Congenital Immunodeficiencies Flashcards by Sarah Peck

What are the 3 SCID immunodeficiencies?

All Rats Amazing

(1) ADA
(2) RAG1/RAG2
(3) Artemis

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(SCID)
ADA 
(1) Immune phenotype
(2) Ab panel
(3) Inheritance
(4) Infections
(5) Vaccination
(6) Treatment

(1) T-, B-, NK-
(2) IgM-, IgG-, IgA-
(3) Autosomal
(4) Severe opportunistic infections
(5) No live vaccines
(6) HSCT

susceptible to viral, bacterial, fungal infections at birth
leads to accumulation of metabolic byproducts (Deoxyadenosine) which is toxic to lymphocytes

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(SCID)
RAG1/RAG2
(1) Immune phenotype
(2) Ab panel
(3) Inheritance
(4) Infections
(5) Vaccination
(6) Treatment

(1) T-, B-, NK+ (CD56)
(2) IgM-, IgG-, IgA-, high IgE
(3) Autosomal
(4) Severe opportunistic infections
(5) No live vaccines
(6) HSCT

impaired VDJ recombination which leads to defective expression of pre-TCR and pre-BCR

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(SCID)
Artemis
(1) Immune phenotype
(2) Ab panel
(3) Inheritance
(4) Infections
(5) Vaccination
(6) Treatment

(1) T-, B-, NK+ (CD56)
(2) IgM-, IgG-, IgA-
(3) Autosomal
(4) Severe opportunistic infections
(5) No live vaccines
(6) HSCT

increased risk of developing lymphomas

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What are the 7 selective B cell immunodeficiencies?

ALL HAVE T+ and NK+

Bad Cats Are Good At HuMping TooMuch

BTK agamma-globulinemia
Common variable (CVID)
IgA
IgG subclass
Agamma-globulinemia
Hyper-IgM syndrome
Transient hyper-IgM

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(SELECTIVE B CELL)
BTK Agamma-Globulinemia
(1) Immune phenotype
(2) Ab panel
(3) Inheritance
(4) Infections
(5) Vaccination
(6) Treatment

(1) T+, B-, NK+
(2) IgM-, IgG-, IgA-
(3) X-linked
(4) Recurrent bacterial infections
(5) No live vaccines
(6) HSCT

mutation in tyrosine kinase – BTK
BTK gene found on X chromosome
caused by defect in rearrangement of IgG heavy chain genes
B cell maturation halted at Pre-B cell stage and doesn’t leave bone marrow
likely find normal or decreased Pre-B cells in bone marrow and IgM heavy chains in cytoplasm

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(SELECTIVE B CELL)
Agamma-Globulinemia
(1) Immune phenotype
(2) Ab panel
(3) Inheritance
(4) Infections
(5) Vaccination
(6) Treatment

(1) T+, B-, NK+
(2) IgM-, IgG-, IgA-
(3) Autosomal
(4) Recurrent bacterial infections
(5) No live vaccines
(6) HSCT

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(SELECTIVE B CELL)
Common Variable (CVID)
(1) Immune phenotype
(2) Ab panel
(3) Inheritance
(4) Infections
(5) Vaccination
(6) Treatment

(1) T+, B-, NK+
(2) low IgG, low IgA, SOMETIMES low IgM
(3) N/A
(4) Recurrent (extracellular) bacterial infections, autoimmune diseases, lymphomas
(5) No restrictions
(6) Depends on sxs

caused by mutations in either receptors for B cell growth factors (maturation/activation) or costimulators (T-B collab)
characterized by defect in Ab production
B cells fail to differentiate into plasma cells
not typically dx until 20-30 YO

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(SELECTIVE B CELL)
IgA
(1) Immune phenotype
(2) Ab panel
(3) Inheritance
(4) Infections
(5) Vaccination
(6) Treatment

(1) T+, B+, NK+
(2) IgM+, IgG+, IgA-
(3) Autosomal but higher in male
(4) Mostly asymptomatic – higher risk of developing mucosal infections b/c IgA found in mucous membranes, dx based on hx of recurrent encapsulated bacterial infections
(5) No restrictions
(6) Depends on sxs

IgA produced in response to B cell secretion of IL-5 or TGF-β (NOT HAPPENING HERE)
B cells respond to lack of IgA by overproducing IgE which leads to increase in allergic rxns
pathogens causing infection in mucosal lining often look similar to self antigens which causes immune system to start attacking our own cells (molecular mimicry)

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(SELECTIVE B CELL)
IgG Subclass
(1) Immune phenotype
(2) Ab panel
(3) Inheritance
(4) Infections
(5) Vaccination
(6) Treatment

