1 / 146

BASIC IMMUNOLOGY

BASIC IMMUNOLOGY. Prepared by: Dr. D. L. Boyd, DDS Oral & Maxillofacial Pathologist Associate Professor Reference: Kaplan Review Notes. IMMUNE SYSTEM. Collection of Organs, Tissue, & soluble Factors to defend against Bacteria, Viruses, & Tumor cells. Consist of:

Anita
Download Presentation

BASIC IMMUNOLOGY

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. BASIC IMMUNOLOGY Prepared by: Dr. D. L. Boyd, DDS Oral & Maxillofacial Pathologist Associate Professor Reference: Kaplan Review Notes

  2. IMMUNE SYSTEM • Collection of Organs, Tissue, & soluble Factors to defend against Bacteria, Viruses, & Tumor cells. • Consist of: • Primary (central) Lymphoid Organs in which Leukocytes develop • Secondary (peripheral) Lymphoid Organs & Tissues in which Immune Response occur. • Leukocytes in Blood • Mature in Marrow (B cell) or Thymus (T-cell)

  3. CELLS OF THE IMMUNE SYSTEM • MONOCYTES & MACROPHAGES • Control infections not overcome by Neutrophils • Associated with chronic infections • Main role in cell-mediated immunity • Act as Ag presenting cell to T-Lymphocyte • Activated by γ-Interferon (lymphokine)

  4. MONOCYTES / MACROPHAGES • Formation: • Stem cell  Monoblast  Promonocyte  circulating Monocyte  tissue Macrophage • Mature in the Blood • Secrete Inflammatory Mediator & Cytokines • Interleukins (IL-1, 8, 12) Prostaglandin (PG) Thromboxane (TBx) Leukotriene (LT) Interferon (IF) Collagenase Elastase Complement components Lysozymes Tumor Necrosis Factor (TNFα) Lipase

  5. MONOCYTES / MACROPHAGES Have on cell surface: Fc Receptors  allow uptake of Immune Complexes Class 11 MHC molecules  present Antigenic peptides to T-cells Monocytes  Macrophage with different names: Kupffer cell in sinusoid of Liver Alveolar macrophage in Lung Microglial in Brain

  6. MONOCYTES / MACROPHAGES • Morphology: • Epithelioid: (From Monocytes) • In Granulomas • Activated by immune response to Antigen • Multinucleated Giant Cells formed by fusion of Macrophages

  7. MONOCYTES / MACROPHAGES • Activation: • Stimulated by Lymphokines (γ-Interferon) • Kill Microbs + Tumor cells • When activated: • Have increased lysosomal hydrolytic enzymes • Increase Chemotactic response to C5a & Cytokines from Lymphocytes, Neutrophils & Fibroblasts

  8. MONOCYTES / MACROPHAGES • Activation (cont) • Opsonization can occur: • Phagocytosis of Antigen coated with C3b and Antibody • Increase in Size, and Number of Pseudopodia + Pinocytotic vesicoles

  9. MONOCYTES / MACROPHAGES • Present Antigens to T-Lymphocytes: • Antigen undergo phagocytosis or pinocytosis • Antigen degraded in cytoplasm to small Peptides • Peptides non-covalently bind to Class 11 MHC molecules in Endosomal vesicle  complex transported to cell surface  stimulate Class 11-restricted Antigen-specific Helper T cells (CD4)

  10. MONOCYTES / MACROPHAGES • Pocess Exogenous Ag  present Epitopes in groove of Class 11 MHC • CD4 T cells with receptors specific for the Epitope react with Epitope-MHC complex and release Lymphokines • Pocess Endogenous Ag  presented to CD8 T cells on Class 1 MHC

  11. MACROPHAGES & NEUTROPHILS • Phagocytize Bacteria coated with Complement • C3b binds to Bacteria Opsonized by Ab  binds to Receptor on Phagocytic cell  Phagocytosis • Fc receptor on Macrophage useful for Opsonization of Bacteria by Ab  hold bacteria close  Engulfment  Phagocytosis

  12. DENTRITIC CELLS • Present in Blood, LNs, Epithelial cells • Digest & process Ag to present to T-cells • Examples: • Langerhan cells (resides within Epithelium) • Veild cells (Afferent Lymphatics) • Interdigitating reticular cells (Spleen & LNs)

