Immunodeficiency Chapter 5

Immunodeficiency

• Immunodeficiency results from defects in the innate or adaptive immune systems, making individuals prone to recurrent and severe infections by various pathogens.
• Even microorganisms that do not normally cause disease can act as pathogens in a compromised host, causing opportunistic infections.

Types of Immunodeficiency

• Primary immunodeficiency: a genetic defect in the immune system that one is born with.
• Secondary (Acquired) immunodeficiency: a decrease in immune responses caused by a secondary factor or occurrence.

Immunodeficiency Diseases

• Defects in B cells or antibody production.
• Defects of T cells with or without concurrent B cell defects.
• Phagocyte and/or Natural killer cell defects.
• Complement system defects.
• Recurrent infections with pyogenic bacteria (e.g., S. aureus, S. pyogenes) indicate B-cell deficiency, while recurrent infections with fungi, viruses, or protozoa indicate T-cell deficiency.

Primary Immunodeficiency

• Usually involves a genetic defect in immune responses, affecting B-lymphocytes, T-lymphocytes, or both.
• Lymphocytes may be completely absent, present in very low levels, or present but not function normally.

B-Lymphocyte Disorders

• Examples include X-linked agammaglobulinemia (XLA) or Bruton syndrome.
• XLA is characterized by:
  • Absence of B cells and all immunoglobulins (IgG, IgA, IgM, IgD, and IgE).
  • The gene responsible is Btk (Bruton tyrosine kinase), which is mainly expressed in B cells.
  • Mutation at the Btk gene blocks B cell development and reduces immunoglobulin production.
  • XLA is more common in males, with X-linked recessive inheritance.
  • Patients are prone to develop serious and even fatal infections, especially pyogenic bacterial infections.

Diagnosis and Treatment of XLA

• Diagnosis typically begins with a history of recurrent infections, mostly in the respiratory tract, through childhood.
• Blood tests show a complete lack of circulating B cells and low levels of all antibody classes.
• Treatment involves intravenous immunoglobulin (IVIg) therapy every 3-4 weeks, which generates passive immunity and boosts the immune system.

Selective Immunoglobulin Deficiencies

• IgA deficiency is the most common, and may be caused by a failure of heavy chain gene switching.
• Patients with IgA deficiency typically have recurrent lung infections.
• Patients with selective IgM deficiency or deficiency of one or more of the IgG subclasses also have recurrent sinopulmonary infections caused by pyogenic bacteria.

T Cell Immunodeficiency Diseases

• DiGeorge syndrome:
  • Caused by the deletion of a portion of chromosome 22.
  • Characteristics include:
    • Little or no cell-mediated immunity.
    • May involve B cell deficiencies if the disorder involves T4-helper lymphocytes and/or T8-lymphocytes.
  • Signs and symptoms may include:
    • Bluish skin due to poor circulation of oxygen-rich blood.
    • Breathing problems.
    • Spasms around the mouth, hands, arms, or throat.
    • Developmental delays or learning difficulties.
    • Low levels of calcium in the blood.
    • Cleft palate and other facial abnormalities.
    • Increased risk of mental health conditions, such as Schizophrenia, ADHD, and Autism Spectrum Disorders.

Nezelof Syndrome

• Autosomal recessive congenital immunodeficiency condition due to underdevelopment of the thymus.
• Characterized by:
  • Recurrent chronic pulmonary infections.
  • Oral and cutaneous candidiasis.
  • Failure to thrive.
  • Chronic diarrhea.
  • Skin infection.
  • Urinary tract infection.
  • Gram-negative sepsis.
• Treatment includes:
  • Antimicrobial therapy.
  • IV immunoglobulin.
  • Bone marrow transplantation.
  • Thymus transplantation.

Hyper-IgM Syndrome

• Patients have a high concentration of IgM but very little IgG, IgA, and IgE.
• Caused by a mutation in the gene encoding the CD40 ligand in CD4-positive helper T cells.
• Characteristics include:
  • Severe, recurrent pyogenic bacterial infections.
  • Normal numbers of T cells and B cells.
• Treatment involves gammaglobulin therapy, which results in fewer infections.

Interleukin-12 Receptor Deficiency

• Patients have disseminated mycobacterial infections.
• The absence of the receptor prevents IL-12 from initiating a Th-1 response, which is required to limit mycobacterial infections.

