Immunodeficiency Flashcards
Severe combined immunodeficiency (SCID)
Low B AND T cells
Block in the development of the lymphoid stem cell
X-linked (Bruton) hypogammaglobulinemia
Normal T cells but LOW OR NO B cells
Block between the pre-B cell and the B cell.
Common variABle immunodeficiency
Normal # of pre-B cells and B cells, but the B cells are difficult to trigger to make specific antibody
DiGeorge syndrome
Thymic stroma is derived in the embryo from the 3rd and 4th pharyngeal pouches.
Abnormal development –> stroma won’t support thymic lymphoid development –> Absent T cells, no B cells.
Deletion on chromosome 22
Characterize the infections you would expect in a pure B cell deficiency and in a pure T cell deficiency.
T deficiencies: intracellular pathogens, including viruses, certain bacteria, and yeasts and fungi, especially Candida albicans and Pneumocystis jirovecii.
B deficiencies: “high-grade” (extracellular, pyogenic = pus-producing) bacterial pathogens such as Staphylococcus aureus, Haemophilus influenzae and Streptococcus pneumoniae.
Describe the clinical features which, although not immunological, are part of DiGeorge syndrome.
CATCH-22 Cardiovascular Abnormal face Thymus Clefts Hypo-parathyroidism 22 (chromosome)
Discuss the incidence of selective IgA deficiency, and the associated syndromes.
Most common immunodeficiency disease
Freq = 1/500
Usually asymptomatic, but pt may have
- diarrhea and sinopulmonary infections,
- increased frequency and severity of allergies
- Familial tendency
- 10-15x more frequent in celiac pts
Describe the immunological problem of the Nude mouse, and name the human immunodeficiency condition it resembles.
Nude mice fail to make a thymic stroma (and hair) and so they have no T cells, similar to DiGeorge kids
Name the enzyme which is absent in certain cases of SCID. Discuss possible approaches to replacing this enzyme.
Adenosine DeAminase (ADA) - adenosine accumulates in all cells but apparently impairs lymphocyte development most severely.
RBCs are full of ADA. Administer IRRADIATED RBCs (because you can’t guarantee that there are no WBCs in there. If foreign lymphocytes get in, they’ll attack and there’s no way to stop them). In fact, anytime an immunodef pt is given blood, you should irradiate it. (PEG-ADA could be given too; PEG helps it stay in the blood)
Discuss transplantation therapy in immunodeficiency diseases. Include a consideration of possible complications.
DiGeorge: fetal thymus or cultured thymic stromal cells have been used to try to minimize the risk of graft-versus-host disease. Some success is claimed; better diagnosis would aid in the selection of appropriate cases.
For SCID: bone marrow transplantation has about a 50% success rate, but graft-versus-host disease is always a problem. It is better to transplant purified stem cells than whole bone marrow. Sibling donors are the best, and a good Class II MHC match is imperative.
Given a child with recurrent infections, describe in principle tests which could be done to determine if there is a T, B or combined immunodeficiency, or a PMN, macrophage or complement problem.
B cell:
- Serum protein electrophoresis
- Quantitative IgG, IgA, IgM levels
- Specific Abs to prior immunizations
- ABO isohemagglutinins
T cells
- Skin test with recall Ag panel
- Total lymphocyte count
Phagocytes
- WBC count, differential, morphology
- NBT test, oxidative burst
Complement
- CH50
- Assay for C1inh (inhibitor)
Describe the contents and routes of administration of commercial gamma globulin (IVIG) and indicate the conditions in which it can be useful replacement therapy.
ROA: IV, but recently Sub-cut @home was approved
Condition: B cell function is deficient
Name two viruses which are immunosuppressive in humans. Discuss a possible mechanism for the immunosuppression caused by one of these viruses.
HIV infects CD4 T cells which are killed directly by the virus and by CD8s attacking them
