Immunodeficiency diseases Flashcards
1
Q
Primary immunodeficiency
A
- Congential–many manifest in infancy (between 6 mths and 2 yrs)
- Can affect T or B lymphocyte functions in adaptive immunity.
- Detected through multiple recurrent infections.
- B cell and combined B and T cell disorders more common types
2
Q
Secondary immunodeficiency
A
- Due to complications of cancer, infection, malnutrition, immunosupression, irradiation, chemo
- Far more common than primary form
3
Q
X-linked agammaglobulinemia (Bruton’s agammaglobulinemia)
A
- FAILURE OF B CELL PRECURSORS TO DEVELOP INTO MATURE B Cells
- mutation in x-linked gene that encodes cytoplamic tyrosine kinase
- Decreased/absent B cells in peripheral blood
- Decreased/absent Ig
- No plasma cells
- Underdeveloped germinal centers in lymph nodes and Peyer’s patches
- Clinical symptoms appear around 6 mths
- -Recurrent sinopulmonary bacterial infections
- -certain viral infections that require neutralizing Ab
- -often persistent girardia infection
- risk of autoimmune diseases
- Treatment: prophylactic Ig therapy
4
Q
Common variable immunodeficiency
A
- FAILURE OF B CELLS TO DIFFERENTIATE INTO PLASMA CELLS
- Decreased Ig production
- Normal # of B cells in blood, but no plasma cells
- B cell lymphoid areas (germinal centers) are hyperplastic
- Sporadic and inherited forms exist
- Diagnosis based on exclusion
- Symptoms similar to X-linked agammaglobulinemia
- Both sexes affected equally
- Onset in childhood or adolescence
- Treatment: prophylactic Ig therapy.
- Increased risk of autoimmne diseases lymphoid malignancies, increased gastric cancer risk
5
Q
Isolated IgA deficiency
A
- FAILURE OF B CELLS TO DIFFERENTIATE INTO IgA PRODUCING PLASMA CELLS
- IgA levels decreased
- May be familial or acquired from infection
- Most asymtomatric (1 in 600 ind. of european descent)
- Mucosal defenses weakened in those with symptoms.
- -Sinopulmonary and diarrhea (giaradia)
- -High risk of respiratory tract allergies, increased autoimmune disease risk
- -May develop severe, even fatal ractions to transfused blood products (normal IgA in blood product acts like foreign antigen)
6
Q
DiGeorge Syndrome (Thymic hypoplasia)
A
- T CELL DEFICIENCY DUE TO FAILURE OF 3rd AND 4th PHARYNGEAL POUTCHES TO DEVELOP
- Variable loss of T cell mediated immunity (thymic hypoplasia or lack of thymus, tetany or lack of parathyroid glands, congenital heart or great vessel defects, facial abnormalities)
- Usually sproadic deletion of chromosome 22q11.
- Low T lymphocyte levels in peripheral blood, and T cell areas in spleen and lymph nodes depleted.
- Susceptible to fungal, viral and pneumcysitis jiroveci infections.
- Serum Ig levels may be normal or reduced depending on the severity
7
Q
Hyper IgM syndrome
A
- CAN MAKE IgM, BUT DEFICIENT IN ABILITY TO MAKE IgG, IgA, IgE (DEFECT IN CLASS SWITCHING)
- Elevated IgM levels, no IgA, no IgE, and very low levels of IgG.
- Normal T and B lymphocytes in peripheral blood
- Defects in ability of CD4+ T helper cells to deliver activating signals to B cell s and macrophages (needed for class switching)
- Over 1/2 have X-linked recessive mutation in gene encoding CD40 ligand
- Recurrent pyogenic infections, risk for IgM induced cytopenias, suscceptible to pneumocystis jiroveci
8
Q
Severe combined immunodeficiency (SCID)
A
- PROFOUND DEFECTS IN BOTH HUMORAL AND CELL MEDIATED IMMUNITY
- w/o hematopoietic stem cell transplant, death occurs within 1 yr
- Thrush, extensive diaper rash, FTT. Extremely susceptible to reccurent, severe infections by wide range of pathogens
- Many different genetic mutations. Most common form is X-linked and due to gene encoding common gamma-chain subunit of cytokine receptors. Other types are inherited as autosomal recessive disorders. Most common autosomal recessive form is deficiency in adenosine deaminase (ADA).
- Reduced cytokine signal and impaired T cell development.
- Treatment: hematopoietic stem cel transplantation. Some have also been treated with gene therapy (but some then developed acute T-cell leukemias
9
Q
Immunodeficiency with thrombocytopenia and eczema (Wiscott-Aldrich Syndrome)
A
- X-LINKED RECESSIVE DISORDER WITH THROMBOCYTOPENIA, ECZEMA, VULNERABILITY TO RECURRENT INFECTION LEADING TO PREMATURE DEATH
- Mutations in gene encoding Wiscott-Aldrich Syndrome Protein (WASP), on short arm of X chromosome. Believed to be responsible for linking membrane receptors to actin filaments. Mutation leads to defects in cell migration and signal transduction
- Depletion of T lymphocytes and variable loss of cell-mediated immunity.
- Ab production to polysaccharide antigens absent
- Low IgM levels (increased risk of infection with encapsulated organisms)
- IgG levels normal, IgE, IgA levels often elevated.
- Risk for Hodgkin lymphoma
- Treatment: hematopoietic cell transplantation
10
Q
X-linked lymphoproliferative syndrome
A
- INABILITY TO ELIMINATE EBV, LEADING TO SEVERE AND SOMETIMES FATAL INFECTIOUS MONO AND B CELL LYMPHOMAS
- Most cases due to mutation in SLAM-associated protein (invovled in activation of NK cells and T and B lymphocytes
11
Q
Chediak-Higashi syndrome
A
- Rare autosomal recessive disorder
- Recurrent pyogenic infections, partial oculocutaneous albinism, progressive neuro abnormalities, mild coagulation defects
- CHS1/LYST (BEACH family)–> DEFECTIVE FUNCTION OF PHAGOSOMES AND LYSOSOMES IN PHAGOCYTE FUNCTION
- Diagnoisis: pahogenomic cytoplamsic granules in leukocytes
12
Q
Complement system deficiencies
A
C5-C9 increased risk of recurrent neisserial infections!
Impaired membrane attack complex that is involved in lyisis of organisms
13
Q
Causes of secondary immunodefieciency
A
- Immunosuppressive therapy (meds)
- Microbial infections
- Malignancy
- Disorders of biochemical homeostasis
- Autoimmune disease
- Severe burn injury
- Exposure to radiation/toxic chemicals
- Asplenia/hyposplenism
- Aging
14
Q
What type of infection are patients without a spleen at risk for? Why?
A
- Increased risk of bacterial infection with encapsulated organisms (especially strep pneumoniae).
- Recieve vaccinations for S. pneumoniae, H. influenzae, N. meningitidis
- Loss of splenic macrophages post-splenectomy
15
Q
3 ways one could suspect immunodeficiency
A
- Clinical history
- Presents with opportunistic infection from signature organisms (Nocardia, oral canidiasis, invasive aspergillus, pneumocystis jiroveci pneumonia)
- Presents with repeated infections