Severe Combined Immunodeficiency Disease (SCID)

• Recurrent infections caused by bacteria, viruses, fungi, and protozoa occur in early infancy.
• Both B cells and T cells are defective.
• Immunoglobulin levels are very low.
• Patients have a weak immune system that is unable to fight off even mild infections.
• Pneumonia is the most common presenting infection in these infants.
• Fatal infections, such as C. albicans and viruses, are common.
• SCID is a group of inherited diseases, all of which are due to a defect in the differentiation of an early stem cell.
• There are two types: X-linked and autosomal.

Wiskott-Aldrich Syndrome (WAS)

• Characteristics include:
  • Thrombocytopenia (small platelets and a reduced number of platelets).
  • Recurrent pyogenic infections.
  • Hemorrhagic manifestations.
  • Eczema.
  • Recurrent infections.
  • To remember the characteristics of Wiskott-Aldrich syndrome, use the acronym WAITER.

Here are the study notes:

• Immunodeficiency Diseases*
• Immunodeficiency diseases result from defects in components of the innate or adaptive immune systems, leading to an inability to combat certain diseases.
• Types:
  • Primary immunodeficiency: genetic defect in the immune system
  • Secondary (Acquired) immunodeficiency: normal immune system compromised by a secondary factor
• Examples:
  • Defects in B cells or antibody production
  • Defects of T cells with or without concurrent B cell defects
  • Phagocyte and/or Natural killer cell defects
  • Complement system defects
• Wiskott-Aldrich Syndrome (WAS)*
• Characterized by:
  • Thrombocytopenia (low platelet count)
  • Recurrent pyogenic infections
  • Hemorrhagic manifestations
• X-linked recessive inheritance
• Severe Combined Immunodeficiency Disease (SCID)*
• Characterized by:
  • Recurrent infections caused by bacteria, viruses, fungi, and protozoa
  • Both B cells, T cells, and/or NK cells are defective
  • Immunoglobulin levels are very low
• Types:
  • X-linked (75% of cases)
  • Autosomal
• X-Linked Agammaglobulinemia (XLA/Bruton Syndrome)*
• Characterized by:
  • Complete lack of antibodies in the bloodstream
  • Recurrent pyogenic bacterial infections
• Caused by a mutation in the Btk (Bruton tyrosine kinase) gene, responsible for B cell development and maturation
• X-linked recessive inheritance, affecting males
• DiGeorge Syndrome*
• Caused by a deletion of a portion of chromosome 22
• Characterized by:
  • Little or no cell-mediated immunity
  • May involve B cell deficiencies
  • Increased risk of infections and mental health conditions
• Hyper-IgM Syndrome*
• Characterized by:
  • High concentration of IgM and low levels of IgG and IgA
  • Recurrent pyogenic bacterial infections
• Caused by a mutation in the gene encoding CD40 ligand in CD4-positive helper T cells
• Interleukin-12 Receptor Deficiency*
• Characterized by:
  • Disseminated mycobacterial infections
  • Absence of IL-12 receptor prevents Th-1 response

Now, for the 20 MSQs, I'll provide you with 5 questions to get you started:

1. Which of the following is a type of primary immunodeficiency disease? a) HIV/AIDS b) DiGeorge Syndrome c) X-Linked Agammaglobulinemia (XLA) d) Rheumatoid Arthritis e) Cancer

Answer: c) X-Linked Agammaglobulinemia (XLA)

2. Which syndrome is characterized by thrombocytopenia and recurrent pyogenic infections? a) Wiskott-Aldrich Syndrome b) DiGeorge Syndrome c) X-Linked Agammaglobulinemia (XLA) d) Hyper-IgM Syndrome e) Interleukin-12 Receptor Deficiency

Answer: a) Wiskott-Aldrich Syndrome

3. What is the underlying cause of X-Linked Agammaglobulinemia (XLA)? a) Mutation in the IL-2 receptor gene b) Mutation in the Btk gene c) Deletion of a portion of chromosome 22 d) Defect in the CD40 ligand gene e) Lack of immunoglobulins

Answer: b) Mutation in the Btk gene

4. Which of the following is a characteristic of Hyper-IgM Syndrome? a) Elevated levels of IgG and IgA b) High concentration of IgM and low levels of IgG and IgA c) Complete lack of antibodies d) Increased risk of fungal infections e) Defect in the IL-12 receptor gene

Answer: b) High concentration of IgM and low levels of IgG and IgA

5. What is the mode of inheritance of Wiskott-Aldrich Syndrome? a) Autosomal dominant b) Autosomal recessive c) X-linked recessive d) Mitochondrial inheritance e) Unknown

Answer: c) X-linked recessive

Let me know if you'd like me to generate more questions!