Cells, Tissues, & Organs of The Immune System Chapter 2 PDF

‫‪Immunology‬‬ ‫ﺗﻔرﯾﻎ ‪ :‬ﻣﺎﻟك اﻟﻌﺑوﺷﻲ ‪ ،‬ﻋﺑد اﻟﺣﻛﯾم أﺑو رﺟﺎ‪ ،‬أﺳﻣﺎء ﺻرﻣﺔ‪ ،‬اﺣﻣد ﻧوري‬ ‫ﺗدﻗﯾق‪ :‬ﻓﺗﺣﻲ ﻣﻠﺣم‪ ،‬اﺣﻣد ﻧوري‪ ،‬اﻣﯾر ﻋواﺷرة‬  Chapter 2 Cells, Tissues, & Organs of The Immune System 2019-2020 Immunology 7105306 2 ...

‫‪Immunology‬‬ ‫ﺗﻔرﯾﻎ ‪ :‬ﻣﺎﻟك اﻟﻌﺑوﺷﻲ ‪ ،‬ﻋﺑد اﻟﺣﻛﯾم أﺑو رﺟﺎ‪ ،‬أﺳﻣﺎء ﺻرﻣﺔ‪ ،‬اﺣﻣد ﻧوري‬ ‫ﺗدﻗﯾق‪ :‬ﻓﺗﺣﻲ ﻣﻠﺣم‪ ،‬اﺣﻣد ﻧوري‪ ،‬اﻣﯾر ﻋواﺷرة‬  Chapter 2 Cells, Tissues, & Organs of The Immune System 2019-2020 Immunology 7105306 2  ‫ﻟﻤﺤﺔ ﺳﺮﯾﻌﺔ ﻋﻦ اﻟﺘﺸﺎﺑﺘﺮ‬ ‫ﻏﺎﻟﺒﯿﺔ ﺧﻼﯾﺎ اﻟﺠﮭﺎز اﻟﻤﻨﺎﻋﻲ أﺻﻠﮭﻢ )‪ (origin‬ﻣﻦ ‪ Hematopoietic stem cells‬وﻓﻲ ﻣﻨﮭﻦ ‪ two lineages‬ﺑﺘﯿﺠﻲ ﻣﻨﮭﻦ‬ ‫اﻟﺨﻼﯾﺎ اﻟﻤﻨﺎﻋﯿﺔ وھﻦ ‪.Lymphoid and myeloid‬‬ ‫ال ‪ lymphocytes‬ﺑﺘﻢ اﻧﺘﺎﺟﮭﺎ ﺑﺎل ‪ bone marrow‬و ال ‪ B cells‬ﺑﺼﯿﺮﻟﮭﺎ ‪ differentiation‬ﻓﻲ ‪ Bone marrow‬اﻣﺎ ال‬ ‫‪ T cell‬ال ‪ differentiation‬ﺑﺎل‪Thymus‬‬ ‫‪ Phenotypic cells‬ﺑﻨﻼﻗﯿﮭﻦ ﺑﺎل ‪ circulation‬ﻋﻠﻰ ﺷﻜﻞ ‪granulocytes or monocytes‬‬ ‫ال ‪monocytes‬ﺑﺼﯿﺮ إﻟﮭﺎ ‪ differentiation‬أﻛﺜﺮ ﻟﻤﺎ ﺑﺘﺮوح ﻋﻠﻰ ال ‪ tissue‬اﻟﻲ رح ﺗﻌﻤﻞ ﺑﯿﮭﺎ وﺑﺨﺘﻠﻒ اﺳﻤﮭﺎ ﺣﺴﺐ‬ ‫ﻣﻮﻗﻌﮭﺎ‪ ،‬ﻓﺈذا ﻛﺎﻧﺖ ب‪ blood stream‬ﺑﻜﻮن اﺳﻤﮭﺎ ‪ monocyte‬وﻓﻲ ال‪ tissue‬ﺑﻜﻮن اﺳﻤﮭﺎ ‪ macrophage‬وال‬ ‫‪ macrophage‬ﺣﺴﺐ اﻟﻌﻀﻮ اﻟﻲ ﺑﺘﻜﻮن ﻓﯿﮫ رح ﺗﻮﺧﺬ اﺳﻢ ﺧﺎص ﺑﯿﮫ‪ ،‬ﻣﺜﻞ ‪ Kupffer cells‬اﻟﻤﻮﺟﻮدة ﻓﻲ ‪.liver‬‬ ‫أﻧﻮاع ال ‪ polymorphonuclear cells‬ھﻨﻲ ‪eosinophils, basophils and neutrophils‬‬ ‫ﺑﺘﻜﻮن ﺧﻼﯾﺎ ‪ neutrophils‬ﺑﺎﻟﻌﺎدة ‪ ،short lived phagocyte cell‬ﯾﻌﻨﻲ ﻓﺘﺮة ﺣﯿﺎﺗﮭﺎ ﻗﺼﯿﺮة وھﻲ ﻣﻦ أھﻢ اﻟﺨﻼﯾﺎ ﻓﻲ‬ ‫‪ innate immunity‬ﻟﺬﻟﻚ ﺑﺘﻜﻮن ﺑﺄﻋﺪاد ﻛﺒﯿﺮة ﻓﻲ ال‪ Blood‬وﻓﻲ ‪ ،sites of acute inflammations‬وﻟﻤﺎ ﺗﻜﻮن ﻓﻲ‬ ‫ال‪ blood‬ﺑﺘﻜﻮن ﻋﻠﻰ ﺷﻜﻞ ‪) mirginated cells‬ﺑﺘﻜﻮن ﻣﺎﺳﻜﺔ ﻋﻠﻰ ﺟﺪران اﻷوﻋﯿﺔ اﻟﺪﻣﻮﯾﺔ( وﺑﻜﻮﻧﻦ ﻓﻲ وﺿﻊ اﻻﺳﺘﻌﺪاد‬ ‫ﻷي ﺣﺎﻟﺔ ‪ ،emergency‬وﻟﮭﺬا اﻟﺴﺒﺐ ‪ neutrophils‬ﺳﮭﻞ ﺟﺪا ً ﯾﺮﺗﻔﻊ ال ‪ count‬ﺗﺒﻌﮭﺎ ﻓﻲ ‪ blood stream‬ﺑﺴﺒﺐ أي ‪strees‬‬ ‫أو أي اﺷﻲ ‪ urgent‬ﺻﺎر ﺑﺎﻟﺠﺴﻢ‪.‬‬ SUMMARY Most cells of the immune system derive from hematopoietic stem cells. The primary lymphoid organs in mammals are the thymus and bone marrow, where lymphocyte differentiation occurs. Phagocytic cells are found in the circulation as monocytes and granulocytes. Monocytes differentiate into macrophages that reside in tissues (e.g. Kupffer cells in the liver). Neutrophils are short lived phagocytes present in high numbers in the blood and at sites of acute inflammation. inflammatory ‫ ﻛﻞ ھﺬول إﻟﮭﻢ دور ﻓﻲ‬Eosinophils, basophils, mast cells, and platelets,with cytokines ‫وﻟﻜﻦ ھﺬول اﻟﺨﻼﯾﺎ ﺑﻜﻮن دورھﻦ رﺋﯿﺴﻲ وأوﺿﺢ‬neutrophils ‫ ﺻﺢ ﻓﻲ ﺧﻼﯾﺎ ﻏﯿﺮھﻦ زي ﻣﺎ ﺣﻜﯿﻨﺎ ﻓﻮق ﻋﻦ‬. response.inflammation ‫ﻓﻲ ﻋﻤﻠﯿﺔ‬ ‫ وﺑﻌﺪ ﻣﺎ‬innate immunity ‫ وھﻲ ﺟﺰء ﻣﻦ‬certain tumor cells ‫ و‬viral-infected cells ‫ ﺑﺘﺘﻌﺮف وﺑﺘﻘﺘﻞ‬-:NK.apoptosis (programmed cell death) ‫ﺗﺘﻌﺮف ﻋﻠﻰ اﻟﺨﻼﯾﺎ اﻟﻤﺼﺎﺑﺔ أو اﻟﺴﺮطﺎﻧﯿﺔ ﺑﺘﻘﻮم ﺑﺘﺤﻔﯿﺰھﺎ ﻣﺸﺎن ﺗﺪﺧﻞ ﻓﻲ‬ ‫ وﻟﻜﻨﮭﺎ‬innate immunity ‫ ﻷﻧﮭﺎ ﻣﻦ ﺧﻼﯾﺎ‬innate and adaptive immune systems ‫ ﺑﺸﻜﻠﻮا راﺑﻂ ﻣﮭﻢ ﺑﯿﻦ‬-:APCs T-Cells ‫ ﻣﺜﻞ‬adaptive immunity ‫ ﻟﺨﻼﯾﺎ‬activation ‫ ﺣﺘﻰ ﯾﺼﯿﺮ‬antigen ‫ ﻟﻞ‬activation or presenting ‫ﺑﺘﻌﻤﻞ‬.‫( اﻟﺘﻲ ﺗﻌﺘﺒﺮ اﻟﺨﻼﯾﺎ اﻟﻤﺤﻮرﯾﺔ واﻟﻤﺮﻛﺰﯾﺔ ﻓﻲ ﺟﮭﺎز اﻟﻤﻨﺎﻋﺔ‬T-Helper ‫)وﺧﺎﺻﺔ‬ ‫ وﺑﺎل‬functionally ‫ وﺑﺎﻟﻮظﯿﻔﺔ‬phenotypically ‫ ﻣﺠﻤﻮﻋﺔ ﻣﻦ اﻟﺨﻼﯾﺎ إﻟﻲ ﺑﺘﺨﺘﻠﻒ ﺑﺎﻟﺸﻜﻞ‬-:Lymphocytes.morphology ‫ ﺗﺒﻌﮭﻢ وأﺳﻤﺎءھﻢ‬surface ‫ ﻋﻠﻰ‬antigen recepters ‫ ﻓﻲ ﻋﻨﺪھﻢ‬-:B&T Lymphocytes.Antibodies ‫ ﺗﺒﻊ‬structure‫ ﻧﻔﺲ ال‬BCR‫( و ال‬BCR) B Cell Receptor & (TCR) T Cell Receptor  SUMMARY Eosinophils, basophils, mast cells, and platelets, together with cytokines and complement, take part in the inflammatory response. NK cells recognize and kill virus-infected cells and certain tumor cells by inducing apoptosis. Antigen-presenting cells link the innate and adaptive immune systems and are required by T cells to enable them to respond to antigens. Lymphocytes are heterogeneous phenotypically, functionally, and morphologically. B lymphocytes and T lymphocytes express specific antigen receptors called the B cell receptor (BCR) and T cell receptor (TCR) respectively. 2019-2020 Immunology 7105306 6  ً‫ ( وﻛﻞ وﺣﺪة ﻣﻨﮭﻦ إﻟﮭﺎ أﻧﻮاع ﻣﺨﺘﻠﻔﺔ ﻓﻤﺜﻼ‬TH, TC and Treg) T-Cells ‫ ﻣﻦ‬3 major subpopulations ‫ﻓﻲ ﻋﻨﺎ‬.‫ وھﻜﺬا‬TH2‫ و‬TH1 ‫ ﻓﻲ ﻣﻨﮭﺎ‬TH.innate immunity ‫ و دورھﺎ ﺑﻜﻮن ﺑﺎل‬lymphocyte ‫ ﻧﻮع ﻣﻦ أﻧﻮاع‬NK cells ‫ال‬ plasma & memory ‫ ل‬bone marrow ‫ ﺑﺎل‬differentiation ‫ ﺑﺼﯿﺮﻟﮭﺎ‬-:B cells ‫ وﻟﮭﯿﻚ‬thymus ‫ ﻓﻲ‬further development ‫ وﻟﻜﻨﮭﺎ ﺑﺘﺤﺘﺎج ل‬bone marrow ‫ ﺑﺎل‬production ‫ ﺑﺼﯿﺮ إﻟﮭﺎ‬-:T cells.‫ رح ﻧﺸﺮﺣﮭﻢ ﺑﺂﺧﺮ اﻟﺸﺎﺑﺘﺮ‬negative and positive selections ‫ وﺑﺘﺘﻌﺮض ل‬،T cells ‫اﺳﻤﮭﺎ‬.‫ ﺗﺒﻌﮭﺎ ﻣﻨﺎﺳﺐ ﻟﻠﺠﺴﻢ‬structure and behavior ‫ ﺑﺘﻢ اﺧﺘﯿﺎر اﻟﺨﻠﯿﺔ ﻣﺸﺎن ﺗﻈﻞ ﻋﺎﯾﺸﺔ ﻷن ال‬-:Positive selection.‫ ﻓﮭﻮ اﺧﺘﯿﺎر اﻟﺨﻠﯿﺔ ﻣﺸﺎن ﺗﻤﻮت ﻷﻧﮫ اﻟﺠﺴﻢ ﻣﺎ رح ﯾﺤﺘﺎﺟﮭﺎ‬negative selection ‫أﻣﺎ‬ ‫ ﺑﻜﻮن‬bone marrow ‫ ﻓﻠﻤﺎ ﻧﺤﻜﻲ‬،bone marrow ‫ وﺑﻌﺪ اﻟﻮﻻدة ﺑﺘﺘﻜﻮن ﺑﺎل‬liver ‫ ﺑﺘﺘﻜﻮن ﻗﺒﻞ اﻟﻮﻻدة ﻓﻲ ال‬B cells.‫ﻗﺼﺪﻧﺎ ﺑﻌﺪ اﻟﻮﻻدة‬ MALT ‫ ﻣﺜﻞ‬secondary lymphoid organs and tissues ‫ ﺑﮭﺎﺟﺮوا إﻟﻰ ﻣﻜﺎن ﻋﻤﻠﮭﻢ وھﻮ‬Lymphocytes ‫ ﻋﻦ ال‬malt ‫ ﻣﺴﺆول ﻋﻦ اﻟﻠﯿﻤﻒ و‬lymph nodes ‫ ﻣﺴﺆول ﻋﻦ اﻟﺪم و‬spleen ‫ )ال‬, lymph nodes and spleen mucosa ‫ ﻟﻞ‬blood stream ‫ ﻋﻠﻰ ﺷﻜﻞ ﺣﺮﻛﺔ ﻣﺴﺘﻤﺮة داﺧﻞ ال‬lymphocytes recirculate around the body ‫ﻣﻌﻈﻢ ال‬.thoracic duct and right lymphatic duct ‫ وﺑﺘﺮﺟﻊ ﻛﻤﺎن ﻟﻠﺪم ﻣﻦ ﺧﻼل‬lymphoid tissues There are three major subpopulations of T cells which have helper,cytotoxic and regulatory activities (TH,TC andTreg). B cells can differentiate into antibody-secreting plasma cells and memory cells. T cells developing in the thymus are subject to positive and negative selection processes. Mammalian B cells develop mainly in the fetal liver and from birth onwards in the bone marrow. This process continues throughout life. B cells also undergo a negative selection process at the site of B cell generation. Lymphocytes migrate to, and function in, the secondary lymphoid organs and tissues. Secondary lymphoid organs and tissue protect different body sites – the spleen responds to blood borne organisms; the lymph nodes respond to lymphborne antigens; and the mucosa- associated lymphoid tissue (MALT) protects the mucosal surfaces. Most lymphocytes recirculate around the body; there is continuous lymphocyte traffic from the blood stream into lymphoid tissues and back again into the blood via the thoracic duct and right lymphatic duct. 2019-2020 Immunology 7105306 8  Cells of the Immune System 2019-2020 Immunology 7105306 9  KEY CONCEPTS ABOUT IMMUNE CELLS 1. The principle cells of the immune system: Antigen-presenting cells ó Lymphocytes => Effector cells 2. All immune cells are derived from “Hematopoietic stem cells” in Bone Marrow (BM) (& Fetal liver during fetus). 