Immunodeficiency Syndromes - Monteleone 4/14/16 Flashcards Preview

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Flashcards in Immunodeficiency Syndromes - Monteleone 4/14/16 Deck (23):

primary immunodeficiency



4 types

conds characterized by intrinsic immune system defects : inherited or de novo genetic defects

  • immune system that is either hampered or absent
  • show increased susceptibility to infection, autoimmune diseases, malignancies!


four types:

1. B cell defects

2. T cell defects

3. complement defects

4. phagocytic system defects

*most common?

antibody > combined > phagocytic > cellular > complement



components of immune system

  • innate vs adaptive
  • cellular vs humoral


  • cellular: monocytes/macrophages/DCs, NK cells
  • humoral: complement
    • fx (either solo or with abs): kill microbes, lyse cells, opsonization, effect chemotaxis
    • contributes to post-tissue damage infl


  • cellular: T cells
    • fx: cytotoxicity; help activate B cells to produce antibodies; cytokine secretion
  • humoral: B cells → antibodies
    • bind and form immune complexes
      • neutralize
      • opsonize for phagocytosis, often with complement
    • targets cells for NK cell ADCC


types of immunoglobulins

  • fraction
  • major fx

IgG (75% of serum Ig; major in extravascular spaces)

  • half life: 23 days
  • main ab that controls infection (not first)


  • first Ig produced
  • good at lysing microorganisms


  • important in mucosal immunity


  • binds to basophils and mast cells 
  • parasitic infection and allergy



warning signs of immune deficiency

infections (more than normal number)

  • 4+ ear
  • 2+ serious sinus
  • persistent thrush, skin fungal infection
  • 2+ deepseated infections (ex. septicemia)

abnormal antibiotic req

  • need for IV antibiotics to clear infection
  • 2 or more months on antibiotics with little effect


  • recurrent/deep skin/organ abscesses


index of suspicion

1. frequency/severity of infection

2. duration of infection

3. susceptibility to abnormal infectious agents

4. response to antibiotics



index of suspicion for diff components of immune response 

[types of orgs]

T cells → mucocutaneous candidiadis, persistent resp infection, diarrhea, failure to thrive

  • fungal, herpes virus infections

B cells → sinopulmonary

  • bacterial, parasitic, enterovirus infections

phagocytes → skin infections, visceral abscesses

  • bacterial, fungal infections


  • nontuberculous mycobacteria, Salmonella

complement → Neisseria bacteria (meningitis, gonorrhea)



severe combined immunodeficiency

virtually complete lack of immune fx

  • diminished or absent T cells
  • specific gene defects determine impact on B cells and complement

without treatment, prognosis is death by infection/failure to thrive in first year


DiGeorge Syndrome

defect impacting organs derived from 3rd and 4th pharyngeal arches

  • cardiac: tetralogy of Fallot
  • face: low set ears, cleft palate
  • parathyroid: hypocalcemia
  • thymus: atresia = low/absent T cells

tx: thymus or bone marrow transplant


ataxia telangiectasia

  • variable T cell defect: low CD3/CD4
  • defects in B cells → IgA, IgE deficiency
  • neurologic defects → loss in motor skills, unsteady gait
  • telangiectasias (tiny spider veins) appearing in later childhood
  • increased susceptibility to infection

due to gene mutation


Wiskott Aldrich syndrome

  • progressive T cell syndrome
  • also affects B cells
  • small platelets, thrombocytopenia with petechiae/bruising/bleeding
  • eczema
  • infections: upper resp and opportunistic
  • high incidence of autoimmunity and lymphoid malignancy

X linked (mostly boys)


B cell (antibody deficiencies)

  • agammaglobulinemia
  • IgA deficiency: most common primary immunodef!
  • hyperIgM syndrome
  • common variable immunodef (CVA)
  • X-linked lymphoprolif syndrome (Duncan's)
  • transient hypogammaglobulinemia of infancy


selective IgA deficiency

  • most common primary immunodef
  • only IgA deficient/absent
  • usually asymptomatic, sometimes get recurrent infections/allergies/autoimmune disease
  • sometimes progress to Common Variable Immunodef

sometimes coincident with IgG2 deficiency


what's special about IgA?

  • secretory IgA = 2-4 IgA monomers linked by two addtl chains (J chain and another; formed in IgA-producing plasma cells) + secretory component (polypep that prevents proteolytic degradation in intestine)

no treatment: 



intrinsic B cell disorder : defect in Bruton Tyr kinase → maturation arrest of preB cells → all Igs decreased or absent

  • also B cells nearly absent in blood/periph

X linked or (rare) autosomal

tx: IV or subcut Igs


common variable immunodef

low levels of serum Igs

  • usually normal levels of B cells..something else is off → either lack of CD4 fx or too many CD8s
  • often dont develop recurrent infection until 2nd/3rd decade of life

unclear genetic/inheritance pattern

tx: IV, subcutaneous Ig replacement


phagocytic disorders

  • chronic granulomatous disease
  • neutropenia: chronic or cyclic
  • Chediak-Higashi syndrome
  • leukocyte adhesion deficiency
  • hyperIgE syndrome (Job's)


chronic granulomatous disease

X linked (70%) or auto recessive (30%)

mutation of any of four genes → improper functioning of phagocyte oxidase pathway (NADPH is a role-player) → can't produce necessary superoxide

variable onset, usually in childhood

recurrent life threatening infections

  • catalase-positive bacteria (S. aureus) and fungi
  • granuloma formation
  • pulmo, lympho, hepatic, cutaneous infections most common


Chediak-Higashi syndrome

rare autosomal recessive

defect in protein that transports material into lysosome → large abnormal granules in neutrophils, melanocytes, hair, Schwann cells, CNS

recurrent cutaneous, sino-pulmo infections

partial occulo-cutaneous albinism, mental retardation, late neruopathy and lymphoproleiferative syndrome


tx: bone marrow transplantation


complement deficiencies

classical pathway

  • early components (1-4): increased susceptibility to infection, autoimmune disease 
  • late components (5-9): susceptible to Neisseria infections

alt pathway

  • roperdin
  • Factor H
  • Factor I


evaluation for T cell disorders

  • history
  • CBC with diff, platelet count
  • T cell subset
  • HIV serology
  • delayed hypersensitivity skin tests: PPD, anergy
    • tell whether T cell is actually functioning


evaluation for B cell disorders

  • history
  • CBC with diff, platelet count
  • quantitative immunoglobulins: IgG, IgA, IgM
  • IgE level
  • IgG subclasses
  • pre/post vaccination titers
  • T cell subsets


evaluation for phagocytic disorders

  • history
  • CBC with diff, platelet count
  • examine peripheral smear
  • neutrophil ox burst test


evaluation for complement disorders

  • history
  • total complement level (CH50)
  • individual complement component levels