Organization of the immune system


Published on

Immune system, lymphoid organs

1 Comment
1 Like
  • I think , there's something wrong with this Powerpoint. Pls check
    Are you sure you want to  Yes  No
    Your message goes here
No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

Organization of the immune system

  1. 1. ORGANIZATION OF THE IMMUNE SYSTEM DR. SUFI H. Z. RAHMAN MBBS, MD (Immunology) Lecturer, Medical Faculty, AUCMS
  2. 2. Objectives ◆Identify the major components of the lymphatic system (organs, cells and vessels) and explain their functions ◆List the primary and secondary lymphoid organs ◆Discuss the development of lymphoid organs in brief ◆Explain the functions of the immune system
  3. 3. Introduction There is a huge number of microorganisms in our environment that can infect us, but we are remaining uninfected How are we defending them? Our immune system defends these organisms and provides immunity to infection
  4. 4. Introduction Immunity State of protection from infections or resistance to infections Immune system Collections of cells, tissues and molecules that mediate resistance to infections Immune response The coordinated reaction of cells and molecules to eliminate the invading organisms
  5. 5. Major components of the Immune System ◆Lymphoid organs • Primary or central • Secondary or peripheral ◆Lymphatic vessels ◆Cells • Lymphocytes • Antigen presenting cells • Other leukocytes ◆Molecules • Antibody • Complement • Cytokines
  6. 6. Primary or Central Lymphoid Organs ◆These organs are the sites of maturation of lymphocytes before they encounter any antigen ◆Primary or central lymphoid organs include 1. Bone marrow 2. Thymus ◆During their maturation in these organs lymphocytes • Acquire phenotypic features • Become self tolerant • Acquire clonal diversity • Become capable of recognizing and responding to specific foreign antigen (become immunocompetent)
  7. 7. Secondary or Peripheral Lymphoid Organs ◆These organs are the sites of interaction of mature lymphocytes with antigens and antigen presenting cells (APCs) ◆Mature lymphocytes from circulation migrate and reside in these organs ◆Microorganisms and APCs carrying microbial or tumour antigens also migrate to these organs through blood or lymph ◆Lymphocytes, antigens and APCs come in close proximity and can interact in these organs
  8. 8. Secondary or Peripheral Lymphoid Organs ◆These organs also bring different types of lymphocytes (helper T cells, cytotoxic T cells and B cells) in close proximity ◆This close proximity of different types of lymphocytes optimizes their interaction with each other by direct contact or by cytokines ◆Interaction between different lymphocytes generates effective immune response
  9. 9. Secondary or peripheral lymphoid organs include 1. Lymph nodes 2. Spleen 3. Mucosa associated lymphoid tissue (MALT) • Tonsils • Peyer’s patches • Lymphocytes in the mucosa of GIT, Respiratory and Urinary tract 1. Cutaneous associated lymphoid tissue (CALT) Secondary or Peripheral Lymphoid Organs CALT is some times called tertiary lymphoid organ
  10. 10. Lymphoid Organs
  11. 11. T helper cell Lymphocytes in Lymphoid Organs
  12. 12. Bone Marrow Primary Lymphoid Organs Found in the medullary cavity of compact bones and interstices of spongy bone Consists of haematopoitic and stromal tissue Stromal tissue support maturation of cells by providing growth factors and cytokines
  13. 13. Bone Marrow ◆Site of haematopoisis ◆Site of maturation of B cells ◆B cells rearrange their immunoglonulin gene segments to generate clonal diversity ◆Acquire B cell receptors for antigen recognition (mIgM) ◆Self-reactive B cells undergo apoptosis (clonal deletion) ◆B cells that are not self reactive enter circulation Primary Lymphoid Organs
