Primary Immunodeficiency Diseases (PIDs) Flashcards

Vocabulary-style flashcards covering Primary Immunodeficiency Diseases (PIDs), including phagocyte system deficiencies, antibody deficiencies, and combined immunodeficiencies (SCID).

Primary Immunodeficiency Diseases (PIDs)

A heterogeneous group of genetic defects resulting in a decrease in the quantity or quality of immune system components, usually manifesting in childhood with recurrent or severe infections.

Neutropenia Grading (Mild)

Absolute Neutrophil Count (ANC) between $1000$ and $1500$.

Neutropenia Grading (Moderate)

Absolute Neutrophil Count (ANC) between $500$ and $1000$.

Neutropenia Grading (Severe)

Absolute Neutrophil Count (ANC) under $500$.

Severe Congenital Neutropenia (SCN)

A condition characterized by an arrest at the Pro-Myelocyte stage, failing to convert to Myelocytes, leading to a severe decrease of neutrophils in peripheral blood.

Cyclic Neutropenia

A type of blood neutropenia characterized by recurrent drops in neutrophil levels occurring in $21$-day ($3$-week) cycles.

Diapedesis

The process of a leukocyte exiting a blood vessel to reach a site of injury.

Leukocyte Adhesion Deficiency (LAD)

An Autosomal Recessive (AR) disorder where neutrophils are produced in sufficient numbers but cannot reach the site of infection due to defects in rolling, adhesion, or diapedesis.

LAD Type 1

The most common form of LAD, caused by a defect/lack of $\beta 2$-Integrin expression ($CD11$ and $CD18$), leading to defective strong adhesion.

LAD Type 2

A form of LAD caused by a mutation in the fucose transporter gene and absence of Sialyl Lewis X ($CD15s$), resulting in a defect at the rolling stage.

LAD Clinical Hallmark Laboratory Finding

Severe leukocytosis (WBC counts of $40$ to $50$ thousand) in the absence of leukemia, caused by leukocytes accumulating in the blood because they cannot reach tissue.

Chronic Granulomatous Disease (CGD)

A defect in the phagocyte oxidase ($phox$) enzyme complex causing an inability to produce free radicals ($\text{Superoxide}$) and kill phagocytosed microbes.

CGD Primary Inheritance

X-linked ($gp91 phox / CYBB$ mutation) is the most common form, while four other types are autosomal recessive.

Catalase-positive organisms

The hallmark organisms causing infection in CGD, including $\text{Staphylococcus aureus}$, $\text{Aspergillus}$, $\text{Nocardia}$, $\text{Serratia}$, and $\text{Burkholderia}$.

DHR Assay (Dihydrorhodamine 123)

The gold standard diagnostic test for CGD, performed with flow cytometry to measure neutrophil oxidative burst.

NBT (Nitroblue Tetrazolium)

An older CGD diagnostic test where a normal state shows a color change from pink to blue; this change does not occur in CGD patients.

Chediak-Higashi Syndrome (CHS)

A condition caused by mutation in the $LYST$ gene, leading to defective phagosome-lysosome fusion and the presence of Giant Granules in neutrophils.

CHS Clinical Manifestations

Oculocutaneous albinism (silvery hair), recurrent pyogenic infections, and bleeding disorders due to lysosomal abnormalities in platelets.

Hyper IgE Syndrome (Job's Syndrome)

A disorder characterized by recurrent skin/respiratory infections, chronic eczema, and a very high $IgE$ level (Cut-point $> 2000 IT/mL$).

STAT3 mutation (AD-HIES)

The genetic defect associated with the Autosomal Dominant form of Hyper IgE syndrome, manifesting as coarse faces, saddle nose, and failure to shed primary teeth.

DOCK8 gene defect (AR-HIES)

The genetic defect associated with the Autosomal Recessive form of Hyper IgE syndrome, involving severe skin involvement and risk of progression to lymphoma.

X-Linked Agammaglobulinemia (Bruton's XLA)

A mutation in the $BTK$ enzyme gene causing an arrest of Pro B to Pre B cell conversion, resulting in absent B cells and lymphoid tissues like tonsils.

Common Variable Immunodeficiency (CVID)

A condition where B cells are present but fail to differentiate into plasma cells, associated with a high prevalence of autoimmune diseases and gastric cancer.

Selective IgA Deficiency (SIgAD)

The most common primary immunodeficiency ($1$ in $600$ to $700$ people), which can lead to anaphylaxis upon receiving blood products due to Anti-$IgA$ production.

Hyper IgM Syndromes (HIGM)

A group of disorders caused by a defect in Class Switching, resulting in normal or high $IgM$ but severely low $IgG$ and $IgA$.

SCID Phenotype: $T^{-} B^{+} NK^{-}$

The cellular phenotype of the most common form of SCID, caused by a Gamma chain ($\gamma$ chain) mutation (X-linked).

SCID Phenotype: $T^{-} B^{-} NK^{-}$

The cellular phenotype equivalent to Adenosine Deaminase ($ADA$) enzyme defect, featuring a severe accumulation of toxic metabolites.

SCID Phenotype: $T^{-} B^{-} NK^{+}$

The cellular phenotype equivalent to $RAG1/RAG2$ gene defects, involving a defect in receptor recombination.

Wiskott-Aldrich Syndrome (WAS) Triad

The classic presentation of a boy with: 1. Eczema 2. Recurrent infections (like otitis) 3. Thrombocytopenia (low and small platelets).

IPEX Syndrome

A genetic defect in $FOXP3$ (X-linked) manifesting as enteropathy (severe diarrhea), polyendocrinopathy, and severe eczema.

DiGeorge Syndrome

A developmental disorder presenting with facial dysmorphism, cleft palate, ventricular septal defect, hypocalcemia (seizures), and absence of the thymus.

X-Linked Lymphoproliferative Syndrome (XLP)

A condition characterized by increased susceptibility to EBV infection and severe proliferation of lymphocytes.

Pneumocystis jirovecii

An infection indicative of a cellular immune/T cell defect, commonly seen in HIGM1 due to $CD40$ Ligand defect.