Presentation on theme: "Immunology Faculty of Medicine University Of Jordan DIL-1 18 Sep 2012"— Presentation transcript:
1 Immunology Faculty of Medicine University Of Jordan DIL-1 18 Sep 2012 Mohammed El-Khateeb
2 Outline Short History The Origin of Immune Concept Overview of Immunity to MicrobesFeaturesComponentsOrgansCellsMoleculesAdaptive ImmunityInnate Immunity
3 Historical Perspectives In ancient times, many serious infection diseases, such as smallpox, plague and cholera etc, caused inumerable people dead.
4 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 time15th centurry: Chinese andTurks use dried crusts ofsmallpox as ”vaccine”1798: Edward Jenner –smallpox vaccineIn 1670, Chinese medicalpractitioners : variolation
5 The Origin of Immune Concept-I The term “Immunity”Latin word “Immunitas” => Protection from legal prosecution (Roman senators)Biological definition => Protection from infectious diseases2. The concept of immunity existed in ancient Greek & Chinese => the experienced viewThe medical view of immunity => Edward Jenner (1796)Observation => Milkmaids generally get No SmallpoxHypothesis => Pus from vaccinia (cowpox)=> Protect milkmaids from smallpoxTest Inoculate materials from cowpox pusProtect a young boy from smallpox(Protective immunity)Vaccinia Vaccination (also called Immunization)
6 The first vaccination against smallpox Table 1-2. Features of Innate and Adaptive ImmunityTable 1-2. Features of Innate and Adaptive ImmunityThe first vaccination against smallpoxExudate 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 smallpoxThis table lists the major characteristics and components of innate and adaptive immune responses. Innate immunity is discussed in much more detail in Chapter 2.Adopted from
7 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 tolerance1953-Medawar set up animal model of acquired immune tolerance in newborn period.
9 The Origin of Immune Concept-II 4. The concept of “Immunity” developed gradually over time through many scientific findings:=> Robert Koch (1905 Nobel Laureate) => Infectiousdiseases 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”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 Humoral Or Cellular Immunity? Pasteur Did Not Know How Vaccination WorkedBehring and Kitasato (1890) Proposed Serum Was Responsible For ImmunityElvin Kabat (1930), gamma-globulin, AntibodyAntibodies Were Present in Body Fluids=HumorTherefore: Humoral Immunity
12 Immunology HistorySince 1901 there have been 19 Nobel Prizes for immunological research.Examples: Discovery of human blood groups (1930) and Transplantation immunology(1991)
13 Key concepts about immunity-I 1. The immune system has evolved to (1) Protect against theinvading pathogens (or foreign substances) and to(2) Maintain tissue homeostasis (damaged cells or cancer).Meanwhile, microbes (outside) and tumors (inside) have evolved tosurvive in the host.2. The immune system (in vertebrates) consists of (1) Innateimmunity and (2) Adaptive immunity=> An integrated system of host defense=> Cells & molecules function cooperativelyAntigen-presenting cells => Lymphocytes => Effector cells3. 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
14 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 infection6. The immune system may fail => Immunodeficiency,Hypersensitivity, & Autoimmune diseases.7. Normal immune responses can be obstacles in medicalcases, e.g., organ transplantationBetter Understanding of ImmunologyHelp manipulate immune responsesSolve the medical problems
15 THE IMMUNE SYSTEMThe immune system includes:Tissues,CellsMolecules
18 Lymphoid System Primary lymphoid organs Secondary lymphoid organs Bone marrowThymusGeneration & DevelopmentSecondary lymphoid organsOrganizedLymph nodesSpleenLess organized; MALT: GALT&BALTInitiation of the adaptive immune responsePrimary role is generation of specific immune responses.All connected to blood and lymph circulation.All have defined structure (B cell zones, T cell zones...)
19 Bone marrow Structure Function Microscopic Hematopoiesis Less well defined than thymusRole of stromal cellsFunctionHematopoiesisB cell maturationB cell selectionPuts out mature, naive B cells
20 B cell development Stem cell B cell in Bone marrow (fetal liver) Delete self reactive B cells generated by accident.Stem cell B cell in Bone marrow (fetal liver)+5-15% of the circulating lymphoid pool+Defined by the presence of surface immunoglobulin (BCR).+BCR associated with two accessory molecules CD79a and CD79b.