3. Immune cells are divided into two major lineages: => Lymphoid & Myeloid => Multiple cell types =>express distinct “Surface molecules (markers)” =>Classification ‫واﻧﻣﺎ اﻟﮭم وظﺎٔﯾف اﺧرى ﻓﺑﻧﻌرف ﺷو اﺻﻠﮭم‬classifications ‫ ھدول ﻣش ﺑس ﺑﺳﺎﻋدوﻧﺎ ﺑﺎل‬، ‫اﺧر ﺳطر ﺑﺎﻟﻧﻘطﺔ اﻟﺛﺎﻟﺛﺔ‬ differentiation ‫ووظﺎٔﯾﻔﮭم وﺑﻧﻌرف ﺷو اﻟﺧﻠﯾﺔ اﻟﻲ ﺻﺎروھﺎ ﺑﺎﻟزﺑط ﺑﻌد ﻣﺎ ﺻرﻟﮭم‬ 4. Development and differentiation of different cell types depend on “Cell Interactions and Cytokines”. ‫اﻧﮭﺎ ﺗﺗﺧﺻص وﺗﺻﯾر ﺧﻠﯾﺔ ﻣﻌﯾﻧﺔ‬differentiation ‫و‬development ‫ﯾﻌﻧﻲ ﺷو اﻟﻲ ﺑﺧﻠﻲ اﻟﺧﻠﯾﺔ ﯾﺻرﻟﮭﺎ‬ ‫ﺑﺻﯾر ﺑﯾﻧﮭم‬molecules ‫ﯾﻌﻧﻲ ﯾﺻﯾر ﻋﻧﺎ‬cell interaction ‫وﺗﺻﯾر وظﯾﻔﺗﮭﺎ ﻣﺣددة اول اﺷﻲ اﻧو ﯾﺻﯾر‬ ‫ﺗﺎﻧﻲ ﻣﻣﻛن ﻣن ﺧﻼل ال‬molecule ‫ﻣﻊ‬contact ‫ﺑﺻرﻟﮫ‬molecule ‫ﯾﻌﻧﻲ‬physical contact messeges ‫اﻟﻲ ﺣﻛﯾﻧﺎ ﻋﻧﮭم ال‬cytokines ‫اﻟﻲ ذﻛرﻧﺎھم ﻗﺑل ﺷوي ﺑﺎﻻﺿﺎﻓﺔ ﻟل‬surface molecules ‫اﻟﻲ ﺑﺗم اﻧﺗﺎﺟﮭم ﻣن ﺧﻠﯾﺔ وﺑﺗروح ﻋﻠﻰ ﺧﻠﯾﺔ ﺗﺎﻧﯾﺔ‬ 2019-2020 Immunology 7105306 1 0  ‫‪ -1‬إذا ﺑﻧطﻠﻊ ھون ﺑﺣﻛﯾﻠﻧﺎ ﻋن ال‬ ‫ھون ﺑورﺟﯾﻧﺎ ﻛﯾف ﻋﻣﻠﯾﺔ ال ‪differentiation‬‬ ‫‪hematopoietic stem cell‬‬ ‫وﺑﺣﻛﯾﻠﻧﺎ ﻛﯾف ﻋﻣﻠﯾﺔ ال‬ ‫‪ development‬ﺑﺷﻛل ﻣﻔﺻل ﺷوي‬ ‫‪ -3‬وھون ﺑﺣﻛﯾﻠﻧﺎ ﻋن ال ‪ myeloid progenerator cell‬اﻟﻲ ﺑﺗطﻠﻌﻠﻧﺎ‬ ‫ال ‪ granulocyte‬ﺑﺎﻹﺿﺎﻓﺔ ﻟل ‪ megakaryocytes‬اﻟﻲ ھﻲ ﺑﺗطﻠﻌﻠﻧﺎ‬ ‫ﺑﺎﻻﺧﯾر ال ‪ platelets‬وﻓﻲ ﻋﻧﺎ ﻛﻣﺎن ﻣﻧﮭم ﺑﯾﺟﻲ ﻋﻧﺎ ال ‪erythrocyte‬‬ ‫‪-2‬ھون ﺑدﻧﺎ ﻧطﻠﻊ ﻋﻠﻰ أﺻل اﻟﺧﻼﯾﺎ‬ ‫اﻟﻲ ﺣﻛﯾﻧﺎ ﻋﻧﮭم‬ ‫ﺣﻛﯾﻧﺎ ﻋن ال ‪common‬‬ ‫‪-4‬ﺑﻌد ﻣﺎ ﻧﺗطﻠﻊ ھون‬ ‫‪lymphoid progenitor cell‬‬ ‫ﺑﺣﻛﯾﻠﻧﺎ ﻋن اﻟﺧﻼﯾﺎ‬ ‫ﺣﻛﯾﻧﺎ ﻋن ال‬ ‫اﻟﻲ ﺑﺗطﻠﻌﻠﻧﺎ ال ‪ 3‬ﺧﻼﯾﺎ اﻟﻲ ﺣﻛﯾﻧﺎ‬ ‫‪lymphocytes‬‬ ‫ﻋﻧﮭم اﻟﻲ ھم ال ‪،Natural killer‬‬ ‫ھون ﺑﺣﻛﯾﻠﻧﺎ ﻋن ال‬ ‫‪B cell ،T cell‬وازا ﺑدﻛم ﻋن ال‬ ‫‪polymorphonuclear‬‬ ‫‪ t regulatory‬ﻛﻣﺎن‬ ‫‪ cells‬اﻟﻲ ھﻣﻲ‬ ‫‪،neutrophils‬‬ ‫‪،eosinophil‬‬ ‫‪ basophils‬واﻻﺿﺎﻓﺔ‬ ‫ﺑﺣﻛﯾﻠﻧﺎ ﻛﻣﺎن ﻋن ال‬ ‫ھون اذا ﺑدﻧﺎ ﻧرﺟﻊ ﻟل ‪ t cell‬وال ‪b‬‬ ‫‪ monocyte‬ﻛﻧوع ﻣن‬ ‫اﻧواع ال‬ ‫‪ cell‬ﺑﺄﻧواﻋﮭم اﻟﻲ ﺑﻌد ﻣﺎ ﺑروﺣو ﻋﻠﻰ‬ ‫‪granulocytes‬‬ ‫ال ‪ blood‬ﺑروﺣو ﻋﻠﻰ ال ‪lymph‬‬ ‫‪ node‬ﺑﻌدﯾن ﺑﺻﯾرو ﻋﻧﺎ ال‬ ‫‪ effector cells‬ﺑﺻرﻟﮭم‬ ‫‪ activation‬ال ‪ b cell‬ﺑﺗﺻﯾر‬ ‫‪ plasma cell‬طﺑﻌﺎ ﺑﺎﻹﺿﺎﻓﺔ ﻟل‬ ‫‪ memory‬وال ‪ t cell‬ﺑﺗﺻﯾر‬ ‫ﻋﻧﺎ ‪ activated t cell‬ﺑﺎﻹﺿﺎﻓﺔ ﻟل‬ ‫‪ memory‬وال ‪ NK cell‬ﺑﺗﺻﯾر‬ ‫‪ activated cell‬ھﺎي اﻟﺧﻠﯾﺔ ﻣن ال‬ ‫‪ innate immunity‬ھدول اﻟﺗﻧﺗﯾن‬ ‫‪-5‬ھﺎي ال ‪monocyte‬ﻟﻣﺎ ﺗوﺻل ﻟل ‪ tissue‬ﺣﻛﯾﻧﺎ ﺑﺻرﻟﮫ‪differentiation‬‬ ‫ﻣن ال ‪adaptive immunity‬‬ ‫ﺑزﯾﺎدة وﺑﺗﺻﯾر ‪ macrophage‬وﺣﻛﯾﻧﺎ ﺣﺳب ﻋﻠﻰ أي ‪ organ‬ھﻲ راﺣت‬ ‫ﺑﺻرﻟﮭﺎ أﺳﻣﺎء ﻣﺧﺗﻠﻔﺔ رح ﻧﺷوﻓﮭﺎ ﻟﻘدام‬ ‫وھون ﺑﺣﻛﯾﻠﻧﺎ ﻋن ال ‪ mast cell‬ﻛﻣﺎن اﻟﻲ ﺑﺗﻛون ﻣوﺟودة ﻓﻲ ال ‪tissue‬‬  CELLS OF THE IMMUNE SYSTEM-I ‫ھﺎي أﺻل اﻟﺧﻼﯾﺎ اﻟﻣﻧﺎﻋﯾﺔ وﺑﺗﻧﻘﺳم ﻟﻧوﻋﯾن‬ B ‫ ﺑﺗﻧﻘﺳم ﻟل‬Common lymphoid progenitor cells, T cells and NK Lymph ‫ﺑﺗروح ﻋﻠﻰ‬B cells, T cells and NK.‫ ﻣﺷﺎن ﯾﻘوﻣن ﺑﻌﻣﻠﮭن‬nodes ‫ اﻟﻲ‬granulocyte ‫ ﺑﺗﻌطﯾﻧﺎ‬Myeloid progenitor ‫ﺑﺗروح ﻋﻠﻰ اﻟدم وﺑﺗﺗﻣﺎﯾز ﻷﻧواع ﻋدﯾد ﻣﻧﮭن‬ unkown ‫ و‬macrophage ‫ ﺑﺗﺻﯾر‬monocyte mast cell ‫ إﻟﻲ ﺑﺻﯾر‬precursor of mast cells.‫طﺑﻌﺎ ﺑﺗﻣﺎﯾزن ﻓﻲ اﻷﻧﺳﺟﺔ‬.‫ إﻟﻲ ﺑﺗﺗﻣﺎﯾز ﻟﻣﻛوﻧﺎت اﻟدم‬megalartcyte ‫وﺑﻌطﯾﻧﺎ‬ 1. Originated from Bone Marrow (BM) 2. Two major lineages: - Lymphoid - Myeloid 3. NK cells - Large Granular Lymphocytes (LGL) NK => LGL 2019-2020 Immunology 7105306 1 2 Cells of the Immune System-II ‫ﺗﻘرﯾﺑﺎ ﻧﻔس اﻟﺳﻼﯾد اﻟﺳﺎﺑق‬ development ‫ وال‬bone marrow‫ھون ﺑﺣﻛﯾﻠﻧﺎ ﻓﻲ ال‬ ‫ ھﻲ ﻣش ﺧﻼﯾﺎ ﻟﻛن ﺑﯾﺟو‬Platelets ‫طﺑﻌﺎ اﻟـ‬ ‫ﺑﺣﻛو ﻋﻧﮭﺎ زي أﻛﯾﺎس ﻓﯾﮭﺎ اﻟﻣواد اﻟﻲ ﺑﺗﻠزم ﻓﻲ‬ T lymphocytes are Recognition ‫ واﻟـ‬inflammation ‫ﻋﻣﻠﯾﺔ اﻟـ‬ first derived from ‫ ﻟﻠﺧﻼﯾﺎ‬Development ‫ واﻟـ‬Activation ‫واﻟـ‬ Cytokines ‫ﻣﺛل اﻟـ‬ BM and further educated in Thymus for maturation. B Cell ‫اﺗطﻠﻌوا ﻋﻠﻰ اﻟـ‬ ‫ﻛﯾف ﺑﺗطﻠﻊ‬ developed cell ‫ﻛـ‬ ‫اﻟﻲ ھﻲ ﺑﺗﺻﯾر ﺧﻠﯾﺔ‬ ‫ﺟﺎھزة ﺑﺗروح‬ ‫ ﺑﻌدﯾﮭﺎ ﻣن‬blood ‫ﻟﻠـ‬ ‫ ﺑﺗروح ﻋﻠﻰ‬Blood ‫اﻟـ‬ ‫ او ﻋﻠﻰ اﻟـ‬tissue ‫اﻟـ‬ Lymphoid secondary organs ‫وﺑﺗﺗﺧزن ھﻧﺎك وﺑﺻﯾر‬ ‫زي ﻣﺎ ﺣﻛﯾﻧﺎ‬ ‫ ﺑﺷﻛل‬movement ‫ﻣﺳﺗﻣر ﻻﺣظو ﺷو‬ recirculating ‫ﻛﺎﺗب‬ lymphocytes blood ‫ﺑﺗروح ﻣن اﻟـ‬ lymph ‫ﻋﻠﻰ اﻟـ‬ ‫ وﻣن اﻟـ‬node ‫ ﻋﻠﻰ‬lymph node ‫ وﺑﺎﻟﻌﻛس‬blood ‫اﻟـ‬  ‫‪CELLS OF INNATE IMMUNITY-I‬‬ ‫طﺒﻌﺎ اﺣﻨﺎ ﻋﺎرﻓﯿﻦ اﻧﻮ ﻛﻞ اﻟﺨﻼﯾﺎ اﻟﻤﻨﺎﻋﯿﺔ ﺳﻮاء ‪ innate‬او ‪ adaptive‬ﻓﮭﻲ ﺟﺎي ﻣﻦ ال ‪hematopoietic stem cells‬‬ ‫ ‬ ‫اﻟﻠﻲ ھﻮ ﻣﻮﺟﻮد أﺻﻼ ﺑﺎل ‪bone marrow‬‬ ‫ وظﯿﻔﺔ ال ‪ innate immune cells‬اﻧﮭﺎ ﺗﻌﻤﻞ ‪ identification‬و ‪ killing‬ﻟﻠﻤﯿﻜﺮوب اﻣﺎ‬ ‫‪.1‬ﻟﺤﺎﻟﮭﺎ )ﻣﺜﻞ ال ‪(phagocytes‬‬ ‫‪.2‬ﻋﻦ طﺮﯾﻖ اﻧﮭﺎ ﺗﺼﯿﺮ )‪ APC(antigen presenting cell‬و ﻣﻨﮭﺎ ﺑﺘﻨﺸﻂ ال ‪ lymphocytes‬اﻟﻠﻲ ھﻮ ﻋﺒﺎرة ﻋﻦ‬ ‫‪ adaptive‬و ﻋﺸﺎن ھﯿﻚ ﺑﻨﻌﺘﺒﺮ اﻧﻮ‪APC is a link between innate and adaptive immune response‬‬ ‫طﺒﻌﺎ ﺑﻨﻌﺮف اﻧﻮ ال ‪ innate‬ﻗﺎدرة اﻧﮭﺎ ﺗﻔﺮق ﺑﯿﻦ ‪ self and non-self antigens‬طﺐ ﻛﯿﻒ؟ ھﺴﺎ ﺑﻜﻮن ﻓﻲ ﻛﻞ ﻣﯿﻜﺮوب‬ ‫ ‬ ‫زي ﻋﻼﻣﺔ ﻋﺎﻣﺔ ﺑﯿﻨﮭﻦ ﻛﻠﮭﻦ ﺑﺘﺪل ﻋﻠﻰ اﻧﻮ ھﺎي اﻟﺨﻠﯿﺔ ھﻲ ﻣﯿﻜﺮوب )ﯾﻌﻨﻲ ﺑﺘﻜﻮن ‪ (common‬و ﻛﻤﺎن ﺑﻜﻮن اﻟﺘﻨﻮع ﻓﯿﮭﺎ‬ ‫ﻛﺜﯿﺮ ﻣﺤﺪود )‪ (limited diversity‬و طﺒﻌﺎ ﻓﻲ ‪ receptors‬ﺑﺨﻼﯾﺎ ال ‪ innate‬ﺑﺘﻘﺪر ﺗﺘﻌﺮف ﻋﻠﻰ ھﺎي اﻟﻌﻼﻣﺎت و ﻣﻦ‬ ‫اﻷﻣﺜﻠﺔ ﻋﻠﯿﮭﺎ اﻧﻮ ﻓﻲ ﻋﻼﻣﺔ اﺳﻤﮭﺎ ‪ PAMP‬ﺑﺘﻌﺮف ﻋﻠﯿﮫ ‪) PRR receptors‬طﺒﻌﺎ ال ‪ PRR‬أﻧﻮاع ﻋﺸﺎن ﯾﻀﻤﻦ اﻧﻮ ﺷﺎﻣﻞ‬ ‫أي ﺗﻨﻮع ﺻﺎر ﺑﺎل ‪(PAMP‬‬ CELLS OF INNATE IMMUNITY-I Innate immune cells are derived from Bone Marrow..1 Their primary function is to identify and kill microbes. Antigen-presenting cells.2 (APCs) additionally function to present Ag to and activate lymphocytes. Innate immune cells recognize the common microbial structures PAMPs through.3 Pattern-Recognition Receptors (PRRs) -limited diversity. 