  13. GRANULOCYTES • NEUTROPHILS (PMNs) • 60% of leukocytes (white blood cells) • Have receptor for Fc region of IgG & C3b • Release Matrix Metalloproteinase (MMP) • First to arrive in acute inflammation, actively killing bacteria, by generation of Hydrogen peroxide & Oxygen free radicals releasing LPS. • Cytoplasm contain Lysosomal Peroxidase + Acid Hydrolases • Cytoplasmic granules contain digestive enzyme (Myeloperoxidase) & Lactoferrin (binds Fe)

  14. GRANULOCYTES • NEUTROPHIL – SUMMARY • Kill microbes by: • Toxic Oxygen molecule • Digestive Enzymes stored within Lysosomal granules

  15. GRANULOCYTES • EOSIONPHILS (1 –3% of leukocytes) • Have receptors for Complement • Bi-lobed nucleus + red granules (Giemsa stain) • Chemotactic factors for Eosinopkils: • Histamine C5a LTB4 PAF • ECF-A (anaphylaxis) • Mostly in parasitic(*MBP)& allergic conditions • Contents & Functions: Histaminase Pyrogen (fever) Peroxidase (kill bacteria) Aryl sulfatase (degrade LT) *Major Basic Protein

  16. EOSIONPHILS • CLINICAL CORRELATION • Classically seen with: • Atopic allergies • Worm infections • Collagen Vascualr diseases • Neoplastic disorders • Skin rash • Granules (histaminase, arylsulfatase) help control allergic reactions

  17. CELLS OF THE IMMUNE SYSTEM • BASOPHILS (1% of leukocytes) (smallest) • Contain much granules with: • RNA Mucopolysaccharide • Histamine (hypersensitivity madiator) • Have receptors for Fc portion of IgE • IgE binding  degranulation  Histamine allergic reactions

  18. CELLS OF THE IMMUNE SYSTEM (cont) • LYMPHOCYTES (30% of circulating WBC) • B Lymphocytes: • Differentiate into Plasma cells  Antibodies • CDb5-positive  IgM • CDb5-negative  IgG, IgA, IgE • Memory B cells:generated after exposure to Ag • Mature B cell: have surface IgM & IgD that bind Ag  cause B cell  Ab • B cell respond to: • T-cell-independent Ag  Ig without CD4 cells • T-cell –dependent Ag  regulate T-cells  B cell Ab

  19. CELLS OF THE IMMUNE SYSTEM • T LYMPHOCYTES: • Helper T cells (CD4 positive) • Stimulate B-Lymphocytes  Plasma cell  Ab • Promote cytotoxic T- cell (CD8) response • Activation due to recognition of Class 11 MHC on Antigen-presenting cells • Produce Lymphokines, Differentiation Factors, Inflammatory Cytokines (IL-2) • Cytotoxic T cell (CD 8 +) • Recognize Foreign Ag & Class 1 MHC • Lyse virus infected cells & tumor cells

  20. CELLS OF THE IMMUNE SYSTEM • Natural killer (NK) cells(10 -15% of Lymphocytes) • Kill Tumor cells • Defend against Viral infections • Recognize Foreign Ag independent of MHC • Mediate Ab-dependent cellular toxicity (ADCC) • Kill Opsonized or Ab-coated cells • Activated by Cytokines (γ- Interferon)

  21. LYMPHOCYTES • SUMMARY: • T Helper cell  CD4+ • Cytotoxic T cells  CD8+ • TDTH cell  delayed-type Hypersensitivity • Has CD$ in its membrane • Antibody-Dependent cellular toxicity (ADCC) • Linked to NK cells, Neutrophils • Have Fc Receptors

  22. LYMPHORETICULAR SYSTEM • Primary (central) Lymphoid Organs: • Bone marrow & Thymus (child & adult) • Hematopoiesis & Lymphopoiesis occur here • Secondary (peripheral) Lymphoid Organs: • Lymph Nodes Spleen • Mucosa-Associated Lymphoid Tissue (MALT) • Waldeyers Ring: Lingual Tonsil + Soft Palate LNS + Tonsils + Adenoids • Gut- Associated Lymphoid Tissue (GALT) • Peyer’s patch

  23. LYMPHORETICULAR SYSTEM • Secondary (peripheral) Lymphoid Organs: • Bronchus-Associated Lymphoid Tissue (BALT) • Trap & present Ag to Lymphocytes  Immune Response • Protect all surfaces and fluids of the body • Extracellular fluid or Lymph filtered thru LNs, and tissues of MALT • NOTE: Primary filter of Blood = Spleen + Liver

  24. LYMPHORETICULAR SYSTEM • BONE MARROW • A primary organ • Site for Hematopoiesis + B cell maturation • Site of origin of Stem cell  T-cell production • A secondary organ: site for Plasma cell  Ab • Contains activated T cells

