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BASIC IMMUNE FUNCTIONS

BASIC IMMUNE FUNCTIONS. CELL MEMORY-IMMEDIATLY RECOGNIZE INVADERS ON SECOND EXPOSURE CELL SPECIFICITY- ANTIGENS RECOGNITION OF SELF-DETECTS SELF FROM NONSELF. GENETIC BASIS OF IMMUNOLOGY. HUMAN LEUKOCYTE ANTIGEN DETERMINES SELF FROM NONSELF HLA A,B,C FOUND ON ALL NUCLEATED CELLS

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BASIC IMMUNE FUNCTIONS

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  1. BASIC IMMUNE FUNCTIONS • CELL MEMORY-IMMEDIATLY RECOGNIZE INVADERS ON SECOND EXPOSURE • CELL SPECIFICITY- ANTIGENS • RECOGNITION OF SELF-DETECTS SELF FROM NONSELF

  2. GENETIC BASIS OF IMMUNOLOGY • HUMAN LEUKOCYTE ANTIGEN • DETERMINES SELF FROM NONSELF • HLA A,B,C FOUND ON ALL NUCLEATED CELLS • HLA D FOUND ONLY ON LYMPHOCYTES

  3. MAJOR HISTOCOMPATIBILITY COMPLEX • GENETIC REGION THAT CONTROLS HLA EXPRESSION • CLASS I GENES A,B,C • IMMUNOSURVEILLANCE • CLASS II GENES D • IMMUNE REGULATION • CLASS III GENES C2,C4,B • COMPLEMENTREGULATION

  4. MACROPHAGES • INDUCTION OF T LYMPHOCYTES • SITE OF IMMUNE GENE CONTROL • AUGMENTS KILLING AND PHAGOCYTOSIS • SECRETES A VARIETY OF CYTOKINES

  5. T-LYMPHOCYTES • T-HELPER (T4) • CYTOTOXIC T CELL • SUPPRESSOR T CELL (T8) • DELAYED SENSITIVITY T

  6. B-LYMPHOCYTES • PRECURSOR TO PLASMA CELLS • SOURCE OF IMMUNOGLOBULINS • ANTIBODIES • TYPICALLY REQUIRE T CELL INDUCTION • MAY PRODUCE MULTIPLE ANTIBODIES

  7. IMMUNOGLOBULINS • IgA • PRINCIPLE OCULAR SURFACE ANTIBODY • IMMUNOLOGIC PAINT • SECRETORY PROTECTS FROM LYTIC ENZYMES • IgD • POORLY UNDERSTOOD • MAY REACT EARLIER THAN IgM

  8. IMMUNOGLOBULINS • IgM • PRIMARY ANTIBODY DURING FIRST EXPOSURE • IMPORTANT IN RETINAL/CHOROIDAL • IgG • PRIMARY ANTIBODY IN SECOND EXPOSURE • IgE • MEDIATOR OF ALLERGY

  9. OTHER IMMUNE CELLS • K CELLS • NON T NON B LYMPHOCYTES • DIRECT CELL DESTRUCTION • NK CELLS • LARGE GRANULAR LYMPHOCYTE • ADCC • TUMORS, PARASITES

  10. IMMUNE CELLS • POLYMORPHONUCLEAR LEUKOCYTES(PMN’S, POLYS, NEUTRAPHILS) • PRIMARY PHAGOCYTIC CELL • ENZYMATIC DESTRUCTION(MYELOPEROXIDASE, PEROXIDASE, SUPEROXIDE • LANGERHAN CELL • NONMACROPHAGE ANTIGEN PRESENTOR

  11. IMMUNE CELLS • BASOPHILS/MAST CELLS • MEDIATORS OF ALLERGIC REACTION • GRANULATION PRODUCTS • EOSINOPHILS • PHAGOCYTIZE IgE COMPLEXES • PROTEINS(MBP) • ENZYMES • SLOWS ALLERGIC RESPONSE

