Immunodeficiency Disorders Flashcards
is when the immune system errs by failing to protect the host from disease-causing agents or from malignant cells.
Immunodeficiency
Immunodeficiency
• Classification
- Based on the cause
- Based on component affected
Classification
- Based on Cause
- Primary Immunodeficiency
- Secondary Immunodeficiency
Based on Cause
• conditions resulting from a genetic or developmental defect in the immune system
Primary Immunodeficiency
Based on Cause
• loss of immune function and results from exposure to various agents
- Secondary Immunodeficiency
Disease-carrying gene(s)
Child born with IgA deficiency, CVI, SCID, or others
primary immune deficiency
Secondary
- Intravenous (IV) drug abuse unsafe sexual activity, and other risk behaviors
• Mainutrition
› Chronic diseases (such as diabetes)
• Medications (such as corticosteroids)
Development of AIDS or other secondary immune deficiency
Impaired (weakened immune response
Secondary Immune Deficiency
Classification
Based on Component Affected
- B cell
- T cell
- Phagocyte
- Complement
• Encapsulated bacteria (S. pneumoniae)
• AIDS (affects CD4 Thelper cells)
• Pyogenic infections (i.e. caused by bacteria)
• Lack of MAC (Neisserial infections)
- B cell
- T cell
- Phagocyte
- Complement
Types of Immunodeficiencies
B Cell
T cell
Combined B & T
Phagocyte
Complement
B Cell
Bruton’s X-linked Aggamaglobulinemia
Common Variable Immunodeficiency
Disorders
Transient Hypogammaglobulinemia
of the Newborn
Hyper IgM
Hyper IgE
IgA deficiency
Isolated IgG Subclass Deficiency
T cell
DiGeorge Syndrome
Purine-nucleoside phosphorylase deficiency
Combined B & T
Severe Combined Immunodeficiency
a. Bare Lymphocyte Syndrome
b. X-linked SCID
c. Adenosine Deaminase Deficiency
Wiskot-Aldrich Syndrome
Ataxia Telangiectasia
Phagocyte
Chronic Granulomatous Disease
Chediak-Higashi Syndrome
Leukocyte Adhesion Defect
Complement
МАС Deficiency
Bruton’s X-Linked Agammaglobulinemia
- - discoverer
Dr. Ogden Bruton
- Is a rare genetic disorder that affects the body’s ability to fight infection
- Absence of BTK gene that codes for enz (Bruton’s tyrosine kinase)
Bruton’s X-Linked Agammaglobulinemia
- Immature B cells will not undergo maturation due to lack of enzyme
- Symptoms appear after 6-9 months of age
Bruton’s X-Linked Agammaglobulinemia
Recurrent fungal, protozoan, viral
infections
Recurrent bacterial infections
Bruton’s X-Linked
Agammaglobulinemia
- enzyme needed for differentiation into a mature B cell
Tyrosine kinase
- Failure of mature B cells to become plasma cells
- Unknown mechanism (idiopathic)
Common Variable Immunodeficiency (CVI)
CVI
- Congenital presentation; _____\deficiency
IgA and IgG
● Failure of the mature B cells to respond to T cells
thus they cannot differentiate into plasma cells
Common Variable Immunodeficiency
CVI DETECTION
- (+) B cell:
• CD19 and CD20
• Nylon test
• Electron microscopy
• Mitogen (LPS & DEXTRAN)
- LOW ANTIBODIES
- HYPOGAMMAGLOBULENEMIA OF 2 OR MORE IMMUNOGLOBULIN ISOTYPE
CVI
- Failure of B cells to produce antibodies due to delayed maturation of T cell in thymus
Transient Hypogammaglobulinemia
- Also referred to as Pediatric
Hypogammaglobulinemia
Transient Hypogammaglobulinemia
- Starts at 4 months and upon clearance of maternal IgG, there is persistently lower IgG levels that can last up to 3 years
Transient Hypogammaglobulinemia
T cell-independent B cell activation
_____secretion
IgM
T cell-dependent B cell activation
____secretion
IgG
- Increased levels of IgM
- Low levels of all other isotypes: IgG, IgA, IgD, IgE
X-Linked Hyper IgM Syndrome
X-Linked Hyper IgM Syndrome
- Absence of____ ligand on Thelper cell
- No class switching
CD40
CD40 present on the surface of B cells will react with CD40 ligand on Thelper cells to initiate class switching of____ to_____
IgM to IgG
- Impaired IL-2 production
- Hyperactive Th2
- Prone to allergic reactions
Hyper IgE
- Most common primary immunodeficiency
- Failure of B cells to become IgA-producing plasma cells
IgA deficiency
- Unknown mechanism (idiopathic)
- Recurrent gastrointestinal and respiratory infection
IgA deficiency
Isolated IgG Subclass Deficiency
- Protein antigens:
IgG1 and IgG3
