Immunodeficiency Flashcards
Which class of immunodeficiency has absence of lymphoid tissue and profound lymphopenia?
Severe combined immunodeficiency disorder (SCID)
Examples:
Adenosine deaminase deficiency
What is X-linked (Bruton) agammaglobulinemia (XLA)? When and what bacteria do infants get?
BTK defect –> prevents pre-B cells from maturing and exiting bone marrow –> Reduced Ig levels
Sinopulmonary infections with encapsulated bacteria after 6 months old (when maternal antibodies decrease) - antibody opsonization needed for phagocytosis
Small/absent lymphoid tissue
What viral infections can X-linked agammaglobulinemia predispose to?
Chronic enteroviral infection (e.g. meningoencephalitis) (Coxsackie, Echovirus, Polio - due to lack of antibodies to neutralize disease
What is treatment for X-linked (Bruton) agammaglobulinemia?
Immunoglobulin replacement therapy
Prophylactic antibiotics if failed
What bacteria susceptibility due to chronic granulomatous disease with reduced phagocytic activity?
Impaired oxidative burst (defective NADPH oxidase) leads to recurrent infections caused by catalase+ bacteria (S aureus, Serratia, Burkholderia, Nocardia) and fungi (eg Aspergillus)
NORMAL T and B cell levels
Chronic granulomatous disease granuloma locations
Digestive tract
GU tract
Chronic granulomatous disease prophylaxis
Bactrim, itraconazole
Severe combined immunodeficiency
Defective IL-7 driven T cell development in thymus; leading to low B cells
T: Viral, fungal, opportunistic
B: Sinopulmonary and GI bacterial
Chronic diarrhea, failure to thrive
What is a named variant of SCID?
Adenosine deaminase deficiency - deficient formation of mature B and T cells
How is SCID diagnosed?
Absence of T receptor excision circles in dried blood (newborn screening)
Common variable immunodeficiency
Hypogammaglobulinemia, so less severe than Bruton
Due to impaired differentiation of B cells into plasma cells
Presents at later age with normal T and B cell levels
CVID is associated with what noninfectious conditions?
Atopic (eg asthma, eczema) or autoimmune (eg RA) conditions
Wiskott-Aldrich
X-linked recessive - important for regulation of actin cytoskeleton remodeling needed for cellular migration and immune synapse formation
Bleeding from microthrombocytopenia
Recurrent infections
Eczema
Wiskott-Aldrich treatment
Hematopoietic stem cell transplant
Hyper-IgM
High IgM, low IgA and IgG
X-linked recessive CD40 ligand (on T cells) mutation, which impairs binding to CD40 on B cells (impairs class switching, leading to sinopulmonary) and APCs (leading to viral, opportunistic)
Lymphocytosis and neutropenia during infection
Impaired growth from high energy expenditure and poor intake during illness
Treat with antibiotic prophylaxis and IVIG
Hyper-IgE
Defective Th17 cells –> defective neutrophil proliferation/chemotaxis to site of infection
Cold abscesses, afebrile, well-appearing
Often S aureus, Candida
Recurrent sinopulmonary
Chronic, severe atopic dermatitis in first few weeks of life
Eosinophilia
Autosomal dominant
Selective IgA deficiency
May be asymptomatic, but could also:
Hx of recurrent sinopulmonary and Gi infections
Concomitant atopic and autoimmune disorders
Selective IgA deficiency should beware what?
Blood transfusion anaphylactic reaction - use epinephrine
Defective opsonization is due to what?
Low IgG or complement (C3), predisposing to encapsulated bacteria and sinopulmonary infections
Leukocyte adhesion deficiency
Due to reduced CD18 component of integrins on neutrophil surface
Poor neutrophil chemotaxis, leading to recurrent skin and mucosal infections without purulence
Delayed wound healing (e.g. delayed separation of umbilical cord >3 wks)
Absence of purulence with repeated skin and mucosal infections suggests…
Leukocyte adhesion deficiency
Diagnosis of chronic granulomatous disease
Dihydrorhodamine 123 (flow test that is green if normal)
What immunodeficiency may cause inflammatory bowel disease in a toddler?
Chronic granulomatous disease –> impaired ROS production –> severe, recurrent infections
CGD –> impaired ROS production –> impaired degradation of inflammatory cytokines –> inflammation and diffuse granuloma formation in GI/GU tracts
Pigment-laden histocytes are seen, representing lipofuscin accumulation due to impaired lipolytic activity
Early complement deficiency is susceptible to…
Late is susceptible to…
Early:
Recurrent sinopulmonary bacteria (C3 deficiency)
Childhood SLE
Late:
Recurrent encapsulated bacteria, particularly Neisseria (C5-C8 deficiency)
Hyper-IgE syndrome
Impaired neutrophil chemotaxis –> cold (nontender, nonfluctuant) abscesses
Recurrent Neisseria infections suggests what immunodeficiency?
Complement deficiency
What immunodeficiency is associated with ocular injection?
Ataxia-telangiectasia - immune defects can be variable (can affect both humoral and cellular) but at least recurrent sinopulmonary infections
Due to defective DNA repair
What infections does IFN-g deficiency predispose to?
Disseminated mycobacterial disease (IFN-g mediates intracellular killing of mycobacteria by macrophages)
What is cyclic neutropenia?
Recurrent episodes of reduced peripheral neutrophils, fever, sore throat, and LAD every 3 weeks
What is transient hypogammaglobulinemia of infancy?
Prolonged (age >6 mo) IgG nadir - asymptomatic or recurrent respiratory infections in infancy
May also atopy (eg eczema, food allergies)
Low IgG (+/- decreased IgA or IgM) but normal antibody response to vaccines
Chediak-Higashi syndrome
Lysosomal trafficking disorder - giant granules will accumulate within neutrophils
Recurrent infections and neutropenia
Oculocutaneous albinism
Neurologic abnormalities
Oculocutaneous albinism suggests…
Chediak-Higashi syndrome
When are infants considered high-risk towards highly allergenic food?
Known/suspected IgE-mediated food allergy
Severe, refractory eczema
Refer to allergy testing (IgE levels, skin testing) and consider in-office feeding
Why does hyper-IgM come with decreased levels of all Ig except IgM?
CD40 ligand deficiency on T cells
Which immunodeficiency has recurrent Neiserria, meningicoccal, or gonococcal infections?
Terminal complement deficiency (C5-C9)
Mke sure to give meningococcal vaccine and antibiotics as needed
Increased IgE and IgA but decreased IgM
Wiskott-Aldrich
Bleeding, eczema, recurrent otitis media
Wiskott-Aldrich
Giant granules in neutrophils
Chediak-Higashi - defect in neutrophil chemotaxis and microtubule polymerization
Recurrent S aureus infections and abscesses
Job syndrome (Hyper-IgE)
Partial oculocutaneous albinism
Chediak-Higashi - overwhelming S pyogenes, S aureus, and Pneumococcus infections
