immunodeficiencies part II

Question 1

suspected primary immunodeficiencies:

• recurrent sinopulmonary bacterial infections:
• reccurent viral and/or fungal infections:
• recurrent skin abscesses and/or fungal infections:
• bacteremia or meningitis with encapsulated bacteria:

Answer 1

• screen humoral immunity
• screen cellular immunity
• screen for phagocyte defect
• screen for complement deficiency

Question 2

hemopoietic stem cell transplant:

if issue is both related to a ____ in a cell derived from bone marrow and the symptoms are severe or lethal, then replacing teh bone marrow with the efective gene with healthy bone marrow is a cure

Answer 2

gene

Question 3

severe combined immunodeficiency disorders (SCID):

• function of both ____ and ____ cells are impacted, how this happens varies
• issues is either early in lymphocyte development, meaning ____ , ____ , and ____ cells are absent OR
• issue is later in ____ cell development so T cells are absent while others are present but still lacking T dependendt activities ( ____ and ____ class switching)
• typically assocaited with severe ____
• characterized by chronic ____ and failure to ____
• fetus with SCID is at risk for ____

Answer 3

• B and T
• T , B , and NK
• T, IgG and IgA
• lymphopenia
• diarrhea, thrive
• abortion

Question 4

general trends with SCID:

• typically normal at ____ and shows symptoms a few months later after maternal ____ depleted
• phenotype
  
  • T cells always ____
  • ____ , ____ , ____ will always be ____ (no TD activitation)
• hemopoietic stem cell transplant (HSCT) is ____ for these patients
• they can barely fight infections as it is so no ____ vaccines

Answer 4

• birth, IgG
• • low/absent
    
    • IgG, IgE, and IgA, low/absent
• curative
• live/weakened

Question 5

Adenosine Deasminase (ADA) Deficiency:

• lack of ADA → buildup of ____ → cell toxicity
• immune phenotype
  
  • what cells are absent:
• B cells:
• mechanism
  
  • adenosine build up blocks nucleotide metabolism and lymphocytes prilferate a lot so they need DNA
  • adenosine deaminase converts toxic adenosine deaminase → ____ , which is not harmful

Answer 5

• deoxyadenosine
• • T , B, and NK cells
• low/absent IgG, IgA, and IgM
• • deoxyinosine

Question 6

artemis deficiency:

• artemis is an enzyme in VDJ recombination and serves to repair:
• immune phenotype:
• Abs absent:
• HSCT is ____ for these patients
• increased risk for developing ____
• special stuff:

Answer 6

• double stranded breaks
• T-, B-, NK+
• low/absent IgG, IgA, and IgM
• curative
• lymphomas
• radiosensitivity

Question 7

RAG1/RAG2 deficiency:

• what’s wrong:
• ____ recessive
• mechanism: RAG is only used in V(D)J recombination so only T and B cells will be affected becuase they cannot produce TCRs/BCRs
• immune phenotype:
• Abs absent:
• special stuff:

Answer 7

• lack of RAG1/RAG2
• autosomal
• • T-, B-, NK+
• IgG, IgA, and IgM
• OMENN syndrome: partial function of RAG1/RAG2 leads to severe erythroderma, splenomegaly, eosinophilia, and HIGH IgE

Question 8

common gamma chain Deficiency (IL2-Ry/CD25):

• whats wrong:
• mechanism: is used in multiple cytokine receptors, including IL-2R and IL-15R. IL-2R signaling is needed for T cell activation and IL-15 is responsbiel for NK cell proliferation
• most ____ SCID (45% of all cases)
• ____ recessive
• immune phenotype:
• Abs:

Answer 8

• lack of common gamma chain
• • common
• X-linked recessive (boys more common)
• T-, B+, NK-
• IgM+, IgG-, IgE-, IgA-

Question 9

jak3 deficiency:

• whats wrong:
• mechanism: Jak3 kinase associates with the cytoplasmic tail of the common chain and is responsible for creating the signal generated by the receptors
• causes defect in ____ signaling
• ____ recessive
• immune phenotype:
• Abs:

Answer 9

• lack of Jak3, a kinase
• • IL-2
• autosomal
• T-, B+, NK-
• IgM+, IgG-, IgE-, IgA-

Question 10

IL-7Ra deficiency:

• whats wrong:
• mechanism: IL-7 stimulates differentiatio of lymphoid progenitors into T cells
• ____ recessive
• immune phenotype:
• Abs:

Answer 10

• lack of IL-7Ra
• • autosomal
• T-, B+, NK+
• IgM+, IgG-, IgE-, IgA-

Question 11

CD3 deficiency:

