Deficiency of Adaptive Immunity (Immune Deficiencies) Flashcards
Indicate locations of abnormalities of development in:
DiGeorge syndrome
Severe combined immunodeficiency (SCID)
X-linked (Bruton’s) hypogammaglobulinemia
Common variable immunodeficiency
Digeorge Syndrome: 3rd and 4th pharyngeal pouches that give rise to the lymphoid part of the thymus.
SCID: Block in the development of the lymphoid stem cell in the bone marrow.
X-linked (Bruton’s) hypogammaglobulinemia: Block between development of pre B cell to B cell in the bone marrow.
Common variable immunodeficiency: B cells are difficult to trigger to make specific antibody in a lymph node.
Characterize the infections you would expect in a pure B cell deficiency and in a pure T cell deficiency.
T cell deficiencies are associated with severe infections, including viruses, certain bacteria, and yeasts/fungi.
B cell deficiency is characterized by infections with high grade (extracellular, pyogenic–> pus producing) bacterial pathogens, such as staph aureas, hamephilus influenzae and strep. pneumoniae.
Describe the clinical features which, although not immunological, are part of DiGeorge syndrome.
Unexplained convulsions in infancy which can be controlled by Calcium.
Abnormalities in the development of the great vessels of the heart.
Cell mediated immunity is also depressed–> viral and fungal infections are common.
Discuss the incidence of selective IgA deficiency, and the associated syndromes.
Most common immunodeficiency disease (1/500). Usually asymptomatic, patient may have diarrhea, sinopulmonary infections, or an increased frequency and severity of allergies.
Describe the immunological problem of the Nude mouse, and name the human immunodeficiency condition it resembles.
Nude mice fail to make thymic stroma, and thus cannot make T cells. They resemble DiGeorge syndrome.
Name the enzyme which is absent in some cases of SCID. Discuss possible approaches to replacing this enzyme.
SCID patients often lake the enzyme Adenosine Deaminase (ADA)–> causes adenosine to buil-up in all cells, most greatly affects lymphocytes.
ADA can be replaced using PEGylated purified ADA (stabilized with polyethylene glycol).
Discuss transplantation therapy in immunodeficiency diseases. Include a consideration of possible complications.
Transplantation is an option, but graft-versus-host disease is a problem. Purified stem cells are a better choice for SCID.
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 cells initial tests: serum protein electrophoreisis, quantitative IgG, IgA, IgM levels, specific Abs to prior immunizations, ABO isohemagglutinins.
B cell advanced tests: Ab responses to novel antigens, sequencing of suspect genes
T cells initial tests: Skin test with recall Ag panel; total lymphocyte count
T cells advanced tests: CD3, CD4, CD8 counts; mitogen responses, MLR, cytokine measurements
Phagocytes initial: WBC count, differential, morphology; NBT test, oxidative burst
Phagocytes advanced: Assays for phagocytosis, chemotaxis, genetics
Complement initial: CH50, Assay for C1inh inhibitor
Complement advanced: Individual complement component levels.
Describe the contents and routes of administration of commercial gamma globulin (IVIG) and indicate the conditions in which it can be useful replacement therapy.
An IVIG is about 99% IgG (half life of 3 wks), it is given IV or subcutaneously. It is useful in treating conditions where 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.
Measles, mononucleosis, cytomegalovirus, HIV.
CMV destroys the bone marrows ability to make lymphocytes.
