Inherited Immunodeficiency of Acquired Immunity

Question 1

X-linked agammaglobulinemia

Answer 1

mutation that renders Bruton’s tyrosine kinase ineffective
inability of B cells to survive bone marrow development
susceptible to extracellular bacteria and some viruses (influenza bc abs important for immune response to this)
underdeveloped tonsils

Question 2

Pre-B cell receptor deficiency

Answer 2

defect in lamba 5 surrogate light chain that results in death of B cells
susceptible to extracellular and viral infections

Question 3

x-linked hyper IgM syndrome CD40 ligand defect

Answer 3

CD40 defect results in inability of T cells to activate B cells and macrophages
higher IgM than in immunocompetent individual
no germinal centers

Question 4

x-linkes hyper IgM syndrom AID deficiency

Answer 4

unable to class switch but have fully activated B cells
IgM levels higher than in those with CD40 deficiency
would rather have AID deficiency bc still able to activate B cells  
will have germinal centers

Question 5

selective IgA deficiency

Answer 5

genetic mutation unknown
pt’s at risk for anaphylactic reactions following blood transfusions-react to the IgA in the donor blood
increased chance for developing asthma, systemic lupus erythematosus and rheumatoid arthritis

Question 6

selective IgG deficiency

Answer 6

genetic mutation unknown

most important is IgG1 deficiency-susceptibility to bacterial and viral pathogens

Question 7

IgG1 deficiency

Answer 7

susceptible to bacterial AND viral pathogens

Question 8

IgG2 deficiency

Answer 8

susceptible to encapsulated bacteria

Question 9

common variable immunodeficiency

Answer 9

is characterized by hypogammaglobulinemia, and it leaves patients susceptible to recurring bacterial infections and some viral infections
group of 150 disorders, unknown genetics

Question 10

ataxia telangiectasia

Answer 10

genetic defect in ATM gene (encodes DNA repair enzyme)
clinical triad:
1. ataxia (cerebellar defects)
2. spider angiomas
3. either IgA or IgE deficiency (IgA most common)
elevated alpha-fetoprotein levels are also common

Question 11

IL-12 signal deficiency

Answer 11

leads to deficiency in IFN-gamma production and thus
diminished ability to produce TH1-type CD4 effector cells and the inability to fully activate macrophages
susceptibility observed in patients with this condition is to disseminated mycobacterial infections

Question 12

Job’s syndrome (hyper IgE syndrome)

Answer 12

deficiency of STAT-3 function resulting in reduced IFN-gamma production by Th1 T cells
immune response polarized towards Th2
high IgE in the blood
neutrophils don’t respond to chemotactic signals
eczema and recurrent abscesses with Staph aureus
characteristic features: broad nose, frontal bossing (which is an unusually prominent forehead with a very prominent brow ridge), deep set eyes, and retention of primary teeth

Question 13

Chronic Mucocutaneous Candidiasis

Answer 13

from undefined T cell dysfunction leaves patients susceptible to Candida sp

Question 14

TAP-1/2 deficiency

Answer 14

low number of CD8 T cells bv MHC class 1 unstable if peptide not bound
little amount of CD8 T cell positive selection in the thymus
bare lymphocyte syndrome
susceptible to some viral and bacterial infections

Question 15

CD8 alpha chain defect

Answer 15

essentially the same phenotype as a TAP transporter deficiency for the same reasons
susceptible to viral and some bacterial infections

Question 16

perforin deficiency

Answer 16

nonsense mutation of perforin

are highly susceptible to viral and some intracellular bacterial infections

Question 17

Defects in CD4 T cells result in ___

Answer 17

SCID

Question 18

Bare lymphocyte syndrome

Answer 18

lack MHC class II molecules 
no acquired CD4 T cell or B cell response

Question 19

Wiskott-Aldrich Syndrome

Answer 19

defect in cytoskeletal reorganization
can’t deliver effector molecules onto target cells (goes for CD4 and CD8 T cells)
prevents proper cytokine signaling from effector T cells to B cells and macrophages
see thrombocytopenia think WAS

Question 20

Adenosine deaminase (ADA) or Purine nucleotide phosphorylase deficiencies

Answer 20

accumulation of toxic nucleotide catabolites that kills almost all lymphocytes during their development.
No T cells or B cells

Question 21

Common gamma chain deficiency

Answer 21

gamma/c is a component of several important cytokine receptors, and a deficiency of this protein prevents signaling through each of those receptors
no functional B cells and no effector T cells

Question 22

Janus kinase deficiency (Jak3)

Answer 22

essentially identical to common gamma chain deficiency

Question 23

CD3 deficiency

Answer 23

a patient having no CD4+ or CD8+ T cells

from nonfunctional CD3 delta, epsilon, or zeta chain

Question 24

Thymic aplasia

Answer 24

is no development of a T cell repertoire in the absence of the thymus

Question 25

Complete DiGeorge Syndrome

Answer 25

absence of thymus or non-functional thymus
patients have high susceptibility to bacterial, fungal, and viral infections, including opportunistic pathogens
treat with thyme transplant

Question 26

Zap 70 deficiency

Answer 26

tyrosine kinase that associates with ITAMs during T cell receptor signaling, and it is required for transduction of signals through the TCR
have a near total absence of CD8+ T cells, but normal numbers of non-functional CD4+ T cells
treat with bone marrow transplant

Question 27

Omenn syndrome

Answer 27

mis-sense mutations that result in RAG-genes that are only partially active
no B cells, and low numbers of T cells that are oligoclonal and autoreactive
patients are susceptible to all types of infections, and they also suffer from autoimmune disease that is manifested in the skin and the intestinal tract
treat with bone marrow transplant

Question 28

Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED)

Answer 28

deficiency of the gene that encodes the autoimmune regulator (AIRE) that is expressed in the thymic medulla
polyglandular autoimmunity that results in underproduction of many hormones, total baldness (alopecia totalis), malabsorption of intestines (diarrhea), and a number of other maladies

Question 29

Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked Syndrome (IPEX)

Answer 29

genetic deficiency of FoxP3 expression by Tregs
early onset (typically 1st year of life) autoimmunity manifested in a variety of tissues
clinical triad of 1) watery diarrhea, 2) eczematous dermatitis, and 3) endocrinopathy (type 1 diabetes). Also typical to display Coomb’s positive anemia, autoimmune thrombocytopenia, autoimmune neutropenia, and tubular nephropathy
treat with immune suppression or bone marrow transplant

Question 30

Autoimmune Lymphoproliferative Syndrome (ALPS)

Answer 30

is characterized by lymphadenopathy and splenomegaly
results from a mutation that results in no expression of functional Fas, Fas-ligand, or caspase 10
immune cells fail to undergo apoptotic death following an immune response, resulting in overpopulation of secondary lymphoid tissues
autoimmune hemolytic anemia and neutropenia, thrombocytopenia, lymphadenopathy, splenomegaly, and a large number of double-negative (CD4-/CD8-) T cells
treat with immunosuppression and IVIg