WBC DISORDER Flashcards
NONMALIGNANT LEUKOCYTE DISORDERS
❑ Congenital defects of leukocyte number and function
❑ Morphologic abnormalities of leukocytes
❑ Quantitative abnormalities of leukocytes
❑ Infectious Mononucleosis
Congenital defects of
leukocyte number and function
1.Severe Combined Immunodeficiency disorder (SCID)
2. Wiskott-Aldrich Syndrome (WAS)
3. 22q11 Syndromes
4. Bruton tyrosine kinase Deficiency
5.Chédiak – Higashi Syndrome
6. Congenital defects of phagocytes
7. Leukocyte Adhesion Disorders
8. Defects of respiratory burst
9.WHIM syndrome
Affects both cellular and humoral immunity
Severe Combined Immunodeficiency disorder (SCID)
Patients exhibits : ⇣ T cells, poorly functioning B cells,hypogammaglobulinemia
Severe Combined Immunodeficiency disorder (SCID)
Gamma chain deficiency : mutations in?
IL2RG gene
(IL 2,4,7,9,15,21)
Severe Combined Immunodeficiency disorder (SCID)
- X linked disease
Caused by one of 400 mutations in the WAS gene : (⇣ levels of
WASp proteins)
Wiskott-Aldrich Syndrome (WAS)
⇣ B cells, T NK cells neutrophils, monocytes are dysfunctional
Wiskott-Aldrich Syndrome (WAS)
Therapies for Wiskott-Aldrich Syndrome (WAS)
Therapies : eltrombopag, romiplostim, Gene therapy
- Microdeletion in chromosome band 22q11.2
- Absence or decreased size of thymus
- Low number of T lymphocytes
22q11 Syndromes
22q11 Syndromes classified as immunodeficiency, includes:
✓DiGeorge Syndrome
✓Sedlackova syndrome
✓Caylor cardiofacial syndrome
✓Shprintzen syndrome
✓Conotruncal anomaly face syndrome
➢Bruton tyrosine kinase Deficiency
- Antibody deficiency
mutation in the gene encoding Bruton tyrosine kinase
⇣ production of BTK which is important for B-cell development, differentiation and signaling
Chédiak – Higashi Syndrome mutation in the?
CHS1 LYST gene on chromosome 1q42.1-2
CHS1 LYST gene on chromosome 1q42.1-2
encodes for a protein that regulates the morphology and function of lysosome related organelles.
giant lysosomal granules in granulocytes, monocytes, and lymphocytes
Chédiak – Higashi Syndrome
Inclusions that resembles the fused lysosomal granules in CHS Chédiak – Higashi Syndrome
Pseudo Chédiak – Higashi
are cytoplasmic inclusions that are seen in patients with acute myeloid leukemia, chronic myeloid leukemia and myeloidyplastic syndrome (MDS)
Pseudo Chédiak – Higashi
- Congenital neutropenia (CN)
Congenital defects of phagocytes
Low neutrophil count
Congenital neutropenia (CN)
Caused by 24 kinds of genes
Congenital defects of phagocytes or Congenital neutropenia (CN)
- Treatment :
-antibiotic prophylaxis,
-G-CSF (higher dose
have been assoc. with increased risk of malignant transformation)
Congenital defects of phagocytes
defects of motility
Leukocyte Adhesion Disorders
- inability of neutrophils and monocytes to move from circulation to the site of inflammation (called
extravasation)
Leukocyte Adhesion Disorders
Consequences:recurrent severe bacterial & viral
infections
Leukocyte Adhesion Disorders
Hematopoietic stem cell transplant is the only curative treatment.
Leukocyte Adhesion Disorders
Leukocyte Adhesion Disorders * Types:
LAD I, II, III, SDS
Chronic Granulomatous disease (CGD)
Defects of respiratory burst
caused by mutations in genes responsible for proteins
that make up the reduced form of nicotinamide adenine
dinucleotide phosphate (NADPH) oxidase
Defects of respiratory burst
patients experience life-threatening catalase-positive bacterial and fungal infections
Defects of respiratory burst
WHIM meaning
warts, hypogammaglobulinemia, infections
myelokathexis syndrome
a defect in intrinsic and innate immunity
WHIM syndrome
mutations in the CXCR4 gene located at 2q22
WHIM syndrome
patients experience recurrent bacterial infections and are
highly susceptible to human papillomavirus (HPV) infection,
which leads to warts, which can be widespread and resistant
to treatment
WHIM syndrome
WHIM syndrome Treatment
anitibiotic prophylaxis,immunoglobulin
replacement
G-CSF
CXCR4 receptor antagonist
