Immunological disorders Flashcards
What is severe combined immunodeficiency (SCID)
Most severe condition causing immunodeficiency - have almost no immunity to infections. Result in no or dysfunctioning T and B cells.
Presentation of SCID
Persistent and severe diarrhoea, failure to thrive, opportunistic infections, unwell after live vaccinations, Omenn syndrome
Cause of SCID
More than 50% caused by mutations in the common gamma chain on X chromosome that codes for interleukin receptors on T and B cells. X linked recessive inheritance
What is Omenn syndrome
Rare cause of SCID, result of mutation in recombination - activating gene that codes for important proteins in T and B cells - autosomal recessive
Features of Omenn syndrome
Red, scaly, dry rash, hair loss, diarrhoea, failure to thrive, lymphadenopathy, hepatosplenomegaly
Management of SCID
Fatal unless treated, treating underlying infections, immunoglobulin therapy, minimising risk of new infections with sterile environment, avoiding live vaccines and performing hepatopoietic stem cell transplantation
T cell disorders in children
DiGeorge syndrome, Purine nucleoside phosphorylase deficiency, Wiskott-Aldrich syndrome, Ataxic Telangiectasia, AIDS
What causes DiGeorge syndrome
Microdeletion on chromosome 22 leading to development defect in the third pharyngeal pouch and third branchial cleft
Features of DiGeorge syndrome (CATCH22)
Congenital heart disease
Abnormal faces
Thymus gland incomplete
Cleft palate
Hypoparathyroidism -> hypocalcaemia
22nd chromosome affected
What causes purine nucleoside phosphorylase deficiency
Autosomal recessive condition where the PNP enzyme which helps break down purines is dysfunctional, so toxic levels of dGTP build up
Features of PNP deficiency
Toxic levels of dGTP causes low levels of lymphocytes so immunity to infection gradually gets worse
What is Wiskott-Aldrich syndrome
X linked recessive disorder with a mutation on the WAS gene. Causes abnormal functioning of T cells.
Features of WAS
Thrombocytopenia, immunodeficiency, neutropenia, eczema, recurrent infections, chronic bloody diarrhoea
What is ataxic telangiectasia
Autosomal recessive condition affecting gene coding ATM serine/threonine kinase protein on chromosome 11 - problems in DNA coding
Features of ataxic telangiectasia
Low T cells and immunoglobulins.
Ataxia, telangiectasia particularly in sclera and damaged areas of skin, predisposition to cancers, slow growth and delayed puberty, accelerated aging, liver failures
B cell disorders in children
Selective immunoglobulin A deficiency, common variable immunodeficiency, X-linked agammaglobulinaemia
Main features of selective immunoglobulin A deficiency
Low levels of IgA and normal levels of IgM and IgG. Often asymtomatic and never diagnosed. Tendency to get recurrent mucous membrane infections such as LRTIs and autoimmune conditions
What are the features of common variable immunodeficiency
Genetic mutations in genes coding for components of B cells, resulting in IgA and IgG with or without deficiency in IgM
Presentation of common variable immunodeficiency
Unable to develop immunity, lower RTIs, prone to immune disorders, such as RA and cancers such as non-hodgkins lymphoma
What is Bruton’s agammaglobulinaemia
X linked recessive condition resulting in abnormal B cell development and deficiency in all classes of immunoglobulins
Types of complement disorders
C1 esterase inhibitor deficiency, mannose-binding lectin deficiency.
C2 esterase deficiency associated with immune complex disorders such as SLE
What does C1 esterase deficiency cause
Intermittent angiooedema in response to minor triggers such as viral infections or stress
Test for C1 esterase deficiency
Levels of C4 which will be low
What is mannose-binding lectin deficiency
Inhibition of the alternate pathway of the complement system - lots of poeple affected but some can be susceptible to infection (CF) which can cause more severe variant