(1) T+, B+, NK+
(2) IgM+, IgG+, IgA+, IgE+
(3) Autosomal
(4) Mostly asymptomatic
(5) No restrictions
(6) Depends on sxs

typically associated with poor responses in children to vaccines that contain polysaccharide Ags

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(SELECTIVE B CELL)
Hyper-IgM Syndrome
(1) Immune phenotype
(2) Ab panel
(3) Inheritance
(4) Infections
(5) Vaccination
(6) Treatment

(1) T+, B+, NK+
(2) IgM+, IgG-, IgA-
(3) X-linked and autosomal
(4) Encapsulated opportunistic infections – esp bacterial infections
(5) POLIO not recommended
(6) HSCT is definitive treatment for this

believe X-linked version caused by defect in CD40L (males only), most common form
could be due to autosomal deficiency in CD40

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(SELECTIVE B CELL)
Transient Hyper-IgM
(1) Immune phenotype
(2) Ab panel
(3) Inheritance
(4) Infections
(5) Vaccination
(6) Treatment

(1) T+, B+/-, NK+
(2) IgM+, IgG-, IgA-
(3) N/A
(4) Encapsulated opportunistic infections
(5) POLIO not recommended
(6) Depends on sxs

instead of producing IgG beginning at 6 months of age, these infants don’t produce IgG and IgA for up to 36 months
IgM normal or HIGH
typically normalize btwn 2-4 years of age

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What are the 7 selective T cell immunodeficiencies?

(1) Common γ Chain
(2) IL-7R α Chain
(3) Jak3
(4) CD3
(5) MHC Class I (BLS I)
(6) MHC Class II (BLS II)
(7) DiGeorge Syndrome

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(SELECTIVE T CELL)
Common γ Chain / Jak3
(1) Immune phenotype
(2) Ab panel
(3) Inheritance
(4) Infections
(5) Vaccination
(6) Treatment

(1) T-, B+, NK-
(2) IgM+, low IgG, low IgA
(3) Unknown – common deficiency is inherited as autosomal recessive
(4) Severe opportunistic infections
(5) No live vaccines
(6) HSCT

results from mutation in JAK3 (tyrosine kinase)
causes defect in IL-2R signaling which is key cytokine in proliferation of all T cells – can’t have proliferation of CD4 or CD8
causes defect in IL-15R signaling which is key cytokine in proliferation of NK cells

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(SELECTIVE T CELL)
IL-7R α Chain
(1) Immune phenotype
(2) Ab panel
(3) Inheritance
(4) Infections
(5) Vaccination
(6) Treatment

(1) T-, B+, NK+
(2) IgM+, IgG & IgA & IgE are absent or VERY LOW
(3) Autosomal recessive
(4) Severe opportunistic infections
(5) No live vaccines
(6) HSCT

IL-7 normally functions in promoting proliferation of B and T cells, and survival of memory cells
Abs low or absent due to absent T cell co-stimulatory signaling

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(SELECTIVE T CELL)
CD3
(1) Immune phenotype
(2) Ab panel
(3) Inheritance
(4) Infections
(5) Vaccination
(6) Treatment

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(1) T-, B+, NK+
(2) IgM+, IgG-, IgA-
(3) Autosomal recessive
(4) Recurrent viral infections
(5) No live vaccines
(6) HSCT

mutations occur in delta, gamma, epsilon, or zeta chains
typically present in infancy with lymphoenia (decreased T cell numbers)
infants exhibit failure to thrive, opportunistic infections, and chronic diarrhea

(SELECTIVE T CELL)
MHC Class I (BLS I)
(1) Immune phenotype
(2) Ab panel
(3) Inheritance
(4) Infections
(5) Vaccination
(6) Treatment

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(1) T+, B+, NK-
(2) IgM+, IgG+, IgA+
(3) Autosomal recessive
(4) Recurrent viral infections – due to absence of CD8+ cells
(5) No restrictions
(6) Depends on sxs

caused by mutation in TAP1 or TAP2
normal Ab production
NK cells exhibit low killing activity

(SELECTIVE T CELL)
MHC Class II (BLS II)
(1) Immune phenotype
(2) Ab panel
(3) Inheritance
(4) Infections
(5) Vaccination
(6) Treatment

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(1) CD4 lymphopenia
(2) IgM+, IgG-, IgA-
(3) Autosomal recessive
(4) Severe opportunistic infections – recurrent resp, GI and urinary tract infections; death in early childhood likely
(5) No live vaccines
(6) HSCT

professional APCs unable to activate CD4+ cells – leading to deficient production of TH cells
MHC class II genes are intact on chromosome 6
mutations present in genes that encode for transcription factors that regulate expression of MHC class II genes

(SELECTIVE T CELL)
DiGeorge Syndrome
(1) Immune phenotype
(2) Ab panel
(3) Inheritance
(4) Infections
(5) Vaccination
(6) Treatment

