Immunology of the skin MUDr. Langerová Eliška Immune reactions  Specific vs. Non- specific  Cellular immunity ( against viruses, mycotic elem., IC bacteria, cancer, GvH reaction, Cellmediated reaction )  vs. Humoral (EC bacteria, some viruses, toxins) Cellular immunity  Non-specific:  fagocyting cells, NK cells, keratinocytes, mast cells, fibroblasts…  Specific:  T- lymphocytes, APC Humoral immunity • Non- specific: • complement system, proteins of acute reaction • Specific: • antibodies produced by B- lymphocytes SIS (skin immune system)  Functional unit - epidermis, dermis, blood vessels, lymphatics, lymph nodes SIS  Cells - Keratinocytes - Langerhans cells - dermal denritic cells - fibroblasts - Lymphocytes - Macrophages - Granulocytes - Mast cells  All units of SIS cooperate x redundant  Communication : selectins, integrins, cytokines Cytokines  Polypeptides  Changes in cellular proliferation, differentiation, migration  Stimulate imunoglobulins and cellular immunity  Specific receptors  Pleotropic effect Cytokines- 5 groups  1. interleukins:  Leukocytes ( lymfokiny, monokiny)  2. interferons (α,β,γ):  Antivirotic  Synthesis of Ig by B-lymphocytes, activate macrophages, NK cells, lymphocytes-T  Antiproliferative → cytostatic/cid against tumours Cytokines – 5 groups  3. chemokins:  Induce inflammation ( eg. IL 8)  Chemotaxes  Physiological migration of leukocytes  4. Colony stimulating factors (CSF):  Prolifer. of specific pluripotent cells of bone marrow in adults  Granulocytic vs. Macrofages Cytokines – 5 groups:  5. tumor necrosis factor (TNF):  TNFα (kachektin)  Growth f., interleukins  TNF β (lymfoxin)  Cytotoxic  effects: support cellular, humoral imm., proinflammatory, regulation of hematopoesis, cell proliferation, differentiation, healing wounds Other mediators:  Neuropeptides (substance P)  Eikosanoidy – allergic reactions, inflammation Physiological reactions:  Elimination of extracorporal and bodie´s „damaged“ structures  Phases: aferent, amplification, effector  Damage of skin → non- spec. immume reaction = acute inflammation  keratinocytes, complement sys., fagocyt. cells ( polymorfonuclears, macrophages), NK , mast cells, cytokins, activation of lysosomal enzymes,….. →fagocytosis / cytolysis of most of patogens  Rest activate SPECIFIC immune system  Specific :  T+B – lymphocytes  APC ( Langerhans cells,dermal denritic cells, macrophages, keratinocytes), fagocytes, cytokines, complement  HLA compatibility between APC and lymphocytes Immunological reaction  In the skin- swallow of antigen by APC → to the sentinel lymph node → remodelation of „naive“ Tlymphocyte to „memory“ T-cell →  → differentiation to cytotoxic ( CD 8+) and helper (CD4+) → subpop. Th1 (supress Ig) and Th2 ( support Ig)  Activation of B-lymfocyte → differentiate to plasmocytes → produce Ig ( IgM) Immunological memory  Memmory T and B lymphocytes  Secondary immune reaction  Effector cells and Ig (mainly IgG)- more, quicker reaction, longer Homing • Sensitized T cells return to the skin Pathological immune reactions  Immunodeficiency - insufficiency  Autoimmune deseases – bad tolerance  Allergies  Intensified defensive reaction  Alergens, haptens  Harmful  80% of allergies- on skin and mucosae Allergies : division Coombse-Gell- IV types:  Type I: immediate hypersensitivity reaction (mediated by IgE and mast cells)  Type II: Humoral cytotoxic reaction (mediated by IgG, IgM, C)  Type III: Immune complex reaction (mediated by IgG, IgM, IgA and C)  Type IV: Cell-mediated reaction (lymphocytes, lymphokines) Type I: immediate hypersensitivity r. (mediated by IgE and mast cells)  Seconds to minutes (x latent -hours- mites)  Anaphylaxis , Angioedema  Urticaria  Atopy  Sting  allergy to food Type II: Humoral cytotoxic reaction (mediated by IgG, IgM, C)  Complement/ antibody mediated cytolysis  6 hours  Hemolysis in newborns, hemolytical anemia, purpura, pemphigus vulgaris,pemfigoid bullosus, DHD, ….. Type III: Immune complex reaction (mediated by IgG, IgM, IgA and C)  6-12 hours  Vasculitis – subpapilar, periadnexal vessels  SLE, erythema nodosum,EEM, DHD- cytotox type  Arthus reaction – localised variant ( eg. Insulin) T. IV: Cell-mediated r.(lymphocytes, lymphokines)  sensitised T cells → antigen specific receptors  Effector- macrophages  delayed hypersensitivity – 7 days –refractory phase – after 1st contact, 24-72 hours after 2nd…n contact  intracellular microorganisms – eg. TBC- tuberkulin r., viruses, mykotic, parazites, cancer  allergic contact dermatitis Langerhans cell