21 Thymus Structure Gross Microscopic Bi-lobed Lies above heart Capsular Lobules with outer cortex and inner medulla
23 T-CELL DEVELOPMENT +Stem cell T cell in Thymus +Delete self reactive TcR generated by accident.+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-
24 ThymusFunctionTakes in immature T cells and puts out mature (immunocompetent) T cellsIncreased diversity of T cellsT cell selection
25 Thymus T cell selection Athymic condition Based on MHC/Ag complex recognitionRecognize MHC/Non self AG complexesRecognize MHC/Self Ag complexesDo not recognize MHC/Ag complexesAthymic conditionNaturalOther
26 Lymph Nodes Structure Gross Bean-shaped structures Drains major segments of lymphatic system
31 High Endothelial Venules HEVBlood enters lymph node via the artery Post capillary venules in the paracortex have cuboidal endothelial cellsHIGH ENDOTHELIAL VENULES - specialised properties to allow lymphocytes and nothing else into the lymph node
32 Recirculation Non-lymphoid cells Lymphoid cells Pass through the blood vessels in the lymph node and continue arterio-venous circulationHEVLymphoid cellsAdhere to and squeeze between High Endothelial Venules (HEV), then percolate through the lymph node and exit via the efferent lymphatic vesselHEV
33 Lymphocyte recirculation NAÏVE CELLSMEMORY CELLSCells & antigens from a site of infectionare trapped in draining lymph node.Cells proliferate and re-enter theRECIRCULATING LYMPHOCYTE POOLto re-seed the peripheral lymphoid organsCells enter blood, are seeded to the peripheral lymphoid organs via arterial circulationand return via lymphatics
34 Lymph Nodes Function 1st line of response to antigens Secondary follicle (Germinal center) is site of B cell proliferation, differentiationSpecificity is high>90% of B cells die through apoptosisAfter Ag stimualtion lymphocyte numbers up by 50X in efferent lymphatic vesselLymphadenopathy
35 Tonsils Follicular structure Contains lymphocytes, macrophages, mast cellsGerminal centers appear in response to AgProtective role in URI
36 Appendix Associated with intestines Responds to Ag Role in GI immune response
37 MALT Lymphoid tissues below epithelium Presence of B cells Ag presented through unique cell (M cell)Preferentially responds with IgA antibodyVilliGC
38 Spleen Structure Gross Microscopic Ovoid organ in upper left quadrant of abdomenMicroscopicCompartmentalizedRed pulpWhite pulpPeriarticualr lymphoid sheathSite of Ag presentationMajor cell typesLymphocytesMacrophagesDendritic cellsRBCs
39 Spleen Primary follicle Central arteriole Red pulp Periarteriolar lymphocytic sheathGerminal centreMarginal zoneSecondary follicleTrabecularartery
40 Central arteriolePeriarteriolarlymphocytic sheathMarginal zoneVenous sinusTrabeculaeGerminal centre
47 Neutrophils 60-70% of WBCs Multi-lobed nucleus Granulated cytoplasm Life span is 2-3daysProminent in inflammatory responseLeukocytosis is marker for infectious processActively phagocytic
48 Eosinophils ~2% of WBCs Bi-lobed nucleus Granulated cytoplasm Stains with acid dye (eosin)Prominent in response to parasitic infectionsPhagocytic
49 Basophils <1% of WBCs Lobed nucleus Heavily granulated cytoplasm Stains with basic dyeProminent in allergic responsesNon-phagocytic
50 Monocytes and Macrophages Large WBCsMonocytes are circulatingprecursorsMacrophagesPhagocytic“Fixed” throughout the body, e.g. Liver (Kupffer)Activated by cytokines and gamma interferonAPCSecretes numerous immune response factors
51 Macrophage Different names in different tissues Monocyte (blood) Kupffer cells (liver)Mesangial cells (kidney glomerulus)Microglia (brain)Alveolar macrophages (lung)Histiocyte (connective tissue)
56 Lymphocytes ~30-40% of WBCs T Lymphocytes Mature in thymus Have TCRs Recognize Ag on cells onlyTwo subpopulations:Helper/Inducer (CD4)Suppressor (CD8)
57 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
58 Natural Killer Cells Detected for anti-tumor activity Lack T and B cell markersLack Ag receptorsInvolved with Ab-dependent cell-mediated cytotoxicity
59 How do you tell different cell types apart? 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.
60 Key CD Ags to remember CD3 on all T cells, NO B cells. CD1 present on developing thymocytes but not on T cellsAmong T cells there are two main sub-groups:CD4 “helper T cell”CD8 cytotoxic T cellCD19 and 20 are on B cells but not T cells.CD56 is on NK cells but not other types of lymphocytes.
Your consent to our cookies if you continue to use this website.