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IM1003: Medical Immunology Introduction to immunological disease principles Prof. L. Ziegler-Heitbrock

IM1003: Medical Immunology Introduction to immunological disease principles Prof. L. Ziegler-Heitbrock. The complement system. C1qrs. C3. C4C2. antibody. C3a. C3b. C56789. bacteria. C5b678. C5a. PolyC9. chemotaxis. Membrane attack complex. MBL: mannose binding lectin.

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IM1003: Medical Immunology Introduction to immunological disease principles Prof. L. Ziegler-Heitbrock

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  1. IM1003: Medical Immunology Introduction to immunological disease principles Prof. L. Ziegler-Heitbrock

  2. The complement system C1qrs C3 C4C2 antibody C3a C3b C56789 bacteria C5b678 C5a PolyC9 chemotaxis Membrane attack complex

  3. MBL: mannose binding lectin Ante-antibody Hoffman et al. (1999) Science 284:1313-8

  4. granulocytes macrophages Phagocytosis and intracellular killing

  5. Innate Immune Response Invasion of the same Microbe Invasion of Microbe

  6. 2 systems of immune defence Innate (present from the beginning) Fixed repertoire Recognises rough differences Soluble mediators (complement, MBL) Cells (granulocytes, macrophages) Adaptive (acquired during life) Flexible repertoire Recognises subtle differences Memory Soluble mediators (antibodies) Cells (B cells, T cells)

  7. B T Effector Cells of the Adaptive Immune System B cell receptor Proteins Sugars Lipids Anything T cell receptor Proteins

  8. Fab Fab Fc Antibody Immunoglobulin (Ig)

  9. B 1 B cell makes 1 Antibody During an immune response many different B cells making many different antibodies are activated; the response is polyclonal. For diagnostic and therapeutic purposes a monoclonal antibody may be advantageous. How can monoclonal antibodies be generated?

  10. T cell receptor (TCR) recognises foreign peptide together with an MHC class I or II molecule (also termed HLA molecule) MHC molecule T cell receptor Foreign peptide Major Histocompatibility Complex, Human Leukocyte Antigen

  11. Adaptive Immune Response More and better B and T cells Invasion of the same Microbe Invasion of Microbe

  12. Immune Defence Against Infection T T Extracellular bacteria anti-bacterial antibody C lysis, phagocytosis Intracellular bacteria CD4+ helper cell macrophage is activated to kill mycobacteria IFNg Viruses CD8+ killer cell infected cell is killed

  13. What can go wrong with the immune response ? a) Hyper reactivity Allergy Autoimmunity • Immunodeficiency • Malignancy

  14. IgE

  15. type I antigen Type I allergy house dust mite IgE Fc receptor mast cell degranulation

  16. type II Self cell surface antigen IgG target cell K cell Anti-erythrocyte antibodies leading to hemolytic anemia cytotoxic action IgG target cell complement mediated lysis

  17. type III Lupus erythematodis immune complex deposition tissue C3a C5a basement membrane polymorphs

  18. type IV CD4+ T helper cell activated macrophage or dendritic cell IFNg Type IV (delayed) allergy latex

  19. Antibody against TSH receptor TSH TSH receptor Thyroid epithelial cell Thyroid hormones Thyroid hormones Excessive stimulation of thyroid epithelial cells by antibodies against TSH receptors (Grave’s disease)

  20. Nerve ending Acetyl choline (Ach) Antibody against Ach receptor Ach receptor Muscle Contraction No contraction Inhibition of neuromuscular transmission by antibodies against the acetylcholine receptor (myasthenia gravis)

  21. type I type II antigen IgE IgG target cell K cell Self cell surface antigen cytotoxic action Fc receptor IgG target cell Mast cell degranulation complement mediated lysis type III type IV immune complex deposition Helper T cell activated macrophage or dendritic cell tissue C3a C5a IFNg basement membrane polymorphs type II Stimulating antibody Blocking antibody

  22. What is the basis of tolerance ? Autoreactive Deletion B Receptor down regulation B Blockade of signalling B IL-10 Suppression by Cytokines B

  23. Usually tolerance is intact CH2OH CH2OH OH OH     NHCOCH3 CH2 OH H OH OH CH2OH CH2OH CH2OH OH OH OH A  A NHCOCH3 NHCOCH3 CH3 OH A Anti-B OH OH CH2OH CH2OH CH2OH A OH OH OH  OH NHCOCH3 CH3 OH B OH OH B

  24. If tolerance breaks down antibodies against self are produced. (TSHR), (AChR) = Autoimmune disease

  25. Immunodeficiencies Innate system Adaptive system Inborn MBL deficiency (airway infection) NADPH-oxidase deficiency in phagocytes (chronic granulomatous disease) (bacterial abscesses) Acquired Chemotherapy induced agranulocytosis (severe bacterial infection, sepsis) Inborn Selective IgA deficiency (1/600) (airway infection) X-linked agammaglobulinemia (XLA) (airway infection, enteroviruses) Acquired AIDS: CD4 helper cell depletion (Pneumocystis, CMV) Almost every element of the immune system can be defective, some deficiencies are amenable to gene therapy.

  26. Malignancies of the Immune System Termed Leukemia or Lymphoma Granulocytes Myeloid Leukemia T Lymphocytes T cell Leukemia B Lymphocytes B cell Leukemia B Lymphocytes B cell Lymphoma (Leukemia: increased numbers of white blood cells; Lymphoma: increased size of lymph nodes) Monoclonal antibodies against the normal leukocytes are used to classify the leukemias and lymphomas.

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