Acquired Immunodeficiencies

Question 1

X-linked agammaglobulinemia (XLA)

Answer 1

defect in Bruton’s tyrosine kinase (req. for B cell development)

result: very few B cells
susceptibility: extracellular bacteria and some viruses (no neutralization)
symptom: underdeveloped tonsils

Question 2

lambda5 deficiency

Answer 2

Pre-b cell receptor deficiency: lambda5 is a component of the surrogate light chain that pairs with the heavy chain during somatic recombination of light chain genes

result: apoptotic death of B cells: profound B cell deficiency
susceptibility: extracellular bacteria and some viruses (influenza needs to be neutralized)

Question 3

X-linked hyper IgM syndrome: 2 causes

Answer 3

1. Defect in T helper cell function: defect CD40 ligand expression; cells cannot receive secondary activation signal
2. activation-induced cytidine deaminase (AID) deficiency; req. for isotope switching and somatic hypermutation

Question 4

Selective IgA deficiency

Answer 4

Healthy unless exposed to parasite pathogens
Important parasite: Giardia lamblia (IgA prevents attachment needed for colonization in GI tract)
Risk: producing IgA specific hypersensitivity following a blood transfusions (because they do not make IgA)

Question 5

Selective IgG deficiency

Answer 5

IgG1: susceptibility to many bacterial and viral pathogens
IgG2: susceptibility to encapsulated bacteria

Question 6

Ab deficiency results in susceptibility to_______

Answer 6

extracellular bacteria and fungi, esp. encapsulated bugs that are resistant to phagocytes

Question 7

What is the Tx for Ab deficiencies?

Answer 7

monthly injections of gamma globulin (passive immunization)

Question 8

X-linked hyper IgM syndrome: CD40 ligand deficiency

Answer 8

TH1 cells cannot activate macrophages or B cells
susceptibility: mycobacterium in blood
NO granulomas

Question 9

X-linked hyper IgM syndrome: AID defect

Answer 9

no class switching
CAN still activate effector T cells to supply second signals of activation to B and T cells
can have fully activated IgM B cells
IgM levels higher than in CD40 ligand deficiency

Question 10

When would a person be unable to form germinal centers?

Answer 10

cannot activate B cells

Question 11

When would a person be unable to form granulomas?

Answer 11

defect in macrophages

Question 12

Common variable immunodeficiency (CVID)

Answer 12

group of immunodeficiense with common features (reduced Ab) but different etiologies
Dx doesn’t occur until 2nd or 3rd decade
Present: recurring bacterial and/or viral infections and hypogammaglobulinemia

Question 13

Ataxia telangiectasia

Answer 13

Defect: ATM gene
Elevated: AFP (alpha-fetoprotein)
Result: B and T cell deficiencies (not SCID)
Present: cerebellar defects (ataxia), spider angiomas (telangiectasia), IgA (or IgE deficiency)

Question 14

IL-12 signaling deficiency

Answer 14

Inability to generate TH1 response: decreased IFN-gamma- can’t activate macrophages
Result: normal B cells, T cells, and Ab isotope concentration
Present: disseminated mycobacterial infections

Question 15

Job’s Syndrome

Answer 15

Hyper IgE syndrome
Defect: STAT-3 gene
Result: reduced production of IFN-gamma by TH1 cells and neutrophils that fail to respond to chemotactic signals
Highly polarized toward TH2 response
Present: high IgE; eczema, recurrent accesses with S. aureus, course facial features (broad nose, frontal bossing, deep-set eyes, doughy skin, retention of primary teeth)
FATED (facies, abscess, teeth, IgE, dermatologic)

Question 16

chronic mucocutaneous candidiasis

Answer 16

group of disorders characterized by recurrent or persistent superficial infections of the skin, mucous membranes, and nails with Candida sp.
Caused by T cell dysfunction; undefined cytokine deficiency

Question 17

TAP deficiency

Answer 17

very low MHC class I
Result: CD8 T cell deficiency because very few are positively selected during thymic development
susceptibility: intracellular pathogens

Question 18

Bare lymphocyte syndrome (MHC class I)

