T cells develop: – Progenitor cells from the bone marrow migrate to the thymus – A bilobed structure – Reaches its maximum at birth – Atrophy with age – Cortex contains mostly immature thymocytes Mature & migrate to the medulla – In the medulla they learn to discriminate between self and nonself during fetal development and short time after birth  Primary lymphoid organs T cells: – Leave the medulla – Enter the peripheral blood circulation – Transported to the secondary lymphoid organs DiGeorge syndrome: – Congenital absence of thymus results in an immediate and drastic reduction in T cells that produces a potentially lethal wasting disease  Secondary lymphoid organs The secondary lymphoid organs have two major functions: – Trap and concentrating foreign substances – As main sites of production of Abs and T cells The major secondary lymphoid organs include: – Spleen Responsive to blood-borne antigens – Lymph nodes Protect the body from antigens that enter from: – Skin – Internal surfaces via the lymphatic system – Mucosa-associated lymphoid tissue (MALT): Scattered along mucosal linings Protect against Ags entering the body directly through mucosal surfaces  Spleen Spleen Cross-section of the periarteriolar lymphoid sheath (PALS)  Lymph nodes are clustered in Lymph nodes strategic points in the body: – Neck – Axillae – Groin – Mediastinum – Abdominal cavity Filter Ags from – Interstitial tissue fluid – Lymph during its passage from the periphery to the thoracic duct Two types: – Somatic nodes: Lymph nodes that protect the skin – Visceral nodes: Deep lymph nodes protecting the respiratory, digestive and genitourinary tracts  MALT More than 50% of is lymphoid tissue Mucosa-associated lymphoid tissue is composed of – GALT- line the intestinal tract (Gut) – BALT line the respiratory tract (Bronchus) – Genitourinary tract lining lymphoid tissue Secretory IgA (sIgA) – Major effector mechanism Secreted directly onto the mucosal epithelial surfaces  MALT MALT include – Peyer patches lining the small intestine – Tonsils – Appendix "M" cells – Have numerous microfolds on their luminal surface Absorb Transport Process Present antigens to subepithelial lymphocytes