Immunodeficiencies Flashcards
Genetic causes of SCID (deficiencies in both B and T cells)
- X-linked
- Autosomal
- Blocks in lymphocyte maturation
- About half are X-linked: only males affected
- For X-linked: 99% due to gamma chain signaling subunit mutations leading to absence of T cells (IL-7) and NK cells (IL-15)
- Autosomal SCID: mutations involved in purine salvage pathway: ADENOSINE DEAMINASE (ADA) and PURINE NUCLEOSIDE PHOSPHORYLASE
- mutations in JAK3
- Omenn Syndrome (mutations in RAG1 or RAG2 leading to complete or reduced expression) rare
- Mutations in Kinasefor gamma chain signaling
Characteristics indicating immunodeficiency as underlying disease
- 8+ new ear infections in one year
- 2+ serious sinus infections within 1 yr
- 2+ Pneumonia’s w/in 1yr
- 2+ more months on antibiotics with little effect
- Failure of infant to gain weight or grow normally
- Recurrent deep skin or organ abscesses
- Persistent thrush in mouth or elsewhere on skin after age 1
- Need of IV Antibiotics to clear infections
- 2+ deep seated infections
- Family hx of primary immunodeficiency
basically: (8+ new ear infections, 2+: serious sinus infections, pneumonias, deep skin organ abscesses, deep deated infections; persistent thrush, no weight gain/growth, antibiotics don’t work and need IV antibiotics, family hx)
T cell deficiencies: presentation, nature of pathogen, age of onset
- REduced T cell zones
- LAB: REduced DTH reactions to common antigens
- LAB: Defective T cell proliferative responses to mitogens in nvitro
- Infections: Viral and microbial like Pneumocystitis jiroveci, atypical mycobacteria, fungi
- Virus-assoc malignancies (EBV-assoc lymphomas)
Basically:
Antibody deficiencies: presentation, nature of pathogen, age of onset
- Absent/reduced follicles and germinal centers
- LAB: Reduced Serum Ig levels
Cytokines that use common gamma chain
IL-2, 4, 7 (pro-T cells can’t mature when gamma subunit mutated), 9, 15 (NK cells deficient bc this IL receptor uses a gamma subunit as well), 21
basically: 2,4,7,9,15
Pro-T cells and NK Gamma chain cytokines and their common signaling pathways
IL-7 (VERY IMPORTANT) affects immature T-lymphocytes (esp. pro-T cells) inability to mature
IL-15 affects NK cell proliferation
DiGeorge Syndrome:
clinical features, the immunologic bases of the clinical presentation, the dx tests, tx
clinical features: heart defects, cleft palate, delayed development, INCOMPLETE DEVELOPMENT OF THE THYMUS due to anamalous devlpmnt of 3rd and 4th branchial pouches.
the immunologic bases of the clinical presentation: Deletions on 22q11.2, Low T cell numbers bc no thymus to mature in
dx tests: decreased T cells, normal B cells, normal or decreased serum Ig
tx: gets better with age as small amount of thymus develops.
BASICALLY: T cells can’t mature bc thymus deficient, low T cells in serum.
Bare Lymphocyte Syndrome I and II
clinical features, the immunologic bases of the clinical presentation, the dx tests, tx
immunological mechanism: Failure to express MHC II leading to impaired cell-mediated immunity and T-dependent antibody responses.
mutations: Transcription factors that induce MHC II; cell signal-transducing molecules, cytokines, various receptors
LAB: decreased CD4+ T cells because MHC II responsible for T cell maturation and activation
BASICALLY: MHCII not expressed, CD4+ t cells deficient and also T-dependent antibody responses impaired so often clinically characterized as SCID
Adenosine DeAminase Deficiency
clinical features, the immunologic bases of the clinical presentation, the dx tests, tx
clinical features: defective humoral immunity
immunologic mechanism: decreased ADA leads to buildup of toxic purine metabolites in proliferating cells. This injures lymphocytes which actively proliferate during maturation
Block in T cell maturation>Bcell maturation
mutation: adenosine Deaminase mutation
LAB: reduced serum Ig in ADA deficiency, normal B cells and serum Ig in PNP (purine nucleoside phosphorylase) deficiency
CVID (Common Variable Immunodeficiency)
clinical: poor antibody responses to infections, recurrent infections, Autoimmunity, lymphomas
LAB: reduced IgG, IgA, IgM
mutations/defects relatively unknown, mutations in B cell growth factors, costimulators.
Hyper IgM syndrome (types 1 and 2)
TYPE I: clinical features
the immunologic bases of the clinical presentation: Th cells don’t have CD154 (CD40L) to bind to B cell’s CD40 and induce class switching.
mutations: CD40L from T cells that bind to B cells and macrophages
the dx tests: IgM major serum antibody
TYPE II:
decreased activation induced cytidine deaminase leads to poor class-switching and poor somatic hypermutation
IFNgR1 deficiency
TH1 Deficiency
IL-12bR1 deficiency
TH1 Deficiency
IL-12 deficiency
TH1 Deficiency
Wiskott-Aldrich Syndome (Lymphocyte abnormality)
presentation: eczema, reduce blood platelets, immunodeficiency.
X linked
immunologic mechanism:
mutation: gene that encodes a protein that binds to various adapter molecules and cyotoskeletal components in hematopoetic cells. cause small platelets and leukocytes–>migration failure
