Secondary Immunodeficiency

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Secondary Immunodeficiency

  1. 1. SECONDARY IMMUNE DEFICIENCY w.pongsak,MD
  2. 2. scope <ul><li>Extreme age </li></ul><ul><li>malnutrition </li></ul><ul><li>Metabolic diseases </li></ul><ul><li>- DM </li></ul><ul><li>- uremia </li></ul><ul><li>Surgery and trauma </li></ul><ul><li>Environmental condition </li></ul>
  3. 3. Introduction <ul><li>Primary vs secondary immune deficiency </li></ul><ul><li>Most common cause of SID is… </li></ul><ul><li>Complexity of SID </li></ul><ul><li>What did you know about SID? </li></ul>
  4. 7. Extreme Age <ul><li>Newborn peroid </li></ul><ul><li>Advanced age </li></ul>
  5. 8. Newborn peroid <ul><li>Neonate increase susceptibility to infection than older children </li></ul><ul><li>Fewer marginal zone B cell & decrease CD 21 expression on B cells </li></ul><ul><li>Immature of 2 nd lymphoid organ </li></ul><ul><li>Absent maternal IgG before 32 wks GA </li></ul><ul><li>Defect in innate immunity </li></ul><ul><li>- decrease neutrophil storage pool </li></ul><ul><li>- decrease Neu. Function </li></ul><ul><li>- decrease TLR signaling, cytokine production </li></ul><ul><li>complement </li></ul>
  6. 9. Advanced age <ul><li>Increase elderly in population </li></ul><ul><li>Decline in immune system with age </li></ul><ul><li>Impaired ability to respond to vaccine and to fight infection </li></ul><ul><li>Innate immunity & aging </li></ul><ul><li>Adaptive immunity & aging </li></ul><ul><li>Thymic involution </li></ul><ul><li>CMV and immune senescence </li></ul><ul><li>- aging=> CMV infection </li></ul><ul><li>- CMV infection => aging of immune </li></ul>
  7. 12. Robert R Rich . Clinical immunology 3 rd edition
  8. 13. Robert R Rich . Clinical immunology 3 rd edition
  9. 14. Innate immunity & aging <ul><li>Neutrophil - oxidative burst </li></ul><ul><li>- bactericidal activity </li></ul><ul><li>- Chemotaxis </li></ul><ul><li>M Ǿ - Phagocytic activity </li></ul><ul><li>- Oxidative burst </li></ul><ul><li>- MHC class II expression </li></ul><ul><li>NK cells - Numbers of cells </li></ul><ul><li>- cytotoxicity </li></ul><ul><li>- inflammatory cytokines </li></ul><ul><li>- proliferative response to IL-2 </li></ul>
  10. 15. Adaptive immunity & aging <ul><li>T cell - naïve T cell count </li></ul><ul><li>- memory and effector T cell count </li></ul><ul><li>- diversity of T cell repertoire </li></ul><ul><li>- expression of costimulatory Mol. </li></ul><ul><li>- proliferation capacity </li></ul><ul><li>- T cell signaling </li></ul><ul><li>- activation of naïve T cell </li></ul>CD 28 - CD8 T cells may be CD 27 + or - but CD 28 - CD4 T cells limit to CD 27 - =>loss of CD 40L =Loss of co-stimulatory molecule Thymic involution
  11. 16. <ul><li>B cells - generation of B cell precursors </li></ul><ul><li>- number of B1 cells </li></ul><ul><li>- diversity of B cells repertoire </li></ul><ul><li>- size and number of germinal center </li></ul><ul><li>- expression of costimulatory </li></ul><ul><li>molecule </li></ul><ul><li>- antibody affinity </li></ul><ul><li>- isotype switching </li></ul><ul><li>- specific antibodies for foreign </li></ul><ul><li>antigen </li></ul><ul><li>- serum antibodies specific self </li></ul><ul><li>antigen </li></ul><ul><li>- stimulation of B cells by follicular </li></ul><ul><li>dendritic cells </li></ul>
