21 - Immunodeficiency Disorders Flashcards
Primary (congenital) Immunodeficiency disorder
-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
Secondary (acquired) immunodeficiency disorders
Deficiency or dysfunction of immune cells or plasma proteins caused by infections, disease or medical treatments
Major immune defects underlying immunodeficiency disorders and the infections associated with these defects
- Antibody deficiency (B cells): Bacteria
- Deficiency of complement system proteins: Bacteria (neisseria)
- Neutrophil dysfunction: Bacteria (staph), fungi
- Cellular immune deficiency (T cells and macrophages):
Defects of B cell development or function resulting in antibody and/or immunoglobulin deficiency
- 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
X linked agammaglobulinaemia
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)
Common variable immunodeficiency disorder (CVID)
Impaired B cell activation or survival arising from a mutation in one of many genes encoding proteins critical for B cell functions
Hyper IgM immunodeficiency disorder
- Class switch disorder
- Defect in switching of IgM+ B cells to IgG+ and IgA+ B cells
Cause of hyper IgM immunodeficiency disorder
- CD40 ligand (CD40L) deficiency due to mutation of Xq26
- Impaired IgG production
- High serum levels of IgM and low IgG, IgA
Asplenia associated immunodeficiency
- Impaired marginal zone B cell responses
- Acute overwhelming infection with encapsulated bacteria
- Infection with blood borne parasites
Examples of encapsulated bacteria
- Strep pneumoniae
- HIB
- Neisseria meningitidis
Examples of blood borne parasites
- Malaria
- Babesiosis
Cellular immunodeficiency
- Thymus aplasia (deficiency of all T cells)
- Causes Di george syndrome
- CD4 T cell deficiency
- Disorders of Th1 and Th17 responses
- TNF alpha deficiency
Congenital/genetic disorders of Th1 responses
- IL12 deficiency
- IL12 receptor deficiency
- Complete or partial deficiency of interferon gamma receptor
Acquired disorders of Th1 responses
IFN gamma deficiency caused by anti IFN gamma neurtalising antibodies
Congenital/Genetic Disorders of Th17 immune response
- Th17 T cell deficiency
- IL-17 deficiency
- IL-17 receptor deficiency
Acquired disorders of Th17 immune responses
IL-17 deficiency caused by anti IL-17 neutralising autoantibodies
Severe combined immunodeficiency disorder (SCID)
- 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
Deficiency of complement proteins in classical pathway
- Immune complex disease
- Increased infection susceptibility
Deficiency of complement proteins in lectin pathway
Increased susceptibility to infections, mainly when associated with other immune defects
Deficiency of complement proteins in alternative pathway
- Increased susceptibility to infection, especially to Neisseria meningitidis
Treatment of complement deficiency
- 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
C5 inhibition by Eculizumab therapy
Increases susceptibility to Neisseria sp. infection
Neutrophil deficiency or dysfunction
- Impaired phagocytosis and/or killing of bacteria and fungi resulting from:
- Acquired or congenital neutropenia
- Adhesion molecule deficiency
- Disorders of intracellular killing
HIV Infection on thymus
Decreased production of naive CD4 and CD8 T cells
HIV Infection on lymph nodes
- Abortive infection and pyroptosis of CD4 T cells
-Impaired homeostatic proliferation of naive T cells - Germinal centre dysfunction
HIV infection on GALT
Abortive infection and pyroptosis of CD4 T cells
HIV Infection on spleen
Decreased production of IgM memory B cells
Complications of persistent, uncontrolled viral infection in HIV-1 immunodeficiency
- Hairy leukoplakia of tongue
- Lymphoma
- Retinitis
- Kaposi’s sarcoma
- Neurolofical disease