  14. 14. Thymus Primary Lymphoid Organs ◆It is a flat, bi-lobed organ situated above the heart ◆At birth it weighs 10- 15 gm ◆Its size increases up to puberty (30- 40 gm) ◆Subsequently its size reduces and much of the organ is replaced by fat ◆Each lobe is surrounded by a connective tissue capsule that sends trabeculae inside and divide it in to lobules
  15. 15. Thymus ◆Each lobule is organized into •Outer cortex: Densely packed with maturing T cells called thymocytes •Inner medulla: Sparsely populated with thymocytes ◆Both the cortex and medulla are crisscrossed by a stromal- cell network consisting of thymic epithelial cells, dendritic cells, and macrophages ◆Site of maturation of T cells Primary Lymphoid Organs
  16. 16. Thymus ◆Progenitor T cells (pro T cells) migrate to thymus from bone marrow to mature in its microenvironment ◆During their maturation in the thymus, maturing T cells • Rearrange their T cell receptor (TCR) gene segments to generate clonal diversity • Acquire TCRs and surface CD molecules (CD4 or CD8) • Undergo positive selection that result in self MHC restriction • Undergo negative selection that result in self tolerance • Positive and negative selection is called thymic education ◆Mature T cells with TCRs that are not self reactive enter circulation and migrate to secondary lymphoid organs Primary Lymphoid Organs CD= Cluster of differentiation
  17. 17. Secondary Lymphoid Organs ◆In the normal immune system, there are very few lymphocytes (T and B) specific for any one antigen ◆Anatomic organization of peripheral lymphoid organs enable the APCs to concentrate antigens in these organs so that the specific lymphocyte clone can locate and respond to the antigen
  18. 18. Lymph nodes ◆Lymph nodes are nodular aggregates of lymphoid tissues located along lymphatic channels throughout the body ◆Fluid (lymph) from epithelia, connective tissue and most parenchymal organs is drained by lymphatic channels to lymph nodes Secondary Lymphoid Organs
  19. 19. Lymph nodes ◆Encapsulated bean (or kidney) shaped structures containing a reticular network packed with lymphocytes and APCs ◆Morphologically, a lymph node can be divided into three roughly concentric regions •Cortex: Rich in B cells, also contains macrophages and dendritic cells •Paracortex: Rich in T cells, also contains macrophages and dendritic cells •Medulla: Contains T cells, B cells and Plasma cells Secondary Lymphoid Organs
  20. 20. Lymph nodes ◆Lymph enter into the lymph nodes through afferent lymphatic vessels and exit through the efferent lymphatic vessel ◆Microorganisms carried in lymph come in contact with lymphocytes and APCs while passing through the lymph nodes ◆In addition, APCs can pick up microbes from tissue and parenchymal organs and transport them to the lymph nodes through lymphatic channels ◆Antigens that enter through tissue and parenchymal organs interact with lymphocytes in the lymph nodes and induce immune response Secondary Lymphoid Organs
  21. 21. Spleen Secondary Lymphoid Organs ◆A large lymphoid organ ◆Situated in the upper part of the left side of the abdominal cavity ◆The whole organ is covered by peritoneum except the hilum ◆Splenic artery enters and splenic vein exits through the hilum
  22. 22. Spleen •Red pulp: Network of sinusoids, populated with macrophages, numerous red blood cells and a few lymphocytes •White pulp: Surrounds the branches of the splenic artery, forming periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes • Primary lymphoid follicles: Attached to PALS rich in B cells • Marginal zone: Peripheral to PALS contain Lymphocytes and macrophages Secondary Lymphoid Organs It is surrounded by connective tissue capsule that sends trabeculae inside and divide it in to compartments
  23. 23. Spleen Secondary Lymphoid Organs ◆Largest secondary lymphoid organ ◆More recirculating lymphocytes pass through the spleen daily than all lymph nodes combined ◆Blood borne microorganisms enter spleen, interact with APCs and lymphocytes and induce immune response ◆Site of clearance of immune complexes
