Cell mediated (T cell deficiencies), Combined deficiencies (B and T cell affected)

Question 1

Examples of Selective T cell deficiency

* Cell mediated immunity

Answer 1

1) DiGeorge Syndrome (thymic aplasia)
2) Hyper-IgE syndrome (Job syndrome)

Question 2

Examples of Combined partial B- and T cell deficiency

Answer 2

1) Wiscott-Aldrich Syndrome
2) Ataxia telangiectasia

Question 3

Example of a Complete functional B and T cell deficiency

Answer 3

SCID - Sever Combined immunodeficiency

Question 4

Clinical features of Di George syndrome

Answer 4

1) abnormalities of the face and ears
* low-set ears
* Hypertelorism (increased distance btw the eyes)
* small mouth
* Micrognathia (Underdeveloped jaw)

2) parathyroid insufficiency causing hypocalcemia
3) cardiac malformations resulting in congenital heart disease
4) hypoplastic or aplastic thymus (under developed or absent thymus)

Question 5

Di George syndrome is caused by microdeletion of Chromosome —-q11 –> which results in the deletion of ——– trasncription factor

Answer 5

Di George syndrome is caused by microdeletion of Chromosome 22q11 –> which results in the deletion of TBX1 trasncription factor

Question 6

In In DiGeorge syndrome deletions in TBX1 gene result in failure to form the —– and —— ————

Answer 6

In DiGeorge syndrome deletions in TBX1 gene result in failure to form the 3rd and 4th pharyngeal pouches
* So Absent Thymus and parathyroid

thymus and parathyroid glands arise from the 4 and 3 pharyngeal pouches

Question 7

Lab resutls in Di George syndrome

Answer 7

• normal levels on immunoglobulin
• decreased T-cell levels

Question 8

Pateints w/ Di George have an increased susceptibility to what?

Answer 8

1) Viral infections –> recurrent pneumonia and chronic sinusitus caused by H.influenza (Due to thymic insufficiency
2) Primary hypoparathyoidisim manifested as Hypocalcaemia / low or absent parathyroid hormone (Due parathyroid gland Deficiency)

Question 9

Hyper-IgE Syndrome (Job’s Syndrome)
mutation+ Cf

Answer 9

Learn the ABCDEF’s to get a Job STAT!
* STAT3 mutation
* Cold (non-inflamed) staphylococcal Absceses
* Retained Baby teeth
* Coarse facies (prominant nose, deep set eyes, thickend facial skin, high arched palate, asymmetrical facial appearance)
* Dermatologic problems (eczema)
* ↑ IgE
* Bone Fractrues from minor trauma

Question 10

lab findings in Hyper-IgE syndrome (Job syndrome)

Answer 10

1) ↑ IgE (other immunoglobulins are normal)
2) ↑ Eosinophils
3) ↓ TH17
4) ↓ IFN-γ

Question 11

Mutation is STAT3 will dysregulate —— –> imparied recruitment of neutrophils to site of infection

Answer 11

TH17

Question 12

A deficieny in TH17 will result in?

Answer 12

imapaired recruitment of neutrophils to sites of infection

Question 13

Wiscott-Aldrich syndrome (WAS) is a rare ———— immunodeficinecy disorder

Answer 13

X-linked recessive

Question 14

CF of Wiscott-Aldrich syndrome (WAS)

Answer 14

1) Characterized by the triad of Thrombocytopenia, Eczema and Recurrent infections (WATER
mnemonics)
2) Increased risk of autoimmune disease and malignancy

Question 15

In Wiscott-Aldrich Syndrome what gene is absent?

