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Presentation on theme: "Immunology FACULTY OF MEDICINE UNIVERSITY OF JORDAN DIL-1 18 SEP 2012 MOHAMMED EL-KHATEEB."— Presentation transcript:



3 Outline Short History The Origin of Immune Concept Overview of Immunity to Microbes Features Components Organs Cells Molecules Adaptive Immunity Innate Immunity

4 Historical Perspectives In ancient times, many serious infection diseases, such as smallpox, plague and cholera etc, caused inumerable people dead.

5 A Short History of Immunology ~ 430 B.C: Thucydides describes plague – the ones who had recovered from the disease could nurse the sick without getting the disease a second time 15th centurry: Chinese and Turks use dried crusts of smallpox as vaccine 1798: Edward Jenner – smallpox vaccine In 1670, Chinese medical practitioners : variolation

6 The Origin of Immune Concept-I 1.The term Immunity Latin word Immunitas => Protection from legal prosecution (Roman senators) Biological definition => Protection from infectious diseases 2.The concept of immunity existed in ancient Greek & Chinese => the experienced view 3.The medical view of immunity => Edward Jenner (1796) Observation => Milkmaids generally get No Smallpox Hypothesis => Pus from vaccinia (cowpox) => Protect milkmaids from smallpox Test Inoculate materials from cowpox pus Protect a young boy from smallpox (Protective immunity) Vaccinia Vaccination (also called Immunization)

7 Table 1-2.Features of Innate and Adaptive ImmunityTable 1-2.Features of Innate and Adaptive Immunity Table 1-2.Features of Innate and Adaptive ImmunityTable 1-2.Features of Innate and Adaptive Immunity This table lists the major characteristics and components of innate and adaptive immune responses.Innate immunity is discussed in much more detailin Chapter 2.This table lists the major characteristics and components of innate and adaptive immune responses.Innate immunity is discussed in much more detailin Chapter 2. The first vaccination against smallpox Adopted from Exudate from a cowpox pustule on the hand of milkmaid Nelmes was injected into scratches on the arms of 8 years old Sarah James Phipps, May 14, Follwed by exposure to smallpox

8 Historical Events in Immunology 1881-Loius Pasteur (vaccines) 1884-Elie Metchnikoff (phagocytes) 1890-Emil von Behring* (antibodies) 1895-Jules Bordet* (complement) 1906-August Wasserman (syphilis) 1945-Owen found natural immune tolerance 1953-Medawar set up animal model of acquired immune tolerance in newborn period.

9 Historical Events in Immunology (contd) 1959-Rodney Porter Gerald Edelman* (antibodies) 1960-F McFarlane Burnet* (tolerance) 1975-Cesar Milstein*(monoclonal Ab) Jean Dauset immunogenetics 1987-Susumu Tonegawa* (genetics) 1996-Peter Doherty Rolf Zinkernagel* (MHC)

10 The Origin of Immune Concept-II 4.The concept of Immunity developed gradually over time through many scientific findings: => Robert Koch (1905 Nobel Laureate) => Infectious diseases caused by microorganisms => Louis Pasteur => Vaccines against cholera & rabies => These clinical successes => The search of underlying mechanism of Protection of Infectious Diseases => The development of Immunology 5.Advances in technology (e.g., Cell culture, Monoclonal Ab, Flow cytometry, Genetic engineering…etc) have facilitated our understanding of the immune system and its functions. Descriptive Science => Experimental Science

11 Edward Jenner Eradication of smallpox

12 Humoral Or Cellular Immunity? Pasteur Did Not Know How Vaccination Worked Behring and Kitasato (1890) Proposed Serum Was Responsible For Immunity Elvin Kabat (1930), gamma-globulin, Antibody Antibodies Were Present in Body Fluids=Humor Therefore: Humoral Immunity

13 Immunology History Since 1901 there have been 19 Nobel Prizes for immunological research. Examples: Discovery of human blood groups (1930) and Transplantation immunology(1991)

