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1 IMMUNOPATHOLOGIE. 2 Plan du cours 1. Immunodeficiences primaires 2. Immunodeficiences secondaires 3. Autoimmunite 4. Atopie et inflammation 5. Transplantation.

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Presentation on theme: "1 IMMUNOPATHOLOGIE. 2 Plan du cours 1. Immunodeficiences primaires 2. Immunodeficiences secondaires 3. Autoimmunite 4. Atopie et inflammation 5. Transplantation."— Presentation transcript:

1 1 IMMUNOPATHOLOGIE

2 2 Plan du cours 1. Immunodeficiences primaires 2. Immunodeficiences secondaires 3. Autoimmunite 4. Atopie et inflammation 5. Transplantation et immunosuppreseurs 6. Cancer

3 3 Autoimmunite => Immune Response: protection => host damage Response immune dirigee contre des antigens du soi (auto-antigenes)

4 4 Autoimmunite => Horror autotoxicus (1903) Paul Ehrich 1902:Portier et Richet: anaphylaxis 1903: Maurice Arthus 1904: Donath et Landsteiner: first described autoimmune disease (paroxxysmal cold hemoglobinuria) 1905: vonPirquet et Schick: serum sickness 1906: aTreponema pallidum : crossreactivity cardiolipin 1930s: RA patients: rheumatoid factor (IgM anti Fc of IgG-coated sheep RBSs) 1940s: Peter Medawar: skin rejection 1950s: William J Harrington: platelet depletion by serum transfer from patients with idiopathic thrombocytopenic purpura (autoantibodies) 1950s: peter Miescher&Henry kinkel: SLE patient serum: anti-nuclear (DNA, RNA, nucleoproteins) antibodies 1956: Noel Rose: immunization of healthy rabbits with thyroid extracts -> thyroiditis 1960s: NZB mice models (Marianne & Feliz Bielschowsky) - autoimmune hemolytic anemia; anti-kidney antibodies 1970s: GF Bottazzo; WJ Irvine: anti-pancreatic beta-islet cell Abs in IDM ORGAN SPECIFIC / SYSTEMIC AUTOIMMUNE DISEASES

5 5 Autoimmunite => WE Paul, 6th ed

6 6 Autoimmunite => WE Paul, 6th ed

7 7 Autoimmunite => Hypersensitivity mechanism vers le self Beakdown of immune tolerance Presence of an autoimmune reaction That reaction is of primary importance (not colateral) absence of other causes therapeutic effect

8 8 Antigenes A) Antigenes cryptiques –cristallin: ophtamie sympathique –testicule: vasectomie B)Reactions croisee avec tissus de lhote apres respose immune –S. beta-hemolytique: Abs anti-tissu cardiaque; RAA C) Modification antigeniques des antigenes de lhote –(physico-induites: UV) –(chimio-induites)

9 9 Acteurs cellulaires A) Cellules B –Autoanticorps naturesl: faible affinite; taus faibles, ^ des sujets ages –B1 cells –HMS B) Cellules T –Cellules T autoreactives –Treg; NKT, Th17, Th9 C) Extensions sur des cellules auxiliares –DCs; Mast cells; Macrophages D) Celules cible –Cellules cible du soi normalles –Cellules cible du soi alteree –Cellules microbiennes –Allogeneic cells (fetal)

10 10 Acteurs molleculaires A) Antigenes genetiques B) MHCs C) Cytokines D) Corecepteurs E) Molecules de transmission du signal F) Facteurs transcriptionelles: FoxP3, T-bet, GATA-3, IFR4, microbiens E) interferant (cytokine homologues) D) epitopes mimetiques

11 11 Autoimmunite => Types de reactions dhypersensibilite Burmester & Pezzuto, Atlas de poche dimmunologie

12 12 Autoimmunite => Kuby 5th Immunology

13 13 Autoimmunite => Defects in tolerance induction (central tolerance) =>Defects in tolerance maintenance (peripheral tolerance) =>Defects in isolating priviledged site self antigens =>Immune deviation

14 14 Autoimmunite => Facteurs : Inflammation: –cytokines proinflammatoires (IL-1b, TNF, LT, IL-6); IFN antivirale: NKT; Th17; pDCs, DCs –DC: tolerance / activatoire –eliberation du molecules dallarme du soi (ADN, calreticulins, HMGB1, HSPs, ATP) –activation du recepteurs de limmunitee innee: TLRs Mimetisme antigenique:

15 15 Autoimmunite =>

16 16 Autoimmunite => Anomalies en Treg: IPEX (immune dysregulation, polyendochrinopathy, enteropathy X-linked ): FoxP3 Scurfy mice

17 17 Autoimmunite =>

18 18 Autoimmunite =>Anomalies en CPAs: –modele animal avec reduction en MHC II/B7 sur DCs/macrofages: induction deficitaire ed Treg infections –modele animal avec reduction en cellules B –anomalies en complement –modele animal avec production exageree en cytokines hu: MS, RA: IL-6, TGFb, IL-23: Th17; mAbs peut bloquer hu: glomerulonephrite, SLE, IL-15, IL-27 =>Epitope spreading PG: desmoglein 3 (mucouse) -> desmoglein 1 (peau) GAD: glutamic acid decaboxylase

19 19 Autoimmunite =>SLE (fievre, malaise, fatigue, douleur musculaire, polyarthrite, ERYTHEME facial en aille de papillon/masque de loup; atteinte glomerulaire proliferative focale ou diffuse, SNC, pericardite, myocardite) Ag: nucleosomes / spliceosomes / cumplexe ribonucleoproteiques cytoplasmique IL10: stimulation du B (proliferation + differentiation)

20 20 Autoimmunite =>R. A. (arthrite rheumatoide) Th17: IL17/TNF RF: collection de anti-IgG

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