  12. COMPLEMENT • ACTIVATED BY ANTIBODY • ACTIVATED BY BACTERIAL ENDOTOXIN • +ANTIBODY FOR CELL LYSIS • ACTIVATES CLOTTING • ACTIVATES PHAGOCYTIC CELLS • +PHAGOCYTIC CELLS FOR LYSIS • CELL LYSIS

  13. Autoimmune Disease • Type I Acute Allergic Conjunctivitis • Type II Stevens-Johnson • Type III Arteritis, Marginal Ulcers • Type IV GPC

  14. Ocular Immunology • The Eye Composed of Three Immune Systems • Eyelids-similar responses to skin • Conjunctiva- mucosal system similar to gut, nasopharynx • Internal structures-Immune Privilege

  15. Eyelids • Lid responses are identical to skin • Primarily a cellular response • Activated T-cells (Th1) • Marked swelling, redness • Example: Hordeolum

  16. Conjunctiva • Conjunctiva Associated LymphaticTissue(CALT/MALT) • APC ‘s to nearest lymph node • T-cell proliferation via CD2 pathway(Th2) • Elicit plasma cell production • Example Viral Conjunctivitis

  17. Immunological Components • Lymphocytes, Plasma cells, PMN’s • IgG, IgM, IgA • Langerhans, Macrophages • No Mast cells, No Eosinophils • Few if any cells in the central cornea • More at limbus and conjunctiva

  18. Tears • IgG , IgM, SIgA, IgA • Il’s 1(Th-1), 1B(Th-1), 4(Th-2), 8(Th-2) • TGF(cell growth) • TNF(nuclear factor–B signal transductionpathway) • Endothelin(vasoconstrictor) , fibronectin(wound healing cell adhesion) • GM-CSF

  19. S-IgA • Produced by lacrimal gland • Influenced by tear flow rate • >Flow <S IgA • At night <flow > S IgA • >S IgA > PMN • Protects against overnight infection with closed eye

  20. S-IgA • Hormonal Control • Androgens reduce production • Insulin required for SC component production • Neural Control • Sympathetic and Parasympathetic pathways

  21. Immune Privilege • To some extent in cornea • All internal structures

  22. Immune Privilege • Extreme form of regional immunity • Internal structures are recognized as foreign by conj and lids • Occurs within brain, eye, reproductive organs, fetoplacental tissues • anterior chamber, subretinal space, retinal pigment epithelium, vitreous cavity • Immune response is minimal

  23. IMMUNE PRIVILEGEWHY? • Is it the Anatomy? No lymphatics • A/C Macrophages present to spleen as normal • Differences 1)high level of transforming growth factor beta(downregulator) 2) don’t produce IL-12 3) don’t express CD40 • But systemic immune response do develop

  24. WHY DO WE NEED IMMUNE PRIVILEGE? • Preserve sight • Immune Responses are Th1 or Th2 mediated • Th1 primarily cellular with a great deal of adjacent tissue damage • Th2 primarily humoral less collateral tissue damage

  25. IMMUNE PRIVILEGEHow Does it Work? • Blood Ocular Barrier-difficult for blood born mediators to enter the eye; iris ciliary body, retina, RPE/choriocapillaris • Drainage through venous system force to spleen- humoral responses • APC’s are unique

  26. Reasons for low immunity • Class I and II MHC are poorly expressed on ocular tissue --antigen is presented to T cells with MHC • Activated T-Cells express FAS -effectively kills other T cells by apoptosis • Complement is downregulated by CD59, CD46, MCP(membrane co-factor protein) all expressed on ocular tissue

  27. Cornea • No lymphatic, No vascular supply, perilimbal • FAS ligand active • Examples ulcer central and peripheral • Variety of Cytokines present • IL-1, IL-6, IL-8, IL-10, MAPK(mitogen activated protein kinase) • IL-1 most important • Overstimulation of Il-1 in Corneal melt • IL-10 important in clearing herpes

  28. Wound Healing • Matrix Metalloproteinase(MMP) • Extracellular protein •  MMP > Cancer and Emphysema • Tissue Inhibitor of MMP(TIMP) • Wound Il-1 with  MMP • MMP “resurfaces” wound • Excessive MMP chronic ulcer/neovascularization

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