Immunodeficiency Flashcards
What is a primary (congenital) immunodeficiency?
β a defect in the immune system
What is a secondary (acquired) immunodeficiency?
β caused by another disease
What are three clinical features of immunodeficiency?
β Recurrent infections
β severe infections with unusual pathogens (aspergillus)
β unusual sites (liver abscess)
What are 6 signs of primary immunodeficiency?
β failure of an infant to gain weight or grow normally
β recurrent, deep skin or organ abscesses
β need for IV antibiotics to clear infections
β 2 or more deep seated infections
β family history of primary immunodeficiency
β persistent thrush after age 1
Where do you usually get infections in primary immunodeficiency?
β upper respiratory tract
What are 5 major B lymphocyte disorders?
β X linked agammaglobulinaemia β common variable immunodeficiency CVID β selective IgA deficiency β IgG2 subclass deficiency β Specific Ig deficiency with normal Igs
What is the frequency for the components of the immune system affected in primary immunodeficiency?
β antibody : 50%
β T cell : 30%
β Phagocytes : 18 %
β complement : 2%
Where is the defect in X linked agammaglobulinaemia?
β BTK gene (X chromosome)
What does the BTK gene encode?
β Brutonβs tyrosine kinase
Describe what would normally happen when a pre B cell expresses BTK?
β The BTK is downstream to the pre-B cell receptors
β if there is recognition of self-antigen the receptor has to send a signal via the Brutons tyrosine kinase
β the signal will rescue the cell from the default fate of apoptosis and it progresses to the next stage
What happens in patients with defective BTK?
β the cell dies by apoptosis because it cannot progress onto the next stage
What kind of infections do people with X linked agammaglobulinaemia get and where?
β recurrent bacterial infections
β lung, ears, GI
What are the results of investigations for someone who has X linked agammaglobulinaemia (immune cell levels)?
β B cells absent/low
β Plasma cells absent
β all Igs absent/very low
β T cells and T cell mediated responses are normal
What is the treatment for agammaglobulinaemia?
β IV Ig 200-600mg/kg/month at 2-3 week intervals
What should you not give to people who have X linked agammaglobulinaemia?
β Live vaccines
What are 3 examples of predominant T cell disorders?
β DiGeorge syndrome
β Wiskott-Aldrich syndrome
β Ataxia-telangiectasia
What cells does SCID involve?
β both T cells and B cells
What is the mode of inheritance of SCID?
β 50-60% X linked
β rest are autosomal recessive
What is the presentation of SCID?
β Well at birth but problems occur after the first month
β diarrhoea, weight loss, persistent candidiasis
β severe bacterial/viral infections
β failure to clear vaccines
β unusual infections (CMV, pneumocystis)
What can be the 3 causes of SCID?
β Common cytokine receptor Ξ³ chain defect
β RAG-1/RAG-2 defect
β Adenosine deaminase deficiency
What does having a gamma chain defect affect?
β signal transducing component of of receptors for IL-2, IL-4, IL-7, IL-9, IL-11, IL-15, IL-21
What is IL-7 needed for?
β survival of T cell precursors
What happens if IL-7 is absent?
β Defective T cell development
β Lack in B cell help
What happens with an adenosine deaminase deficiency?
β accumulation of deoxyadenosine and deoxy ATP
β toxic for rapidly dividing thymocytes
What are the results of investigations in people who have SCID (immune cell levels)?
β very low/absent T β normal/absent B β sometimes also absent NK (Ξ³ chain defect affecting IL-15 receptor) βIgs low β reduced proliferation and cytokines
What are the 6 treatments for people with SCID?
β isolation
β blood products from CMV negative donors
β IV Ig replacement
β treating infections
β bone marrow/haematopoietic stem cell transplant
β gene therapy for ADA and Ξ³-chain genes
What is the survival for someone with SCID with an early diagnosis, a good donor match and no infections pre-transplant?
β >80%
What is the survival for someone with SCID with a late diagnosis,chronic infection and poorly matched donors?
β <40%
