Immuno Diseases Flashcards
Cyclic Neutropenia: description, inheritance pattern, cause
Monthly neutropenia (cycles through highs and lows). Clinically serious during episodes of neutropenia
Mutation in Neutrophil elastase (ELANE)
Autosomal dominant
Chediak-Higashi Syndrome: description, inheritance pattern, cause, treatment
Abnormal WBC inclusions (Dohle bodies), lymphoma
Caused by LYST gene (lysosomal trafficking regulator)
Autosomal recessive
Treatment: bone marrow transplant
Myeloperoxidase inheritance pattern?
Autosomal recessive
Clinically mild (late enzyme)
Chronic Granulomatous Disease description, cause and inheritance pattern
“Broken” NADPH enzyme prohibits the creation of superoxide and inhibits phagocytes from digesting what they’ve taken up. We then end up with granulomas.
Inheritance pattern can be x-linked or autosomal recessive (multiple parts of NADPH enzyme can be defunct)
Leukocyte Adhesion Deficiency description and inheritance pattern
Defective leukocyte attachment to endothelium, defective entry of WBCs into sites of infection, and defective innate immune response leading to bacterial infection
Autosomal recessive
What are the two subtypes of Leukocyte Adhesions Deficiency and where is their defect?
LAD-1: CD18 deficiency (part of LFA-1 and MAC-1); decreased adhesion
LAD-2: Sialyl-Lewis^x deficiency; decreased rolling
***LAD-1 is more severe. Adhesion is more important than rolling
What is the clinical phenotype seen in a patient with Leukocyte Adhesion Deficiency?
Widespread bacterial infections in infancy, impaired pus formation, impaired wound healing, persistent leukocytosis, and delayed umbilical cord separation (LAD-1! About 3 weeks)
Bruton’s X-linked agammaglobulinemia (XLA) description, cause, inheritance pattern, treatment
Defective B-cell development. B-cells are arrested in the large Pre-B cell stage due to defective Bruton tyrosine kinase (BTK) enzyme.
Present in infancy/early childhood (have mom’s IgG at first!)
Problem with some viruses too like enterovirus, coxsackie, and echovirus
Also present with arthritis
X-linked recessive & rarely autosomal recessive
Treatment: IV immunoglobulins (IVIG)
Do men with XLA have follicles and germinal centers in their lymph nodes?
No, because they don’t have B cells to develop
People with this disease lack tonsils and adenoids
XLA
Hyper-IgM description and causes
Defective class switching (so we end up with a ton of IgM)
Defects in:
1. CD40L-CD40 signaling. CD40L on CD4 cell, CD40 on B cell, or signaling via NEMO to NFkB is broken
- B cell defects in AID (Activation-Induced cytidine deaminase) or UNG (Uracil-DNA-glycosylase - DNA repair enzyme)
What is the most common defect that causes Hyper-IgM syndrome and what is its inheritance pattern?
Broken CD40L on CD4 T Cell
X-linked recessive
Will there be issues with macrophage actions in hyper-IgM syndrome?
If there is a defect in CD40L-CD40 signaling (primarily issues with CD40L or the downstream TFs, aka NEMO) then yes
CD40 defects will affect B cells and the other class-switching defects are B cell specific
In a patient with hyper-IgM syndrome, were their B cells stimulated by thymus dependent or thymus independent antigen?
independent
we have defects in signaling between CD4 t cells and B cells! No message is getting between them
What type of leukocyte is needed to control Pneumocystis?
Macrophage!
What is the most common inherited immune deficiency?
IgA deficiency
What are the consequences of IgA deficiency?
Most people are asymptomatic; symptomatic if IgG deficiency also present
Sinopulmonary and GI tract infections present
**Sepsis does not occur because IgM and IgG are normal
What is transient hypogammaglobulinemia of infancy?
Delayed production of IgG by the infant. Eventually maternal IgG wanes and there is a transient period with low levels. Self-limited; eventually IgG production increases
What is common variable immunodeficiency (CVID)?
A late-onset form of panhypogammaglobulinemia. Onset in childhood or adulthood
Causes: defective terminal differentiation of B cell to plasma cell, defective T cell help to B cell or autoimmunity
What are the gene mutations known so far in CVID?
TACI, CD19, ICOS
IL-2R gamma chain deficiency description, cause, and inheritance pattern
Common gamma chain shared with multiple receptors is defective. Two of those receptors are necessary for T cell and NK cell development
X-linked recessive inheritance pattern
What would the levels of T cells, NK cells, and B cells be in a person with IL-2R gamma chain deficiency?
T Cell and NK cells would be deficient and B cells would be normal
Adenosine deaminase deficiency (ADA) description, cause, and inheritance pattern
ADA is needed for purine salvage pathway, without this the metabolites of ADA are toxic to common lymphoid precursor
Less CLP means less T, B, and NK cells
Autosomal recessive
What is Wiskott-Aldrich syndrome? Inheritance pattern?
T cell immunodeficiency
WASP protein defect involved in lymphocyte and platelet development (involved w/ cytoskeleton)
X-linked recessive
Clinical phenotype in Wiskott-Aldrich Syndrome:
Lack of antibody production to polysaccharide antigens, thrombocytopenia (& small platelets), eczema
What is ataxia telangectasia?
T cell immunodeficiency
Defect in ATM gene (seronine/threonine kinase) involved in VDJ recombinations
autosomal recessive
Clinical phenotype in ataxia telangectasia?
Loss of coordination (ataxia)/gait disturbance, dilated capillaries of skin and conjunctiva, T cell immune deficiency, predisposition to leukemias and lymphomas
DiGeorge Syndrome description, cause, and inheritance pattern
Malformation of the 3rd & 4th pharyngeal pouches (endoderm!) leading to congenital heart disease: aortic arch, hypoparathyroidism (low calcium), thymic aplasia or hypoplasia, unusual facial appearance
Autosomal dominant on chromosome 22
Sjorgren Syndrome (Sicca syndrome): tissue/organ involvement, clinical presentation, and autoantibodies
Destruction of lacrimal and salivary glands
Presents with dry eyes (conjunctivitis, corneal ulceration, corneal perforation) and dry mouth (caries, oral cancer)
AutoAb: SS-A/Ro, SS-B/La
Note: can be primary (unassociated with other autoimmune diseases) or secondary (associated with other autoimmune diseases)
Scleroderma (aka systemic sclerosis): tissue/organ involvement, clinical presentation, and autoantibodies
Involves skin & esophagus
Presents with fibrosis of hands, reflux in esophagus, and loss of facial expression
AutoAb: Scl-70
Dermatomyositis: tissue/organ involvement, clinical presentation, and autoantibodies
Skeletal muscle & skin involvement
Presents with skin rash & skeletal muscle tenderness and weakness
AutoAb: anti-Jo-I