  24. 24. Mucosa Associated Lymphoid Tissue (MALT) ◆Group of lymphoid tissues located under the epithelium of the gastrointestinal, respiratory and urogenital systems ◆Their structure ranges from loose, barely organized clusters of lymphoid cells in the mucosa (e.g. in lamina propria) to well organized structures like • Tonsils • Peyer’s patches ◆Majority of the lymphocyte in MALT are memory cells Secondary Lymphoid Organs
  25. 25. Tonsils ◆Palatine, nasopharyngeal, lingual and tubal tonsils form Waldeyer’s ring at the site of entry of pathogens through digestive and respiratory tracts ◆Contain lymphocytes, macrophages and plasma cells Secondary Lymphoid Organs
  26. 26. Peyer’s patches ◆Present in the submucosal layer of the ilium beneath the lamina propria ◆These are nodules of 30–40 lymphoid follicles ◆Lamina propria of the intestine also contains lymphocytes, plasma cells and macrophages Secondary Lymphoid Organs
  27. 27. Cutaneous associated lymphoid tissue (CALT) Collection of lymphocytes under the epithelium of skin Majority are memory cells These are the sites of immune responses to antigens that breach the epithelium of skin Secondary Lymphoid Organs At any time, more than half of the body’s lymphocytes are in the MALT and CALT reflecting their large size
  28. 28. Lymphatic Vessels ◆The lymphatic system is a part of the circulatory system ◆It comprises a network of lymphatic vessels that carry a clear fluid called lymph unidirectionally toward the heart ◆Blood does not directly come in contact with the tissue cells ◆Constituents of the blood exit the microvascular exchange blood vessels (capillaries) to become interstitial fluid, which comes into contact with the tissue cells ◆Lymph returns excess protein and excess interstitial fluid to the circulation ◆Lymph also transports fats from the digestive system
  29. 29. Lymphatic Vessels ◆Lymphatic vessels from tissue drain to the regional lymph nodes through afferent lymphatic vessels ◆Efferent lymphatic vessels from these nodes drain into another group of lymph nodes
  30. 30. Lymphatic Vessels ◆Efferent lymphatic vessels form lymphatic trunks that ultimately drain into lymphatic ducts (thoracic duct on the left and right lymphatic duct on the right side) ◆Thoracic duct and right lymphatic duct drain into the internal jugular veins at their junction with subclavian veins ◆Thereby it carries fluid from tissue to the blood circulation
  31. 31. Lymphatic Vessels ◆Lymph may pick up microorganisms and cancer cells from tissue and parenchymal organs, bring them to lymph nodes where they come in contact with APCs and lymphocytes and induce immune response ◆Macrophages, dendritic cells and lymphocytes that migrate to tissues can also return back to circulation through lymphatic vessels ◆So lymphatic system is an important part of the immune system
  32. 32. Lymphocyte Recirculation Lymphocytes are recirculating cells that migrate to secondary lymphoid organs in search of antigens If they do not encounter antigen, they can come back to the circulation again
  33. 33. Cells of the Immune System ◆Cells of the immune system are generated in the bone marrow ◆The process of generation is called haematopoisis ◆The microenvironment of the bone marrow stroma support cell generation and maturation ◆From bone marrow the cells are released into the circulation
  34. 34. Cells of the Immune System Functionally cells of the Immune System can be classified as 1. Immunocompetent cells 2. Antigen presenting cells 3. Effector cells
  35. 35. Cells of the Immune System ◆Capable of recognizing specific antigens and providing immune response to that particular antigen ◆These cells possess 4 attributes of adaptive immunity 1. Antigenic specificity 2. Diversity 3. Immunological memory 4. Self/ non-self recognition ◆Only mature T and B lymphocytes have these characteristic attributes and are called ICC Immunocopmpetent cells (ICC)