14 Key concepts about immunity-I 1. The immune system has evolved to (1) Protect against the invading pathogens (or foreign substances) and to (2) Maintain tissue homeostasis (damaged cells or cancer). Meanwhile, microbes (outside) and tumors (inside) have evolved to survive in the host. 2. The immune system (in vertebrates) consists of (1) Innate immunity and (2) Adaptive immunity => An integrated system of host defense => Cells & molecules function cooperatively Antigen-presenting cells => Lymphocytes => Effector cells 3. Innate immunity is evolutionally the more conserved host defense system: - Existed in both Invertebrates & Vertebrates - Provides the first line of defenses against infections - Activates and Programs adaptive immune responses

15 Key concepts about immunity-II 5. Adaptive immunity evolved later: - Existed only in Vertebrates - Provides the more potent and diverse defenses against infections - Develops as a response to infection and adapts to the infection 6. The immune system may fail => Immunodeficiency, Hypersensitivity, & Autoimmune diseases. 7. Normal immune responses can be obstacles in medical cases, e.g., organ transplantation Better Understanding of Immunology Help manipulate immune responses Solve the medical problems

16 THE IMMUNE SYSTEM The immune system includes: Tissues, Cells Molecules

17 Organs of the Immune System

18 The lymph system and sites of lymphoid tissue

19 Lymphoid System Primary lymphoid organs Bone marrow Thymus Generation & Development Secondary lymphoid organs Organized Lymph nodes Spleen Less organized; MALT: GALT&BALT Initiation of the adaptive immune response Primary role is generation of specific immune responses. All connected to blood and lymph circulation. All have defined structure (B cell zones, T cell zones...)

20 Bone marrow Structure Microscopic Less well defined than thymus Role of stromal cells Function Hematopoiesis B cell maturation B cell selection Puts out mature, naive B cells

21 Stem cell B cell in Bone marrow (fetal liver) B cell development Delete self reactive B cells generated by accident % of the circulating lymphoid pool +Defined by the presence of surface immunoglobulin (BCR). +BCR associated with two accessory molecules CD79a and CD79b.

22 Thymus Structure Gross Bi-lobed Lies above heart Microscopic Capsular Lobules with outer cortex and inner medulla


24 + Delete self reactive TcR generated by accident. T-CELL DEVELOPMENT +Stem cell T cell in Thymus +TCR ab (90-95%)or gd (5-15%) T helper (CD4)>>>Th1 or Th2 (cytokine profiles) T cytotoxic Tc (CD8) Most of circulating gd T cells are double negative CD4-8-

25 Thymus Function Takes in immature T cells and puts out mature (immunocompetent) T cells Increased diversity of T cells T cell selection

26 Thymus T cell selection Based on MHC/Ag complex recognition Recognize MHC/Non self AG complexes Recognize MHC/Self Ag complexes Do not recognize MHC/Ag complexes Athymic condition Natural Other

27 Lymph Nodes Structure Gross Bean-shaped structures Drains major segments of lymphatic system


29 Lymph Nodes Structure Microscopic Major cell types Lymphocytes Macrophages Dendritic cells Cortex/paracortex/medulla Follicles Primary Secondary

30 5. Medullary cords (Macrophage & plasma cell area) Medullary sinus 6. Efferent lymphatic vessel Artery Vein 4. Germinal centre (site of intense B cell proliferation) 3. Secondary lymphoid follicle Paracortical (T cell) area 2. Primary Lymphoid follicle (B cell area) 1. Afferent lymphatic vessel. Lymph, Ag, & cells with captured Ag drained from tissues enters here Lymph node

31 Paracortex Cortex Germinal centre Marginal zone Subcapsular zone Lymphoid follicle /nodule

32 HEV Blood enters lymph node via the artery Post capillary venules in the paracortex have cuboidal endothelial cells HIGH ENDOTHELIAL VENULES - specialised properties to allow lymphocytes and nothing else into the lymph node High Endothelial Venules

33 Non-lymphoid cells Pass through the blood vessels in the lymph node and continue arterio-venous circulation Recirculation HEV Lymphoid cells Adhere to and squeeze between High Endothelial Venules (HEV), then percolate through the lymph node and exit via the efferent lymphatic vessel

34 Lymphocyte recirculation Cells enter blood, are seeded to the peripheral lymphoid organs via arterial circulation and return via lymphatics Cells & antigens from a site of infection are trapped in draining lymph node. Cells proliferate and re-enter the RECIRCULATING LYMPHOCYTE POOL to re-seed the peripheral lymphoid organs NAÏVE CELLS MEMORY CELLS