2019-2020 Immunology 7105306 9  ‫‪CLASSES OF INNATE IMMUNE CELLS‬‬ ‫ھﺎي اﻟﺴﻼﯾﺪ ﻛﺜﯿﺮ ﻣﮭﻤﺔ‬ ‫ھﻮن ﺑﺤﻜﻲ ﻋﻦ أﻧﻮاع ال ‪ innate cells‬و وظﯿﻔﺔ ﻛﻞ وﺣﺪة‬ ‫‪ :Macrophages.1‬ﺑﺘﻌﻤﻞ ‪ phagocytosis‬و ﺑﺘﻌﻤﻞ ‪ activation‬ﻋﺸﺎن ﺗﺤﺎول ﺗﻘﺘﻞ ال ‪bactericidal ) microbe‬‬ ‫‪ (mechanisms‬و ﻛﻤﺎن ﻣﻤﻜﻦ ﺗﺼﯿﺮ ‪ APC‬ﻓﻲ ﺣﺎل ﻣﺎ ﻗﺪرت ﺗﻘﺘﻞ اﻟﻤﯿﻜﺮوب )طﺒﻌﺎ ﻟﻤﺎ ﺗﻜﻮن ﺑﺎﻟﺪم اﺳﻤﮭﺎ ‪(monocyte‬‬ ‫‪ :Dendritic cells.2‬ھﺎي ﺑﺘﻌﻤﻞ زي ﺷﺮطﻲ ﺑﺎﻟﺸﺎرع ﻟﻘﺎ ﺣﺪا ﻣﺨﺎﻟﻒ ﻟﻠﻘﺎﻧﻮن ﻗﺎم ﻣﺴﻜﻮ و ﺳﺤﺒﻮ ﻋﻤﺮﻛﺰ اﻟﺸﺮطﺔ ‪.‬ھﺎي‬ ‫اﻟﺨﻼﯾﺎ ﺑﺘﺸﺘﻐﻞ ﺑﺎﻻطﺮاف )‪ (peripheral sites‬وﻟﻤﺎ ﺗﻼﻗﻲ اﻧﺘﺠﯿﻦ ﺑﺘﻤﺴﻜﻮ و ﺑﺘﺴﺤﺒﻮ ﻣﻌﮭﺎ ﻟﺤﺘﻰ ﺗﻮﺻﻞ ال ‪lymph‬‬ ‫‪ nodes‬و ﺑﺘﻌﻤﻞ ‪ antigen presenting‬ل‪lymphocytes‬‬ ‫‪ :Neutrophils.3‬ﺑﺮﺿﻮ ‪ phagocytosis and activating bactericidal mechanisms‬و ﺑﺘﻜﻮن ﻣﮭﻤﺔ ﻓﻲ اﻟﺪﻓﺎع‬ ‫ﺿﺪ ‪extracellular microbes‬‬ ‫‪ :Eosinophil.4‬ﺑﺘﻌﻤﻞ ﻋﻠﻰ ﻣﻘﺎوﻣﺔ ‪ antibody coated parasites‬ﻋﻦ طﺮﯾﻖ ‪IgE‬‬ ‫‪ :Basophil.5‬ﺑﺮﺿﻮ ﺑﺸﺘﻐﻞ ب ‪ IgE‬و ﻛﻤﺎن اﻟﻮ دور ﺑﺎل ‪) allergy‬ﺻﺢ ﻣﻜﺘﻮب ‪ unknown‬ﺑﺲ ھﯿﻚ ﺣﻜﻰ اﻟﺪﻛﺘﻮر(‬ ‫‪ :Mast cells.6‬اﻟﮭﻦ ﻋﻼﻗﺔ ﺑﺎل ‪ allergy‬و ﺑﺘﻄﻠﻖ ‪histamine‬‬ ‫‪ :NK.7‬ﻣﺴﺆوﻟﺔ ﻋﻦ ال ‪ virally infected cells & tumor cells‬و اﻟﮭﺎ ﻛﻤﺎن دور ﺣﻨﻮﺧﺬو ﻛﻤﺎن ﺷﻮي‬  CLASSES OF INNATE IMMUNE CELLS Innate immune cells are classified as following: - Monocyte/Macrophage - Dendritic cell (DC) - Polymorphonuclear granulocyte (PMN; Neutrophil, Eosinophil, Basophil) - Mast cell - NK cells (lymphocyte) => Killing virus-infected cells & tumors 2019-2020 Immunology 7105306 10 ‫& ‪DEVELOPMENT OF MONOCYTES‬‬ ‫‪GRANULOCYTES‬‬ ‫ طﺐ ﺑﻨﻌﺮف اﻧﻮ اﺻﻞ ﻛﻞ اﻟﺨﻼﯾﺎ ال ‪ innate & adaptive‬ھﻲ ‪ hematopoietic stem cells‬ﺑﺲ طﺒﻌﺎ ﻓﻲ أﺳﺎﺳﺎت‬ ‫ﺑﺘﻤﺸﻲ ﻋﻠﯿﮭﺎ اﻟﺨﻼﯾﺎ ﻋﺸﺎن ﺗﺤﺪد اﯾﺶ اﻟﺨﻼﯾﺎاﻟﻠﻲ ﺑﺘﺤﺘﺎﺟﮭﺎ اﻛﺜﺮ ﻣﻦ اﻟﺜﺎﻧﯿﺔ و ھﺎد اﻟﻤﻌﯿﺎر ھﻮ ال ‪.cytokines‬ﺷﻮي اﺣﺎ ﻣﺶ‬ ‫ھﺎي اﻟﻠﻲ ﺑﻨﺴﺘﺨﺪﻣﮭﺎ ﻟﻠﺘﻮاﺻﻞ ﺑﯿﻦ اﻟﺨﻼﯾﺎ ﺷﻮ ﺧﺼﮭﻦ ﺑﺎل ‪.development‬اﻓﺮض ﻣﻌﻲ اﻧﻮ دﺧﻞ ‪ parasite‬ﻋﻠﻰ اﻟﺠﺴﻢ ﺷﻮ‬ ‫ﺑﻠﺰﻣﻨﺎ؟ ﺑﻠﺰﻣﻨﺎ ‪ eosinophils‬و ﺑﺸﻜﻞ ﻛﺒﯿﺮ ﻋﺸﺎن ﺗﺘﻤﻜﻦ ﺗﻘﻀﻲ ﻋﻠﯿﮫ ف اﻟﻠﻲ ﺑﺼﯿﺮ اﻧﻮ اﻟﺨﻼﯾﺎ ﺑﺘﻨﺸﺮ ‪ cytokines‬ﻣﺤﺪدة‬ ‫ﻋﺸﺎن ﺗﻮﺟﮫ ال ‪ development‬ﻟﻤﺴﺎر ﺗﺼﯿﺮ ﻓﯿﮫ ‪) eosinophil‬رﻛﺰ ﻋﺎﻟﺮﺳﻢ ﻛﯿﻒ ﻓﻲ ‪ cytokine‬زي ﻛﺈﻧﮭﺎ ﻋﻼﻣﺎت‬ ‫طﺮﯾﻖ *ﺟﻮا اﻟﺪواﺋﺮ اﻟﺤﻤﺮ* و اﻷﺳﮭﻢ اﻟﺤﻤﺮا ﻛﯿﻒ ﺻﺎر ‪ development‬ل ‪(eosinophil‬‬ ‫ طﺒﻌﺎ ال ‪ lymphocytes‬ﺑﺘﻘﺪر ﺗﻔﺮز ھﺎي ال ‪ cytokines‬ﻋﺸﺎن ﺗﺤﺪد ال ‪ development of myeloid cell‬و اﻟﻌﻜﺲ‬ ‫ اﻷﺳﻤﺎء ﻣﺶ ﺣﻔﻆ ﺑﺲ اﻓﮭﻢ ﺷﻮ اﻟﻠﻲ ﺻﺎر‬ DEVELOPMENT OF MONOCYTES & GRANULOCYTES 1.Myelopoiesis – Development of myeloid cells. 2. Cytokines from stromal cells, myeloid, & lymphoid cells are involved in this process. CFU: colony forming units GEMM: granulocytes, erythrocytes, monocytes, and megakaryocytes GM-CSF : granulocyte–macrophage colony- stimulating factor TP: Thrombopoietin B: basophil BFU-E: erythrocytic burst-forming unit DC: dendritic cell Epo: erythropoietin Immunology 71053062019-2020 11  ‫‪MATURATION OF MACROPHAGES‬‬ ‫اﻟﺼﻮرة ﺑﺘﻮﺿﺢ اﻟﻤﺮاﺣﻞ اﻟﻠﻲ ﺑﺘﻤﺸﻲ ﻓﯿﮭﺎ ﻟﺤﺪ ﻣﺎ ال ‪ mono blast‬ﺗﺼﯿﺮ ‪) macrophage‬ﺣﻔﻆ( طﺒﻌﺎ ﻣﺎ ﻧﻨﺴﻰ اﻧﻮ ﺑﺎﻟﺪم اﺳﻤﮭﺎ‬ ‫‪ monocyte‬و ﻟﻤﺎ ﺗﺼﯿﺮ ب ‪ tissue‬ﺑﺸﻜﻞ ﻋﺎم ﺑﺼﯿﺮ اﺳﻤﮭﺎ ‪) macrophage‬ﻣﺎ ﺑﺘﻐﯿﺮ ﺗﺮﻛﯿﺒﮭﺎ وﻻ اﺷﻲ زي ﻧﻘﻮل اﺳﻢ واﺣﺪ‬ ‫ﺑﺎﻟﮭﻮﯾﺔ اﺣﻤﺪ ﺑﺲ ﺑﺎﻟﺸﺎرع ﺑﻨﺎدوه ﻋﺒﺪﷲ( و ﻣﻤﻜﻦ ﯾﺘﻐﯿﺮ اﺳﻤﮭﺎ ﺣﺴﺐ ال ‪) tissue‬ﻣﺜﻼ ﺑﺎل‪ lung‬اﺳﻤﮭﺎ ‪alveolar‬‬ ‫‪ (macrophage‬و ھﻜﺬا ﺑﺲ اﺳﻤﮭﺎ اﻟﻌﺎم ﺑﺎل ‪ tissue‬ھﻮ ‪macrophage‬‬ ‫طﺒﻌﺎ ﻓﻲ ﺑﺎﻟﺮﺳﻤﺔ ﻛﻠﻤﺔ ‪ activation‬و ھﺎد ﻻﻧﻮ ﺑﻤﻌﻈﻢ اﻟﻮﻗﺖ ﺑﺘﻜﻮن ‪ inactive‬و ھﺎن اﻟﻘﺼﺪ ھﻮ ال ‪ cidal activity‬ﯾﻌﻨﻲ ال‬ ‫‪inactive macrophage‬ﺑﺘﻘﺪر ﺗﻌﻤﻞ ‪ phagocytosis‬ﺑﺲ ﻣﺎ ﺑﺘﻘﺪر ﺗﻘﺘﻞ ال ‪ pathogen‬ﻻﻧﮭﺎ ‪inactive‬‬ ‫طﺐ وﯾﻨﺘﺎ ﺑﻜﻮﻧﻠﮭﺎ ‪activation‬؟ ﻟﻤﺎ ﺗﺘﻌﺮف ﻋﺎﻧﺘﺠﯿﻦ )‪ (recognition‬و ﻧﺘﯿﺠﺔ ﻟﮭﺎد اﻻﺷﻲ رح ﺗﺼﯿﺮ ﻋﺪة ﺳﯿﻨﺎرﯾﻮھﺎت ﺣﻨﯿﺠﯿﮭﺎ‬ ‫ھﺎي أﺳﻣﺎء ال‪macrophages‬‬ ‫اﻟﻣﺧﺗﺻﺔ ب ‪ tissue‬ﻣﻌﯾن‬ MATURATION OF MACROPHAGES 2019-2020 Immunology 7105306 12 Activated Macro  KEY CONCEPTS OF MONOCYTES/MACROPHAGES ‫ ﻣﺜﻼ اﻟﻠﻲ ﺑﺘﻌﯿﺶ ﻓﺘﺮات‬neutrophils ‫ اﻧﮭﺎ ﺑﺘﻌﯿﺶ ﻓﺘﺮات طﻮﯾﻠﺔ ﻟﻜﻦ اﻋﺪادھﺎ ﻗﻠﯿﻠﺔ ﻋﻠﻰ ﻋﻜﺲ‬phagocyte ‫ﻣﻦ ﺧﺼﺎﺋﺺ ال‬ ‫اﻗﺼﺮ و ﺑﺘﺘﻮاﺟﺪ ﺑﺎﻋﺪاد اﻛﺒﺮ‬ (‫ )ﺣﺘﻤﺮ اﻟﻤﯿﻜﺎﻧﺰم ﻣﻌﻨﺎ‬phagocytosis & killing pathogens ‫وظﯿﻔﺘﮭﺎ ال‬ ‫ ھﻲ اﻟﻠﻲ ﺧﻠﺖ ال‬scavenger receptors ‫( و‬PAMP... ‫ )ذاﻛﺮ ﻋﺸﻮ ﺑﺘﻌﺮف؟‬PRR ‫ ﻣﺜﻞ‬receptors ‫طﺒﻌﺎ وﺟﻮد ال‬ specificity ‫ طﺒﻌﺎ دون وﺟﻮد‬non-self antigens‫ ﺗﺘﻌﺮف ﻋﻠﻰ ال‬phagocyte antigen presenting ‫ و ﺗﻌﻤﻞ‬inflammation ‫ﻗﺎدرة اﻧﮭﺎ ﺗﺒﺪأ ال‬ 1. Relatively long-lived and distributed throughout the whole body. 2. Engulf and kill pathogens by phagocytosis. 3. Express various receptors to recognize different Histoplasma capsulatum in macrophage pathogens, e.g. PRR, Scavenger receptor,….etc. 4. Trigger inflammation and Antigen presentation  ‫ ﺑﻌﺑر ﻋن ﺷﻛﻠﮭﺎ ﺟوا‬blood film ‫ و اﻟﺻورة اﻟﻣﻠوﻧﺔ ھﻲ ﻋﺑﺎرة ﻋن اﺷﻲ اﺳﻣو‬phagocyte‫اﻟﺻورة ﺑﺗوﺿﺢ ﻣﻛوﻧﺎت ال‬ ‫ ﺑﺳﺗﺧدﻣوه ﻟﯾﻔرﻗوا ﺑﯾن اﻟﺧﻼﯾﺎ ﻣن ﺷﻛﻠﮭﺎ‬blood film ‫ و طﺑﻌﺎ ھﺎد ال‬blood ‫ال‬ (Monocyte...... ‫؟‬blood film ‫)اﯾش ﺑﻛون اﺳﻣﮭﺎ ﻟﻣﺎ ﯾﺗم ﺗﺻوﯾرھﺎ ﺑﺎل‬ blood film ‫ھﺎد ھو ال‬ pinocytotic vesicles (PV), lysosomal granules (G), mitochondria(M), and isolated rough endoplasmic reticulum cisternae (E) 23 PHAGOCYTOSIS BY INNATE IMMUNITY (1) phagocytosis ‫ﺧﻄﻮات ال‬ ‫ )ﻣﺜﻞ‬common ‫( ﺑﺎﻟﻌﻼﻣﺔ ال‬PRR & scavenger ‫ )ﻣﺜﻞ‬receptor ‫ ﺑﺘﺼﯿﺮ ﻣﻦ ﺧﻼل ارﺗﺒﺎط ال‬:Recognition.1 (PAMP phagosome ‫ ﺑﻨﺴﻤﯿﮭﺎ‬vesicle ‫ ﺟﻮا‬phagocyte ‫ ﺟﻮا ال‬pathogen ‫ ﺑﺘﺘﻢ اﻟﺒﻠﻌﻤﺔ و ﺑﺼﯿﺮ ال‬:Phagocytosis.2 phagolysosome ‫ وﺣﺪة اﺳﻤﮭﺎ‬vesicle ‫ ﻟﯿﻜﻮﻧﻮا‬lysosome ‫ ﺑﺎل‬phagosome ‫ ﺑﻨﺪﻣﺞ ال‬:Fusion.3 NO & ROS ‫ و ﺷﻐﻼت ﺑﺘﺪﻣﺮ اﻟﺨﻼﯾﺎ ﻣﺜﻞ‬lysosome ‫ ﺑﺘﻢ ﻋﻦ طﺮﯾﻖ اﻻﻧﺰﯾﻤﺎت اﻟﻤﻮﺟﻮدة ﺑﺎل‬:Pathogen lysis.4 ‫ ﺑﺘﺨﻠﺺ ﻣﻦ ﺑﻮاﻗﻲ اﻟﺘﺤﻠﯿﻞ‬:Exocytosis.5 Q: which phase requires the activation of the phagocyte ? A: fusion ‫)ﻻﻧﮭﺎ ﻟﻣﺎ ﺗﺻﯾر ﺧﻠص رح‬ (pathogen ‫ﯾﻣوت ال‬  PHAGOCYTOSIS BY INNATE IMMUNITY (2) ‫ ﺷﻐﻼت‬3 ‫ ﻣﻤﻜﻦ ﯾﻌﻤﻞ‬recognition ‫ال‬ ‫ وﻏﯿﺮو ﻓﯿﻤﻮت‬ROS ‫ و‬lysosomal enzyme ‫ ﻟﻞ‬pathogen ‫ و ﯾﻌﺮض ال‬fusion ‫ ﻋﻦ طﺮﯾﻖ اﻧﻮ ﯾﻌﻤﻞ ال‬:Killing.1 adaptive immunity ‫ و ﺑﺘﻨﺸﻂ ال‬inflammation ‫ اﻟﻠﻲ ﺑﺘﻌﻤﻞ‬:Release cytokines.2 tissue‫ ﺧﺮب اﺷﻲ ﺑﺎل‬pathogen‫ ﻻﻧﻮ اﻛﯿﺪ ال‬repair‫ ﺑﺘﻔﺮز ﺷﻮﯾﺔ ﻣﻮاد ﺑﺘﺴﺎﻋﺪ ﻋﺎل‬:Tissue remodeling.3 ‫‪Ag-presenting cells (APCs) link the innate & adaptive immune‬‬ ‫‪systems‬‬ ‫رح ﻧﺤﻜﻲ ﻋﻦ اﻟﺤﺎﻻت اﻟﻠﻲ ﺣﺘﺼﯿﺮ ﺑﻌﺪ ‪ phagocytosis‬ﯾﺎ اﻣﺎ‬ ‫ ﺑﺘﻀﻞ ﺑﺎل ‪ innate‬ﺑﻄﺮﯾﻘﺘﯿﻦ‬ ‫‪.1‬اﻧﻮ ال ‪ phagocyte‬ﯾﻘﺪر ﯾﻘﺘﻞ ال ‪ pathogen‬ﻣﺒﺎﺷﺮة‬ ‫‪.2‬ﻟﻮ ﻣﺎ ﻗﺪر ﺑﯿﺠﻲ ‪ NK‬ﺑﺤﻔﺰ ال ‪ phagocyte‬اﻧﮭﺎ ﺗﻌﻤﻞ ‪ apoptosis‬ﯾﻌﻨﻲ ﺗﻤﻮت ﻋﺸﺎن ﯾﺘﺨﻠﺺ ﻣﻦ ال‪pathogen‬‬ ‫اﻧﻮ ﯾﻠﺠﺄ ﻟﻞ ‪ adaptive‬ﻋﻦ طﺮﯾﻖ اﻧﮭﺎ ﺗﺘﺤﻮل ل ‪ APC‬ﺑﻤﺴﺎﻋﺪة ال ‪) MHC molecule‬ال ‪ T cell‬ﺑﺘﻜﻮن‬ ‫ ‬ ‫‪)developed‬ﻣﻮﺟﻮدة ﺑﺎل ‪ (but inactive (secondary sites‬ف ﺑﻨﺸﻂ ال ‪ T cell‬ﻓﺒﺘﻘﻮم ال ‪ T cell‬ﺑﺘﻨﺸﻂ ال ‪B‬‬ ‫‪ cell‬و ﺑﺘﺮد ﺗﻨﺸﻂ ال ‪) phagocyte‬ﺑﺘﻮﺧﺬ و ﺑﺘﻌﻄﻲ(‬ ‫ھﺎن اﻟﻠﻲ ﻋﺷﻣﺎل اﻟﺧط اﻷﺣﻣر ﻋﺑﺎرة ﻋن‬ ‫‪ innate‬ﺑﺷﻛل ﻛﺎﻣل و اﻟﻠﻲ ﻋﺎﻟﯾﻣﯾن ھو‬ ‫‪ innate‬ﻗﺎم و ﻧﺷط ‪adaptive‬‬  ‫‪POLYMORPHONUCLEAR GRANULOCYTES: NEUTROPHILS‬‬ ‫‪ neutrophils‬اﻟﮭﺎ ﻋﺪة ﺻﻔﺎت ﻣﻨﮭﺎ‬ ‫ال‬ ‫ﺑﺘﺸﻜﻞ ‪ 95%‬ﻣﻦ ‪PMN‬‬ ‫ ‬ ‫ﺑﺘﺸﻜﻞ ﻧﺴﺒﺔ ﻛﺒﯿﺮة ﻣﻦ ‪) (70%) white blood cells‬و ال‪ lymphocyte‬ﺗﻘﺮﯾﺒﺎ ‪ (30%‬ﻓﺘﻘﺮﯾﺒﺎ ال ‪ WBC‬ﺑﺘﺘﻜﻮن ﻣﻦ‬ ‫ ‬ ‫‪ neutrophils & lymphocytes‬ﺑﺸﻜﻞ أﺳﺎﺳﻲ )ﺑﻨﺤﻜﻲ ﻋﻦ ‪ (range‬و ھﺎي اﻟﻨﺴﺒﺔ اﻟﻄﺒﯿﻌﯿﺔ ﺑﺎل ‪)CBC‬ﻓﺤﺺ دم(‬ ‫ﻋﻤﺮھﺎ ﻗﺼﯿﺮ‬ ‫ ‬ ‫اﻟﻨﻮاة ﺑﻨﻘﺪر ﻧﻘﺴﻤﮭﺎ ﻟﻌﺪة اﻗﺴﺎم )‪* (lobes‬ﻛﯿﻒ ﻣﺜﻼ ال‪liver‬ﻋﻨﺪو ‪ *4 lobes‬ﺷﻮف اﻟﺸﻜﻞ ﻋﺎﻟﯿﻤﯿﻦ‬ ‫ ‬ ‫ﺣﻜﯿﻨﺎ ﻋﻦ وظﯿﻔﺘﮭﺎ ‪phagocytosis & releasing cytotoxic substances‬‬ ‫ ‬ ‫ﻟﻤﺎ ﺗﻜﻮن ‪ mature‬ﺑﻨﺴﻤﯿﮭﺎ ‪ segments‬و اذا ‪ immature‬ﺑﺘﻜﻮن ‪ band‬و اذا زاد ﻋﺪد ال ‪ band‬ﻋﻦ اﻟﺤﺪ اﻟﻄﺒﯿﻌﻲ ھﺎد دﻟﯿﻞ‬ ‫ ‬ ‫ﻋﻮﺟﻮد ﻣﺸﻜﻠﺔ )اذا ذاﻛﺮﯾﻦ ﺑﺎل‪ development‬اﻟﺨﻼﯾﺎ ﺑﺘﺒﻌﺖ ‪ cytokines‬ﻋﺸﺎن ﺗﻮﺟﮫ ال ‪ stem cells‬اﻧﮭﺎ ﺗﺼﯿﺮ‬ ‫‪ neutrophil‬و ﻣﻨﮭﺎ ﺑﻨﺘﺞ ‪ band neutrophils‬ﺑﺎﻋﺪاد ﻛﺒﯿﺮة(‬ ‫ﺷو اﺳم ھﺎي اﻟﺻورة ؟‬ ‫‪Answer: blood film‬‬  POLYMORPHONUCLEAR GRANULOCYTES: NEUTROPHILS 1. Comprise over 95% of granulocytes 2. Short-lived (2-3 days) 3. Multi-lobed nucleus 4. Kill pathogens by phagocytosis & releasing cytotoxic substances. 50 - 70% of WBCs Segments = mature cells Bands = immature cells 2019-2020 Immunology 7105306 28  BASOPHILS & MAST CELLS: CRITICAL FOR IMMUNITY AGAINST PARASITES ‫اﺗطﻠﻌو‬critical for immunity against parasites , ‫أﻧﮭﺎ‬mast cells ‫و ال‬basophils ‫ھون ﺑﺣﻛﻲ ﻋن ال‬ ‫ﻷﺟزاء اﻟﺧﻠﯾﺔ ﺑﺗﻛون‬acidity ‫ﺑﺗﻛون ﻟوﻧﮭﺎ ﺑﻧﻔﺳﺟﻲ ﺑﺗﻛون ﻣﺎﺧدة ﻟون ﺻﺑﻐﺔ ﻣﻌﯾﻧﺔ ﻻن ال‬basophils ‫ﻛﯾف ال‬ staining ‫ﻣﺧﺗﻠﻔﺔ ﻓﺑﺗوﺧذ ﺻﺑﻐﺎت ﻣﺧﺗﻠﻔﺔ ﻓﺎﺣﻧﺎ ﻣﻧﻣﯾزھم ﻟﻣﺎ ﻧﻌﻣل‬ 2019-2020 Immunology 7105306 29  EOSINOPHILS blood stream ‫وﻟوﻧﮭﺎ وﻛﯾف اﺣﻧﺎ ﻣﻧﻘدر ﻧﻣﯾزھﺎ ﻓﺎل‬eosinophils ‫ھﺎي ﺷﻛل ال‬ 2019-2020 30 Immunology 7105306 ‫‪DENDRITIC CELLS (DCS) AS AG-PRESENTING‬‬ ‫)‪CELLS (APCS‬‬ ‫ال ‪dendritic cells‬ﻣﻦ اﻟﺨﻼﯾﺎ اﻟﻤﺸﮭﻮرات ﺑﺎل ‪ antigen presenting cells‬و ﺑﺘﻌﻤﻠﻮ ﺑﻄﺮﯾﻘﺘﯿﻦ‪:‬‬ ‫‪ : active presentation.1‬ھﻮن ﺑﺤﻜﯿﻠﻨﺎ اﻧﮫ ‪immature DC‬ﻋﻤﻠﺖ ‪ phagocytosis‬وﺻﺎرت ‪mature‬‬ ‫‪ antigen presenting cell‬ﻓﺒﺘﻌﻤﻞ ‪ antigen presentation‬ﯾﻌﻨﻲ ﺑﺘﻌﻤﻞ ﻟﻠﻤﺎﯾﻜﺮوب ‪processing‬ﺑﻌﺪﯾﻦ‬ ‫ﺑﺘﻌﺮض ‪fragments‬ﻣﺤﺪدة ﻣﻦ اﻻﻧﺘﺠﯿﻦ ﻟﻞ ‪T cells‬ﺷﻮﻓﻮ ﻛﯿﻒ اﻻﺳﮭﻢ ‪ cytokines‬راﯾﺤﺔ وﺟﺎي ﻻﻧﮫ اﻟﻨﻮﻋﯿﻦ‬ ‫ﺑﻌﻤﻠﻮ ‪activation‬ﻟﺒﻌﺾ وﺑﺄﺛﺮو ﻋﻠﻰ ﺑﻌﺾ ‪ ،‬طﯿﺐ ﻟﯿﺶ اﺳﻤﮭﺎ ‪active presentation‬؟ ﻻﻧﮭﺎ ھﻲ ﻣﺶ ﺑﺲ‬ ‫ﻣﺴﻜﺖ ال ‪antigen‬وﻋﺮﺿﺘﮫ ‪ ،‬ھﻲ ﻋﻤﻠﺘﻠﮫ ‪processing ،‬ﻋﺸﺎن ھﯿﻚ ﺳﻤﯿﻨﺎھﺎ ‪،‬ﻓﻲ ﻋﻨﺎ‬ ‫‪ :passive presentation.2‬ﺑﺘﻌﻤﻠﻮ‪، follicular DC‬ﺑﺘﻮﺧﺪ ال ‪antigen‬ﻧﻔﺲ ﻣﺎ ھﻮ ﺑﻜﻠﺸﻲ راﺑﻂ ﻋﻠﯿﮫ ﺳﻮاء‬ ‫‪antibody‬او ‪complement‬وﺑﺘﻤﺴﻜﮫ ﺑﺎﻻﯾﺪﯾﻦ ﺗﺒﻌﺎﺗﮭﺎ ﺑﺪون ﻣﺎ ﺗﺪﺧﻠﻮ ﺟﻮاﺗﮭﺎ ﻓﺒﺘﻌﻤﻠﮫ ‪presentation‬‬ ‫ﺑﺘﻮرﺟﯿﮫ ﻟﻞ ‪B cells‬ﻓﻤﻨﺴﻤﯿﮫ ‪passive‬طﺒﻌﺎ ً ﺗﺬﻛﺮو ﻣﻌﻠﻮﻣﺔ اﻧﮫ ال ‪B cells‬ﺑﺘﺘﻌﺮف ﻋﻠﻰ اﻻﻧﺘﺠﯿﻦ ﻛﺎﻣﻞ ﻧﻔﺲ ﻣﺎ‬ ‫ھﻮ ‪ ،‬ﺑﯿﻨﻤﺎ ال ‪T Cell‬ﺑﻜﻮن ال ‪receptor‬ﻣﺪﻟﻞ ﺑﺤﺘﺎج ﻓﻘﻂ ‪fragments‬ﻣﻦ ال ‪antigen‬‬ DENDRITIC CELLS (DCS) AS AG-PRESENTING CELLS (APCS) FDC:Follicular DC 2019-2020 Immunology 7105306 32  KEY CONCEPTS OF DENDRITIC CELLS (DCS) 1. Most effective Ag-presenting cells linking innate and adaptive immunity 2. High MHC-II expression on DCs 3. Several types of DCs: Myeloid DCs (also known as conventional DCs) Lymphoid DCs => Plasmacytoid DCs Lymphoid organ-specific DCs: Follicular DCs in Lymph nodes (lacking MHC-II) Interdigitating Dcs in Lymph nodes & Thymus antigen- ‫ﺑﺎل‬professional ‫طﺑﻌﺎ ً ﺣﻛﯾﻧﺎ ﻣن ﻗﺑل اﻧﮭﺎ‬key concepts of dendritic cells ‫ھون ﺑﺣﻛﯾﻠﻧﺎ ﻋن ال‬ high expression ‫وﻓﻲ ﻋﻧدھﺎ‬adaptive immunity ‫ﻣﻊ ال‬innate immunity ‫واﻧﮭﺎ ﺑﺗرﺑط ال‬presenting cells presenting ‫ ﯾﻠﻲ ھو اﻻﯾد ﯾﻠﻲ رح ﯾﺣﻣل اﻻﻧﺗﺟﯾن ﻓﺑﺗﺣﺗﺎﺟﮫ اﻟﺧﻠﯾﺔ ﺑﻛﺛره ﻻن وظﯾﻔﺗﮭﺎ ﺗﻌﻣل‬MHC-ii molecule ‫ﻟل‬ several types of DCs ‫ﻓﻲ ﻋﻧﺎ‬ myeloid Dc lymphoid Dc ‫ ﻻﻧﮭﺎ‬MHC molecules ‫ ﻣﺎ ﺑﻛون ﻋﻧدھﺎ‬follicular DC ‫ ال‬. lymphoid organ specific DCs passive presentation ‫ﺑﺗﻌﻣل‬ ‫ ﺧﻼﻟﯾﺎت‬، ‫ ھﺎي ﺑﺗﻛون ﺑﯾن اﻟﺧﻼﯾﺎ‬: interdigitating cells in lymph nodes & thymus 2019-2020 Immunology 7105306 33 ‫‪MYELOID AND PLASMACYTOID DENDRITIC‬‬ ‫)‪CELLS (DCS‬‬ ‫ھون ﻣﻘﺎرن ﺑﯾن ال ‪myeloid and plasmacytoid DCs‬‬ ‫أول اﺷﻲ ﺑﺣﻛﯾﻠﻧﺎ ﻋن ال ‪origin‬وأﻧﮫ ﻛل وﺣدة ﺟﺎي ﻣن ‪line‬ﻣﺧﺗﻠف ‪ ،‬وﻣواﻗﻌﮭم ﻛﻣﺎن ﻣﺧﺗﻠﻔﺔ ﻧﻔس ﻣﺎ اﺣﻧﺎ ﺷﺎﯾﻔﯾن‬ ‫ﻋﻠﻰ اﻟﺟدول )ﻗرأھم ﻗراءة( وﺣﻛﻰ أﻧﮫ ﻧﻌرف ﻣﻌﻠوﻣﺔ اﻧﮫ ﺑﻛون ﺑﺎل ‪secondary lymphoid organs‬ﻏرف ﻟﻠﺧﻼﯾﺎ‬ ‫اﻟﻣﺧﺗﻠﻔﺔ ﻓﮭﺎي اﻟﺧﻼﯾﺎ ﺑﺗﻛون ﻣوﺟودة ﻓﻲ ﻏرف ال ‪T cell ،‬اﻟﺑﺎﻗﻲ ﻗراءة ﻋن اﻟﺟدول‬ ‫‪2019-2020‬‬ ‫‪Immunology 7105306‬‬ ‫‪34‬‬  MIGRATION OF ANTIGEN-PRESENTING CELLS (APCS) INTO LYMPHOID TISSUES Langerhans’ cells (DC) are found in the epidermis and in mucosa , they are rich in MHC class II molecules, and carry processed antigens. antigen presenting cells ، ‫ھون ﻣﻌطﯾﻧﺎ ﻣﺛﺎل ﻋﻠﻰ ال‬ ‫ﺑﺗﻛون ﻣوﺟودة ﺑﺎﻟﺑﺷرة وﺑﻛون‬cells ‫ھون ﻋﻧﺎ ﻻﻧﺟرھﺎﻧز‬ ‫ﺑﺗﺗﻌرف ﻋﻠﻰ اﻻﻧﺗﺟﯾن‬MHC molecules ، ‫ﻓﯾﮭﺎ ﻛﺛﯾر‬ ‫وﺑﺗروح ﻋﻠﻰ ﻣرﻛز اﻟﺷرطﺔ‬phagocytosis ‫وﺑﺗﻌﻣﻠﮫ‬ ‫ﻟل‬activation ‫وﺑﺗﻌﻣل‬lymph nodes) ) ‫واﻻﺷﯾﺎء‬antibodies ‫ﻓﺑﺗم اﻧﺗﺎج ال‬lymphocytes ، (HEV, high endothelial venule) ‫اﻟﻣﺧﺗﻠﻔﺔ ﯾﻠﻲ ﺑﺗﺳﺎﻋدﻧﺎ ﻟﺣﺗﻰ ﻧﻘﺿﻲ ﻋﺎﻟﻣﺎﯾﻛروب‬ 2019-2020 Immunology 7105306 35  ‫ھﻲ ﺑﺗﻛون ﻣن‬natural killer cells ‫ھون ﻣﻧﺣﻛﻲ ﻋن ال‬ innate immunity ، ‫ﻟﻛﻧﮭﺎ ﻣن ال‬lymphocytes ‫ال‬ 2019-2020 Immunology 7105306 36  ‫‪CELLS OF ADAPTIVE IMMUNITY‬‬ ‫ھﻮن ﺑﺤﻜﯿﻠﻨﺎ ﻋﻦ ال ( ‪cells of adaptive immunity ،‬اﻟﺪﻛﺘﻮر ﻗﺮأ اﻟﺘﻌﺮﯾﻒ ﻗﺮاءة(‬ ‫ﺑﻌﺪﯾﻦ ﺑﻠﺶ ﺑﺎﻟﻨﻘﻄﺔ اﻟﺜﺎﻧﯿﺔ وﺣﻜﻰ اﻧﮫ ﺑﻜﻮن ﻋﻠﻰ ال ‪lymphocytes‬ﻋﺒﺎرة ﻋﻦ ‪antigen receptors‬ﯾﻠﻲ ھﻢ ال ‪T cell‬‬ ‫‪receptor‬وال ‪B cell receptor ،‬اﻟﻨﻘﻄﺔ اﻟﺜﺎﻧﯿﺔ ﯾﻠﻲ ھﻲ ‪specificity ،‬ﻣﻦ ﻛﻠﻤﺔ ‪clone‬اﻛﯿﺪ ﻣﺘﺬﻛﺮﯾﻦ ﻛﻠﻤﺔ ‪clonal‬‬ ‫‪selection ،‬وﻓﻲ ‪diversity‬ﯾﻌﻨﻲ ﻛﻞ ﺧﻠﯿﺔ ﻋﻠﯿﮭﺎ ‪reseptor‬ﻣﺤﺪد ‪against specific antigen ،‬طﺒﻌﺎ ً ﺑﺘﻮﺻﻞ‬ ‫ال ‪lymphocytes‬اﻟﻰ ‪ 9-7^10‬ﺧﻠﯿﺔ ‪ ،‬ﯾﻌﻨﻲ ﻗﺎدرة ﺗﺘﻌﺮف ﻋﻠﻰ ﻧﻔﺲ اﻟﻌﺪد ﻣﻦ اﻻﻧﺘﯿﺠﯿﻨﺎت ‪ ،‬ﺑﺎﻻﺿﺎﻓﺔ اﻧﮫ ﺑﻜﻮن ﻋﻨﺎ ال‬ ‫‪memory‬ﺷﺮﺣﻨﺎھﺎ ﺳﺎﺑﻘﺎ ً ‪.