8. This type of host defense is always present in healthy individuals, prepared to block the entry of microbes and to rapidly eliminate microbes that do succeed in entering the host tissues
38. LANGERHANS’ CELLS Premier APC for external eye rich in class II MHC molecules Abundant in corneo-scleral limbus, less in peripheral cornea, absent from central 1/3rd of cornea
41. NUEUTROPHILS Account for 90% granulocytes Stimulated by chemotactic agents: Complement components Fibrinolytic & kinin system components Products from other leucocytes, platelets
42. NUEUTROPHILS Release their contents & result in : Phagocytosis of micro-organisms Type II antibody-dependent cell-mediated cytotoxicity Type III hypersensitivity reactions (immune-complex-mediated diseases)
43. EOSINOPHILS 3-5% of circulating PMNs Special role in : Type 1 hypersensitivity - Allergic conditions & parasitoses Type III hypersensitivity reactions
45. MAST CELLS Indistinguishable from basophils Predominant cells in type 1 hysersensitivity - allergic responses Also participate in Type II, III, IV hypersensitivity reactions (role not clear) 2 types: Mucosal Mast Cells Connective Tissue Mast Cells
46. PLATELETS Cells for blood clotting Involved in immune response to injury: Adhere to & aggregate at the endothelial surface Release prermeability-increasing molecules Cause type III hypersensitivity reaction: Antigen-antibody immune complex > Activation of mast cells > release of Platelet-activating factor > activation of platelets
47.
48. If T cells are present > entire array of immune responses & tolerance possible
49. If T cells are absent > only primitive antibody response is possible, no Cell-mediated response
61. Hazards of Immunity Inadvertent injury to normal host tissues Development of Autoimmunity
62. Special Case of the Eye :Immune Privilege Dilemma of the eye: Needs to be protected Prevent injury to normal tissues Certain forms of immunity are permitted and others are suppressed
63. Immune Privileged Sites Sites in the body where foreign tissue grafts can survive for extended periods of time whereas similar grafts placed in conventional sites are acutely rejected by the host: Cornea Anterior chamber Lens Vitreous cavity Subretinal space
71. Establishment of Ocular Immune Privilege Three different strategies : Immunologic Ignorance Peripheral tolerance to ocular-derived antigens Development of an intraocular immunosuppressive microenvironment.
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73.
74. Central & Peripheral Tolerance to Self-Antigens Immature lymphocytes specific for self-antigens may encounter these antigens in the generative lymphoid organs and are deleted (central tolerance). Mature self-reactive lymphocytes may be inactivated or deleted by encounter with self antigens in peripheral tissues (peripheral tolerance)
75. Intraocular immunosuppressive microenvironment There are also local factors within the eye that inhibit the components of the immune response to reinforce the protection provided by immune privilege.
77. CORNEAL TRANSPLANTATION : ACCEPTED OR REJECTED Immune privilege plays an important role Factors that help in prevailing immune privilege : Reduced & impaired expression of MHC class I and II molecules in corneal cells. Thus the net antigenic load is reduced. Cornea lacks both blood & lymph vessels. Prevents antigenic information escaping from tissues and migration of APC.
78. Cornea is deficient in Bone-marrow derived cells (Langerhans Cells). Absence of APC lengthens the time for graft recognisation. Secretion of molecules with immunosuppressive properties to inhibit macrophages, NK cells, APC, T cells, B cells. Expression of surface molecules that inhibit immune effectors. ACAID in recepients
90. ANATOMY OF THE IMMUNE SYSTEM AT THE OCULAR SURFACE TEAR FILM & INTEGRATED PROTEINS: Specific IgA antibodies Lysozymes : destroy bacterial cell wall Lactoferrin : binds iron Tear-specific prealbumin : scavenger of bacterial products Angiogenin : antimicrobial effect within tear film Others antimicrobial molecules to recruit leucocytes: Specific leucocyte-protease inhibitor, Interleukin-8 IF-gamma-inducible protein, Macrophage inhibitory protein IL-6, macrophage-CSF
91. MUCOSAL IMMUNE DEFENSE MECHANISMS AT THE OCULAR SURFACE The eye-associated lymphoid tissue (EALT) is the mucosa-associated lymphoid tissue for immune protection of the ocular surface and its mucosal adnexa. It is anatomically continuous from the lacrimal gland throughout the conjunctiva- and lacrimal drainage-associated lymphoid tissue (i.e. CALT and LDALT, respectively). It consists of a diffuse lymphoid tissue of T lymphocytes and IgA-secreting plasma cells, including accessory leukocyte populations in all organs and of lymphoid follicles in conjunctiva- and lacrimal drainage-associated lymphoid tissue (in the drawing, large blue cells represent plasma cells, small blue cells represent B cells and small black cells represent T cells). Protective as well as aggressive factors inside the tear film, which connects the different parts of the ocular surface and protects it from the external environment, are a major component of ocular surface immunity. The organs are also connected by lymphocyte recirculation via specialized vessels with each other and with the rest of the immune system.
92. Mucosal, like systemic, immunity uses two approaches for defense, the innate and the adaptive immune system.
93. Innate immunity at ocular surface Evolutionary Old system : detection and destruction of microbial pathogens Phagocytes, macrophages, Langerhans’ cells, neutrophils, mast cells Chemokines and specific antimicrobial peptides like Beta-Defensin, Collectins, bactericidal permeability-increasing protein, etc
94. Specific adaptive immunity at the ocular surface Lymphoid cells with high degree of specificity, variability, and immune regulation Afferent antigen uptake & processing Recognition of antigens Differentiation & proliferation of lymphocytes Action of effector lymphocytes
95.
96. DEFENCE STRATEGIES AT OCULAR SURFACE The Immune Privilege Approach : Predominant at day time The Proinflammatory Approach : Predominant at night time
116. Three genetically linked mechanisms: General hyper-responsiveness : positive skin reactions to a broad range of environmental allergens Regulation of serum IgE levels Sensitivity to specific antigens
117. THERAPY OF TYPE I REACTIONS Environmental control Mast cell stabilizers Systemic antihistamines Topical steroids (for acute intervention only) Desensitization immunotherapy Plasmapheresis Intravenous gamma globulin Cyclosporine (systemic and topical) Psychiatric intervention for the patient and family
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119. Type II Hypersensitivity Reaction 3 types: Antibody- and complement-mediated lysis Antibody dependent cell-mediated cytotoxicity inhibition of transmission of the nerve impulse by antibodies
120. Antibody- and complement-mediatedlysis of a nucleated cell as a consequence of formation of the membrane attack complex Antibody dependent cell-mediated cytotoxicity through the action of either an NK or a K cell with surface antibody specific for a target cell Inhibition of transmission of the nerve impulse by antibodies against acetycholine receptors as occurs in myasthenia gravis
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122. THERAPY FOR TYPE II REACTIONS immunosuppressive chemotherapy has been the mainstay of treatment
123. Type III Hypersensitivity Reaction Schematic representation of the formation and deposition of immune complexes in vessel walls in type III hypersensitivity
124. THERAPY FOR TYPE III REACTIONS large doses of corticosteroids, of immunosuppressive chemotherapeutic agents, or both
135. An autoantibody recognizes and interacts with an antigen present as a natural component of the individual synthesizing the autoantibody
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138. Postulated mechanism for Autoimmunity Various genetic loci may confer susseptibility to autoimmunity, probably by influencing the maintainance of self-tolerance. Environmental triggers, such as infections and other inflammatory stimuli, promote the influx of lymphocytes into tissue and the activation of self-reactive T cells, resulting in tissue injury
139. Sequestered Antigen Anatomically isolated Not in contact with the T and B lymphoid cells Examples : myelin basic protein sperm antigens Crystalline lens protein antigens. When released, it can activate both T and B cells.