Cell mediated (T cell deficiencies), Combined deficiencies (B and T cell affected) Flashcards
Examples of Selective T cell deficiency
* Cell mediated immunity
1) DiGeorge Syndrome (thymic aplasia)
2) Hyper-IgE syndrome (Job syndrome)
Examples of Combined partial B- and T cell deficiency
1) Wiscott-Aldrich Syndrome
2) Ataxia telangiectasia
Example of a Complete functional B and T cell deficiency
SCID - Sever Combined immunodeficiency
Clinical features of Di George syndrome
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)
Di George syndrome is caused by microdeletion of Chromosome —-q11 –> which results in the deletion of ——– trasncription factor
Di George syndrome is caused by microdeletion of Chromosome 22q11 –> which results in the deletion of TBX1 trasncription factor
In In DiGeorge syndrome deletions in TBX1 gene result in failure to form the —– and —— ————
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
Lab resutls in Di George syndrome
- normal levels on immunoglobulin
- decreased T-cell levels
Pateints w/ Di George have an increased susceptibility to what?
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)
Hyper-IgE Syndrome (Job’s Syndrome)
mutation+ Cf
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
lab findings in Hyper-IgE syndrome (Job syndrome)
1) ↑ IgE (other immunoglobulins are normal)
2) ↑ Eosinophils
3) ↓ TH17
4) ↓ IFN-γ
Mutation is STAT3 will dysregulate —— –> imparied recruitment of neutrophils to site of infection
TH17
A deficieny in TH17 will result in?
imapaired recruitment of neutrophils to sites of infection
Wiscott-Aldrich syndrome (WAS) is a rare ———— immunodeficinecy disorder
X-linked recessive
CF of Wiscott-Aldrich syndrome (WAS)
1) Characterized by the triad of Thrombocytopenia, Eczema and Recurrent infections (WATER
mnemonics)
2) Increased risk of autoimmune disease and malignancy
In Wiscott-Aldrich Syndrome what gene is absent?
WAS protein (WASP)
Wiskott-Aldrich Syndrome
Mutation in ——— gene; leukocytes and platlets unable to recognize actic cytoskeleton –> defective antigen presentation
WAS
lab tests in Wiscott-Aldrich syndrome
1) Lower than normal IgM
2) decreased lymphoyctes (normal at birth)
3) decrease in CD4+
Ataxia Telaniectasis is an ——- diseases characterized by neurodegeneration, immune dysfunction, radiosensitivity and cancer predisposition
Autosomal Recessive
* combined deficiency
Ataxia Telangiectasia is caused by defects in ——— –> failure to detect DNA damage–> failure to halt the progression of cell cycle –> mutation accumulates
ATM gene
Ataxia Telangiectasia is caused by defects in ATM gene –> failure to ————––> failure to halt the progression of cell cycle –> mutation accumulates
Detect DNA damage
Clinical features of Ataxia Telangiectasia
triad:
1) Cerebral defects (Ataxia)
2) Spider Angiomas (Occular telangiectasia)
3) IgA deficiency
4) Hypersensitivity to radiation (limit X-ray exposure)
Lab findings in Ataxia Telangiectasia
1)↓ IgA, IgE, IgG
2) increased risk to cancer (lymphoma and leukemia)
3) ↓ of B and T cells
———– is s the most severe form of CID
SCID
In SCID ther is [Complete/Incomplete] functional T and B cell deficiency
Complete
most common form of SCID
XSCID (X-linked)
XSCID is caused by a deficiency of?
γ-chain of IL-2 receptor (IL2Rγc)
* IL-2R gamma chain
X-linked SCID causes failure of development of which cells ?
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
characteristics of X-linked SCID
Failure to thrive, chronic diarrhea, thrush, recurrent viral, bacterial, fungal and protozoal infections very early in life
Lab finding in X-linked SCID
1) Low levels of circulating lymphocytes
(cells are unresponsive to mitogens)
Absence of ———– results in an autosomal
recessive form of SCID characterized by absence of T
cells
IL-7 receptor (IL-7R)
SCID caused by Absence of IL-7 receptor (IL-7R) is characterised by the Absence of what cells?
T cells only
* NK cells are normal (since no deficiency in IL-15 receptors)
Absence of ———– results in an autosomal
recessive form of SCID characterized by defects in T,B and NK cells
ADA (Adenosine deaminase enzyme)
Absence of ADA results in an autosomal
recessive form of SCID characterized by absence of what cells?
B, T and NK cells
All forms of SCID are X-linked [Dominant/Recessive] disorders?
X-linked Recessive
Mutations in ——– or ———- results in an autosomal recessive form of SCID characterized by absence of T and B cells, but normal NK cells
RAG1 or RAG2
(they become non-functional)
Mutations in ** RAG1 or RAG2** results in an autosomal recessive form of SCID characterized by absence ?
T and B cells
* normal NK cells
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
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
———— permits diagnosis of SCID at birth
(TRECs)- T cell receptor excision circels
Infants with SCID have undetectable or very low levels of ———-, They also have absence of ———–, ————– (lymph node biopsy) and ———– (flow cytometry)
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)