Answer 15

WAS protein (WASP)

Question 16

Wiskott-Aldrich Syndrome

Mutation in ——— gene; leukocytes and platlets unable to recognize actic cytoskeleton –> defective antigen presentation

Answer 16

WAS

Question 17

lab tests in Wiscott-Aldrich syndrome

Answer 17

1) Lower than normal IgM
2) decreased lymphoyctes (normal at birth)
3) decrease in CD4+

Question 18

Ataxia Telaniectasis is an ——- diseases characterized by neurodegeneration, immune dysfunction, radiosensitivity and cancer predisposition

Answer 18

Autosomal Recessive

* combined deficiency

Question 19

Ataxia Telangiectasia is caused by defects in ——— –> failure to detect DNA damage–> failure to halt the progression of cell cycle –> mutation accumulates

Answer 19

ATM gene

Question 20

Ataxia Telangiectasia is caused by defects in ATM gene –> failure to ————––> failure to halt the progression of cell cycle –> mutation accumulates

Answer 20

Detect DNA damage

Question 21

Clinical features of Ataxia Telangiectasia

Answer 21

triad:
1) Cerebral defects (Ataxia)
2) Spider Angiomas (Occular telangiectasia)
3) IgA deficiency
4) Hypersensitivity to radiation (limit X-ray exposure)

Question 22

Lab findings in Ataxia Telangiectasia

Answer 22

1)↓ IgA, IgE, IgG
2) increased risk to cancer (lymphoma and leukemia)
3) ↓ of B and T cells

Question 23

———– is s the most severe form of CID

Answer 23

SCID

Question 24

In SCID ther is [Complete/Incomplete] functional T and B cell deficiency

Answer 24

Complete

Question 25

most common form of SCID

Answer 25

XSCID (X-linked)

Question 26

XSCID is caused by a deficiency of?

Answer 26

γ-chain of IL-2 receptor (IL2Rγc)

* IL-2R gamma chain

Question 27

X-linked SCID causes failure of development of which cells ?

Answer 27

1) T cells (IL-7)
2) NK cells (IL-15)

*NOTE: B cells develop but are not functional

* IL-7 and IL-15 are essential for early development of and NK cells

Question 28

characteristics of X-linked SCID

Answer 28

Failure to thrive, chronic diarrhea, thrush, recurrent viral, bacterial, fungal and protozoal infections very early in life

Question 29

Lab finding in X-linked SCID

Answer 29

1) Low levels of circulating lymphocytes
(cells are unresponsive to mitogens)

Question 30

Absence of ———– results in an autosomal
recessive form of SCID characterized by absence of T
cells

Answer 30

IL-7 receptor (IL-7R)

Question 31

SCID caused by Absence of IL-7 receptor (IL-7R) is characterised by the Absence of what cells?

Answer 31

T cells only
* NK cells are normal (since no deficiency in IL-15 receptors)

Question 32

Absence of ———– results in an autosomal
recessive form of SCID characterized by defects in T,B and NK cells

Answer 32

ADA (Adenosine deaminase enzyme)

Question 33

Absence of ADA results in an autosomal
recessive form of SCID characterized by absence of what cells?

Answer 33

B, T and NK cells

Question 34

All forms of SCID are X-linked [Dominant/Recessive] disorders?

Answer 34

X-linked Recessive

Question 35

Mutations in ——– or ———- results in an autosomal recessive form of SCID characterized by absence of T and B cells, but normal NK cells

Answer 35

RAG1 or RAG2
(they become non-functional)

Question 36

Mutations in ** RAG1 or RAG2** results in an autosomal recessive form of SCID characterized by absence ?

Answer 36

T and B cells
* normal NK cells

Question 37

SCID caused by mutations in RAG1 or RAG2 (they become non-functional) –> failure of ——— recombination (=———–) in developing lymphocytes –> Complete lack of —— and ——— cells but normal NK cells

Answer 37

SCID caused by mutations in RAG1 or RAG2 (they become non-functional) –> failure of V(D)J recombination (= DNA rearrangement) in developing lymphocytes –> Complete lack of T and B cells but normal NK cells

Question 38

———— permits diagnosis of SCID at birth

Answer 38

(TRECs)- T cell receptor excision circels

Question 39

Infants with SCID have undetectable or very low levels of ———-, They also have absence of ———–, ————– (lymph node biopsy) and ———– (flow cytometry)

Answer 39

Infants with SCID have undetectable or very low levels of TRECs, They also have absence of Thymic shadow, germinal centers (lymph node biopsy) and T cells (flow cytometry)