Immunodeficiency

Question 1

What is primary immunodeficiency?

Answer 1

Immunodeficiency resulting from genetic defects (congenitcal/ inherited). Deficiency is causing disease.
PRESENTATION: recurrent infection in young, increased susceptibility to infection, allergy, autoimmunity, abnormal lymphocyte proliferation, cancer

Question 2

What is secondary immunodeficiency?

Answer 2

Aquired immunodeficiency as the result of other diseases or conditions

Question 3

Give examples of different types of Primary immunodeficinecy

Answer 3

1. Combined immunodeficiencies
2. Combined, with syndromic features
3. Antibody deficiencies
4. Immune dysregulation
5. Phagocyte defects
6. Defects in innate immunity
7. Autoinflammatory disorders

Question 4

What is Combined immunodeficiency? Give examples

Answer 4

Affects both B and T cells with no syndromic features
EXAMPLES:
- TB+ severe combined immuno deficiency/ X-linked SCID
- TB SCID (adenosine deaminase deficiency/ ADA SCID)
- Less profound combined immunodeficiencies (CD40L deficinency)

Question 5

Examples of Combined immunodeficiency with syndromic features

Answer 5

Both B and T cells effect and affects other part of body
EXAMPLE:
- Fox N1 deficinecy: deficiency in gene leads to no functioning thymus, no hari and thymic epithelium fails to develop, causes alopecia, no T cells (B cells normal but don’t work properly without help if T cells)

Question 6

Example of antibody deficiencies

Answer 6

Humoral/ B-cell defects: lack of antibodies leading to recurrent sepsis, bacterial infection of airways, chronic gastroenteritis, failure to thrive
EXAMPLES:
- Bruton’s tyrosine kinase deficiency: mutation in gene, prevents B cell development, results in low antibody levels
- CD40L deficiency
- IgA deficiency

Question 7

Example of phagocyte defects

Answer 7

Chronic graulomatous disease
- No superoxide burst which usually kills bacteria
- Multiple granulomas form due to defective elimination of bacteria
- Defect in NADPH enzyme
- Phagocytes lack cellular energy to kill bacteria
- Infection not controlled well - chronic infection

Question 8

Example of autoinflammatory disorders

Answer 8

Defect affecting inflammasome - Familial Mediterranean Fever
IL-10/ 10R deficiency: usually suppresses immune system, lacks receptor so less able to do this, inflammation of gut, can cause Crone’s disease

Question 9

What can cause secondary immunodeficinecy? Describe the mechanisms of these:

Answer 9

HIV - depletion of CD4+ T helper cells
Protein-calorie malnutrition - metabolic derangement inhibits lymphocyte maturation and function
Irradiation and chemotherapy treatments for cancer - decreased bone marrow precursors for all leukocytes
Cancer metastases to bone marrow
Removal of spleen - decreased phagocytosis of microbes