Allergy & Immunology Flashcards
DiGeorge Syndrome
- MoI for 22q11 microdeletion?
- Abnormal development of what pharyngeal pouches?
- Susceptible two what types of infxn? (2)
- What mineral deficiency?
- thymic aplasia
- parathyroid hypoplasia
- cardiac defects
- facial defects
DiGeorge Syndrome
- -AD or sponataneous 22q11 microdeletion
- -abnormal development of 3rd and 4th pharyngeal pouches
- thymic aplasia –> abnormal cell-mediated immunity –> low T cells (less than 500) –> poor defense against fungal, viral infxn
- parathyroid hypoplasia –> hypocalcemia –> neonatal hypocalcemic seizures and tetany
- cardiac defects
- facial defects: hypertelorism, low-set ears, mandibular hypoplasia, fish mouth
Bruton’s agammaglobulinemia
- recurrent infections by age 1
- lymphoid hypoplasia
- Mode of inheritance?
- Which level is normal? Which level is very low?
- -CD3 T lymphocytes
- -CD19 T lymphocytes - What types of Abs are deficient?
- Tx?
Bruton’s agammaglobulinemia
- -X linked (boys only)
- -very low CD19 T lymphocytes (B-cells)
- -normal CD3 T lymphocytes (T-cells)
- -deficiency in all Ab classes
- -Tx: IVIGs (and abx)
- recurrent infections by age 1
- lymphoid hypoplasia (eg, small tonsils and adenoids; no splenomegaly or lymphadenopathy
Wiskott-Aldrich Syndrome
- What is the clinical triad? (WATER)
- Mode of inheritance?
- Normal IgG levels. What about IgA, IgE, and IgM?
Wiskott-Aldrich Syndrome
–Thrombocytopenic purpura, Eczema, Recurrent infxn
(WATER)
–XLR
–normal IgG; increased IgA, IgE; low IgM
- Abs cannot form against polysaccharide encapsulated bacteria
- -N meningitidis, S. pneumo, H. influenzae
- often presents as prolonged bleeding from circumcision
- -decreased platelet production
*later, often die from P. carinii or Herpes
Selective IgA Deficiency
*most common, often mild
IgA - important role in mucosal barrier protection
–> recurrent sinopulmonary and GI infxn
*fatal anaphylactic reaction if given blood with IgA
What organism associated with GI infxn?
Selective IgA Deficiency
- -recurrent sinopulmonary and GI infxn
- -GI: giardia
- -fatal anaphylactic rxn if given blood with IgA
Hyper-IgM Syndrome
Mode of inheritance?
Pathophys: No isotype switching among B cells due to absence of what on the T cell?
–high IgM; low IgA, IgE, IgG
Features
- -recurrent sinopulmonary infxns with encapsulated bacteria
- -frequent viral infxns
- -increased risk for opportunistic infxns (eg, P. jiroveci)
- -decreased growth secondary to energy expenditure and poor intake during infxns
Hyper-IgM Syndrome
–XL
Pathophys: absent T cell CD40 ligand prevents B cell isotype switching
–high IgM; low IgA, IgE, IgG
Features
- -recurrent sinopulmonary infxns with encapsulated bacteria
- -frequent viral infxns
- -increased risk for opportunistic infxns
- -decreased growth
Tx
- -Abx prophylaxis
- -IVIG
Common Variable Immune Deficiency
- -hypogammaglobulinemia of all classes
- -equal sex distribution
- -no IgG response to vaccines
Increased risk of what type of cancer?
Increased risk of what type of disease?
Common Variable Immune Deficiency
- -hypogammaglobulinemia
- -increased risk of lymphoma
- -increased risk of autoimmune disease
NB: in contrast to Bruton’s agammaglobulinemia, there is low risk for enteroviral meningitis
NB
- -Bruton’s: low B cells; low Ig’s of all types
- -CV: normal B cells; low Ig’s of all types
Presentation: infant; severe and opportunistic viral, bacterial, fungal, and protozoal infxns; chronic diarrhea; failure to thrive
- -pneumonia, otitis media, sepsis, cutaneous infxns
- -GVHD from maternal T cells crossing placenta
- -small or absent thymus and lymphoid tissue
- Dx?
- Most common mode of inheritance?