‬‬ ‫‪ -٣‬ﺑﺤﻜﯿﻠﻨﺎ اﻧﮫ ال ‪lymphocytes‬ﻋﻨﺎ ‪three major groups :‬‬ ‫‪- B cells ١‬ﯾﻠﻲ ھﻢ ﺑﻨﺘﺠﻮ ‪antibodies‬واﻟﮭﻢ دور ﺑﺎل ‪humoral immunity‬اي اﻟﻤﻨﺎﻋﺔ اﻟﺴﺎﺋﻠﺔ ‪ ،‬ﯾﻌﻨﻲ ﻓﺶ ﺧﻼﯾﺎ ‪.‬‬ ‫‪T cells -٢‬ﻣﻨﮭﺎ اﻧﻮاع ﻣﺨﺘﻠﻔﺔ ‪ ،‬وھﻲ ﺑﺘﺸﺘﻐﻞ ﻋﻠﻰ ال ‪cell mediated immunity‬وﺑﺘﻌﻤﻞ ﺗﻨﻈﯿﻢ و ‪regulate‬ﻟﺨﻼﯾﺎ‬ ‫ﻣﻨﺎﻋﯿﺔ اﺧﺮى‬ ‫‪NK cell -٣‬ھﻲ ﺑﺘﺸﺘﻐﻞ ك ‪innate immunity‬‬  CELLS OF ADAPTIVE IMMUNITY 1. Lymphocytes are the key players of the adaptive immunity. 2. Lymphocytes are able to specifically recognize and respond to diverse antigens. => Antigen (Ag) receptors on lymphocytes => Specificity (Clone), Diversity (Repertoire: total number of Ag-specific lymphocytes in an individual; 107-9), & Memory 3. Lymphocytes are classified into three major groups: - B cells => Antibodies => Humoral immunity - T cells => Multiple subtypes => Cell-mediated immunity & Regulate other immune cells - NK cells => Innate immunity 2019-2020 Immunology 7105306 38  ‫‪CLASSES OF LYMPHOCYTES‬‬ ‫ھﻮن ﻣﻮرﺟﯿﻨﻲ ال ‪classes of lymphocytes‬‬ ‫‪- ١‬ﻋﻨﺎ ال ‪B cells‬ﯾﻠﻲ ﺣﻜﯿﻨﺎ ﺑﺼﯿﺮﻟﮭﺎ ‪activation‬وﺑﺘﺼﯿﺮ ‪plasma cells‬ﺗﻨﺘﺞ ‪antibodies‬‬ ‫‪- ٢‬ﻋﻨﺎ ال ‪T cells‬ﺷﻮﻓﻮ ﻛﻢ اﻧﻮاﻋﺎ ﻛﺜﺎر )اﻟﺪﻛﺘﻮر ﻋﺪدھﻦ ﻗﺮاءة(‬ ‫‪NK cells -٣‬‬ ‫‪- ٤‬وﻋﻨﺎ ‪subtypes‬ﻣﻦ ﻛﻞ ‪class‬‬ ‫ﻧﺸﻮف وظﯿﻔﺔ ﻛﻞ وﺣﺪة‬ ‫‪ -١‬ﺑﺤﻜﯿﻠﻨﺎ ال ‪B lymphocytes‬وظﯿﻔﺘﮭﺎ ( ‪phagocytosis‬ﺑﻠﻌﻤﺔ( ‪complements activation ،‬وﻛﻤﺎن ﺑﺘﻌﻤﻞ‬ ‫‪neutralization of microbes‬ﻣﻦ ﺧﻼل اﻧﺘﺎج ال ‪antibodies‬‬ ‫‪- ٢‬اﻟﮭﺎ وظﺎﺋﻒ ﻣﮭﻤﺔ ‪ ،‬ﺗﻨﺸﯿﻂ ال ‪macrophages ،‬اﻟﮭﺎ دور ﺑﺎل ‪inflammation ،‬ﻛﻤﺎن ﺑﺘﻌﻤﻞ ‪activation‬ﻟﻞ ‪B‬‬ ‫‪cells‬وﻛﻤﺎن ﻟﻞ ‪T cells‬‬ ‫‪- ٣‬وظﯿﻔﺔ ال ‪T cytotoxic‬اﻧﮭﺎ ﺑﺘﻌﻤﻞ اﺗﻼف وﺗﺨﺮﯾﺐ ﻟﻠﺨﻼﯾﺎ اﻟﻤﺼﺎﺑﺔ‪kill infected cell ,‬‬ ‫‪- ٤‬ال ‪regulatory T cells‬ﺑﺘﻌﻤﻞ ‪suppression for immune respond ،‬ﺑﻌﺪ ﻣﺎ ﻋﻤﻠﻨﺎ ردة اﻟﻔﻌﻞ اﻟﻤﻨﺎﻋﯿﺔ ﺑﺪﻧﺎ‬ ‫اﺷﻲ ﯾﻮﻗﻔﮭﺎ‬ ‫‪ -٥‬ال ‪NK‬ﻛﻤﺎن ﺑﺘﻘﺘﻞ اﻟﺨﻼﯾﺎ اﻟﻤﺼﺎﺑﺔ ﺑﺎﻻﺿﺎﻓﺔ ﻟﻠﺨﻼﯾﺎ اﻟﺴﺮطﺎﻧﯿﺔ‬ CLASSES OF LYMPHOCYTES 1. B cells => Plasma cells => Abs 2. T cells: - T helper cells - T cytotoxic cells - T regulatory cells => suppress immune responses 3. NK cells 4. Subtypes in each class 2019-2020 27 Immunology 7105306 ‫‪T cells vs B cells‬‬ ‫طﺑﻌﺎ ﻓﻲ ﻓروﻗﺎت ﺑﯾن ال ‪ B cells & T cells‬و ﻛﻣﺎن ﺑﯾن أﻧواﻋﮭم )‪) (subtypes‬ﻣﺛل اﻟﻔرق ﺑﯾن ‪ (Tc&Th‬و ھﺎي‬ ‫اﻟﻔروﻗﺎت ﻣوﺿﺣﺔ ﺑﺎﻟﺟدوﻟﯾن ھﺎي اﻟﺳﻼﯾد و ﺑﻌد )اﻟﻔروﻗﺎت ھﻲ ﻋﺑﺎرة ﻋن ‪ specialized receptors‬و ﺑﻧﺳﺗﺧدﻣﮭﺎ‬ ‫ﻟﻠﺗﻔرﯾق ﺑﯾن اﻟﺧﻼﯾﺎ ﺑطرق ﻣﻌﯾﻧﺔ(‬ ‫ب ‪ T cells‬ﻣوﺟود ‪ TCR‬وﻣﻧﮫ ﻧوﻋﯾن ‪ (more common) alpha.beta‬و ﻛﻣﺎن ‪ Delta.gamma‬اﻣﺎ ب ‪B cells‬‬ ‫ﻣوﺟودة ‪) BCR‬ﺑﻧﺳﻣﯾﮭﺎ ‪ (immunoglobulin‬و ﺑﻛون ھو ال ‪antibody‬‬ ‫ ‪ CD3‬اﻟو دور ﺑﺎل ‪ signaling‬و ھو ﺟزء ﻣن ‪TCR‬‬ ‫ ‪ CD4&CD23‬ﻓﻲ ‪ Th‬ﻓﻘط‬ ‫ ‪ CD8‬ﻣوﺟود ﺑس ﺑﺎل ‪Tc‬‬ ‫اﻟﺠﺪاول ﻣﮭﻤﺔ ﻛﺜﯿﺮ ﺑﺲ اھﻢ اﺷﻲ ﻓﯿﮫ ﺗﺎﻋﻮن ال ‪complex‬‬ ‫ھون ﻛل اﻟﻣوﺟودات ب ‪ B‬و ﻣش ﻣوﺟودات‬ ‫ب ‪ CD79) T‬وظﯾﻔﺗﮭﺎ ‪(signaling‬‬  ‫ھﺎد ﻧﻔﺲ ﻣﺒﺪأ اﻟﺴﻼﯾﺪ اﻟﻠﻲ ﻗﺒﻞ ﺑﺲ اﺷﻤﻞ و ﻣﻔﺼﻞ اﻛﺜﺮ )ﺣﻔﻈﻮ رح ﯾﺴﮭﻞ ﻋﻠﯿﻨﺎ ﻟﻘﺪام ﻋﻠﻰ ﺣﺴﺐ ﻛﻼم اﻟﺪﻛﺘﻮر(‬ ‫ذاﻛﺮﯾﻦ اﺷﻲ اﺳﻤﻮ ‪MHC‬؟ اﻟﻠﻲ ﻣﺴﺆول ﻋﻦ ‪ antigen presenting‬و ﺑﺮﺑﻂ ب ‪ T cell receptor‬؟ اه ﻓﻲ ﻣﻨﻮ ﻧﻮﻋﯿﻦ‬ ‫‪ MHCI‬ﺑﺮﺑﻂ ب ‪ CD8‬و ‪ MHCII‬ﺑﺮﺑﻂ ب‪ CD4‬و ھﺎد اﻻﺷﻲ اﻷﺳﺎﺳﻲ‬ ‫ھﺴﺎ ﻓﻲ ﻋﻨﺎ ‪ receptor‬اﺳﻤﻮ ‪ CD28‬ﺑﺮﺑﻂ ﺑﺎﻧﺘﺠﯿﻦ ‪ B7‬و ھﺎد ﺑﺴﺎﻋﺪ ارﺗﺒﺎط ال ‪ MHC‬ﺑﺎﻻرﺗﺒﺎط ﺑﺎل ‪Tcell receptor‬‬ ‫)ﻋﺸﺎن ھﯿﻚ ﺳﻤﯿﻨﺎه ‪) (co stimulatory‬رح ﻧﯿﺠﻲ ﻋﻠﯿﮫ ﺑﻌﺪﯾﻦ(‬ ‫‪42‬‬  Q&As Which of the following functions is specialized for one subtype of cells A. Signal transduction B. Adhesion to MHCI molecule C. Adhesion to MHCII molecule D. B+C You want to isolate B cells from the blood, to do that you have to target ….. A. CD5 B. CD32 C. CD40 D. B+C Answers in next slide  ‫‪ : C.1‬اﻟﻘﺼﺔ و ﻣﺎ ﻓﯿﮭﺎ اﻧﻮ ﻛﻞ ‪ marker‬اﻟﻮ ‪ function‬ﻣﻌﯿﻨﺔ و ھﺎي ال ‪ function‬ﻣﻮﺟﻮدة ﺑﺎﻟﺨﻠﯿﺔ‬ ‫اﻟﻠﻲ ﻋﻨﺪھﺎ ال ‪) marker‬ﯾﻌﻨﻲ ﻣﺜﻼ ‪ CD21‬ﺑﻌﻤﻞ ك‪ receptor‬ل ‪ c3d‬و ھﺎد ال ‪ marker‬ﻣﻮﺟﻮد‬ ‫ﻋﻠﻰ ‪ B cell‬ف اﻧﺎ ﺑﻔﮭﻢ اﻧﻮ ‪ B cell‬ﻗﺎدرة ﺗﺴﺘﻘﺒﻞ ال ‪ (c3d‬ھﺴﺎ ﻋﻨﺎ اول ‪ function‬اﻟﻠﻲ ھﻮ ﺑﻌﻤﻠﮭﺎ‬ ‫‪ CD4,CD2, CD8, CD40, CD45‬ﯾﻌﻨﻲ أي ﺧﻠﯿﺔ ﻓﯿﮭﺎ ﻋﺎﻻﻗﻞ واﺣﺪ ﻣﻦ ھﺎي ال ‪markers‬‬ ‫ﺑﺘﻌﻤﻞ ‪ signal transduction‬و ﻟﻤﺎ ﻧﺮﺟﻊ ﻟﻠﺠﺪول ﺑﻨﺸﻮف اﻧﮭﻢ ﻛﻠﮭﻢ ﺑﻌﻤﻠﻮھﺎ ‪..‬ﻧﻔﺲ اﻻﺷﻲ ﺑﺎل‬ ‫‪ MHCI‬ﺑﻨﻼﻗﻲ اﻧﻮ ﺑﻌﻤﻠﻮ ‪ Tc&NK‬اﻣﺎ ال ‪ MHCII‬ﻣﺎ ﺑﻘﺪر ﯾﺴﺘﻘﺒﻠﻮ ﻏﯿﺮ ‪ Th‬ﻋﺸﺎن ھﯿﻚ ﺑﻄﻠﻊ‬ ‫اﻟﺠﻮاب ‪) C‬ﻟﻮ ﻛﺎن ﻓﻲ اﺷﻲ ﻣﺸﺘﺮك ﺑﯿﻦ ‪ Tc&Th‬ﺑﺮﺿﻮ ﺑﻨﻌﺘﺒﺮو ﻏﻠﻂ ﻻﻧﻮ طﻠﺐ ‪function‬‬ ‫ﺧﺎﺻﺔ ب ‪ subtype‬ﻣﻌﯿﻦ(‬ ‫‪D.2‬‬  LYMPHOCYTES microscope ‫ و ﻣﺎ ﺑﻧﻘدر ﻧﻼﺣظﮭﺎ ﻋﺎل‬receptors ‫ ﻻﻧو اﻟﻔرق اﻟوﺣﯾد ھو‬lymphocytes‫ﻣﺎ ﺑﻧﻘدر ﻧﻔرق ﺑﯾن ال‬ (large & small lymphocytes ‫اﻟﻌﺎدي ﻛﻣﺎن ﺷوي رح ﻧﻌرف ﻛﯾف ﻧﻔرق )طﺑﻌﺎ ﺑس ﺑﻧﻘدر ﻧﻔرق اﻟﺣﺟم ل‬ Small Lymphocytes Large Granular Lymphocytes 2019-2020 Immunology 7105306 45  PLASMA CELLS-AB SECRETION plasma cell ‫ھﺎي‬ ‫ﯾﻼ ﻋﺎﻟﺳﻼﯾد اﻟﻠﻲ ﺑﻌدو ﺗﻠﺗﮭﯾش‬ 2019-2020 Immunology 7105306 46  ‫‪FUNCTIONAL T CELLSUBSETS‬‬ ‫ھون ﺑوﺿﺢ ال ‪ subtypes‬ﻟل ‪) T cell‬اﻟﻣوﺿوع ﺷﺑﮫ ﻋﻠم اﻟﺗﺻﻧﯾف ﺑﻧﺟﯾب اﻟﻣواﺻﻔﺎت اﻟﻌﺎﻣﺔ ﺑﻌدھﺎ ﺑﻧﺗﺧﺻص‬ ‫‪More common‬‬ ‫ﺑﺗرﺑط ﻣﻊ ‪MHCI‬‬ ‫ﺑﺗرﺑط ﻣﻊ ‪MHCII‬‬ ‫‪2019-2020‬‬ ‫‪Immunology 7105306‬‬ ‫‪47‬‬  THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE 2011 immunology ‫ﻧﺎس اﺧذوا ﻧوﺑل ﻻﻧﺟﺎزات ﻓﻲ ال‬ Ralph M. SteinmanJules A. HoffmannBruce A. Beutler The Nobel Prize in Physiology or Medicine 2011 was divided, one half jointly to Bruce A. Beutler and Jules A. Hoffmann "for their discoveries concerning the activation of innate immunity" and the other half to Ralph M. Steinman "for his discovery of the dendritic cell and its role in adaptive immunity". 2019-2020 Immunology 7105306 48  ‫‪IDENTIFICATION OF CELL POPULATIONS‬‬ ‫ﺣﻜﯿﻨﺎ ﻋﺸﺎن ﻧﻔﺮق ﺑﯿﻦ ال‪ lymphocyte‬ﺑﻠﺰﻣﻨﺎ طﺮق ﻣﻌﯿﻨﺔ ‪..