W13.1 Flashcards
Primary Immunodeficiency
inherited dysfunctions of the immune system
- Rare (except IgA deficiency), but there are more than 120 immune deficiencies
- Defects can occur at each arm of the IS
Arms of the immune system
Adaptive and Innate
A - T cells and B cells
I - Macs/DCS and Neutrophils
Manifestations (immunoDef)
Determined by IS arm affected: Humoral immunity, T-cell immunity, Phagocytes, Complement
- Interactions between various arms of IS:
- Further deficiency on other arms
- Hyperactivity on other arms (allergy, autoimmunity)
- The clinical symptoms associated with immune deficiencies range from very mild or subclinical to severe recurrent infections or failure to thrive
Humoral (ImmunoDef)
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Types - Humoral (ImmunoDef)
- Temporary Hypogammaglobulinemia of the Infant (THI)
- Bruton’s Agammaglobulinemia/X-linked Agammaglobulinemia
- IgA Deficiency
- Common Variable Immunodeficiency
- (Note: Humoral and Cellular arms interact)
Evaluations (age) - Humoral (ImmunoDef)
- In evaluating immunoglobulin deficiency states, it is important to remember that blood levels of immunoglobulins change with age
- IgM reaches normal adult levels first, around 1 year of age, followed by IgG at about 5 to 6 years of age.
- In some normal children, IgA levels do not reach normal adult values until adolescence.
THI (ImmunoDef)
- Low levels of IgG from 3 mo-1 year of age are normal
- If persists —> THI
- IgG drops below 2SD age-adjusted mean; IgM or IgA may/may not be affected
- Unknown mechanism
- Cellular immunity normal
- Normal CD19+ B cells
Ba (ImmunoDef)
- Bruton’s agammaglobulinemia (BA)
- X chromosome–linked, affects males almost exclusively (also called XLA)
- Bruton’s tyrosine kinase (Btk) enzyme deficiency -> no pre-BcR signal necessary for survival
- Arrested differentiation at the pre-B cell stage -> no B cells or plasma cells
- No mature CD19 positive B cells + deficiency of all Ig classes
- Normal T cells
- Recurrent bacterial infections in infancy, as maternal IgG clears
Difference between THI and Ba immunodef
BA:
- Age (beyond 2 yrs age)
- No CD19+ B cells in peripheral blood §Abnormal histology of lymphoid tissues
(small or absent lymph nodes)
IgA deficiency (ImmunoDef)
- Most common ImmunoDef
- Many patients are asymptomatic. § In symptomatic pts:
- infections of the respiratory and gastrointestinal tract
- increased tendency to autoimmune diseases (SLE, RA, CD, thyroid AI) and allergy
CVI (ImmunoDef)
- Common variable immunodeficiency (CVI)
- Most common primary immune deficiency with a severe clinical syndrome, low incidence
- recurrent bacterial infections (sinusitis and pneumonia), shingles (herpes zoster)
- Commonly IgA+IgG deficiency, selective IgG deficiency may occur.
- Normal numbers of mature B cells
Isolated IgG subclass deficiency
may not affect total IgG below 2SD, but result in an abnormal distribution of the IgG subclasses.
- If recurrent infections but normal total IgG -> test different subclasses if clinical picture suggests immunoglobulin deficiency.
Laboratory Diagnostics (ImmunoDef)
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Laboratory Diagnostics (ImmunoDef) * SPE *
Protein Electrophoresis (SPE)
- Major plasma protein separation
- Ig in gamma region
- Diffuse smear indicates polyclonal g (normal)
- Quantitative decrease in gamma region suggests ImmunoDef
- Further analysis
- Monoclonal bands produce narrow intense bands
- one or more monoclonal bands indicates clonality of responseà cancer
- Further analysis
Laboratory Diagnostics (ImmunoDef) * IFE *
- After electrophoresis in SPE, specific antibody to Ig isotype is added to gel and visualized
- Similar interpretation to SPE but also provides info regarding Ig isotype affected