35 Lymph Nodes Function 1 st line of response to antigens Secondary follicle (Germinal center) is site of B cell proliferation, differentiation Specificity is high >90% of B cells die through apoptosis After Ag stimualtion lymphocyte numbers up by 50X in efferent lymphatic vessel Lymphadenopathy

36 Tonsils Follicular structure Contains lymphocytes, macrophages, mast cells Germinal centers appear in response to Ag Protective role in URI

37 Appendix Associated with intestines Responds to Ag Role in GI immune response

38 MALT Lymphoid tissues below epithelium Presence of B cells Ag presented through unique cell (M cell) Preferentially responds with IgA antibody GC Villi

39 Spleen Structure Gross 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

40 Spleen Red pulp Primary follicle Central arteriole Periarteriolar lymphocytic sheath Germinal centre Marginal zone Secondary follicle Trabecular artery

41 Central arteriole Periarteriolar lymphocytic sheath Germinal centre Trabeculae Venous sinus Marginal zone


43 Spleen Function Filters out older RBCs Responds to Ag in circulatory system Produces activated B cells Splenectomy

44 Cells of the Immune System


46 Myeloid Lineage Granulocytes Eosinophils Basophils Megakaryocytes Erythrocytes Dendritic cells

47 Lymphoid Lineage T Lymphocytes B Lymphocytes Natural Killer Cells

48 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 Actively phagocytic

49 Eosinophils ~2% of WBCs Bi-lobed nucleus Granulated cytoplasm Stains with acid dye (eosin) Prominent in response to parasitic infections Phagocytic

50 Basophils <1% of WBCs Lobed nucleus Heavily granulated cytoplasm Stains with basic dye Prominent in allergic responses Non-phagocytic

51 Monocytes and Macrophages Large WBCs Monocytes are circulating precursors Macrophages Phagocytic Fixed throughout the body, e.g. Liver (Kupffer) Activated by cytokines and gamma interferon APC Secretes numerous immune response factors

52 Macrophage Different names in different tissues Monocyte (blood) Kupffer cells (liver) Mesangial cells (kidney glomerulus) Microglia (brain) Alveolar macrophages (lung) Histiocyte (connective tissue)

53 Some Factors Secreted by Activated Macrophages

54 Mast Cells Found in many different tissues Contains granules which release histamine Play role in allergic reactions

55 Dendritic Cells Have long dendrites Major role as APC Stimulated by innate response Have co-stimulatory molecules constitutively Have constitutive MHC II expression Phagocytic and endocytic


57 Lymphocytes ~30-40% of WBCs T Lymphocytes Mature in thymus Have TCRs Recognize Ag on cells only Two subpopulations: Helper/Inducer (CD4) Suppressor (CD8)

58 Lymphocytes B Lymphocytes Mature in bone marrow Have membrane-bound Ab(~10,000 per cell) Go from naive to activated. Plasma cells are Ab secretors ~1-2 week life span

59 Natural Killer Cells Detected for anti-tumor activity Lack T and B cell markers Lack Ag receptors Involved with Ab-dependent cell-mediated cytotoxicity

60 Physical appearance: Lymphocytes small, granulocyte larger with granules that stain in different ways with dyes used in lab. (Differential cell count) CD Ag system: over 250 cell surface proteins distinguished with Abs used as a diagnostic tool. Allows us to positively identify different cell types, function, state of activation. How do you tell different cell types apart?

61 CD3 on all T cells, NO B cells. CD1 present on developing thymocytes but not on T cells Among T cells there are two main sub-groups: CD4 helper T cell CD8 cytotoxic T cell CD19 and 20 are on B cells but not T cells. CD56 is on NK cells but not other types of lymphocytes. Key CD Ags to remember


63 T-Cell Products, Interleukines, Lymphokines Interferons B- Cell Products Antobodies (imunoglobulines) Macrophage Productes

64 INNATE IMMUNITY PHYSICAL BARRIERS Skin, mucous membrane CELLS granulocytes, monocytes, macrophages CHEMICAL BARRIERS pH, lipids, enzymes ACQUIRED IMMUNITY HUMORAL B cells antibodies CELL MEDIATED T cells lymphokines MP


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