Immunodeficiencies Flashcards
Describe primary vs. secondary immunodeficiencies
Immunodeficiencies = lack of an immune system or failure of components of the immune system that increases susceptibility to infection
- -> primary = congenital
- -> secondary = acquired (AIDs, malnutrition)
Defect in humoral immunity result in what?
Infections by extracellular bacteria
If cell mediated immunity is impaired
Infections with viruses and intracellular bacteria
If humoral and Cell mediated immunity are defective then…
infections with all classes of microorganisms
What causes more susceptibility to developing cancer?
- EBV –> lymphomas
- HPV –> skin cancers
- T cell deficiencies lead to increase risk due to T cell immunosurveillance role in preventing cancer
Describe general characteristics of B cell Deficiency.
Diagnostic parameters:
- Serum Ig levels decreased
- skin test reactions are normal
lymphoid tissue = germinal centers are decreased or absent (no proliferating B cells)
Infectious agent susceptibility: primarily extracellular bacteria
Describe general characteristics of T cell Deficiency
Diagnostic parameters:
- Serum Ig levels are normal or reduced
- skin test reactions are decreased
Lymphoid tissue has normal follicles, but decrease paracortical regions (no T cells to produce paracortex)
Infectious agent susceptibility = viruses, intracellular bacteria, fungi
Define X-linked agammaglobulinemia
Absence of mature B cells –> little serum immunoglobulin
- normal bone marrow pre-B cells, so block exists in maturation
- molecular basis of disease: mutations/deletions in B cell tyrosine kinase (involved in signal transduction)
- -X-linked disease –> restricted to males.
Subject to recurrent infections by pyogenic bacteria (extracellular bacteria they have problems with)
T cell immunity intact –> not many viral or fungal infections (don’t give them vaccines)
Define Common variable immunodeficiency
Mature B cells CAN NOT differentiate into plasma cells leads to decrease antibodies
–> affects males and females to increase susceptibility to recurrent bacterial infections (extracellular bacterial infections)
Two types:
- Congenital (born with it) or sporadic (develop later in life)
- High incidence of autoimmune disease
Define Selective IgA deficiency
Inherited or acquired (embryonic rubella infection or drug exposure)
–> Asymptomatic, but some may have increased infections of mucosal sites
–> IgM can compensate for missing IgA that is transported across mucosa
***–> develop anti-IgA antibodies which can cause severe or fatal transfusion reactions if given plasma containing IgA
Diagnosis:
- B cells with surface IgA, but no differentiation into plasma cells
- T lymphocytes function intact
- may have increase allergy, GI tract disease, autoimmune disease
Define Hyper IgM syndrome
Overabundance of IgM antibody + lack of other antibody isotypes:
Two types
- X-linked hyper IgM syndrome = inherited deficiency of CD40L on T cells –> CD40 not engaged on B cells –> no isotype switching
- Hyper IgM type 2 syndrome = inherited mutation in the gene activation-induced cytidine deaminase which prevents isotype switching
Define DiGeorge syndrome (congenital thymic hypoplasia)
Deficiency of T cells due to hypoplasia or agenesis of the thymus:
- -> Defective maturation of T cells causes poor cell mediated immunity against viruses and fungi
- -> immunoglobulin levels near normal, even though T cells severely decrease.
Treatment:
–> T cell function increases with age - extrathymic maturation
Severe combined immunodeficiency
Failure of B and T cells to develop from bone marrow stem cell: Spleen, lymph nodes, tonsils, appendix not populated by B and T cells
–> little or no humoral or cell-mediated immunity and die from overwhelming infection with the 1st year of life if not treated.
Causes:
-Deficiency of adenosine deaminase
- RAG1/RAG2 deficiency (failure to rearrange immunoglobulins)
-X-linked SCID (mutations in genes)
Chronic Granulomatous Disease
Recurrent bacterial infections from early childhood:
–> defect in NADPH oxidase causes neutrophils can’t produce superoxide anion during respiratory burst
Usually fatal even with aggressive antibiotic therapy with many patients
- amenable to bone marrow transplantation or gene therapy
- interferon-gama therapy can prompt neutrophils to start producing superoxide
Define Myeloperoxidase deficiency
Decreased or absent myeloperoxidase
- -> myeloperoxidase produces hypochlorous acid from H2O2 and chloride ions (potentially antibacterial or antifungal)
- -> No increase susceptibility to infection in these individuals due to compensatory immune mechanisms.
- -> there can be a decrease ability to ward of fungal infections (candida yeast)
