primary and secondary immune deficiency

What are the two main types of immune deficiency?

Primary immune deficiency (intrinsic, usually inherited) and secondary immune deficiency (acquired due to factors like malnutrition, disease, drugs, or HIV).

What is the prevalence of primary immune deficiency (PID)?

PID has a prevalence of 1 in 100 to 1 in 1000 for slIgA deficiency and 1 in 100,000 live births for SCID.

What are the initial signs of primary immune deficiency?

Signs include susceptibility to infections, such as 8 respiratory tract infections per year in children or more than 4 in adults, and chronic infections unresponsive to treatment.

What genetic factors contribute to primary immune deficiency?

Genetic defects can lead to missing enzymes, developmental arrest in immune differentiation, absent/non-functional proteins, and abnormal DNA repair.

How is primary immune deficiency diagnosed?

Diagnosis includes recurrent opportunistic infections, genetic testing, family history, and assessments of immunoglobulin production and immune function.

What is X-linked SCID and its characteristics?

X-linked SCID occurs exclusively in males, characterized by very few T/NK cells, defective B cells, and high susceptibility to infections. Symptoms usually appear before 3 months.

What is the treatment for SCID?

Treatment includes hematopoietic stem cell transplantation (HSCT), with options for matched or haploidentical donors, and gene therapy using retroviral vectors.

What is CD40 ligand deficiency?

CD40 ligand deficiency (X-linked hyper-IgM syndrome) is caused by a mutation in the CD40L gene, leading to severe immune deficiency and susceptibility to life-threatening infections.

What are the symptoms of Hyper IgM syndrome?

Symptoms include frequent severe infections in infancy, pneumonia, sinus infections, ear infections, and chronic diarrhea.

What are the common primary antibody deficiencies?

Common primary antibody deficiencies include selective IgA deficiency, common variable immune deficiency (CVID), and recurrent bacterial infections.

What role does the actin cytoskeleton play in T-cell function?

The actin cytoskeleton is essential for T-cell movement and division, requiring rapid reorganization for effective function.

What are the key features of Wiskott-Aldrich syndrome (WAS)?

WAS is characterized by a triad of increased bleeding tendency, recurrent infections, and eczema, with variable phenotypes based on mutations.

How is WAS treated?

Treatment includes avoiding live vaccines, administering IVIG for infections, and considering bone marrow transplantation.

What is the success rate of HSCT for immune deficiencies?

The success rate is about 90% with HLA-identical sibling donors and 50% with haploidentical donors.

What are the symptoms of complement deficiencies?

Symptoms include lupus-like syndromes such as malar flush, arthralgia, glomerulonephritis, and vasculitis.

What is the significance of the IL-2 receptor gene in X-linked SCID?

Mutations in the IL-2 receptor gene (IL2RG) are critical for lymphocyte maturation and function, leading to severe immune deficiency.

What is the typical age of diagnosis for primary immune deficiencies?

About 80% of affected individuals are diagnosed over the age of 20.

What is the male-to-female ratio for primary immune deficiencies in children?

The male-to-female ratio is 5:1 in children.

What are some common infections associated with primary antibody deficiencies?

Common infections include recurrent bacterial infections of the respiratory and gastrointestinal tracts, particularly from Strep pneumoniae and H. influenzae.

What is the role of CD40 in immune response?

CD40 engagement is critical for B cell proliferation, immunoglobulin switching, and germinal center formation.

What are the implications of gene therapy for immune deficiencies?

Gene therapy can restore immunity but carries a high risk of leukemia.

What are the signs of end-organ damage in primary immune deficiency?

Signs include conditions like bronchiectasis due to chronic infections.

What is the prevalence of selective IgA deficiency?

Selective IgA deficiency affects approximately 1 in 600 Northern Europeans, often without clinical symptoms.

What is the function of the actin cytoskeleton in T-cells?

It provides an internal scaffold essential for T-cell movement and division.

Phagocyte problems

Lead to bacterial infections (Staph, Pseudomonas, TB, Burkholderia)

Complement problems

Result in infections from encapsulated bacteria (Neisseria, Haemophilus, Strep pneumoniae)

T cell problems

Cause issues with intracellular bugs (TB, atypical mycobacteria) + viral + fungal infections

Antibody problems

Result in infections from encapsulated bacteria (Haemophilus, Strep)

DiGeorge syndrome

Characterized by no thymus = no T cells

SCID

Stuck at early progenitor stage of T cell development

Bare lymphocyte syndrome

Inability to express HLA molecules

Omenn syndrome

Involves faulty apoptosis in T cell development

Cytokine deficiencies

Result in inability to activate T cells properly

Pre-BCR checkpoint

Involves the BTK gene

Pre-TCR checkpoint

Involves the CD3 gene

VDJ recombination

Involves RAG1, RAG2, ARTEMIS genes

Wiskott-Aldrich syndrome (WAS)

A condition affecting B cell function and platelet size

WASP protein functions

Forms microvilli on B cells, helps cell migration and chemotaxis, makes immune synapses, organizes phagocytic cups, enables integrin function

Tiny platelets in WAS

Normal = 2.29±0.1μm, WAS = 1.83±0.1μm, leading to bleeding problems

X-linked agammaglobulinemia

Condition where B cells can't mature

CVID

Condition where the body can't make IgG properly

Hyper-IgM syndrome

Characterized by T cell co-stimulation failure

Selective IgA deficiency

Affects only IgA production

IgM

First responder antibody, neutralizes + opsonizes (10 binding sites!)

IgG

Best opsonizers, can cross the placenta

IgA

Guardian of mucosal surfaces

IgE

Involved in mast cell attachment and allergies

Classical complement pathway

Triggered by antibodies

Alternative complement pathway

Activated directly by microbes

Lectin complement pathway

Activated by mannose-binding

Chronic Granulomatous Disease

Caused by NADPH oxidase deficiency, leading to inability to kill catalase-positive bacteria

Reactive oxygen species

O₂⁻ and Cl₂ produced by NADPH oxidase