  25. LYMPHORETICULAR SYSTEM • BONE MARROW STRUCTURE • Very large tissue (3 – 5% body mass) • In Long bones + Cranium + Ribs + Iliac crest • Two Functional Parts: • Vascular + Adipose • Hematopoietic • Blood cells from single Stem cell

  26. LYMPHORETICULAR SYSTEM • HEMATOPOIETIC CELL DIFFERENTIATION • Pluripotent Stem cell  Myeloid + Lymphoid progenitor cells • Myeloid Stem cell give rise to: • Monocyte  Macrophage • Eosinophil • Basophil • Megakaryocyte  Platelet • Erythroblast  Erythrocyte

  27. LYMPHORETICULAR SYSTEM • Lymphoid Stem cell give rise to: • Pre-B cell  Late pre-B cell  Immature B cell  Mature B cell  Plasma cell  Abs • Pre-T cell (enters Thymus)  Helper T cell + Cytotoxic T cell + TDTHcell • NK cell • Stimuli for Differentiation: • Colony-stimulating Factors Erythropoietin Thymosin Ags (self or foreign)

  28. LYMPHORETICULAR SYSTEM • After maturation in Thymus or Bone marrow, Lymphocytes migrate to Spleen + LNs + MALT • THYMUS • Development: From 3rd + 4th Pharygeal Pouches Located in Mediatinum Maximum weight in Puberty, slowly involutes

  29. LYMPHORETICULAR SYSTEM • THYMUS (cont) • Organization: • Stroma: • Connective tissue capsule  invaginates into Parenchyma as Septa  divides into Lobules • Cortex: • Differentiating Thmocytes surrounded by meshwork of Epithelial Reticular cell + Macrophages

  30. LYMPHORETICULAR SYSTEM • THYMUS • Organization: (cont) • Medulla: • Epithelial Reticular cells + Mature T cells • Hassall corpuscles = concentrically arranged dead / dying Reticular cells + Macrophages + Neutrophils + Nuclear material ?origin

  31. LYMPHORETICULAR SYSTEM • THYMUS (cont) • THYMECTOMY result in: • Poor development of other Lymphoid tissue • Absence of cell-mediated immunity • DeGeorge syndrome (congenital absence) • Decrease B and T cells  increase infections  death • Also Hypoparathyroidism  Tetanus

  32. LYMPHORETICULAR SYSTEM • THYMOSIN • Lymphokine that stimulate Thymus-dependent zones in Lymphoid tissues • Produced by Thymic Epithelium • LYMPHATICS • Plasma filtered from Capillaries  Tissues  Veins  Interstitial Fluid  Excess (Lymph) Lymphatic vessels  LNs  Lymphatic vessels  Thoracic Duct  Left Subclavian Vein

  33. LYMPHORETICULAR SYSTEM • LYMPH NODES • Most common site for adaptive immune response • Filters Lymph of Foreign bodies • Encapsulated, kidney shaped, concave side with Hilum (entry & exit of Blood vessels + Nerves)

  34. LYMPHORETICULAR SYSTEM LYMPH NODES (cont) • Stroma: • CT capsule extends into and divides the parenchyma • Reticular cells  Reticular fibers  network  filters Lymph + suspend Lymphocytes & Macrophages • Facilitates cell-to-cell & Ag-receptor interactions

  35. LYMPHORETICULAR SYSTEM • LYMPH NODES (cont) • Cortex: • Composed of Lymphatic nodules (B cells) • Diffuse Lymphatic tissue (T cells) • Mixes with Supcapsular & Peritubular Sinuses (Macrophages) • Lymphatic Sinuses: • Lymphatic passageways • Lined with Endothelial cells • Receive Lymph  Medulla

  36. LYMPHORETICULAR SYSTEM • LYMPH NODES • Cortex: (cont) • Germinal centers: • Inside Nodules of Cortex • Mainly B cells  Plasma cells  Abs • Where Ags are processed  increase in number + develpoment of Germinal centers

  37. LYMPHORETICULAR SYSTEM • LYMPH NODES • Medulla: • In center of LN • Contain medullary cords of Lymphoid tissue  extend into Cortex • Medullary Sinuses transmit Lymph to Hilium  exists thru Efferent Lymphatics

  38. LYMPH NODES • CLINICAL CORRELATION: • Receive Lymph from defined and limited regions of the Body • Example: Pericoronitis around Mandibular 3rd molars  Submandibular LNs • Neoplasms can metastasize to via LNs • Example: Breast, Lung, GIT, Prostate, Kidney cancer  Jaws