‬ھﺴﺎ رح ﻧﻮﺧﺬ ھﺎي اﻟﻄﺮق ‪.‬‬ ‫طﺒﻌﺎ ﻛﻞ ھﺎد ﺑﻨﻌﻤﻠﻮ ﻋﺸﺎن ﻧﻔﺮق ﺑﯿﻦ اﻟﺨﻼﯾﺎ و ﻧﻌﺰﻟﮭﻦ اﻣﺎ ﻟﺪراﺳﺘﮭﻦ او ﻧﻌﻤﻞ ‪ tests‬او ﻟﻠﻌﻼج‬ ‫رح ﻧﺤﻜﻲ اول اﺷﻲ ﻋﻦ ال ‪immunoflourescence‬و اﻟﻠﻲ ﺑﺘﻢ ﺑﻄﺮﯾﻘﺘﯿﻦ‬ ‫‪ :Direct immunofluorescence.1‬ﻋﻦ طﺮﯾﻖ اﻧﻲ ﺑﺠﯿﺐ ‪ antibody‬ﻣﺨﺼﻮص ل ‪ CD‬ﻣﻌﯿﻦ ﻣﺜﻼ ﺑﺪي اﻋﺰل ال ‪Th‬‬ ‫ﺑﻘﻮم ﺑﺠﯿﺐ ‪ antibody‬ﻣﺨﺼﻮص ل ‪ CD4‬و ﻋﻠﯿﮫ ﻣﺮﻛﺐ ﻣﺎدة ﻣﺸﻌﺔ و ﺑﺤﻄﮫ ﺑﺎﻟﻮﻋﺎء اﻟﻠﻲ ﻓﯿﮫ اﻟﺨﻼﯾﺎ و ﺑﻌﻤﻞ‬ ‫‪..washing‬ھﺴﺎ ال ‪ antibodies‬اﻟﻠﻲ ﻣﺎ ارﺗﺒﻄﺖ ﺑﺎﺷﻲ رح ﺗﺮوح اﻣﺎ اﻟﻠﻲ ﺿﻠﺖ راﺑﻄﺔ ﺑﺎل ‪ CD4‬ﯾﻌﻨﻲ راﺑﻄﺔ ﺑﺎل ‪Th‬‬ ‫ف ﻗﺪرﻧﺎ ﻧﺤﺪد ﻣﻮﻗﻌﮭﺎ‬  ‫‪IDENTIFICATION OF CELL POPULATIONS‬‬ ‫‪ : Indirect immunofluorescence.2‬ھﻮن ﺑﺠﯿﺐ ‪ antibody‬ﻣﺨﺼﻮص ﻟﻞ‪ CD‬اﻟﻤﻌﻨﻲ و ﻻﻧﻮ رﺑﻂ ﻣﺒﺎﺷﺮة ﺑﺴﻤﯿﮫ‬ ‫‪ primary‬ﺑﺲ ھﺎد ﻣﺎ ﺑﻜﻮن ﻋﻠﯿﮫ اﻟﻤﺎدة اﻟﻤﺸﻌﺔ ‪..‬ھﺴﺎ ﺑﻨﻘﻮم ﻧﺠﯿﺐ ‪ antibody‬ﻣﺨﺼﻮص ﯾﺮﺑﻂ ﺑﺎل ‪ primary antibody‬و‬ ‫ﺑﺴﻤﯿﮫ ‪ secondary‬و ھﺎد ﺑﻜﻮن ﻋﻠﯿﮫ اﻟﻤﺎدة اﻟﻤﺸﻌﺔ‬ ‫طﺒﻌﺎ اﻟﻄﺮﯾﻘﺘﯿﻦ ﻣﻔﯿﺪات ﻛﻞ وﺣﺪة و اﻟﮭﺎ ﻣﻮاﻗﻔﮭﺎ و ﻛﻤﺎن ﻣﺮة ھﺎد ﺑﺲ ‪identification‬‬ ‫ﻟﻮ ﻻﺣﻈﺘﻮ اﻧﻮ ﻓﻲ اﻟﻮان ﺑﺎﻟﺼﻮر ال ‪ microscopic‬و ھﺎد ﻻﻧﻮ اﻟﻤﻠﻮن‬ ‫ھﻮ اﻟﻤﺎدة اﻟﻤﺸﻌﺔ‬ IDENTIFICATION OF CELL POPULATIONS 1. Molecules on or in cells => Identification & Classification e.g. CD3, CD4, CD8…. 2. Methods: (1) Immunofluorecence CD: Cluster of Differentiation 2019-2020 Immunology 7105306 51  ‫‪IDENTIFICATION OF CELL POPULATIONS‬‬ ‫ھﺎد اﻟﺠﮭﺎز ﺑﺪو ﺷﻮﯾﺔ ﺗﺮﻛﯿﺰ ‪Flow Cytometry‬‬ ‫ھﺴﺎ ھﺎي اﻟﻄﺮﯾﻘﺔ ﺑﺘﻌﺘﻤﺪ ﻋﺎﻟﻄﺮﯾﻘﺔ اﻟﻠﻲ ﻗﺒﻞ )‪ (immunoflourescence‬و اﻟﻠﻲ ﺑﺼﯿﺮ ﻓﯿﮭﺎ ﻛﺎﻟﺘﺎﻟﻲ‬ ‫ ﺑﺘﻢ ﺗﺠﻤﯿﻊ اﻟﺨﻼﯾﺎ ﻓﻲ اﺷﻲ ﺷﺒﮫ اﻟﻘﻤﻊ ﺑﺤﯿﺚ اﻧﻮ ﺑﻄﻠﻊ ﻣﻨﮫ ﺧﻠﯿﺔ وﺣﺪة ﻛﻞ ﻣﺮة‬ ‫ ﻛﻞ ﻣﺎ ﺗﻨﺰل ﺧﻠﯿﺔ ﺑﻀﺮﺑﮭﺎ ﻟﯿﺰر و ھﺎد اﻟﻠﯿﺰر ﯾﺎ ﺑﺨﺘﺮﻗﮭﺎ ﯾﺎ ﺑﺘﺸﺘﺖ و ﻣﻘﺪار اﻟﺘﺸﺘﺖ ﺑﻜﻮن ﻣﺤﻜﻮم ﺑﻤﻮاﺻﻔﺎت اﻟﺨﻠﯿﺔ )اﻟﺤﺠﻢ‬ ‫اﻟﻤﻜﻮﻧﺎت اﻟﺦ‪ (..‬و ﻣﻦ ھﺎي اﻟﺼﻔﺎت ھﻮ اﻟﻤﺎدة اﻟﻤﺸﻌﺔ اﻟﻠﻲ ﻋﻠﯿﮭﺎ ﻣﻦ ال ‪immunoflourescence‬‬ ‫ ف ﺑﺎﻟﺘﺎﻟﻲ ﻛﻞ ﻣﺠﻤﻮﻋﺔ ﺧﻼﯾﺎ ﺑﺘﺘﺸﺎﺑﮫ ﺑﻤﻮاﺻﻔﺎﺗﮭﺎ )ﻓﻲ ﺣﺎﻟﺘﻨﺎ اﻧﻮ اﻟﺨﻠﯿﺔ ﻋﻠﯿﮭﺎ ‪ antibody‬ﻣﺸﻊ او ﻻ( رح ﯾﺘﺸﺘﺖ اﻟﻠﯿﺰر ﺑﺸﻜﻞ‬ ‫ﻣﺘﺸﺎﺑﮫ و ﺑﺎﻟﺘﺎﻟﻲ ﺑﻨﻘﺪر ﻧﻌﺮف ﻋﺪد اﻟﺨﻼﯾﺎ اﻟﻠﻲ ﻋﻨﺪھﺎ ھﺎد ال ‪ antibody‬اﻟﻤﺸﻊ‬ ‫ﺷﺎﯾﻔﯾن ﻛﯾف ﺷﺑﮫ ﻗﻣﻊ ﺑس‬ ‫ﺧﻠﯾﺔ وﺣدة ﺑﺗﻣر‬ ‫اﻟﻛﺎﺷف اﻟﻠﻲ ﺑﺳﺗﻘﺑل ﺿو ﻣن اﻟﺧﻼﯾﺎ‬ ‫اﻟﻠﻲ ﻋﻠﯾﮭﺎ ‪ antibody‬ﻣﺷﻊ‬ ‫اﻟﻛﺎﺷف اﻟﻠﻲ ﺑﺳﺗﻘﺑل ﺿو ﻣن اﻟﺧﻼﯾﺎ اﻟﻠﻲ‬ ‫ﻣﺎ ﻋﻠﯾﮭﺎ ‪ antibody‬ﻣﺷﻊ‬ ‫‪(2) Flow Cytometry & Sorting‬‬ ‫ھﺎن ﺿرب ﻋﺻﻔورﯾن ﺑﺣﺟر‪:‬‬ ‫ﻋرف ﻛم ﻋدد اﻟﺧﻼﯾﺎاﻟﻣﺷﻌﺔ و ﻛﻣﺎن‬ ‫ﻗدر ﯾﻌزﻟﮭن )‪(sorting‬‬ ‫‪2019-2020‬‬ ‫‪35‬‬ ‫‪Immunology 7105306‬‬  ‫‪IDENTIFICATION OF CELLPOPULATIONS‬‬ ‫طﺐ ھﺴﺎ ﻣﻊ اﺣﺘﺮاﻣﻲ ل ‪ immunofluorescence‬و ‪flow cytometry‬‬ ‫ﺷﻮوو ﺑﺴﺘﻔﯿﺪ ﻟﻤﺎ اﻋﺰل ‪ B cell 100,000‬ﺑﺲ وﻻ وﺣﺪة ﻣﻨﮭﺎ ﺑﺘﻄﻠﻊ ال‪ antibody‬اﻟﻠﻲ ﺑﺪي‬ ‫ﯾﺎه‬ ‫ﻣﻦ ھﻮن اﺟﺖ ﻓﻜﺮة ال‪ ELISPOT‬و ھﺎي ﺑﺘﻘﺪر ﺗﻔﺮق ﺑﯿﻦ ال‪ lymphocyte‬ﻣﻦ ﻧﻔﺲ اﻟﻨﻮع‬ ‫ﺑﻨﺎء ﻋﻠﻰ اﻟﻤﻮاد اﻟﻠﻲ ﺑﺘﻔﺮزھﺎ )‪(specific‬‬ ‫ﻧﻮﺧﺬ ﻣﺜﺎل ﻋﺎل ‪ :B cell‬ھﺴﺎ اﻧﺎ ﺑﺪي اﻋﺰل اﻟﺨﻼﯾﺎ اﻟﻠﻲ ﺑﺘﻔﺮز ‪ antibody‬ﺿﺪ اﻧﺘﺠﯿﻦ ﻣﺤﺪد‬ ‫ﻓﺸﻮ ﺑﻌﻤﻞ ؟‬ ‫‪.1‬ﺑﻘﻮم ﺑﻌﺒﻲ وﻋﺎء ﻣﻦ اﻻﻧﺘﺠﯿﻦ و ﺑﺤﻂ ﻓﯿﮫ ‪) B cells‬ذﻛﺮك ﺑﺈﺷﻲ؟ ‪(clonal selection‬‬ ‫طﺒﻌﺎ اذا طﻠﻊ ال ‪ antibody‬اﻟﻤﺨﺼﻮص ﺑﺎﻻﻧﺘﺠﯿﻦ رح ﯾﺮﺗﺒﻂ ﻓﯿﮫ و ﯾﻀﻞ ﻣﻮﺟﻮد‬ ‫‪.2‬ھﺴﺎ ﺑﺪﻧﺎ‪ label‬ﻛﯿﻒ ﺑﺪﻧﺎ ﻧﻌﻤﻠﮭﺎ؟ ﻣﻦ ﺧﻼل اﻧﻲ اﺣﻂ ‪ enzyme‬ﻋﻠﻰ ‪ antibody‬ﺑﺮﻛﺐ‬ ‫ﻋﺎل ‪ antibody‬اﻻوﻻﻧﻲ )اﻷزرق ھﻮ اﻟﻠﻲ اﻧﺎ رﻛﺒﺘﻮ و اﻷﺻﻔﺮ اﺟﺎ ﻣﻦ ‪(B cell‬‬ ‫‪.3‬ﺑﻌﻤﻞ ‪washing‬‬ ‫‪.4‬ﺑﺤﻂ اﻟﻤﺎدة اﻟﻠﻲ ﺣﺘﻜﻮن ﺑﻤﺜﺎﺑﺔ ال ‪ substrate‬ﻟﻼﻧﺰﯾﻢ و ﻟﻤﺎ ﯾﺸﺘﻐﻞ ﻋﻠﯿﮭﺎ رح ﯾﺘﻐﯿﺮ اﻟﻠﻮن‬ ‫)ﻛﺈﻧﺎ ﺻﺒﻐﻨﺎه(‬ ‫ﺑﺎل ‪ T cell‬ﻧﻔس اﻟﻣوال ﺑس اﻟﻠﮭم اﻧو اﻟوﻋﺎء ﺑدل اﻧﺗﺟﯾن ﺑﺣﺗوي ‪ antibody‬و ال ‪ T cell‬ﺑﺗطﻠﻊ ‪) cytokines‬ﺷوف اﻟﺳﻼﯾد‬ ‫اﻟﻠﻲ ﺑﻌد(‬ (3) ELISPOT 2019-2020 Immunology 7105306 36  ‫‪IDENTIFICATION & ISOLATION OF CELL POPULATIONS‬‬ ‫ﻓﻲ طﺮﯾﻘﺘﯿﻦ ﺑﻨﺴﺘﺨﺪﻣﮭﻢ ﻟﻞ‪ isolation‬و ﺑﻌﺘﻤﺪوا ﻋﺎل ‪marker‬‬ ‫‪.1‬اﻧﻮ ﻧﺤﻂ ‪ antibody‬ﺑﺮﺑﻂ ﺑﺎل ‪ marker‬ﻋﻠﻰ ﺳﻄﺢ وﻋﺎء ﻓﺎﻟﺨﻼﯾﺎ اﻟﻠﻲ ﻋﻠﯿﮭﺎ ال ‪ marker‬رح ﺗﻠﺰق ﻋﺎﻟﺴﻄﺢ‬ ‫)ﻋﺸﺎن رﺑﻄﺖ ﺑﺎل‪ (antibody‬و ﺑﻌﺪ ﻣﺎ ﻧﻌﻤﻞ ‪ washing‬ﺑﺘﻀﻞ اﻟﺨﻼﯾﺎ اﻟﻠﻲ ﺑﺪﻧﺎ ﯾﺎھﺎ‬ ‫‪.2‬ﺑﻨﺠﯿﺐ ‪ antibody‬ﺑﺮﺑﻂ ﻋﺎل‪ marker‬و ﺑﻨﻐﻠﻒ ال ‪ antibody‬ﺑﻤﺎدة ﺑﺘﻨﺠﺬب ﻟﻠﻤﻐﻨﺎطﯿﺲ )ﺗﺨﯿﻞ اﻧﻚ دﻗﯿﺖ ﻣﺴﻤﺎر‬ ‫ﺑﺨﺸﺒﺔ ف ﻟﻤﺎ ﺗﻘﺮب ﻣﻐﻨﺎطﯿﺲ ﻋﻠﯿﮭﺎ رح ﺗﻨﺠﺬب ﻟﻠﻤﻐﻨﺎطﯿﺲ( ھﺴﺎ ﺑﻌﺪ ﻣﺎ اﻧﺠﺬﺑﺖ ﻟﻠﻤﻐﻨﺎطﯿﺲ ﺑﻨﻌﻤﻞ ‪washing‬‬ ‫ﻓﺒﺘﻀﻞ ﺑﺲ اﻟﺨﻼﯾﺎ اﻟﻠﻲ ﻋﻠﯿﮭﺎ ‪) marker‬ﻻﻧﮭﺎ ﻣﺮﺑﻮطﺔ ﺑﺎﻧﺘﺠﯿﻦ ﻣﻐﻠﻒ ﺑﻤﺎدة ﺑﺘﻨﺠﺬب ﻟﻠﻤﻐﻨﺎطﯿﺲ(‬ ‫طرﯾﻘﺔ ‪2‬‬ ‫طرﯾﻘﺔ ‪1‬‬ IDENTIFICATION & ISOLATION OF CELL POPULATIONS ‫أﺳﻣﺎء اﻟطرق‬ Isolation of lymphocyte subpopulations – panning Cell separation by immunomagnetic beads. 2019-2020 Immunology 7105306 37  Anatomy & Functions of Lymphoid Tissues & Organs 2019-2020 Immunology 7105306 58  Lymphoid Tissues & Organs lymphocyte ‫ اﻟﻠﻲ اﻟﮭﺎ دور ﻓﻲ ﺣﯿﺎة ال‬tissues‫ھﺴﺎ ﺑﺪﻧﺎ ﻧﺒﻠﺶ ﻧﺤﻜﻲ ﻋﻦ ال‬ ‫ﻋﻨﺎ‬ ‫ ﻟﻞ‬development & selection & maturation ‫ ھﻲ اﻟﻠﻲ ﺑﺘﻌﻤﻞ ﻋﻠﻰ‬:Primary lymphoid organs lymphocytes ‫ و‬activation ‫ و ﺑﺼﯿﺮﻓﯿﮭﺎ‬differentiated lymphocyte ‫ ھﻲ اﻟﻠﻲ ﺑﺘﻌﯿﺶ ﻓﯿﮭﺎ ال‬: secondary lymphoid organs (‫ زي اﻟﻤﺨﺰن‬secondary ‫ ﻣﻜﺎن اﻹﻧﺘﺎج و‬primary ‫ )ﺑﺎﺧﺘﺼﺎر‬effectors functions bone marrow (Bcells) & thymus (Tcells) ‫ ﻣﺜﻞ‬primary‫ال‬ lymph nodes (lymph) & spleen (blood) & MALT (mucosa) ‫ ﻣﺜﻞ‬Secondary (11&12‫ )ارﺟﻊ ﻟﺴﻼﯾﺪ‬lymphocytes ‫ ﻣﺎﺑﻘﺘﺼﺮ ﻓﻘﻂ ﻋﺎﻧﺘﺎج ال‬bone marrow ‫ال‬ Lymphoid Tissues & Organs Primary lymphoid organs:BM & Thymus => Lymphocyte development, selection, & maturation. 2nd lymphoid organs: Lymphoid nodes & Spleen => Lymphocyte activation & effector functions BM Þ Other immune cells Eg. DCs, Macrophages, PMNs primary & secondary ‫ﻣﺛل ﻣﺎ ﻣﻼﺣظﯾن ﺑﺎﻟﺻورة ھﺎي ال‬ lymphoid organs (MALT ‫)ﻛل اﻟﻠﻲ ﺑﻣرﺑﻊ ازرق ھو‬ ‫ ﻻﻧو ﻣﻣﻛن ﯾﻌﻣل‬primary & secondary ‫ ﻋﺑﺎرة ﻋن‬BM ‫)ھون ﺣط‬ (B cells ‫ ﻟل‬activation 2019-2020 Immunology 7105306 60  THE LYMPHATIC SYSTEM ‫ ﺑﺗﻌﻣل ﻋﺎﻧﮭﺎ ﺗﺳﺣب‬dendritic cells ‫ و ﺗوزﯾﻌﮭن ﺑﺎﻟﺟﺳم و ﺷرح ﻛﯾف ال‬lymph nodes ‫ھﺎن ﻣﻌﻧﻲ ﯾﻔرﺟﯾﻧﺎ ال‬ antigen presenting ‫ و ﺗﻌﻣل‬lymph nodes‫اﻻﻧﺗﺟﯾن ﻟل‬ Link to the blood circulation system 2019-2020 Immunology 7105306 61 BONE MARROW 1. The site of generation of all immune and blood cells Thymocytes: developing T cells in thymus 2. Upper anterior thorax (above the heart). 