Immunodeficiency Flashcards
(25 cards)
Severe Combined Immunodeficiency Disorder (SCID)
Early developmental block of immune system, lymphopenia of both B- and T-cells, more than half of these diseases are X-linked recessive, other SCIDs are autosomal recessive
SCID-X1
Most common of the SCIDs, defect is in the gene for the gamma chain that forms part of the receptors for IL-2 and other cytokines necessary for lymphoid development, or their signaling pathways
Autosomal recessive SCID
Patients lack the enzyme adenosine deaminase (ADA); so adenosine accumulates in all cells but impairs lymphocyte development selectively
X-Linked (Bruton) Agammaglobulinemia
Normal T-cells but low or no B-cells (& Abs), developmental block from Pre-B-cell to B-cell, tyrosine kinase gene defective, bacterial infections manifesting in pneumonia and chronic diarrhea, oral polio vaccine could revert to infect these kids
X-Linked Hyper IgM Syndrome
CD40 on B-cell or CD40-Ligand on Tfh defective, Tfh cells can’t help B-cells with Ig class-switching, lots of IgM and very little IgG or IgA.
Common Variable Immunodeficiency (CVID)
Group of conditions, Can see innate immunity as well as B and T cell defects, low serum IgG, recurrent bacterial infections, treated with IVIG or SCIG
DiGeorge Syndrome
3rd/4th pharyngeal pouches do not develop correctly, thymus cannot develop, absent T-cells with normal B-cells, Cell-mediated immunity is depressed, viral and fungal infections are common, large deletion (45-gene) on chromosome 22, parathyroids are also derrived from the same embryonic tissues thus patient may present in infancy with convulsions controllable with calcium, great vessels of heart develop abnormally
CATCH-22
DiGeorge Syndrome: defect on chromosome 22.
Calcium: can’t develop parathyroid properly, seizures. Appearance: facial development affected.
Thymus: decrease of T-cells.
Clefts: cleft palate common.
Heart: defects in great vessels of heart.
Associations with T-cell deficiencies
Severe infections with intracellular pathogens i.e. viruses, certain bacteria, yeasts, and fungi, especially Candida albicans and Pneumocystis jirovecii
Associations with B-cell deficiencies
Infections with extracellular, pyogenic (“high-grade”) bacterial pathogens, e.g. Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae
Transient Hypogammaglobulinemia of Infancy
Noticed about 6 mo after birth and can last up to 18 mo of age (sometimes longer). Slow to get IgG production going, recurrent and persistent gram-positive bacterial infections, perhaps 15% of all chronic diarrhea in infants is due to this condition.
Selective IgA Deficiency
Most common immunodeficiency disease, usually asymptomatic, may have diarrhea and sinopulmonary infections, or an increased frequency and severity of allergies, runs in families, 10-15x more likely if patient has celiac disease.
Ataxia Telangiectasia
autosomal recessive disease characterized by sinus infections and pneumonia, ataxia (staggering) and telangiectasia (dilated abnormal blood vessels). There is both T and B cell deficiency, not absolute; IgA is especially depressed. There is also an interesting defect in DNA repair which may partially explain the extraordinary incidence of tumors in these patients.
Wiskott-Aldrich syndrome
Platelet and B cell deficiency, eczema, and many bacterial infections. It is X-linked.
Especially immunosuppressive Viral illnesses
Measles, mononucleosis, and cytomegalovirus (CMV) infection–secondary infection is common. Acquired Immune Deficiency Syndrome (AIDS) is the most serious condition involving secondary immunodeficiency.
Treatment of Immunodeficiencies
- Isolation i.e. bubble–impractical.
- Prophylactic antibiotics, must change regularly due to antibiotic resistance.
- Human immunoglobulin, where B cell function is deficient. IVIG most common, but expensive. Slow subcutaneous infusion (SCIG) may also be a possibility.
- Transplantation. In DiGeorge, fetal thymus or cultured thymic stromal cells (Donor’s) have been used to try to minimize the risk of graft-versus-host disease, T-cells are patient’s own.
Treatment 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. For ADA- deficient patients, transfusions of irradiated red cells can be helpful.
Working up defective immunity: Initial tests for B-cells
Serum protein electrophoresis; Quantitative IgG, IgA, IgM levels; Specific Abs to prior immunizations; ABO isohemagglutinins
Working up defective immunity: Advanced tests for B-cells
Ab responses to novel Ags; Sequence suspect genes; Lymph node biopsy
Working up defective immunity: Initial tests for T-cells
Skin test with recall Ag panel; Total lymphocyte count; CD3, CD4, CD8 counts
Working up defective immunity: Advanced tests for B-cells
Mitogen responses, MLR, cytokine measurements; Sequence suspect genes
Working up defective immunity: Initial tests for Phagocytes
WBC count, differential, morphology; NBT test, oxidative burst
Working up defective immunity: Advanced tests for Phagocytes
Assays for phagocytosis, chemotaxis; Sequence suspect genes
Working up defective immunity: Initial tests for Complement
CH50; Assay for C1inh (inhibitor)