  12. 18. Vaccine in elderly <ul><li>Protective efficacy partial loss in elderly </li></ul><ul><li>Occur in both regular vaccine and new vaccine </li></ul><ul><li>New development of vaccine for elderly </li></ul><ul><li>- immunomodulatory adjuvants </li></ul><ul><li>- new antigen that readily ingest by APC </li></ul><ul><li>- live attenuate vaccine is not suitable </li></ul><ul><li>- shortening interval of booster dose </li></ul><ul><li>- repeated dose of booster vaccine </li></ul>
  13. 20. 1.12 1.12 Increase threshold to respond to danger signal Functional defect of APC Progressive loss of naïve T cell Reduce naïve B cell isotype switching and Somatic Hypermutation Increase effector T cell , restrict diversity of T cell Aging of BM caused short duration of protection
  14. 25. Stratergies to reverse or delay immunosenescence <ul><li>Thymic reconstruction </li></ul><ul><li>Reduction of antigenic stimulation </li></ul><ul><li>Depletion of senescent T cells </li></ul><ul><li>- KLRG-1,CD57 marker of sT cells </li></ul><ul><li>Caloric restriction </li></ul><ul><li>- data inconclusive </li></ul>
  15. 27. Malnutrition <ul><li>Most common cause of SID </li></ul><ul><li>Primary and secondary malnutrition </li></ul><ul><li>PCM usually occur with micronutrient def. </li></ul><ul><li>Primary malnutrition </li></ul><ul><li>- atrophy of lymphoid organ </li></ul><ul><li>- T cell deficiency like CTA </li></ul><ul><li>- barrier defect </li></ul><ul><li>- activation of HPA axis </li></ul><ul><li>- Immunoglobulin ? </li></ul><ul><li>- decrease phagocytosis </li></ul><ul><li>- reversible if renutrition </li></ul><ul><li>malnutrition ↔ infection </li></ul>J Allergy Clin Immunol 2005 ;1151119-28
  16. 28. Robert R Rich . Clinical immunology 3 rd edition ?
  17. 29. N=144
  18. 30. <ul><li>Micronutrient deficiency </li></ul><ul><li>- Iron => cofactor in immune function </li></ul><ul><li>- Zinc & copper => essential for thymic hormone,reduce </li></ul><ul><li>Th1 cytokine ,lymphopenia, reprogramming of immune </li></ul><ul><li>loss of NK, T cells </li></ul><ul><li>- Selenium => selenoprotein is antioxidant host defense </li></ul><ul><li>system affecting lymphocyte and NK cell </li></ul><ul><li>- antioxidant vitamin deficiency </li></ul><ul><li>1. vit A def. => panhypogrammaglob.impair mucosal </li></ul><ul><li>barrier,NK ,PMN,M Ǿ, impair Th1 and Th2 </li></ul><ul><li>2. vit C def.=> regulator of redox and metabolic </li></ul><ul><li>checkpoint and survival of immune system </li></ul><ul><li>3. vit E def.=> monocyte/M Ǿ response, influence T cell </li></ul><ul><li>function by reduce PGE2 production </li></ul>J Allergy Clin Immunol 2005 ;1151119-28
  19. 31. J Allergy Clin Immunol 2005 ;1151119-28
  20. 32. J Allergy Clin Immunol 2005 ;1151119-28
  21. 34. N=265
  22. 35. Conclusion: CD4 T and B cell decrease in malnutrition with infectious pt.