3.Multiple lobules => Each has Outer Cortex => Dense T cells Inner Medulla => Sparse T cells Other cells: thymic epithelial cells (TECs), DCs, Macrophages => Cell-cell interactions and Cytokines 2019-2020 Immunology 7105306 64 CELL MIGRATION TO AND WITHIN THETHYMUS developed ‫ ﻣﻦ اول ﻣﺎ ﺗﻨﺼﻨﻊ ﻟﺤﺪ ﻣﺎ ﺗﺼﯿﺮ‬T cell‫ﺑﺪﻧﺎ ﻧﺤﻜﻲ ﻋﻦ ﺣﯿﺎة ال‬ ‫ طﺐ ﻛﯿﻒ ﻋﺮﻓﺖ‬thymus ‫ ﻟﺤﺪ ﻣﺎ ﺗﻮﺻﻞ‬circulation ‫ و ﺑﺘﻤﺸﻲ ﺑﺎل‬bone marrow ‫ ﺑﺎل‬T cell ‫ ﺑﺘﻢ ﺻﻨﺎﻋﺔ ال‬.1 ‫ ﻋﻤﺤﻠﮭﺎ ) و ﺑﺘﺪﺧﻠﮭﺎ ﻣﻦ‬Tcells ‫ ﻋﺸﺎن ﺗﺪل ال‬circulation‫ ﻟﻞ‬chemotaxis ‫ ﺑﺘﺮﺳﻞ‬thymus ‫اﻟﻄﺮﯾﻖ؟ اﻟﻠﻲ ﺑﺼﯿﺮ اﻧﻮ‬ (medulla&cortex ‫ ﺑﻜﻮن ﺑﯿﻦ‬post capillary venule double ‫ )ﻋﺸﺎن ھﯿﻚ ﺑﻨﺤﻜﻲ ﻋﻨﮭﺎ‬CD8 ‫ وﻻ‬CD4 ‫ وﻻ‬TCR ‫ و ھﻲ ﻻ ﻋﻠﯿﮭﺎ‬immature T cell ‫ ﺑﺘﺪﺧﻞ ال‬.2 receptors ‫ ﺗﻌﻤﻞ ﻋﺪة ﺗﻐﯿﺮات ﻋﺎل‬cytokines ‫ اﻧﮭﺎ ﺗﻔﺮز‬TEC/DC&macrophages ‫( و ھﻮن ﺑﺘﺼﯿﺮ ال‬negative ‫ و ھﺎي اﻟﺘﻐﯿﺮات ﻣﻮﺿﺤﺔ ﺑﺎﻟﺠﺪول‬markers ‫و ال‬ ‫ ﺗﺠﺎه اﻟﺪم‬HEV ‫ ﻣﻦ اﺷﻲ اﺳﻤﻮ‬Th& Tc ‫ ﺑﺘﻄﻠﻊ ال‬.3 CD44 CD25 CD4 CD8 Stage CD8 or 4 ‫ ﻣﺎ ﻋﻧدھﺎ‬double negative :DN 8&4 ‫ ﻋﻧدھﺎ‬double positive :DP High None None None DN1 regulation:Reg High High None None DN2 ‫ او‬Tc(cd8+) ‫ ﯾﺎ ﺑﺗﺗﻣﺎﯾز ﻟﺗﺻﯾر‬T cell‫طﺑﻌﺎ ال‬ Development Th(cd4+) ‫ﺗﺻﯾر‬ Med (down reg) High None None DN3 Low (down reg) Med (Down reg) High High DP High Low (down reg) High None TH High Low None High TC  CELL MIGRATION TO AND WITHIN THETHYMUS marker ‫؟ ﻻﻧو ھﺎد ال‬thymus ‫ ﻋﺎل‬immature Tcell ‫ ﺑﻛون ﻋﺎﻟﻲ أﺻﻼ ﻗﺑل ﻣﺎ ﺗدﺧل ال‬CD44 ‫ ﻟﯾش ﺗرﻛﯾز‬ thymus ‫ اﻧﮭﺎ ﺗروح ل‬T cell ‫ ﯾﻌﻧﻲ ﺑﺗوﺟﮫ ال‬1 ‫ اﻟﻠﻲ ھﻲ اﻟﮭﺎ دﺧل ﺑﺎﻟﺧطوة‬homing ‫ﻣﺳؤول ﻋن‬ fibers ‫ و ﺑﺗﺻﯾر ﺗﺗﺣول ﻟﻛﺗﻠﺔ‬atrophy ‫ ﺑﺳن اﻟﺻﻐر و اﻟﺷﺑﺎب ﺑس ﺑﻌدھﺎ ﺑﺻﯾﺑﮭﺎ‬100% ‫ ﺑﺗﻛون ﺷﻐﺎﻟﺔ‬thymus‫ ال‬ (thymic involution ‫ﻟﺣد ﻣﺎ ﺗﺻﯾر ﻣﺎ اﻟﮭﺎ ﻓﺎﯾدة )اﺳم اﻟﻌﻣﻠﯾﺔ‬ ‫ھﺎد اﻟﻣدﺧل‬ postcapillary venules (PCVs) subcapsular region where they HEVs at the corticomedullary junction. ‫ ﻋﺎﻟﺪم‬differentiated T cell ‫ﻣﻦ ھﻮن ﺑﺘﺮوح ال‬ actively proliferate and differentiate into double positive 2019-2020 Immunology 7105306 66 EXPRESSION OF HUMAN T CELL MARKERS DURING DEVELOPMENT ‫ھﺎد ﻧﻔس اﻻﺷﻲ ﺑوﺿﺢ ﻛﯾف ال‬ ‫ ﻋﻠﻰ ﺷﻛل‬development ‫ و ﺑﺷﻛل ﻣﻔﺻل اﻛﺛر‬timeline Terminal deoxynucleotidyltransferase (TdT) 2019-2020 Immunology 7105306 67  ‫ اﻧﮭﺎ ﺗﻌﻤﻞ‬T cells ‫ ﺑﺤﻔﺰ‬cytokine ‫ و ھﻮ‬IL7 ‫ ﺑﻔﺮز‬nurse cells ‫ ﺧﻼﯾﺎ اﺳﻤﮭﺎ‬sub capsular region ‫ﻋﻨﺎ ﺑﺎل‬ proliferation ‫ ﻻزم ﻧﻔﮭﻢ ھﺎد اﻟﻤﻮﺿﻮع‬selection ‫ھﺴﺎ ﻗﺒﻞ ﻣﺎ ﻧﺪﺧﻞ ﻋﺎل‬ ‫( و ھﺎد اﻻﺧﺘﺒﺎر‬positive) ‫( ﻻﻧﮭﺎ ﻧﺠﺤﺖ ﺑﺎﺷﻲ‬selection)‫ ﯾﻌﻨﻲ اﻧﻨﻲ اﺧﺘﺎر اﻟﺨﻠﯿﺔ‬positive selection ‫اﻧﻨﻲ اﺣﻜﻲ‬.1 cortical epithelial network ‫ﺑﺼﯿﺮ ﺑﺎل‬ ‫( و ﺑﺘﺸﺮف ﻋﻠﯿﮫ‬negative) ‫ ﯾﻌﻨﻲ اﻧﻨﻲ اﺧﺘﺎر اﻟﺨﻠﯿﺔ ﻋﺸﺎن ﻓﺸﻠﺖ ﺑﺎﺷﻲ‬negative selection ‫اﻧﻨﻲ اﺣﻜﻲ‬.2 macrophages, DC, interdigitating cells & epithelial cells secondary sites‫ و ﻣﻨﮭﺎ ﻟﻞ‬HEV ‫ ﺑﻨﻮدﯾﮭﺎ ﻟﻠﺪم ﻋﺒﺮ‬selection‫اﻟﻠﻲ ﺑﺘﻨﺠﺢ ﺑﺎل‬ THYMUS-II Subcapsular epithelial cells that produce IL-7 (nurse cells) sustain T lymphoblast proliferation in the outer cortex. Developing T cells interact with the cortical epithelial network where they are positively selected. Apoptotic cells are phagocytosed by macrophages present in the deep cortex and in the medulla. TCR+ thymocytes co-expressing CD4 and CD8 undergo the process of negative selection by interacting with a variety of antigen-presenting cells (APCs), such as dendritic cells, interdigitating cells, macrophages, and epithelial cells. T cells that have survived the selection processes are exported from the thymus via high endothelial venules (HEVs) and lymphatic vessels. 2019-2020 Immunology 7105306 69  ‫‪T CELL DIFFERENTIATION IN THE THYMUS‬‬ ‫ھﺴﺎ ﺑﺪﻧﺎ ﻧﺤﻜﻲ اﯾﺶ اﻟﻠﻲ ﺑﺼﯿﺮ وﻗﺖ ال ‪ differentiation‬ﺑﺎﻟﺘﻔﺼﯿﻞ‬ ‫‪.1‬ﺑﺎل ‪ sub-capsular‬اﻟﻠﻲ ﺑﺼﯿﺮ )ﺑﺸﻜﻞ ﻣﺒﺴﻂ( اﻧﻮ ﻓﻲ اﻧﺰﯾﻤﺎت ﺑﺘﻔﻚ اﻟﺠﯿﻦ اﻟﻤﺴﺆول ﻋﻦ ﺗﻜﻮﯾﻦ ‪ TCR‬و ﺑﺘﺮد ﺗﺮﻛﺒﻮ‬ ‫ﺑﺘﺮاﺗﯿﺐ ﻣﺨﺘﻠﻔﺔ )ﻣﺜﻞ ال ‪ (lego‬و ﻣﻨﮫ ﺑﻨﺘﺞ ‪ TCR‬ﻣﺨﺘﻠﻒ ﺑﻜﻞ ﻣﺮة )و ھﺎد اﻟﺴﺒﺐ اﻧﻮ ال‪ TCR‬ﺑﻜﻮن ‪(specific‬‬ ‫‪.2‬ھﺴﺎ ﻣﺶ ﺷﺮط ﻛﻞ ﺗﺮﺗﯿﺐ ‪ TCR‬ﯾﻜﻮن ﻣﻔﯿﺪ و ‪ functional‬ﻋﺸﺎن ھﯿﻚ أي ﺧﻠﯿﺔ اﻧﺘﺠﺖ ‪nonproductive‬‬ ‫‪ rearrangement‬رح ﯾﺘﻢ ﻗﺘﻠﮭﺎ‬ ‫ﻧﻼﺣظ ھﺎن ﻛﯾف ﻗطﻊ و رﺑط أﺟزاء ﻣﺧﺗﻠﻔﺔ ﻣن اﻟﺟﯾن ﻟﯾﺗﻛون ‪unique TCR‬‬ ‫اﻟﺟﯾن اﻟﻣوﺟود ﺑﺎل‪immature T cell‬‬ ‫ھدول ﺑﻛﻣﻠوا طﺑﯾﻌﻲ‬ ‫ھدول ﻣﺻﯾرھم اﻟﻣوت‬ ‫‪apoptosis‬‬ ‫‪TCR arrangement‬‬  ‫‪.3‬ھﺴﺎ اﻟﺨﻼﯾﺎ اﻟﻠﻲ ﺿﻠﯿﻦ ﻣﻌﻨﺎ ﻋﻨﺪھﻦ‪ productive TCR‬و ﺑﻜﻮﻧﻮا ‪ CD4+ &CD8+‬و رح ﻧﺪﺧﻞ ﻋﻠﻰ اﺷﻲ اﺳﻤﻮ‬ ‫‪ thymic education‬ﺑﺘﻜﻮن ﻣﻦ ﺷﻐﻠﺘﯿﻦ‪:‬‬ ‫ ‪ positive selection‬و ھﺎن ﺑﺘﯿﺠﻲ ال ‪ TEC‬ﺑﺘﻌﻤﻞ ‪) MHC presenting‬طﺒﻌﺎ ﺑﺎل‪ Normal T cell‬ﺑﺘﻢ اﻟﺘﻌﺮف ﻋﻠﻰ‬ ‫ال ‪) MHC‬او ﺑﻤﻌﻨﻰ اﺧﺮ ﻋﻨﺪو ‪ (intermediate affinity‬ﻋﺸﺎن ھﯿﻚ اذا ﻛﺎﻧﺖ ال ‪ T cell‬ﻋﻨﺪھﺎ ‪high or low‬‬ ‫‪ affinity to MHC‬رح ﯾﺼﯿﺮﻟﮭﺎ ‪apoptosis‬‬ ‫ ‪ Negative selection‬ھﺎن ﺑﺘﯿﺠﻲ أي ‪ APC‬ﺑﺘﻈﮭﺮ ‪) self antigen‬ﺑﺎل ‪ normal Tcell‬ﻣﺎ ﺑﺘﻢ اﻟﺘﻌﺮف ﻋﺎﻻﻧﺘﺠﯿﻦ ﻟﯿﺶ؟‬ ‫ﻋﺸﺎن ﻟﻮ ﺗﻌﺮف ﻋﻠﯿﮫ ﺑﺒﻨﻲ ﻣﻨﺎﻋﺔ ﺿﺪو ف ﺑﻨﺼﺎب اﻟﺸﺨﺺ ب ‪ (autoimmune‬ف ﻋﺸﺎن ھﯿﻚ ﺳﻤﯿﻨﺎه ‪ negative‬ﻻﻧﻮ‬ ‫اﻟﻠﻲ ﻓﺸﻠﻦ ﺑﺎﻟﺘﻌﺮف ﻋﺎل ‪ self antigen‬ھﻢ اﻟﻠﻲ ﺣﯿﻌﯿﺸﻮا و اﻟﺒﻘﯿﺔ ﺣﯿﻤﻮﺗﻮا‬ ‫اﻟﻠﻲ ﺻﻔﻰ ﻣﻌﻨﺎ ھﻲ ‪ Tcell‬ﻋﻨﺪھﺎ ‪ TCR‬ﺷﻐﺎل و ﻋﻨﺪو ‪ intermediate affinity to MHC‬و ﻣﺎ ﺑﻘﺪر ﯾﺘﻌﺮف ﻋﺎل ‪self‬‬ ‫‪ antigen‬و طﺒﻌﺎ ‪CD4+&CD8+‬‬ ‫‪.4‬ھﺴﺎ ﺿﻞ ﻧﺤﺪد اﯾﺶ ﯾﺼﯿﺮ ﻧﻮع اﻟﺨﻠﯿﺔ ﻛﯿﻒ ﺑﻨﻌﻤﻞ ھﯿﻚ؟ ﺑﺎﻧﻮ ﻧﺨﻠﯿﮫ ﯾﻔﻘﺪ‬ ‫واﺣﺪ ﻣﻦ ال ‪) markers‬ﯾﺎ ‪ (CD4 or CD8‬و ﺑﻌﺪھﺎ ﺑﺘﺼﯿﺮ ﻋﻨﺎ‬ ‫)’‪Developed T cell (Th ‘CD4+’ or Tc’CD8+‬‬ T CELL DIFFERENTIATION IN THE THYMUS 2019-2020 Immunology 7105306 72  B CELL DEVELOPMENT IN THE BONE MARROW (bone marrow) ‫اﻟﺨﻄﻮات ھﻮن اﺑﺴﻂ ﻻﻧﮭﺎ ﺑﺘﺼﯿﺮ ﺑﻤﻜﺎن واﺣﺪ‬ reticular cells ‫ و ﺑﺘﺴﺎﻋﺪھﺎ ال‬B cell ‫ ل‬development ‫ ﺑﺼﯿﺮ‬.1 (5&6 ‫( )ﺧﻄﻮة‬T cell ‫ )ﺷﺒﮫ ال‬self antigen ‫ﺑﺎﻧﮫ ﻧﻌﺮض ال‬negative selection ‫ ﺑﺘﺨﻀﻊ ل‬.2 development ‫ رح ﺗﻜﻤﻞ‬selection ‫ اﻟﻠﻲ ﺑﺘﻀﻞ ﺑﻌﺪ ال‬.3 ‫ و ﺑﻌﺪھﺎ ﺑﺘﻄﻠﻊ ﻟﻠﺪم‬central sinus ‫ ﺑﺘﺘﻮﺟﮫ ﻋﺎل‬.4  ‫)‪2ND LYMPHOID ORGAN-LYMPH NODE (LN‬‬ ‫ھون ھﺎي اﻟرﺳﻣﺔ ﺑﺗورﺟﯾﻧﻲ ال‪lymph node‬‬ ‫ ‬ ‫ﺧﻠﯾﺔ اﻟـ ‪ t cell‬ﺣﻛﯾﻧﺎ ﺑﻌد ﻣﺎ ﺗﺧﻠص ﻣن اﻟـ ‪ bone marrow‬وﯾن ﺑﺗروح؟ ﻋﺎل‪ thymus‬ﺑﻌدھﺎ؟ ﺑﺗروح ﻋﻠﻰ اﻟـ‬ ‫ ‬ ‫‪lymph node‬‬ ‫ﺣﻛﯾﻧﺎ اﻟـ ‪ lymph node‬ﻓﯾﮭﺎ زي ﻏرف‬ ‫ ‬ ‫اﻟـ ‪ Secondary lymphoid organs‬ﻛﻠﮭم ھﯾك ﺑﻛون ﻓﯾﮭم زي ﻏرف وأﻣﺎﻛن‪ ،‬ﻓﯾﮫ أﻣﺎﻛن ﻟﻠـ ‪ ،t cells‬ﻓﯾﮫ أﻣﺎﻛن‬ ‫ ‬ ‫ﻟﻠـ ‪ ،b cell‬وﻓﯾﮫ أﻣﺎﻛن ﻣﺷﺗرﻛﺔ‬ ‫اﺣﻧﺎ ﺑﻧﻌرف ﻓﯾﮫ ﻋﻧﺎ اﻟـ‬ ‫‪afferent lymphatic‬‬ ‫‪ vessels‬اﻟﻲ ﺑدﺧﻠوا ﻣﻧﮭﺎ‬ ‫واﻟـ ‪efferent‬‬ ‫اﻟﺧﻼﯾﺎ‬ ‫‪lymphatic vessels‬‬ ‫اﻟﻲ ﺑﺧرﺟوا ﻣﻧﮭﺎ اﻟﺧﻼﯾﺎ‬ ‫ﻛل ‪ lymph node‬ﻓﯾﮫ اﻟﮭﺎ‬ ‫‪ artery‬و ‪ veins‬ﻣﺷﺎن ﺗزود‬ ‫ھذه اﻟﺧﻼﯾﺎ ﺑﺎﺣﺗﯾﺎﺟﺎﺗﮭﺎ وﺑﺎﻟﻣواد‬ ‫اﻟﻲ ﻻزﻣﺗﮭﺎ‬ 2ND LYMPHOID ORGAN-LYMPH NODE (LN) LNs => Small nodular ‫ﻣﻨﺘﺸﺮة ﻓﻲ ﻛﻞ اﻟﺠﺴﻢ‬ organ => Body => Lymphocyte activation Lymphocytes => Segregated in the distinct regions of LN The outer cortex => B cell zone (follicle) ‫ھﺎي ﺑﺘﻜﻮن ﻏﺮﻓﺔ ﺧﻼﯾﺎ ﺑﻲ‬ => Germinal Center (2nd follicle)=>B cell activation ‫ھﺎي اﻟﻤﻨﻄﻘﺔ اﻟﻲ ﺑﺘﺘﻔﻌﻞ ﻓﯿﮭﺎ ﺧﻼﯾﺎ ﺑﻲ‬ The inner region => T cell zone 2019-2020 Immunology 7105306 48  ‫‪LYMPH NODE (LN) SECTION‬‬ ‫ھون ﺑورﺟﯾﻧﺎ ﻛﻣﺎن ﻣرة اﻟـ‪Lymph node‬‬ ‫ھﺎي اﻟـ ‪secondary‬‬ ‫‪ follicle‬او اﻟﻲ ھﻲ ﻓﯾﮭﺎ‬ ‫‪ germinal center‬اﻟﻲ‬ ‫ھون ﺑورﺟﯾﻧﺎ اﻟـ‬ ‫ھو ال‪ site‬اﻟﻲ ﺑﺻﯾر ﻓﯾﮫ‬ ‫‪efferent‬‬ ‫‪ activation‬ﻟل‪b cell‬‬ ‫‪lymphatic‬‬ ‫ﻣﺷﺎن ﯾﺻﯾر ﻋﻧﺎ ﻓﯾﮭﺎ‬ ‫‪ vessel‬ﻣن ھون‬ ‫‪production‬‬ ‫ﺑﺗطﻠﻊ اﻟﺧﻼﯾﺎ‬ ‫ھون ﺑورﺟﯾﻧﺎ اﻟـ‬ ‫‪afferent lymphatic‬‬ ‫‪ vessel‬ﻣن ھون ﺑﺗدﺧل‬ ‫اﻟﺧﻼﯾﺎ‬ ‫ﺷو اﻟﻲ ﺑدﺧل اﻟﺧﻼﯾﺎ ﻋﻠﻰ اﻟﺧﻠﯾﺔ اﻟﻠﯾﻣﻔﯾﺔ وﺑطﻠﻌﮭﺎ؟ ﺑﻛون ﻓﯾﮫ ﻋﻧﺎ أﺷﯾﺎء ﺑﻌﻣﻠوﻟﮭﺎ‬ ‫زي ‪ homing‬او ‪ molecules‬ﺑﺗﺳﺎﻋد ﻋﻠﻰ اﻟﻣوﺿوع رح ﺗﺷوﻓو ﻛﻣﺎن ﺷوي‬ ‫‪2019-2020‬‬ ‫‪Immunology 7105306‬‬ ‫‪49‬‬ ‫‪STRUCTURE AND FUNCTION OF THE‬‬ ‫‪GERMINAL CENTER‬‬ ‫ھﺎي اﻟـ ‪ germinal center‬ﻣﻛﺑرھﺎ ھون‬ ‫‪ -2‬ھون ﻓﯾﮫ ‪ stages‬او ‪ steps‬ﻣﻌﯾﻧﺔ ﻻزم ﻧﻔﮭﻣﮭم وﻧﺣﻔظﮭم اﻟﻲ ھﻣﻲ اﻟـ ‪ somatic hypermutation‬ﺑﺻﯾر ﻋﻠﻰ اﻟـ ‪ receptor‬ﺑﻌد ﻣﺎ ﺗﺗﻔﻌل اﻟﺧﻠﯾﺔ زي‬ ‫ﺷوﯾﺔ ﺗﻐﯾﯾرات ﻋﻠﻰ ھذا اﻟـ ‪ receptor‬ﺑﺣﯾث ﺑﺗﺻﯾر اﻟـ ‪ affinity‬ﺗﺑﻌﺗﮫ اﻋﻠﻰ ﻟﻠـ ‪ anti bodies‬ﻣش ﻛﻧﺎ ﻧﺣﻛﻲ اﻧو ﺑﻛون ﻋﻧﺎ زي ﻛﺎﻧﮫ ‪ antibody‬ﺑﺗﻌرف‬ ‫ﻋﻠﻰ ﻣﺟﻣوﻋﺔ ﻣن اﻻﻧﺗﯾﺟﯾﻧﺎت اﻟﻲ ﺑﺗﻛون اﺷﻛﺎﻟﮭﺎ ﻣﺷﺗرﻛﺔ‬ ‫ﻓﻠﻣﺎ ﯾدﺧل ھذا اﻻﻧﺗﯾﺟﯾن وﺗﺗﻌرف ﻋﻠﯾﮫ اﻟـ ‪ b cell‬ﺑﺗﻧﺗﺞ اﻻﺟﺳﺎم اﻟﻣﺿﺎدة ﺑﺻﯾر ﻋﻧﺎ ﺗﻔﻌﯾل وﺗﻧﺷﯾط ﻟﺧﻠﯾﺔ ﺑﻲ‪ ،‬ﺑﺻﯾر ﺷوي ﺗﻐﯾﯾرات ﻋﻠﻰ اﻧﺗﺎج اﻻﺟﺳﺎم اﻟﻣﺿﺎدة‬ ‫ﺑﺣﯾث ﺑﺗﺻﯾر ‪ improvement‬ﻓﺎﻟﺧﻠﯾﺔ اﻟﻲ ﺑﺻﯾر ﻓﯾﮭﺎ ﺗﻐﯾﯾر ﻏﯾر ﻣرﻏوب ﻓﯾﮫ ﺑﺗﻣوت ﻟﻛن اﻟﺧﻠﯾﺔ اﻟﻲ ﺑﺻﯾر ﻓﯾﮭﺎ ‪ improvement‬ﺑﺗﻛﻣل ﺗطور ﻋﺷﺎن ﺗﻧﺗﺞ‬ ‫اﻟـ ‪plasma cells and memory cells‬‬ ‫‪ -1‬ھﺎي ‪ naïve t cell‬ﯾﻌﻧﻲ‬ ‫اﻟﺧﺎﻣﻠﺔ اﻟﻲ ﺑﺗﻛون‬ ‫‪ developed‬وﻣﻣﻛن ﺑﺳﮭوﻟﺔ‬ ‫ﯾﺻرﻟﮭﺎ ‪ activation‬ﯾﻌﻧﻲ ﺑس‬ ‫ﺑدھﺎ ‪ t cell‬ﺗﻌطﯾﮭﺎ إﺷﺎرة او‬ ‫ﺗﯾﺟﻲ ﺗﻛﺑس ﻋﻠﯾﮭﺎ ﻣﺷﺎن ﺗﺷﻐﻠﮭﺎ‬ ‫وﺑﺻﯾر ﻋﻧﺎ ‪clonal‬‬ ‫‪expansion‬‬ ‫‪2019-2020‬‬ ‫‪Immunology 7105306‬‬ ‫‪50‬‬  SPLEEN ‫ ﻟﻛن ﺑﺧﺗﻠف ﻣﯾن اﻻﻧﺗﯾﺟﯾن اﻟﻲ ﺑﻧودﯾﮫ ﻋﻠﯾﮭﺎ‬lymph node ‫ﻧﻔس ﻣﺑدأ اﻟـ‬ 1. The site of immune responses to blood Ags => A filter of blood 2. White pulp => T cell & B cell zones Marginal zone (MZ) Red pulp (RP) 3. T cells => periarteriolar lymphoid sheaths B cells => follicle => marginal zone ‫ﻣﻮزﻋﺎت ﻟﻐﺮف ﻧﻔﺲ‬ ‫اﻟﻤﺒﺪأ اﻟﻲ ﻗﺒﻞ‬ 2019-2020 Immunology 7105306 51 ‫)‪MUCOSA-ASSOCIATED LYMPHOID ORGANS (MALT‬‬ ‫طﺑﻌﺎ ھدول ﻛﻠﮭم ‪secondary lymphoid organs‬‬ ‫وزي ﻣﺎ ﺣﻛﯾﻧﺎ ﻋﻠﻰ اﻟرﺳﻣﺔ اﻟﻲ ﻓﻲ اﻟﺑداﯾﺔ ان ھﻧﺎك ﻓﯾﮫ ﻣﺎﯾﻛروﺑﺎت او‬ ‫اﻧﺗﯾﺟﯾﻧﺎت ﺑﺗﻛون ﻋﻠﻰ ‪ surface‬ﻣﻌﯾن ﺑدﻧﺎ اﺷﻲ ﻧﺗﻌﺎﻣل ﻣﻌﺎه ﻏﯾر اﻟـ‬ ‫‪ lymph nodes‬اﻟﻲ ذﻛرﻧﺎھم وﻏﯾر اﻟـ‪spleem‬‬ ‫ﻣﺛﻼ ﻓﻲ اﻟﻣﻧﺎطق اﻟﻲ ﻓﯾﮭﺎ ال ‪ mucos layer‬ﻓﯾﮫ ﻋﻧﺎ ﺧﻠﯾﺔ ﺑﻧﺳﻣﯾﮭﺎ اﻟـ‬ ‫‪ m cell‬ﺑﺗﻌﻣل ‪ engulfment‬ﻟﻼﺷﯾﺎء اﻟﻲ ﻓوﻗﯾﮭﺎ وﺑﺗدﺧل اﻻﻧﺗﯾﺟﯾﻧﺎت‬ ‫ﻟﻠﻣﻧطﻘﺔ اﻟزرﻗﺎء وﺑﺻﯾر ‪ phagocytosis‬واﻟﺧﻼﯾﺎ ﺗﺄﺧذھﺎ ﻟﻠـ‬ ‫‪ lymph node‬اﻟﻘرﯾﺑﺔ وﺑﺗﺗﻌﺎﻣل ﻣﻌﮭﺎ ﻣﺷﺎن اﻧو ﯾﺻﯾر ‪activation‬‬ ‫ﻟﻠﺧﻼﯾﺎ اﻟﻲ ﺑﺗﻌﻣل ‪ immune response‬وﺑﺗﺗﻌﺎﻣل ﻣﻊ اﻟـ ‪foreign‬‬ ‫‪ antigen‬اﻟﻲ دﺧل‬ ‫‪2019-2020‬‬ ‫‪Immunology 7105306‬‬ ‫‪52‬‬ ‫‪MIGRATION OF LYMPHOCYTES-I‬‬ ‫ھون ﺑده ﯾﺣﻛﯾﻠﻧﺎ ﺷوي ﻋن ال ‪ movements‬ﺗﺑﻌت اﻟﺧﻼﯾﺎ أو ﺷو ﯾﻠﻲ ﺑﺣرﻛﮭﺎ ‪ ،‬ﺑﺣﻛﯾﻠﻧﺎ ﻓﺎل ‪ lymphnodes‬ال‬ ‫‪naive lymphocytes‬ﺑﺗدﺧل ﻣن ﺧﻼل ‪ high endothelial venules‬ﺑﺗدﺧل ﻣن ﺧﻼل ال ‪rolling‬ﺑﻌدﯾن‬ ‫‪adhesion‬ﺑﻌدﯾن ﺑﺻﯾر ‪ transmigration‬ﺑﻌدﯾن ‪ cell to cell interaction‬ﻓﻲ ﻋﻧﺎ ﻣواد ﺑﺗﺳﺎﻋد ﻓﻲ ﻋﻣﻠﯾﺔ‬ ‫ال ‪homing ،‬ھون ﺑﺣﻛﯾﻠﻧﺎ ﻓﻲ ﻋﻧﺎ ‪ T cell homing receptor‬ﻟل ‪ naive T cell‬ﯾﻠﻲ ﺑدﺧل ال ‪ T CELL‬ﺑس ﺗطﻠﻊ‬ ‫ﻣن ال ‪ thymus‬وﺗروح ﻋﻠﻰ ال )‪ lymphnodes‬ﯾﻌﻧﻲ ھو ﯾﻠﻲ ﺑدﻟﮭﺎ وﯾن ﺗروح وﺑدﻟﮭﺎ وﯾن دارھﺎ 😂‬ ‫ﻓﻲ ﻋﻧﺎ‬ ‫‪L-selectin.1‬‬ ‫‪CCR7.2‬‬ ‫ھذول ﺑرﺑطو ﻋﻠﻰ ال ‪ endothelial cells‬ﻋن طرﯾق ال‬ ‫‪L selectin ligand.1‬‬ ‫‪CCL 19 and CCL 21.2‬‬ ‫ال ‪ function‬ﺗﺑﻌﺗﮭم ھﻲ ﺑﺎﻟﻣﺧﺗﺻر ﺑﺳﺎﻋدو‬ ‫ال ‪ T cell‬ﻟﺣﺗﻰ ﺗدﺧل ﻋﻠﻰ ال‪lymphnodes‬‬ ‫‪MIGRATION OF LYMPHOCYTES-I‬‬ ‫‪peripheral‬‬ ‫طﯾب ﻟﻣﺎ ﯾﺻﯾر ﻋﻧﺎ ‪ infection‬ﻓﺎل‬ ‫‪ tissues‬ﺷو ﺑﺧﻠﻲ اﻟﺧﻼﯾﺎ ﺗطﻠﻊ ﻣن‬ ‫ال ‪ lymphnodes‬وﺗروح ﻋﻠﻰ اﻻﻧﺳﺟﺔ ؟‬ ‫ﻓﻲ ﻋﻧﺎ ‪ molecules‬اﺧرى ﻣوﺟودة ﻋﻠﻰ ال ‪T cell‬‬ ‫وﯾﻠﻲ ھﻲ‬ ‫‪E- and P- selectin ligand.1‬‬ ‫‪LFA and VFA.2‬‬ ‫‪CXCR3.3‬‬ ‫‪CCR5.4‬‬ ‫ھذول ﺑرﺑطو ﻋﻠﻰ ھﺎي ال ‪)ligand‬اﻟﻣﺳﺗطﯾل‬ ‫اﻻﺣﻣر( اﻟﻣوﺟودة ﻋﻠﻰ ال ‪endothelial cells‬ﻣن‬ ‫ﺟوا ﻓﺑﺗدﺧﻠﮭﺎ ﻟل ‪site‬ﯾﻠﻲ ﻓﯾﮭﺎ ال ‪ infection ،‬وﻓﻲ‬ ‫ﻋﻧﺎ ال ‪ chemokines‬ﯾﻠﻲ ﺑﺗﻧﺗﺟﮭﺎ اﻟﺧﻼﯾﺎ ‪locally‬‬ ‫ﻣوﺟودة ﻓﺎل ‪ tissues‬ﻟﺣﺗﻰ ﺗﺳﺎﻋد ﻓﻲ ﻋﻣﻠﯾﺔ‬ ‫ال‪movement‬‬ MIGRATION OF LYMPHOCYTES-I 1. In LN, naïve lymphocytes ó HEVs Rolling => Adhesion => Transmigration Adhesion molecules for cell-cell interactions 2.In peripheral infection sites, effector lymphocytes ó blood vessels 2019-2020 53 Immunology 7105306  ‫‪MIGRATION OF LYMPHOCYTES-II‬‬ ‫ھﺎي اﻟرﺳﻣﺔ ﻣوﺿﺣﺔ اﻟﻣوﺿوع أﻛﺛر ‪ migration of lymphocytes‬ھون ﺑﺣﻛﯾﻠﻧﺎ ﻋن‬ ‫ال ‪ integrins‬وال ‪ selectins‬وﯾن ﺑﺗرﺑط وﻛﯾف دور ال ‪ chemokines‬ﻣن اﻟﺧﻼﯾﺎ ‪ ،‬أﻧﮫ ﻛﯾف‬ ‫ﺑﻌﻣل ‪ activation‬او ﺑﻛون اﻟﮫ دور ﻓﺎل ‪ movement‬اﺗطﻠﻊ ﻛﯾف ال ‪ rolling‬ﺑﺗﺻﯾر ﺗﺗدﺣرج‬ ‫ﺑﻌدﯾن اﻟﺧﻠﯾﺔ ﺑﺗﻣﺳك ﻓﯾﮭﺎ ‪ ,‬ﺑﺗﺗرﺑط أﻛﺛر ﺑﺎﻟﺧﻠﯾﺔ ﺑﻌدﯾن ﺑﺗﺻﯾر ال ‪ movement‬ﻟﺟوا ال ‪tissue‬‬ ‫وﺗروح ﻋﻠﻰ ال ‪ target‬ﯾﻠﻲ ﺑدﻧﺎ ﻧودﯾﮭﺎ ﻋﻠﯾﮫ‬ ‫‪2019-2020‬‬ ‫‪Immunology 7105306‬‬ ‫‪83‬‬ ACTIVATION OF LYMPHOCYTES ‫ ھو‬lymphocytes ‫ ﻟل‬activation ‫ھون ﺑدﻧﺎ ﻧوﺧذ ﻋن ال‬ antigen cell ‫ ﻣش ﺑس أﻧﮫ ال‬، ‫ﻣش اﺷﻲ ﺑﺑﺳﺎطﺔ ﺑﺻﯾر‬ ‫ وﺗﺣﻛﯾﻠﮭﺎ اﻋﻣﻠﻲ‬T cell ‫ ﺗورﺟﻲ ال‬presenting ‫ ال‬، ‫ اﺷﻲ ﺛﺎﻧﻲ‬second signal ‫ﻻ ﺑدھﺎ‬activation ، ‫ﻣﻣﻛن ﯾﻛون‬second signal antigen presenting cell ‫ ﻣن ﻧﻔس ال‬.1 cytokines ‫ ﻣن ﺧﻼﯾﺎ ﺛﺎﻧﯾﺔ ﺑﺗﻧﺗﺞ‬.2 ‫ ﺑدھﺎ‬T CELL ‫ ﯾﻌﻧﻲ ﻛﺄﻧﮫ ال‬signal ‫ﺑﺗﯾﺟﻲ ﺑﺗرﺑط وﺑﺗﻌﻣل‬ ‫ﺿرﺑﺗﯾن ﻟﺣﺗﻰ ﺗﺻﺣﻰ اﻟﺧﻠﯾﺔ‬ antigen ‫ اﻻوﻟﻰ ﺑﺗرﺑط ﻋﻠﻰ ال‬signal ‫ ال‬ B cell ‫ او‬T cell ‫ان ﻛﺎن‬receptor ‫ ﻣﻣﻛن ﻣن‬molecules ‫ ھﻲ‬second signal ‫ ال‬ costimmulatory ‫ او ﻣﻣﻛن‬innate immunity ‫ال‬ ‫ﯾﻌﻧﻲ‬lymphocytes ، ‫ ﻣوﺟودة ﻋﻠﻰ ال‬receptors ‫ او ﻓﻲ‬، ‫ ﺗﯾﺟﻲ ﺗﻌﻣل ھﯾك‬cytokines ‫