• whats wrong:
• mechanism: CD3 is the signal transducer of the TCR complex, withotu TCR signaling T cells can’t receive survival signals
• ____ recessive
• immune phenotype:
• Abs:

Answer 11

• lack of a CD3 subunit
• • autosomal
• T-, B+, NK+
• IgM+, IgG-, IgE-, IgA-

Question 12

what is common among all SCID

Answer 12

no live vaccines

treatment is HSCT

Question 13

which SCID is X-linked

Answer 13

common gamma chain

Question 14

B cell selective deficiences:

• B cells may be ____ or ____ with decreased function
• ____ and _____ cells are unaffected
• typical infections are ____ bacteria or abnomrally recurrent

Answer 14

• absent or present
• T and NK
• encapulated

Question 15

which selective B cell immunodeficiencies can be cured with HSCT

which selective B cell immunodeficiencies can be treated symptomatically

Answer 15

BTK agammaglobulinemia and Agammaglobulinemia

IgA, IgG subclass, hyper-IgM syundrome, transient hyper-IgM

Question 16

which selective B cell immunodeficiencies can’t receive live vaccines

which selective B cell immunodeficiencies have no vaccine restrictions

which selective B cell immunodeficieincies is a vaccine for polio not recommended

Answer 16

BTK agammaglobinemia, Agammaglobulinemia

IgA and IgG subclass

Hyper-IgM syndrome and transient hyper-IgM

Question 17

agammaglobulinemia/BTK deficiency:

• most common is ____ and caused by ____ deficiency
• what’s wrong:
• mechanism: BTK is involved in signaling of successful heavy chain formation, without which, B cells undergo deletion
• immune phenotype:
• Ab:
• Clinical presentation: normal at birth, recurrent infections starting after:
• treatment:

Answer 17

• X-linked, BTK
• BTK deficiency
• • T+, B-, NK+
• no Abs of any type
• a few months
• HSCT.

Question 18

IgA Deficiency:

• whats wrong:
• mechanism: there is no single mechanims
• immune phenotype:
• Abs:
• clinical presentation:
• treatment:
• special stuff:

Answer 18

• IgA is not made in sufficient levels
• • T+, B+, and NK+
• absent IgA, normal others
• relatively asymptomatic
• symptomatic
• anti-IgA IgG can be a cause and result in anaphylaxis with immunoglobulin transfusions

Question 19

hyper IgM (HIGM):

• what’s wrong:
• mechanism: inabitliy to perform class switching due to lack of signal
• immune phenotype
• Abs:
• clinical presentation:
• treatment:
• special stuff

Answer 19

• loss of CD40L or CD40
• • T+, B+, NK+
• High IgM, low IgG IgE IgA
• abnormal infection with encapulsated bacteria
• symptomatic
• CD40L = X-linked (more common in men); CD40 = autosomal

Question 20

transient hypogammaglobulinemia of infance:

• what’s wrong:
• immune phenotype:
• Abs:
• clinical presentation
• treatment

Answer 20

• infant starts making their own class switched Abs later tha normal
• T+, B+/-, NK+
• normal IgM; low IgG IgE IgA
• symptomatic

Question 21

isolated IgG subclass deficiencies:

• caused by:
• immune phenotype:
• Abs
• usually ____
• associated with recurrent ____/____ infections involving the ____ ____
• treatment

Answer 21

• defects in several genes
• T+, B+, NK+
• some IgG subclasses are absent; normal others
• asymptomatic
• viral/bacterial, respiratory tract
• symptomatic

Question 22

bare lymphocyte syndrome type II (BLSII):

• whats wrong:
• mechanism: transcription factors for MHC II gene are defective,
• immune phenotype:
• Abs:
• clinical presentation:
• treatment:

Answer 22

• MHC II not expressed on APCs
• • T+, B+, NK-
• all normal
• SCID-like infections
• HSCT

Question 23

MHC I Deficiency:

• whats wrong:
• mechanism: TAP gene is defective resulting in inability to load and present via MHC I
• immune phenotype:
• Abs:
• clinical presentation
• treatment:
• CD4 is ____
• CD8 is ____

Answer 23

• MHC I not expressed on cell surfaces
• • T+, B+, NK-
• normal all
• recurrent viral infections
• symptomatic
• normal
• deficient

Question 24

DiGeorge Syndrome:

• whats wrong:
• mechanism: deletion of a portion of DNA at 22q11.2, this is autosomal dominant
• immune phenotype:
• Abs:
• treatment:
• symptoms

Answer 24

• thymus is hypoplastic
• • T-, B+, NK+
• normal all
• symptomatic
• CATCH 22
  
  • Cardiac abnormalities
  • Abnormal Facies
  • Thymic absence/T cell abnormality
  • Cleft palate
  • Hypocalcemia/Hypoparathyroidism