  23. 36. Metabolic diseases <ul><li>Diabetes Mellitus </li></ul><ul><li>Uremia </li></ul>
  24. 37. Diabetes Mellitus <ul><li>Mortality rate 43% in ketosis with infection </li></ul><ul><li>2/3 of bactermia in hospitalized pts. </li></ul><ul><li>Complexity of risk to infection </li></ul><ul><li>Immune defect in diabetes patients </li></ul><ul><li>- innate immunity </li></ul><ul><li>- humoral innate immunity </li></ul><ul><li>- cellular innate immunity </li></ul><ul><li>- adaptive immunity </li></ul>
  25. 38. <ul><li>Humoral innate immunity </li></ul><ul><li>1. complement function </li></ul><ul><li>- low C4 concentration but no play important </li></ul><ul><li>role in infection </li></ul><ul><li>2. Cytokines </li></ul><ul><li>- low IL-1,IL-6 secretion after LPS </li></ul><ul><li>stimulation </li></ul><ul><li>- advance glycocylated end product ? </li></ul><ul><li>3. Hyperglycemia/Glycosuria </li></ul><ul><li>- enhance virulence of organism such as </li></ul><ul><li>Candida </li></ul><ul><li>- glucosuria enhance bacterial growth such as </li></ul><ul><li>E.coli </li></ul>Defect in innate immunity
  26. 39. <ul><li>Cellular innate immunity </li></ul><ul><li>1. Chemotaxis </li></ul><ul><li>- decrease Neu. Chemotaxis </li></ul><ul><li>- not depend on level of blood glucose </li></ul><ul><li>2. Adherence </li></ul><ul><li>- conflict data </li></ul><ul><li>3. Phagocytosis </li></ul><ul><li>- inverse correlation with HbA1C </li></ul><ul><li>- improve phagocytosis if better control DM </li></ul>
  27. 40. <ul><li>4. Oxidative burst </li></ul><ul><li>- lower in diabetic patients </li></ul><ul><li>- inconsistent data </li></ul><ul><li>5. Killing </li></ul><ul><li>- conflicting result </li></ul><ul><li>- Staph aureus killing is impaired all study </li></ul><ul><li>but not in C. albicans </li></ul><ul><li>Impair chemotaxis and phagocytosis in monocyte </li></ul>
  28. 42. <ul><li>Adaptive immunity </li></ul><ul><li>- CMI </li></ul><ul><li>decrease lymphocyte prolipheration </li></ul><ul><li>after stimulation, abnormal DTH </li></ul><ul><li>- HMI </li></ul><ul><li>normal level and function of Ig </li></ul><ul><li>normal response to vaccine </li></ul>
  29. 44. Uremia <ul><li>Immune dysregulation in ESRD is complex </li></ul><ul><li>metabolic acidosis </li></ul><ul><li>“ Advanced oxidation protein product” </li></ul><ul><li>Uremic toxin syndrome </li></ul><ul><li>Impair immunity cuased by both low and high molecular wt. toxin </li></ul>
  30. 47. Surgery and Trauma <ul><li>Disruption of epithelial barriers and cell destruction </li></ul><ul><li>Excessive response of inflammation </li></ul><ul><li>Nonspecific cell activation cause anergic immune stage to specific Ag </li></ul><ul><li>Increase cortisol level </li></ul>
  31. 48. Robert R Rich . Clinical immunology 3 rd edition
  32. 49. splenectomy <ul><li>Endothelial filtration organ </li></ul><ul><li>Phagocytosis,Opsonin ( IgM) ,complement </li></ul><ul><li>( properdin) </li></ul><ul><li>OPSS - children > adult </li></ul><ul><li>- highest risk in first 3yrs </li></ul><ul><li>- MCM organism =>streptococcus , </li></ul><ul><li>H.influenza, staph. , capnocytophaga, </li></ul><ul><li>intracellular organism </li></ul><ul><li>- prevention 1. immunization </li></ul><ul><li>2. ATB prophylaxis </li></ul><ul><li>3. education </li></ul>
  33. 55. Environmental condition <ul><li>UV light </li></ul><ul><li>- induce T cell apoptosis,anergy </li></ul><ul><li>- poor Ag presentation </li></ul><ul><li>- nonspecific tolerogenic cytokines, Treg </li></ul><ul><li>- humoral immunity and phagocyte relative </li></ul><ul><li>radioresistant but.. </li></ul><ul><li>Space flight </li></ul><ul><li>- weakening T ,NK cell immunity </li></ul><ul><li>- increase release cortisol and suppressive </li></ul><ul><li>cytokines </li></ul><ul><li>- concomittent with sleep disorder,radiation </li></ul><ul><li>- not effect in humural immunity </li></ul><ul><li>High altitude </li></ul><ul><li>- T and NK cell cytopenia </li></ul><ul><li>- decrease serum IgG level </li></ul>
  34. 56. Robert R Rich . Clinical immunology 3 rd edition
  35. 57. conclusion <ul><li>MCM cause of immune def. is malnutrition </li></ul><ul><li>Extreme age and immune deficiency </li></ul><ul><li>Metabolic dis affect immune system </li></ul><ul><li>Surgical condition can effect immune system </li></ul><ul><li>Environmental factor and immune defect </li></ul>
  36. 58. Thank you for your attention
  37. 60. 1.10
  38. 61. 1.10
  39. 63. 1.10
  40. 64. Nature Reviews Immunology 2008;8:685-98

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