  36. 36. Cells of the Immune System Immunocopmpetent cells TH= T Helper, TC= T Cytotoxic
  37. 37. Cells of the Immune System ◆Constitute 40- 60% of circulating WBC population ◆Only cells that bear specific receptors for antigens ◆All lymphocytes are morphologically similar but they differ in lineage, function and phenotype (e.g. CD molecules) ◆Lymphocyte population can be classified as • B lymphocytes • T lymphocytes • Natural Killer (NK) cells Lymphocytes CD= Cluster of Differentiation NK cells do not bear specific receptors for antigen
  38. 38. Cells of the Immune System ◆Mature in bone marrow ◆Constitute 30- 40% of circulating lymphocytes ◆Express membrane bound antibodies or immunoglobulins (mIg) on their surface that serve as receptors for antigen recognition ◆Other important surface markers include: Class I and II MHC molecules, CD20, CD21 (CRII) , CD35 (CRI), CD40, CD45, CD80 (B7.1), CD86 (B7.2) B lymphocytes CR= Complement Receptor
  39. 39. Cells of the Immune System ◆Express B cell receptors (mIg) by which they can recognize soluble or free antigens in circulation or tissue ◆They can recognize antigens that are chemically protein, polysaccharide, nucleic acid or phospholipid in nature ◆Upon activation they differentiate to plasma cells and memory B cells ◆Plasma cells secrete antibodies specific for the inciting antigen ◆Antibodies are effector molecules that eliminate the invader ◆Provide humoral immunity B lymphocytes
  40. 40. Cells of the Immune System ◆Mature in the thymus ◆Constitute 60- 70% of the circulating lymphocytes ◆Express T cell receptors (TCRs) on their surface for recognition of specific antigen ◆Other important surface markers include Class I MHC molecule, CD3, CD4/ CD8, CD28, CD40L, CD45 ◆TCRs can recognize antigens only if it is presented on the surface of APCs by self MHC molecule (self MHC restricted) ◆Can recognize only protein antigens ◆ Provide cell mediated immunity (CMI) ◆Regulate Humoral Immunity and CMI T lymphocytes
  41. 41. Cells of the Immune System Functionally there are 3 subpopulations of T cells Helper T (TH) lymphocytes CD4+ T cells, recognize antigen presented by APCs with Class II MHC Kill cells harbouring intracellular pathogens by macrophages Help Cytotoxic (CD8+) T cells and B cells Cytotoxic T (TC) lymphocytes CD8+ T cells, recognize antigen presented by APCs with Class I MHC Recognize specific antigens on cell surface and kill virally infected cells and tumour cells Regulatory T lymphocytes Usually CD4+ T cells (some times CD8+) Limit immune response T lymphocytes
  42. 42. Cells of the Immune System T lymphocytes
  43. 43. Comparison of B and T lymphocytes Attribute B lymphocytes T lymphocytes Site of maturation Bone marrow Thymus Antigen receptor Membrane immunoglobulin (mIg) T cell receptor (TCR) Surface markers MHC molecules CD molecules Class I & II CD20, CD21 (CRII) , CD35 (CRI), CD40, CD45, CD80 (B7.1), CD86 (B7.2) Class I CD3, CD4/ CD8, CD28, CD40L, CD45 Antigen recognition Can recognize free antigens Do not require antigen presentation Can recognize antigens only when presented on the surface of APCs with self MHC molecules Chemical nature of antigen recognized Proteins, polysaccharides, nucleic acids, phospholipids Only proteins because MHC can present only peptides Role as APC Yes No Cells of the Immune System
  44. 44. Cells of the Immune System ◆Large granular lymphocytes ◆5- 10% of circulating lymphocytes ◆Do not express clonally distributed specific antigen receptors like B or T lymphocytes ◆Capable of rapidly attacking and killing virally infected cells and tumour cells (antigen non- specific) ◆Component of innate immunity ◆Also play a role in adaptive immunity by participating in antibody dependent cell mediated cytotoxicity (ADCC) Natural Killer (NK) cells
