Q1 IMR disease

  1. Primary immunodeficiency disorders affect what 4 components of the immune system?
    • Innate: phagocytic cells, complement
    • Adaptive: B cells, T cells
  2. Types of phagocytic cell disorders
    • Quantitative
    • Qualitative
  3. Quantitative defects of phagocytic cells
    • Neutropenia (congenital or acquired)--> increased susceptibility to bacterial infection
    • Hyposlpenism (reduced number of macrophages in surgical splenectomy - if spleen removed, more susceptible to infection)
  4. Defect of granule formation and content (qualitative phagocytic cell disoder)
  5. Defect in the fusion of phagosome and lysosome
  6. Characteristics of Chediak-Higashi
    • Partial albinism
    • Giant lysosomes
    • Low NL and CTL
    • Impaired lysosomal trafficking
    • Recurrent BACTERIAL infection
  7. Qualitative cell disorder characterized by defects in oxidative metabolism
    Chronic granulomatous disease
  8. Chronic granulomatous disease
    Immune system has difficulty forming the reactive oxygen compound used to kill certain ingested pathogens --> formation of granulomas in many organs
  9. Pathway that is deficient in chronic granulomatous disease
    Hexose monophosphate
  10. Enzyme complex required by phagocytes to produce reactive oxygen species
    PHOX (phagocyte NADPH oxidase)
  11. Symptoms of chronic granulomatous disease
    • Skin lesions --> large granulomatous masses
    • Recurrent fever, pyoderma, pneumonia
  12. Test used to evaluate PHOX activity
    NBT test
  13. Product produced by normal PHOX activity
    • HOCl (bleach)
    • Bleach is most important killing mechanism in cells
  14. Most common PHOX deficiency
  15. Disease with defective adherence and chemotaxis due to integrin defect
    Leukocyte adhesion disease 1(LAD1)
  16. Disease with defective adherence due to selectin fucosylation defect on the rolling cell
    Leukocyte adhesion disease 2 (LAD2)
  17. Symptoms of LAD1
    • Delayed cord separation
    • Skin ulcers
    • Periodontitis
    • Leukocytosis
  18. Symptoms of LAD2
    • Recurrent infections (cell can't get into tissue)
    • Mental retardation
  19. In what cells does latent TB effect?
  20. What is formed when bacteria is taken up into a macrophage?
  21. Action of IL-12 on T cell
    Stimulates T cell to produce IL-2 and then make interferon γ
  22. Action of interferon-γ on macrophage
    Binds interferon-γ receptor --> macrophage activated via nF-KB pathway --> killing of bacteria
  23. Consequence in deficiency in IL-12/interferon-γ pathway
    Can't kill INTRACELLULAR bacteria (e.g. salmonella, TB) -> recurrent salmonella, TB infections
  24. Are staph and strep intracellular or extracellular pathogens?
  25. Are salmonella and TB intracellular or extracellular pathogens
  26. TLR responsible for recognizing LPS
  27. TLR responsible for recognizing DNA, RNA motifs
  28. EDA-ID
    Ectodermal dysplasia with immunodeficiency
  29. NEMO
    • Non-essential modulator of the nF-KB signalling pathway
    • Important for cytokine signalling pathways
    • Activates other enzyme complexes to translocate into nucleus and initiate transciption
  30. Symptoms of ectodermal dysplasia
    • Abnormal development of teeth, hair, nails, sweat glands (-->anhidrosis)
    • Frequent recurrent infections of gram neg rods, gram + cocci, pneumocystic pneumonia, CMV, mycobacteria
  31. Mutation that causes IRAK4
    IL-1 receptor associated kinase (component of TLR signalling pathway)
  32. Symptoms of IRAK4
    • Pneumococcal meningitis
    • Meningococcal meningitis
    • Staph infection
    • Pseudomonas
  33. What do deficiencies in UNC93B1 and TLR3 deficiences cause increased susceptibility for?
    HSV-1 --> encephalitis, meningitis
  34. Early complement deficiencies are associated with what 2 autoimmune diseases?
    • Lupus
    • Scleroderma
  35. Disease caused by C1 inhibitor deficiency
    Hereditary angioedema
  36. Consequences of C3 deficiency
    Recurrent gram + infections
  37. Consequences of late complement deficiences
    Recurrent gram - infections (ex. neisseria)
  38. BTK
    Bruton's tyrosine kinase
  39. What condition is associated with a deficiency in BTK?
  40. Symptoms of agammaglobulinemia
    • Repeated infection with same pathogens (no memory response)
    • Infections by pyogenic encapsulated bacteria (high grade infections)
    • Lots of infections
  41. CVI
    Common variable immunodeficiency
  42. Problem associated with CVI
    Panyhypogammaglobulinemia (patient doesn't produce specific antibodies vs. pathogens)
  43. Combined defect of T and B system
  44. Specific deficiency associated with SCID
    γ chain in the receptors for IL-2,4,7,9,15,21
  45. Mutatations in what genes are associated with Omenn's syndrome
    • RAGs (recombination activating genes)
    • Effects circulating levels of B and T cells
  46. Job's syndrome
    • Elevated IgE
    • Poor antibody and cell-mediated responsess
    • Staph infections
    • Pneumonia, pneumatocoeles
    • Eczema
    • Eosinophilia
    • Course facial features
    • Don't lose baby teeth
    • Boils
    • Nail infections
  47. Deficiency associated with hyper IgE
    STAT3 (signal transducer and activator of transcription)
  48. IPEX
    Immune disregulation, polyendocrinopathy, enteropathy, X-linked
  49. Deficiency associated with IPEX
    • Lack of T-reg cells (i.e. CD4+, CD25+, FoxP3+ cells)
    • --> problems with liver, endocrine organs, autoimmune diarrhea, ezcema
  50. DNA repair defect associated with brain and immune system
    Ataxia telangiectasia
  51. Chronic mucocutaneous candiadias
    • Severe T cell problem
    • Chronic fungal infections
  52. Symptoms associated with DiGeorge's syndrome
    • Athymia
    • Facial defects
    • Heart defects
    • Recurrent infections of viruses, fungi, mycobacteria
Card Set
Q1 IMR disease
Q1 IMR diseases