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(1) T-, B+, NK+
(2) IgM+, low IgG, low IgA
(3) Autosomal DOMINANT
(4) Recurrent viral infections – mostly respiratory infections
(5) No restrictions
(6) Depends on sxs

often have deficiency in mature T cells
results from microdeletion in chromosome 22
classic triad of sxs: cardiac anomalies, hypocalcemia, hypoplastic thymus
if have this disorder then unlikely to reject skin graft b/c T cell response is what mediates rejection of graft

What are the 3 defects of activation and function of T cells? (defects observed after T cell maturation is complete)

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IPEX
ALPS
Wiskott-Aldrich Syndrome (WAS)

IPEX

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X-linked

- self-reactive T cells are not inhibited due to mutation in the FOXP3 gene that results in absent CD4+ CD25+ Treg cells

ALPS

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defects in either Fas (CD95) or FasL (CD95L) gene
results in decreased/no formation of death-inducing signaling complex and resistance and resistance of T cells to apoptosis
sxs: extremely large lymph nodes b/c T cells not dying

Wiskott-Aldrich Syndrome (WAS)

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X-linked disorder
T-, B+, NK-
characterized by thrombocytopenia (few platelets, platelets smaller in size than normal), eczema, cellular and humoral immunodeficiency, autoimmune disease, malignancy
caused by mutations in WASP (protein, produced by all hematopoietic cells in body)
present w/ recurrent bacterial infections with encapsulated bacteria, viral infections, and opportunistic infections
develop combined cellular and humoral immunodeficiency:
(1) low IgM, normal IgG, elevated IgA and IgE
(2) T cell lymphopenia
(3) low NK cytotoxicity

What are the 5 phagocytic cell deficiencies?

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(1) Leukocyte Adhesion Deficiency
(2) Chronic Granulomatous Disease (CGD)
(3) Glucose 6P Dehydrogenase Deficiency
(4) Myeloperoxidase Deficiency
(5) Chediak-Higashi Syndrome

``` (PHAGOCYTIC) Leukocyte Adhesion Deficiency (1) Cellular Abnormality (2) Immune Defect (3) Associated Infections and Other Diseases ```

(1) Defective CD18 cell (cell adhesion molecule) (2) Defective migration of phagocytes into infected tissues (3) Widespread infections with encapsulated infections - neutrophils show low expression of LFA-1 (CD11/CD18) - neutrophil count in blood is twice the normal level b/c cells can't get into tissues

``` (PHAGOCYTIC) Chronic Granulomatous Disease (CGD) (1) Cellular Abnormality (2) Immune Defect (3) Associated Infections and Other Diseases ```

(1) Defective NADPH oxidase, phagocytes cannot produce O2- (2) Impaired killing of phagocytosed bacteria (3) Chronic bacterial and fungal infections; granulomas - more common in males

``` (PHAGOCYTIC) Glucose 6P Dehydrogenase Deficiency (1) Cellular Abnormality (2) Immune Defect (3) Associated Infections and Other Diseases ```

(1) Deficiency in Glucose 6P Dehydrogenase, defective respiratory burst (2) Impaired killing of phagocytosed bacteria (3) Chronic bacterial and fungal infections; anemia induced by certain agents; granulomas - XR hereditary disease - associated w/ anemia b/c enzyme needed for metabolism of RBCs

``` (PHAGOCYTIC) Myeloperoxidase Deficiency (1) Cellular Abnormality (2) Immune Defect (3) Associated Infections and Other Diseases ```

(1) Deficiency of Myeloperoxidaseimn neutrophil granules and macrophage lysosomes, and impaired production of toxic oxygen species (2) Impaired killing of phagocytosed bacteria (3) Chronic bacterial and fungal infections - AR inherited disorder - infections almost exclusively seen in patients who develop DM - MPO catalyzes conversion of H2O2 to HOCL (bleach); enzyme that gives green puss color

``` (PHAGOCYTIC) Chediak-Higashi Syndrome (1) Cellular Abnormality (2) Immune Defect (3) Associated Infections and Other Diseases ```

(1) Defect in vesicle fusion (2) Impaired phagocytosis due to inability of endosomes to to fuse with lysosomes (3) Recurrent and persistent bacterial infections; prone to granulomas caused by strep; effects on many organs - AR disorder - Neutrophils with abnormal giant granules - Granules DO NOT contain Cathepsin G and Elastase - associated with aberrant degranulation and chemotaxis - dx based on finding of azurophilic GIANT cytoplasmic granules in neutrophils and eosinophils, partial albinism, and aberrant NK cell activity

Congenital Immunodeficiencies Flashcards

(29 cards)