immunodeficiency

Question 1

Leukocyte Adhesion Deficiency Syndrome

Answer 1

Mutation in CD18, LFA-1, CR3, and CR4 ->
Neutrophils could not emigrate through the vessel wall to the infected site, can not phagocytize bacteria

*** EXTREME leukocytosis

Delayed separation of the umbilical cord is an earliest sign for this abnormally

Question 2

Chronic Granulomatous Disease

Answer 2

Deficiency in G6PD, NADPH oxidase, superoxide dismutase, myeloperoxidases

results in the formation of a granuloma

Question 3

Test for NADPH Oxidase Deficiency

Answer 3

Nitro Blue - Tetrazolium Test (NBT)

Neutrophils are tested for their ability to phagocytize and reduce NBT

Question 4

Chediak-Higashi Syndrome

Answer 4

defect: lysosomal trafficking regulator protein, LYST ->
Failure to form phagolysosome upon phagocytosis ->
formation of giant granules (giant lysosomes)

Question 5

Defects in IL-12/IFN gamma receptor/signaling

Answer 5

persistent intra-vesicular bacterial pathogens

ex. mycobacterium spp

Question 6

Defect in NK cell Deficiency

Answer 6

Defect in GATA2 gene: absence of NK development in the bone marrow

Defect in CD16 ( IgG Fc receptor) – lack of functional NK : no ADCC

Susceptibility to certain viruses: mainly herpes and papilloma virus

Question 7

B Cell/Antibody Deficiency

Answer 7

Defective Ig response to vaccination

increased susceptibility to extra cellular bacterial infection (polysaccharide capsule) (pus forming )

Question 8

Mutation in Btk

Answer 8

B cell devel stops at the pre-B cell stage

Question 9

X-linked Agammaglobulinemia(XLA)

Answer 9

Bruton’s disease

• Low or no B cell in circulation
• Low Ig or not detectable in serum

Question 10

Common Variable Immunodeficiency: dysgammaglobulinemia

Answer 10

• Absence of proliferation of B cells in response to antigen
• Normal proliferation of B cells but secretion of only IgM
• hypogammaglobulinemia

Question 11

Selective Immunoglobulin Deficiencies

Answer 11

IgA deficiency is more common than IgG and IgM deficiency

Failure of class switch to IgA
level of IgM and IgG are normal 

** Have anti IgA antibodies in serum ->
May cause anaphylactic shock during blood transfusion

Question 12

*** DiGeorge Syndrome

Answer 12

Thymic aplasia
No T cells or few T cells ->
the few T cells present will be abnormal

Susceptible to intracellular infections, such as viruses and fungi

• Abnormally increased distance between the eyes
• Upward slant of the eyes
• Low set, prominent ears with notched ear fold
• Unusual smallness of the jaws

Question 13

Chronic Mucocutaneous Candidiasis

Answer 13

Selective defect in functioning of T cells

Normal T cell mediated immunity to microorganisms other than Candida albicans

B cells function is normal

Question 14

Hyper-IgM Syndrome

Answer 14

1. Deficiency in CD40L (CD154): X-linked
2. Deficiency in CD40
3. Deficiency in AID (Activation-induced deaminase)

–No activation of naïve T CD4 by APC (macrophage/ dendritic) ->
defective T cell medicated immunity

–No isotype switch, High concentration of IgM ->
no IgA and IgG, IgE

Question 15

Combined B and T Cell Deficiency

Answer 15

No CMI, no humoral immunity

Defects in several genes

Question 16

X-linked SCID

Answer 16

IL2/ gamma chain ->

defect in cytokine signaling ->

non-development of t cells and NK cells ->

extreme susceptibility to infections

Question 17

JAK3 deficiency

Answer 17

JAK3 ->

defect in cytokine signaling ->

non-development of t cells and NK cells ->

extreme susceptibility to infections

Question 18

Omenn Syndrome

Answer 18

RAG1, RAG2 ->

deficient V(D)J recombination ->

non-production of T calls and B cells ->

SCID, chronic inflammation

Question 19

*** Wiskott-Aldrich Syndrome (WAS)

Answer 19

WASP/WAS protein ->

defective cytoskeleton functions ->

antibody deficiency, increased susceptibility to infections, thrombocytopenia

Question 20

MHC class II deficiency

Answer 20

transcriptional activators ->

non-production of HLA class II molecules ->

defective CD4 T-cell development ->

increased susceptibility to pyrogen

Question 21

MHC class I deficiency

Answer 21

TAP1, TAP2 ->

impaired production of HLA class 1 molecules ->

failure of CD8 T cell to develop in the thymus ->

repeated respiratory viral infections

Question 22

Severe Combined Immunodeficiency (SCID)

Answer 22

Defect in:

• cytokine receptor (common gamma chain)
• JAK3
• RAG1, RAG2
• WASP/WAS
• MHC II, MHC I

Question 23

Defects in RAG-1 and RAG-2

Answer 23

Omenn syndrome

Clinical features:
•Presents early (one month) 
•Papular scaly rash covering entire body  
(like the Candida albicans) 
• Eosinophilia, IgE elevated 
•Poor prognosis. 
•autoimmune disease, lymphoma 

•Treatment:
early diagnosis and bone marrow transplant

Question 24

Defect in gene WASP gene

Answer 24

Wiskott-Aldrich Syndrome

mutation on a gene (WASP) responsible for cytoskeleton of lymphocytes and platelets

Clinical symptoms:

1. Petechiae
2. Recurrent pyogenic infections 3. Allergic reactions: severe eczema, increased IgE level
3. high risk for malignant lymphoma

Question 25

Defect in MHC I

Answer 25

Bare Lymphocyte Syndrome

Mutation in TAP molecules

Failure in:
CD8 T lymphocyte development in the thymus

Question 26

Defect in MHC II

Answer 26

Bare lymphocyte syndrome

Mutation in transcriptional activator gene : MHC class II transactivator (CIITA)

Deficient in CD4

APC lack MHC II- No antigen presentation