- If MoI is AR, then what is the enzyme deficiency?
Severe Combined Immunodeficiency (SCID)
- -infant; severe opportunistic infections (viral, bacterial, fungal, protozoal)
- -chronic diarrhea
- -F2T
- -X-linked is most common
- -AR: adenosine deaminase (ADA) deficiency
Ataxia-Telangiectasia
What is the clinical triad?
–Other s/s include: mask-like facies, tics, drooling, recurrent respiratory infxn, irregular eye movements
Mode of inheritance?
Why does this mutation of the ATM gene lead to an increased cancer risk?
Ataxia-Telangiectasia
- -triad: ataxia, spider angioma, low IgA
- -progressive ataxia beginning at time of walking
- -oculocutaneous telangiectasias at age 3-6
- -chronic sinopulmonary infxn
AR; mut ATM gene (chr 11) –> ineffective DNA break repair –> increased cancer risk (lymphoreticular)
Chronic Granulomatous Disease
–XLR, AR
Pathophys:
- -enzyme defect - which enzyme?
- -defective intracellular killing: neutrophils and monocytes can ingest but not kill catalase-positive organisms
What is the most common catalase-positive infxn?
Dx Test
- -rhodamine dye has replaced nitroblue tetrazolium test
- negative NBT is abnormal
Recurrent lymphadenitis, pneumonia, skin infxns
Hepatic abscesses
Osteomyelitis at multiple sites
Chronic Granulomatous Disease
–XLR, AR
Pathophys: neutrophils, monocytes can ingest but not kill catalase-positive organisms
- -NADPH oxidase defect
- -S. aureus (others include Pseudomonas cepacia, Aspergillus, Nocardia, Serratia)
- -Recurrent lymphadenitis, pneumonia, skin infxns
- -Hepatic abscesses
- -Osteomyelitis at multiple sites
Tx; bone marrow transplant
Immunology Principles
- B-cell CD marker?
- T-cell CD marker?
- Type of T-cell that helps B-cells produce Abs?
- Type of T-cell that directly kills virus-infected cells?
- Type of Ig that is the primary response to an antigen. Fixes complement but does not cross placenta.
- Type of Ig that is the secondary response to an antigen. Fixes complement, crosses placenta.
- Type of Ig that prevents attachment of bacteria and viruses to mucuous membranes. Released into secretions and early breast milk (colostrum).
- Binds mast cells and basophils; cross-links when exposed to allergen; activates eosinophils
Immunology Principles
B-lymphocyte (CD-19)
T-lymphocyte (CD-3)
- -CD-4 T-cell (helper T-cell) helps B-cells produce Abs
- -CD-8 T-cell (cytotoxic T-cell) directly kills virus-infected cells
IgM
–primary (immediate) response to antigen
IgG
- -secondary (delayed) response to antigen
- -crosses placenta
IgA
- -prevents attachment of bacteria and viruses to mucous membranes
- -present in secretions, colostrum
IgE
–binds mast cells and basophils; cross-links when exposed to allergen; activates eosinophils
Hereditary Angioedema
MoI?
C1 esterase-inhibitor defect
Edema
- -face, limbs, genitalia
- -larynx (life-threatening)
- -intestines –> colicky abdominal pain
- no urtricaria
- episodes usually follow infection, dental procedure, or trauma
Hereditary Angioedema
MoI: AD
C1 esterase-inhibitor defect
Edema
- -face, limbs, genitalia
- -larynx
- -intestines
- no urtricaria
- episodes follow infxn, dental procedure, trauma
Features
- -coagulopathy
- -peripheral neuropathy
- -oculocutaneous albinism
- -frequent bacterial infxns (S. aureus)
Labs
- -pancytopenia
- -neutropenia
- -giant lysosomes in neutrophils
Dx?
Chediak-Higashi Syndrome
MoI: AR
Impaired phagolysosome formation
Features
- -delayed umbilical cord separation
- -recurrent skin and mucosal bacterial infxns
- -necrotic periodontal infxns
- -absence of pus formation at sites of infxn
Labs
–leukocytosis with neutrophil predominance
Dx?
Leukocyte Adhesion Deficiency (Type 1)
MoI: AR
deficient CD18 expression –> impaired ability of leukocytes to exit vasculature, migrate to site of infxn
