1 / 25

Immunology 2008 Lecture 25 Immunodeficiency 10 November

Immunology 2008 Lecture 25 Immunodeficiency 10 November. TODAY Immunodeficiency, Chap. 21. Immunodeficiency. Immunodeficiencies. ● Congenital/Primary genetic or developmental defect ● Acquired/Secondary result of disease or therapy. Efferent/Congenital. Chronic Granulomatous Disease.

loren
Download Presentation

Immunology 2008 Lecture 25 Immunodeficiency 10 November

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Immunology 2008 Lecture 25 Immunodeficiency 10 November

  2. TODAY Immunodeficiency, Chap. 21

  3. Immunodeficiency

  4. Immunodeficiencies ● Congenital/Primary genetic or developmental defect ● Acquired/Secondary result of disease or therapy

  5. Efferent/Congenital Chronic Granulomatous Disease  defect in the ability of MF and PMNs to kill phagocytosed organisms  chronic bacterial infections  several genetic defects in NADP oxidase system  antibiotics (& B.M. transplant?)

  6. Efferent/Congenital Complement Deficiencies  absence of one or another complement component  C1,4: autoimmune diseases, some infections C5-9: Neisseria infections Properdin : many pyogenic infections  maintained with antibiotics Question: Would bone marrow transplant help?

  7. Bruton’s Agammaglobulinemia DiGeorge Syndrome, Thymic Aplasia Severe Combined Immunodeficiency Central/Congenital

  8. Central/Congenital Bruton’s Agammaglobulinemia  bacterial infections starting ~4-8 months  absence of functional B-cells  X-linked recessive, gene for BTK (Bruton’s Tyrosine Kinase)  Intravenous Ig therapy

  9. ? Central/Congenital DiGeorge’s Syndrome, Thymic Hypoplasia  postnatal hypocalcemic tetany, viral and fungal infections within first few months  absence of thymus or functional T-cells  development defect of 3rd & 4th pharyngeal pouches, defective thymus & parathyroid (part of heterogenous family of Cardiovelofacial Syndrome)  sporadic deletions on chromosome 22  supportive therapy, or thymic epithelial transplant ectopic transplant

  10. Central/Congenital Severe Combined Immunodeficiency  overwhelming infections in first year of life  absence of functional T- or B-cells  several genetic defects, including ADA (adenosine deaminase), PNP (purine nucleotide phosphorylase), IL-2Rg (IL-2 receptor gamma, X-linked)  cured with successful B.M. transplant

  11. David the “Bubble Boy”, born with SCID ●Born in 1971; older brother had died of SCID (Pneumocystis infection) one year earlier. ●Potential problem was expected; 50% male, 50% diseased ●“Germ-free” birth, reverse isolation chamber. (Not truly germ-free, 35 species of microorganism identified at age 6).

  12. ● Phagocytic function, ADA & com-plement close to normal. ● IgM low, no IgG, traces of IgA, some IgD (determined with RID)

  13. ●No response to KLH, either by Ab or skin test (CMI). ●No Ab response to typhoid antigen

  14. ●Lymphocytes ~400/cmm (~10% of normal), ~1/3 sIg+, ~2/3 ERFC ●Minimal lymphocyte response to PHA, PWM, MLC. ●“Transfer Factor” given at 10-16 months; poor or no response to fungal skin tests.

  15. ●Bone marrow transplant in 1983 at age 12 (treated with mAb to reduce T-cells) from 15-year-old sister. ●Died 4 months later with a poorly understood pathology

  16. Central/Congenital New Form of Human T-Cell Deficiency Pignata, C. et al., Am. J. Med. Genet. 65, 167-170 (1996) Frank et Al., Nature. 398, 473-4 (1999)  Two sisters in southern Italy, each born with complete absence of scalp hair, eyelashes and eyebrows.  No thymic shadow visible on X-ray, striking impairment of T-cell function.  One sister died at 12 months, the other survived after receiving a B.M. transplant at 5 months  Mutation in WHN gene on chromosome 17 whn is the mutated gene responsible for nu/nu mice, encodes a transcription factor in thymus & skin

  17. Central/Congenital X-Linked Hyper-IgM Syndrome  bacterial infections in first 2 years, upper respiratory and others  low serum IgG, high IgM  X-linked recessive gene  Maintained by intravenous Ig What gene is this?

  18. Classic Three-Cell Interaction from Core Notes

  19. XHIGM - Absence of CD40L Modified to account for generation of B memory cells (IgM) (IgG…)

  20. Leukocyte Adhesion and Migration Important for all aspects of generation and execution of immune responses

  21. Efferent/Congenital Leukocyte Adhesion Deficiency, Type I  Failure to express CD18 b-2 integrin on lymphocytes, monocytes and neutrophils, part of adhesion complexes (including LFA-1) and C3b receptor  Massive bacterial infections by 2 years  Defective migration of lymphoid cells to sites of infection and inflammation  Cured by successful B.M. transplantation

  22. Acquired Immunodeficiencies Secondary to Disease ● Infectious disease (toxins, immunosuppression; HIV…) ● Malignancy (immunosuppression, depression of hematopoiesis) ● Malnutrition (T-selective deficiencies) ● Splenectomy (loss of filtration & phagocytic cells; increased bacterial infections)

  23. Acquired Iatrogenic immunodeficiencies caused by therapeutic intervention ● Cytotoxic drugs, steroids, (malignancies, autoimmune & inflammatory conditions…) ● ALG (anti-lymphocyte globulin) ● Ionizing radiation ● Cyclosporin, FK506 (tacrolimus) (organ grafts, autoimmunity…)

  24. THURSDAY Allergy, Chapter 18 Hybridomas, Appendix 10 MONDAY Exam #2, 9:00 AM Covers all material since the first exam through this week (+HLA genetics & MLR) TUESDAY Tumor Immunology, Chap. 23

  25. Fin

More Related