  45. 45. Cells of the Immune System ◆APCs are specialized cells that display antigens on their surface by MHC molecules to activate T lymphocytes ◆The common portals of entry of microorganisms- the skin, gut and the respiratory tract contain APCs in their epithelium ◆These cells can capture antigens, transport them to peripheral lymphoid organs and display them to T cells Antigen presenting cells (APCs)
  46. 46. Cells of the Immune System ◆Professional APCs include: • Dendritic cells • Macrophages • B lymphocytes ◆APCs express both Class I and Class II MHC molecules on their surface to display antigen to T cells ◆They also express B7 (B7.1 and B7.2) molecules to provide co-stimulatory signal to activate T cells Antigen presenting cells (APCs) Signal 1: Stimulatory signal Signal 2: Co-stimulatory signal TC
  47. 47. Effector cells Cells that eliminate microbes ◆Lymphocytes ◆Neutrophils ◆Monocytes and Macrophages ◆Eosinophils ◆Basophils and Mast cells ◆Natural Killer (NK) Cells Cells of the Immune System
  48. 48. • Plasma cells • Derived from B lymphocytes • Produce antibodies • Antibodies eliminate extracellular pathogens • Effector TH cells • Derived from CD4+ T lymphocytes • Produce cytokines that activate macrophages to eliminate intracellular pathogens • Cytotoxic T cells • Derived from CD8+ T lymphocytes • Induce apoptosis of infected cells Cells of the Immune System Effector cells Humoral Immunity Cell mediated Immunity Effector Lymphocytes
  49. 49. Other effector cells and their roles in Innate and Adaptive Immunity Cells of the Immune System Effector cells Cells Role in Innate Immunity Role in Adaptive Immunity Neutrophils Phagocytosis ADCC Macrophages (Monocytes) Phagocytosis ADCC Pathogen elimination by TH cells Type IV Hypersensitivity Eosinophils ADCC in parasitic infections Type I Hypersensitivity Mast cells and Basophils Inflammation Type I Hypersensitivity NK cells Kill virus infected and tumour cells ADCC ADCC= Antibody dependent cell mediated cytotoxicity
  50. 50. Development of lymphoid organs ◆The epithelia of thymus is developed from 3rd pharyngeal pouch ◆During the late stages of the development of the thymic epithelium, haematopoitic bone-marrow precursors migrate into the thymus and form thymocytes ◆The spleen develops from mesenchymal cells between layers of the dorsal mesentery of the stomach ◆Lymphatic vessels develop from lymph sacs that arise from developing veins, which are derived from mesoderm ◆With the exception of the anterior part of the sac from which the cisterna chyli develops, all lymph sacs become invaded by mesenchymal cells and are converted into groups of lymph nodes
  51. 51. Functions of the Immune System ◆The main function of the immune system is defense against microbial infections • Prevents entry of organisms inside the body • Kills and eliminates organisms that enter the body and prevents establishment of infection • Eradicates established infection ◆Another major function of the immune system is protection from tumours • Continuous surveillance for tumour cells • Kill any tumour cell developed (Tumour develop only when it can evade the immune surveillance)
  52. 52. Importance of the Immune System ◆Individuals with defective immune responses are susceptible to serious, life-threatening infections ◆Stimulating immune responses by vaccination is the most effective method for protecting from infections ◆Immune response is a barrier to successful organ transplantation ◆Clinical trials are showing that cancers can be treated by stimulating the immune response ◆Abnormal immune response (hypersensitivity and autoimmunity) may cause diseases with serious morbidity and mortality
  53. 53. Further Review ◆Levinson W. Review of Medical Microbiology and Immunology. 11th edition. McGraw Hill, 2008. ◆Kindt TJ, Goldsby RA, Osborne BA. Kuby Immunology. 6th ed. WH Freeman, 2006. ◆Abbas AK, Lichman AH. Basic Immunology. 3rd edition. Elsevier, 2011.