1. IMMUNE SYSTEM Dr. Yıldıran1

2. 150 different intracellular signaling pathways Dr. Yıldıran2

3. Again turn thy vision a second time; (thy) vision will come back to thee dull and discomfited in a state worn out. (67-4) Dr. Yıldıran3

4. Human Genom Proteom Microbiome Dr. Yıldıran4

5. Microbiome More than 100 years ago, the human microbiome was defined as; living together with dissimilar organisms (symbiosis), or community of microbes and collection of genomes found in and on the human body. Relman, 2012 Dr. Yıldıran5

6. Immunity Host can recognize self/strange material from itself (microorganisms, antigens etc) and can destroy or make useful them. If this system cannot work properly: –Immune dysregulation Autoimmune disorders (more than 100) Allergy –Immune deficiencies Dr. Yıldıran6

7. Anatomy Lymphoid tissues - primary lymphoid tissues (bone marrow and thymus) - secondary lymphoid tissues (spleen and lymph node)s) Dr. Yıldıran7

8. Organization of the body’s defenses Non-specific defenses: no need to decipher pathogen’s identity. - Physical barriers - Inflammation (in a separate lecture) - Natural cell killers (NK cells) - Complement system Specific defenses: Based on recognition of the pathogen’s identity –Humoral immunity –Cell-mediated immunity Dr. Yıldıran8

9. Main physiologic barriers Hydrochloric acitCiliar epithelia TearsNormal flora Dr. Yıldıran9

10. Non-specific immunity (Innate) Specific immunity (Adaptive) Immune System Dr. Yıldıran10

11. Stem cell Myeloid progenitor Pluripotent Stem cell Lymphoid progenitor Thymus T lr Granulosit-monosit CFUEozinofil CFUBazofil CFU NötrofilEozinofilBazofilMonosit e B lymphocytesT lymphocytes NK cells Granulosit-monosit CFU Cells of immune response develops from common stem cell Dr. Yıldıran11

12. Immune Response Abbas, 2003 Dr. Yıldıran12

13. Specific Immunity Abbas, 2003 Dr. Yıldıran13

14. Weber State University Dr. Yıldıran14 Cellular Humoral

15. (mg/dl) Maternal IgG (in child) IgG IgA IgM Month Year Birth Mean serum immunglobulin level (mg/dl) Maternal IgG (ço IgG IgA IgM Y Age Postnatal Immunglobulin level changes Dr. Yıldıran15

16. Chemotaxis Adhesion Phagocytosis Microbicidal killing Phagocytic system Mainly bacterial and fungal pathogens Dr. Yıldıran16

17. Chronic granulomatous disease Dr. Yıldıran17

18. Complement system Of nine substantial, many blood proteins Opsonization Chemotaxis Neutrolization Lysis of bacteria and cells Anaphylotoxin Complement system also promotes inflammation Dr. Yıldıran18

19. PID Primary Immunodeficiencies Rarely seen genetic and variable diseases Incidense 1/2-10.000 live birth Most important signal is infection. More than 200 diseases Samarghtiean, 2009 Dr. Yıldıran19

20. Clinical Presentation Serious overwhelming recurrent life- threatening infections of predominantly respiratory, GI or skin system. Dr. Yıldıran20

21. Common Infection In one year: –More than two severe infections –More than three RTI (sinusitis, otitis, bronchitis) –Antibiotic need more than two months Dr. Yıldıran Stiehm, Uptodate, 2012 21

22. Think imunodeficiency Dr. Yıldıran Buckley, IDF, 2009 22

23. ESID Classification Primary Immunodeficiencies 1 Predominantly T cell deficiencies 2Antibody deficiencies 3Other well defined immundeficiencies 4Complement deficiencies 5Phagocytic disorders 6Autoimmune and immundysregulation disorders 7Autoinflammatory diseases More than 200 diseases Dr. Yıldıran23

24. Common infection Recurrent absscess Persistent moniliasis Persistent diarrhea Prolonged and/or severe infection Unusual pathogen İllness after live vaccine Need for immunological evaluation Dr. Yıldıran24

25. PID Samples Bruton diseases: Agammaglobulinemia SCID: T cells absent Hereditary Angioedema: C1inh absent CVID: B cell dysfunction Di George Syndrome: 22q11del, thymus hipoplasia CGD: NADPH oxidase deficiency Dr. Yıldıran25

26. Malnutrition Stress Diabetes mellitus İschemic artery disease HIV infection Cirrhosis Nephrotic syndrome Intestinal lymphangiectasis Hemoglobinopathy Neurological dis. Secondary ID Dr. Yıldıran Stiehm, Uptodate, 2012 26

27. AIDS HIV destroys CD4 T cells (adaptive immunity!) Virus contaminates from blood products, sexually or vertically in delivery of newborn. Dr. Yıldıran27

28. Related Lectures Immunodeficiencies Complement system Innate immune system Adaptive immune system Immunoglobulins Self-tolerance Hypersensitivity reactions Dr. Yıldıran28