Flashcards in L14: Immunodeficiencies Deck (26):
Primary vs secondary immunodeficiency
- Primary = congenital
- Secondary = acquired (AIDs, immunosuppressive drugs, disseminated CA, splenectomy, malnutrition)
Defect in humoral immunity typically confers what type of infection(s)
- Extracellular bacterial infection
Defect in cell-mediated immunity typically confers what type of infection(s)
- Viral, intracellular bacterial, fungi infections
What type of cancer are you more likely to get after EBV infection?
What type of cancer are you more susceptible to after an HPV infection?
- Skin CA
B cell deficiency. What are serum Ig levels like? Skin reaction tests? Lymphoid tissue morphology?
- Serum Ig: decreased
- Skin rxn test: normal
- Lymphoid tissue: decrease or absence of germinal tissues
T cell deficiency. What are serum Ig levels like? Skin reaction tests? Lymphoid tissue morphology?
- Serum Ig: normal or reduced
- Skin rxn test: decreased
- Lymphoid tissue: normal follicles, decrease in paracortical regions
List disorders of B lymphocytes:
1.) X-linked (Bruton’s) agammaglobulinemia
2.) Common variable immunodeficiency
3.) Selective IgA deficiency
4.) Hyper IgM syndrome
List disorders of T lymphocytes:
1.) DiGeorge Syndrome
What is X-linked agammaglobulinemia?
- Absence of mature B cells as a result of mutations/deletions in Btk/B cell tyrosine kinase involved in signal transduction. X-linked recessive (males)
- These individuals are subject to recurrent pyogenic (extracellular) bacterial infections, common infections are: pneumonia, otitis media, meningitis, sepsis
- Infections well controlled by monthly injections of pooled gamma globulin and antibiotic therapy
X-linked agammaglobulinemia pts should be given vaccines. True / False
- False, unable to mount antibody response
What is common variable immunodeficiency?
- Intrinsic defect (unknown mechanism) resulting in inability for mature B cells to differentiate into plasma cells
- Increased susceptibility to recurrent bacterial infections. Pts tend to have high incidence of autoimmune diseases
- Given monthly gamma globulin shots and antibiotic treatment
Mature B cells are present in common variable immunodefiency pts. True / False
- True. Not seen in pts with x-linked agammaglobulinemia
What is selective IgA deficiency?
- Inherited or acquired disorder of absence/minimal levels of IgA. Pts are typically asymptomatic, but some have increased infections are mucosal sites. IgM compensates. May have increased allergy, GI tract dz and or autoimmune dz
- Treatment: antibiotics if needed, but don’t require gamma globulin (with small amount of IgA)
IgA is never found in selective IgA pts. True / False
- False. Present in low levels. Also found on B cells with surface bound IgA
Why do selective IgA deficient pts develop severe or fatal transfusion reactions?
- They develop anti-IgA in development
What is hyper IgM syndrome? Two forms of disease?
- Overabundance of IgM and lack of other antibody isotypes
1.) X-linked: inherited deficiency of CD40L on T cells that prevents engagement with CD40 on B cells therefore no isotype switching as mechanism preceeding cytokine release is defective
2.) Type 2: inherited mutation in gene encoding AICD (deaminase), which ?? prevents switching of isotypes
B cells are defective in hyper IgM syndrome. True/False
- False, T cells lack CD40L required in mechanism resulting in isotype switching
What is DiGeorge syndrome?
- aka congenital thymic hypoplasia
- Deficiency in T cells (maturation) d/t hypoplasia or agenesis of thymus resulting from defect in third and fourth pharyngeal pouches in embryogenesis. This deficiency leads to poor cell-mediated immunity against viruses and fungi. These infants usually have low-set ears and fish-shaped mouths
- T-cell function increased with age and is normal by 5 years – extrathymic site/maturation not known
What is SCID? Causes?
- Severe compromised immunodeficiency (aka Swiss type agammaglobulinemia). Failure of B and T cells to develop from bone marrow stem cells (lymphoid sites are not populated by them). There is little to no humoral or cell-mediated immunity and individuals die from infections within the first year of life.
1.) Autosomal recessive: deficiency in adenosine deaminase (ADA), causes accumulation of substrates toxic to lymphocytes. Also PNP deficiency in another form of SCID
2.) RAG1/2 deficiency/mutations: failure to VDJ rearrange in IG and TCR genes
3.) X-linked: mutation in gene for cytokine receptors, lymphocytes cannot develop properly
- Treatment: bone marrow transplantation (gene therapy to transfect autologous bone marrow with ADA gene) = curative
What is chronic granulomatous disease?
- Defect in NADPH oxidase in neutrophils preventing them from producing superoxide anion during respiratory burst, resulting in recurrent bacterial infections
- Treatment: bone marrow transplantation, gene therapy, IFN-gamma therapy (for some pts)
What is myeloperoxidase deficiency?
- Decrease of absence of myeloperoxidase, which converts hydrogen peroxide into hypochlorous acid, an antibacterial and antifungal. No increased susceptibility to infection in these individuals d/t compensatory mechanisms, but decreased ability to ward off fungal infections, particularly Candida yeast
What is Chédiak Higashi syndrome?
- Recurrent bacterial infections d/t disrupted neutrophils and their fusing of lysosomes, which reduces their ability to kill microbes. T cell and NK cell function is also impaired. Pts have metallic silver hair, tend to have bleeding disorders d/t platelet issues and are also vision impaired. Multisystem disorder involving CNS, hepatosplenomegaly, high incidence of lymphoreticular cells
- Treatment = bone marrow transplant
What is Leukocyte Adhesion Deficiency?
- Defect in beta chain of integrins (LFA-1 and MAC-1), prevent neutrophils from adhering to ECs during extravasation. These individuals have recurrent bacterial and fungal infections of skin, lungs and blood. Also wound healing problems. Present with extreme leukocytosis
- Treatment: aggressive abx tx, prophylactic abx in dental work, granulocyte trxnfusion, bone marrow transplant curative
What is Wiskott-Aldrich syndrome?
- X-linked syndrome that presents with triad: immunodeficiency, eczema and thrombocytopenia. There is partial immunodeficiency, near normal T and B cell counts, but response to antigen is poor. Have recurrent infections, predisposed to severe autoimmune dz. Etiology: defective WASP protein that regulates actin cytoskeleton of bone marrow-derived cells. Immune cells cannot traffic to sites of inflammation and they cannot interact properly.
- Treatment: IV gamma globulin and abx prolong survival, bone marrow transplant curative