Answer 18

TAP deficiency

Question 19

alpha chain defect

Answer 19

CD8 alpha chain defect
Result: lack of CD8 expression
susceptibility: intracellular pathogens

Question 20

Perforin deficiency

Answer 20

nonsense mutation

Result: dramatically reduced CTL and NK activity; normal number of CD8

Question 21

SCID

Answer 21

CD4 T cell defects

B cells require effector T cell function

Question 22

Bare lymphocyte syndrome (MHC class II)

Answer 22

No MHC class II
result: unable to mount CD4 T cell responses or B cell response
SCID

Question 23

Wiskott-Aldrich syndrome

Answer 23

defect in cytoskeletal reorganization
result: T cells cannot activate B cells or macrophages; also effects CD8 T cells; normal levels of T and B cells, but affects Ab levels
SCID

Question 24

Adenosine deaminase (ADA)

Answer 24

accumulation of toxic nucleotide catabolites that kills all lymphocytes during their development
NO B or T cells
SCID

Question 25

Purine nucleotide phosphorylase

Answer 25

accumulation of toxic nucleotide catabolites that kills all lymphocytes during their development NO B or T cells SCID

Question 26

common gamma chain deficiency

Answer 26

gamma chain is signaling component of a number of cytokine receptors (IL-2, IL-4, IL-7, IL-9, and IL-15) Result: failure of T cells to proliferate; no effector T cells; still have T cells (no T cell activation), low B cells SCID NORMAL (relatively) NUMBER T CELLS

Question 27

Janus Kinase (Jak3) deficiency

Answer 27

interacts with gamma chain same phenotype as gamma chain SCID

Question 28

CD3 deficiency

Answer 28

No T cell function: lack of CD4 or CD8 T cells | SCID

Question 29

DiGeorge Syndrome

Answer 29

Deletion chromosome 22: q11.2 i.e. | Present: congenital heart disease, palatal abnormalities, learning disabilities, hypocalcemia, facial abnormalities

Question 30

Complete DiGeorge Syndrome

Answer 30

DiGeorge phenotype + absent or nonfunctional thymus result: no T cells Present: high susceptibility to bacterial, fungal, and viral infections SCID Tx: thymic transplant; can't tx other DiGeorge symptoms Hyper IgM

Question 31

ZAP-70 deficiency

Answer 31

ZAP-70: TK that phosphorylates ITAMS via the T cell receptor complex; req. for T cell signaling Result: absence of CD8 T cells and normal levels on non functioning CD4 T cells SCID Tx: bone marrow transplant

Question 32

Omenn Syndrome

Answer 32

Defect: RAG Result: no B cells and low number of oligoclonal auto reactive T cells SCID: fungal bacterial and viral infections Autoimmune: erythroderma, desquamation, alopecia, chronic diarrhea, failure to thrive, lymphadenopathy, and hepatosplenomegaly Tx: bone marrow transplant

Question 33

APECED

Answer 33

Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy Defect: AIRE (transcription factor that regulates expression of self-proteins by epithelial cells in thymic medulla during T cell negative selection) Symptoms: polyglandular autoimmunity (hypoparathyroidism, hypogonadism, adrenal insufficiency, T1DM, hypothyroidism) alopecia totalis, keratoconjunctivitis, tooth enamel hypoplasia, candidiasis, juvenile-onset pernicious anemia, GI problems

Question 34

IPEX

Answer 34

Immune Dysregulation, Polyendocrinopaty, Enteropathy, X-linked syndrome Defect: FoxP3 in CD4 T cells Result: lack of Treg Autoimmune (1st year of life): watery diarrhea, eczematous dermatitis, endocrinopathy (T1DM) Also: Coombs-positive anemia, autoimmune thrombocytopenia, autoimmune neutropenia, and tubular nephropathy Tx: immunosuppression or bone marrow transplant

Question 35

ALPS

Answer 35

Autoimmune Lymphoproliferative Syndrome Defect: no functional Fas, Fas-ligand, or caspase 10; immune cells fail to undergo apoptosis following an immune response Result: large number of CD4-/CD8- T cells Present: lymphadenopathy and splenomegaly; autoimmune hemolytic anemia and neutropenia, thrombocytopenia Tx: immunosuppression and IVIg (passive immunity)