  39. LYMPHORETICULAR SYSTEM • SPLEEN • Peripheral (Upper Left Quadrant of Abdomin) • Filters Blood of old + defective RBCs • Protects against Blood-borne pathogns • Stroma: • Dense CT capsule containing Smooth muscle • Trabeculae branches off Capsule  partition parenchyma of Splenic Pulp • Delicate meshwork of Reticular CT filters Blood

  40. LYMPHORETICULAR SYSTEM • SPLEEN (cont) • Splenic Parenchyma (White & Red Pulp) • White Pulp: • Lymphatic tissue arranged in Sheaths • Increases with Antigenic stimulation • Periarteriolar Lymphocyte Sheath (PALS) • Rich in T cells • Marginal zone mostly B cells  form Primary follicles + Ag  Secondary follicles with Germinal centers (B cells)

  41. LYMPHORETICULAR SYSTEM • SPLEEN • Splenic Parenchyma • White Pulp (cont) • In Marginal Zone, Dendritic cells trap & process Ag, and migrate to PALS to present Ag to Antigen-specific cells • Red Pulp • Mostly RBC-filled sinusoids + Macrophage in Reticular fiber network • Most of Filtration occur here

  42. LYMPHORETICULAR SYSTEM • SPLEEN • Splenic Parenchyma • Red Pulp (cont) • Sinuses of various sizes separated by Pulp (Billroth) cords • RBCs + Platelets exposed to Macrophages in Pulp cords, which phagocytize worn-out or damaged cells • Sinusoids lined by endothelial cells with numerous fenestrations  filtration

  43. LYMPHORETICULAR SYSTEM • SPLEEN • Splenic Parenchyma • Red Pulp (cont) • Phagocytosis mainly by Macrophages outside the sinusoids, by extending finger-like projections into the sinusoids, that push thru the fenestrations between the endothelial cells

  44. SPLEEN • CLINICAL CORRELATION • Patients with Sickle cell anemia undergo gradual infarction of the Spleen  increase risk for septicemia (S. pneumoniae), and other opportunistic infections (Salmonella, meningococci, H. Influenza) • NOTE: • In White Pulp, T cell mostly in central portion of PALS, B cells mostly in marginal zone

  45. LYMPHORETICULAR SYSTEM • GUT-ASSOCIATED-LYMPHOID TISSUE • Non-encapsulated • Located in the Submucosa + Lamina propria • Site of immune responses to ingested Microbs + Food antigens • Structure: • Large follicular aggregates • Peyer patches (Small Intestine – villi)) • Intraepithelial Lymphocytes

  46. LYMPHORETICULAR SYSTEM • GALT (cont) • Function: • Ag-presenting cells (M cell) in the Mucous Membranes endocytose Microbes + Ags  which are presented to T Lymphocytes between the Lymphoid follicles • B cell become activated  form Germinal Centers  become Plasma cells  IgA

  47. LYMPHORETICULAR SYSTEM • GALT • Function (cont) • IgA react with receptor on Intestinal Epithelial cells  crosses cytosol of epithelial cell  cleaved  excreted into lumen of intestine as secretory IgA (sIgA)  protected against hydrolysis by intestinal fluids  destroy Microbes. • sIgA also found in Saliva

  48. LYMPHORETICULAR SYSTEM • BRONCHUS-ASSOCIATED LYMPHOID TISSUE (BALT) • Lymphoid tissue beneath Respiratory mucosa • Tonsils • Organization: • Aggregates of B cells  Plasma cells  Abs  Humoral immune response

  49. LYMPHORETICULAR SYSTEM • Types of Tonsils: • Palatine Tonsils: • Bilateral in the Oropharynx • Dense Lymphoid tissue with Germinal centers • Numerous Epithelial invaginations (crypts) • Lingual Tonsils: • Base and Posterior Lateral Tongue • With an Inflamed Lingual Tonsil, Squamous cell carcinoma MUST be R/O

  50. LYMPHORETICULAR SYSTEM • Types of Tonsils (cont) • Pharyngael Tonsils (Adenoids) • Unpaired aggregate of Lymphoid tissue in the Posterior Wall of the Nasopharynx • Surfaced by Pseudostratified Columnar Epithelium with Cilia + Goblet cells • Waldeyer’s Ring = Ring of Lymphoid tissue located on Soft Palate + Floor of Mouth + Palatine Tonsil + Lingual Tonsil

More Related