Isolated IgG Subclass Deficiency
- Carbohydrate antigens:
IgG2
IgG Subclass Concentration in the Blood
IgG1
IgG2
IgG3
IgG4
70%
20%
6%
4%
T Cell Immunodeficiency
- 22q11.2 deletion syndrome
- Absence of chromosome 22q
DiGeorge Syndrome / DiGeorge Anomaly
T Cell Immunodeficiency
DiGeorge Syndrome / DiGeorge Anomaly
-______ deletion syndrome
- Absence of chromosome___
22q11.2
22q
- Impaired development of 3rd and 4th pharyngeal pouch which will give rise to:
• Hard palate
• Part of aorta
• Parathyroid gland
• Thymus
DiGeorge Syndrome / DiGeorge Anomaly
DiGeorge Syndrome / Anomaly
CATCH 22
Cleft palate
Abnormal faceii (monkey)
Thymic hypoplasia
Cardiovascular disorder
Hypocalcemia
- When DNA is broken down=production of purines
Purine-nucleoside phosphorylase deficiency (PNP Deficiency)
- Impaired metabolism of purines due to mutations in the PNP gene results to toxic purine metabolites
Purine-nucleoside phosphorylase deficiency (PNP Deficiency)
- Accumulation of deoxyguanosine triphosphate (dGTP)
- Number of T cells progressively decreases
Purine-nucleoside phosphorylase deficiency (PNP
Deficiency)
- S/S:
• Neurologic disorders
• Recurrent or chronic pulmonary infections, diarrhea, urinary tract infections (UTI), skin infections
Purine-nucleoside phosphorylase deficiency (PNP Deficiency)
Severe Combined Immunodeficiency
(SCID)
- 3 SCID Types:
a. Bare Lymphocyte Syndrome
b. X-Linked SCID
c. Adenosine Deaminase Deficiency
- absence of Type I (MHC Class I) Type II (MHC Class Il)
aka TAP2 deficiency
Bare Lymphocyte Syndrome
_____SCID - absence of receptors for IL-7 and IL-15
X-Linked
mutations in the ADA gene that codes for adenosine deaminase enzyme
Adenosine Deaminase Deficiency
→ CD43 is present in lymphocytes and platelets
Wiskott-Aldrich Syndrome (WAS)
abnormality in integral membrane (CD43) ;
Wiskott-Aldrich Syndrome (WAS) -
gene responsible for defect:(Wiskott-Aldrich Syndrome)
WASp gene
Triad of WAS
• Decreased platelet survival
• Abnormal skin function (eczema)
• Defects in T and B cell function
Aka______ is a neurodegenerative inherited disorder;
absence of ATS gene which codes for ATM protein
Ataxia-Telangiectasia (AT) Syndrome - aka
Louis-Bar syndrome
gene product is a protein with multiple functions.
One of these is assisting cells to recognize damaged DNA for its repair.
In the nucleus, the product also helps control rate of cell growth and division
ATM
Mutated____ leads to hypersensitivity of cells to radiation because damaged DNA
accumulates instead of being
repaired.
Unregulated cell growth leads to tumor formation.
Cells in the cerebellum die affecting coordinated movement.
In the eye the conjunctiva have small dilated blood vessels (telangiectasias).
Oculomotor apraxia occurs.
ATM
- absence of NADPH oxidase; suppurative infection
Chronic Granulomatous Disease (CGD)
• Semiquantitative assay
* Tests the phagocytic function of polymorphonuclear leukocytes (PMNL)
• Cells reduce a colorless NBT into a blue-black deposit within the cell
• In CGD, the PMNLs will not turn blue
Nitro Blue-Tetrazolium Test (NBT)
- absence of LYST gene (lysosomal trafficking) which codes for LYST protein, important in the fusion of lysosome with phagosome
Chediak-Higashi Syndrome
Chediak-Higashi Syndrome - absence of
____which codes for LYST protein, important in the fusion of lysosome with phagosome
LYST gene (lysosomal trafficking)
Chediak-Higashi Syndrome - absence of
____which codes for LYST protein, important in the fusion of lysosome with phagosome
LYST gene (lysosomal trafficking)
ALBINISM -______ helps transport melanin into melanocytes
lyst protein
Leukocyte Adhesion Defect / Deficiency
(aka Lazy Leukocyte Syndrome)
- Type I: absence of integrin
- Type Il: absence of L-selectin (CD62L) and Sialyl-Lewis X-modified glycoprotein (CD15s)
— Also absence of CD18/CD11 adhesion receptors on T cells, neutrophils, and monocytes
- Results in abnormal adhesion, motility, and chemotaxis of cells
Leukocyte Adhesion Defect / Deficiency
— S/S:
• Delayed wound healing
• Chronic skin infections
Leukocyte Adhesion Defect / Deficiency
Complement Component Deficiency
• Lack of______
• No cytolysis of (intracellular) pathogen
• Recurrent infection
MAC (C5b6789)