21 - Immunodeficiency Disorders

Question 1

Primary (congenital) Immunodeficiency disorder

Answer 1

-Deficiency or dysfunction of immune cells or plasma proteins caused by gene abnormalities
- Immune defects may also cause other immunological diseases (e.g. autoimmunity)
- Often present in childhood
- Dominant or recessive, autosomal or x linked, with complete or incomplete penetrance
- 406 distinct disorders with 430 different gene defects

Question 2

Secondary (acquired) immunodeficiency disorders

Answer 2

Deficiency or dysfunction of immune cells or plasma proteins caused by infections, disease or medical treatments

Question 3

Major immune defects underlying immunodeficiency disorders and the infections associated with these defects

Answer 3

• Antibody deficiency (B cells): Bacteria
• Deficiency of complement system proteins: Bacteria (neisseria)
• Neutrophil dysfunction: Bacteria (staph), fungi
• Cellular immune deficiency (T cells and macrophages):

Question 4

Defects of B cell development or function resulting in antibody and/or immunoglobulin deficiency

Answer 4

• Impaired B cell development in bone marrow
• Impaired B cell activation and/or survival
• Defects of follicular B cell responses, particularly germinal centre dysfunction
• Defects of marginal zone B cell responses

Question 5

X linked agammaglobulinaemia

Answer 5

Impaired development of B cells in bone marrow caused by mutations of Btk gene on X chromosome resulting in deficiency of B cell tyrosine kinase (Btk)

Question 6

Common variable immunodeficiency disorder (CVID)

Answer 6

Impaired B cell activation or survival arising from a mutation in one of many genes encoding proteins critical for B cell functions

Question 7

Hyper IgM immunodeficiency disorder

Answer 7

• Class switch disorder
• Defect in switching of IgM+ B cells to IgG+ and IgA+ B cells

Question 8

Cause of hyper IgM immunodeficiency disorder

Answer 8

• CD40 ligand (CD40L) deficiency due to mutation of Xq26
• Impaired IgG production
• High serum levels of IgM and low IgG, IgA

Question 9

Asplenia associated immunodeficiency

Answer 9

• Impaired marginal zone B cell responses
• Acute overwhelming infection with encapsulated bacteria
• Infection with blood borne parasites

Question 10

Examples of encapsulated bacteria

Answer 10

• Strep pneumoniae
• HIB
• Neisseria meningitidis

Question 11

Examples of blood borne parasites

Answer 11

• Malaria
• Babesiosis

Question 12

Cellular immunodeficiency

Answer 12

• Thymus aplasia (deficiency of all T cells)
• Causes Di george syndrome
• CD4 T cell deficiency
• Disorders of Th1 and Th17 responses
• TNF alpha deficiency

Question 13

Congenital/genetic disorders of Th1 responses

Answer 13

• IL12 deficiency
• IL12 receptor deficiency
• Complete or partial deficiency of interferon gamma receptor

Question 14

Acquired disorders of Th1 responses

Answer 14

IFN gamma deficiency caused by anti IFN gamma neurtalising antibodies

Question 15

Congenital/Genetic Disorders of Th17 immune response

Answer 15

• Th17 T cell deficiency
• IL-17 deficiency
• IL-17 receptor deficiency

Question 16

Acquired disorders of Th17 immune responses

Answer 16

IL-17 deficiency caused by anti IL-17 neutralising autoantibodies

Question 17

Severe combined immunodeficiency disorder (SCID)

Answer 17

• Combined defects of B, T and NK cells resulting in impaired antibody and cell-mediated immune responses
• Often fatal during first two years of life, if not treated
• Treatment often requires allogenic haematopoietic stem cell transplantation

Question 18

Deficiency of complement proteins in classical pathway

Answer 18

• Immune complex disease
• Increased infection susceptibility

Question 19

Deficiency of complement proteins in lectin pathway

Answer 19

Increased susceptibility to infections, mainly when associated with other immune defects

Question 20

Deficiency of complement proteins in alternative pathway

Answer 20

• Increased susceptibility to infection, especially to Neisseria meningitidis

Question 21

Treatment of complement deficiency

Answer 21

• Monoclonal antibodies that target complement proteins are used to treat autoimmune diseases where the C5 response is dysfunctional
• Binding to C5 prevents activation of the terminal membrane attack complex
• Necessary as some autoimmune conditions result in excessive RBC lysis

Question 22

C5 inhibition by Eculizumab therapy

Answer 22

Increases susceptibility to Neisseria sp. infection

Question 23

Neutrophil deficiency or dysfunction

Answer 23

• Impaired phagocytosis and/or killing of bacteria and fungi resulting from:
• Acquired or congenital neutropenia
• Adhesion molecule deficiency
• Disorders of intracellular killing

Question 24

HIV Infection on thymus

Answer 24

Decreased production of naive CD4 and CD8 T cells

Question 25

HIV Infection on lymph nodes

Answer 25

• Abortive infection and pyroptosis of CD4 T cells
  -Impaired homeostatic proliferation of naive T cells
• Germinal centre dysfunction

Question 26

HIV infection on GALT

Answer 26

Abortive infection and pyroptosis of CD4 T cells

Question 27

HIV Infection on spleen

Answer 27

Decreased production of IgM memory B cells

Question 28

Complications of persistent, uncontrolled viral infection in HIV-1 immunodeficiency

Answer 28

• Hairy leukoplakia of tongue
• Lymphoma
• Retinitis
• Kaposi’s sarcoma
• Neurolofical disease