Immunodeficiency Disorders Overview

Study Notes

Immunodeficiency

It is when the immune system fails to protect the body from disease-causing agents or malignant cells.
Immunodeficiency disorders are classified based on the cause and components involved.

Primary Immunodeficiency

It is caused by a genetic or developmental defect in the immune system.
It usually appears by 6 months of age.

Secondary Immunodeficiency

It is caused by loss of immune function due to exposure to agents such as infection, treatment, cancer, and malnutrition.
It can occur at any time of life.

Immunodeficiency (Component Affected)

Complement: Lack of MAC/Cytolysis leads to recurrent infections with intracellular bacteria, especially Neisserial infections.
Phagocyte: An absence of phagocytes leads to pyogenic infections (caused by bacteria) due to the inability to engulf and eliminate them.
B cell: Without sufficient antibody production, there is a lack of IgG to opsonize encapsulated bacteria such as Streptococcus pneumoniae.
T cell: Deficient T cells lead to recurrent viral, fungal, and protozoal infections, with HIV/AIDS as a notable example.

B-Cell System Deficiencies

Agammaglobulinemia: An inherited disorder characterized by low levels of immunoglobulins, making individuals susceptible to infections.
Bruton's X-Linked Agammaglobulinemia:
- This rare genetic disorder affects males primarily, with females being carriers.
- It results from the absence of the BTK gene, which encodes for BTK tyrosine kinase, an enzyme crucial for B cell maturation.
- The disorder prevents the maturation of immature B cells, leading to a lack of B cells.
- Symptoms appear after 6-9 months of age.
- Patients often have small or absent tonsils and adenoids, and their lymph nodes lack germinal centers due to the absence of B cells.
Common Variable Immunodeficiency (CVI):
- Failure of mature B cells to differentiate into plasma cells, resulting in a lack of antibody production.
- Presentation includes IgA and IgG deficiency.
- The mechanism is often unknown (idiopathic), but a genetic mutation is present in 10% of cases.
- The disorder usually occurs in children and adolescents.
- Patients have a normal number of B cells (CD19 and CD20 positive) but fail to produce antibodies in response to mitogens (LPS, Dextran, Pokeweed seed), detectable by various methods, including the Nylon test and electron microscopy.
Transient Hypogammaglobulinemia:
- A condition where B cells fail to produce antibodies due to a delayed synthesis of Abs.
- It may be idiopathic or due to delayed maturation of immune system components, such as Th cells.
- It is also referred to as Pediatric Hypogammaglobulinemia.
- It starts after 6 months or upon the clearance of maternal IgG, with persistently lower IgG levels that can last up to 3 years.