Immunodeficiency Flashcards

Question

What are the features of Chronic Mucocutaneous Candidiasis? * Aetiology/Genetics * Clinical features * Investigations

Answer 1

Aetiology/Genetics * Lack of Th17 cells * Stat-1 gain of function mutation (assoc with autoimmune thyroid disease) * APECED (IL-17 and Il-22 antibodies) * Thymoma associated Clinical features * chronic/recurrent candidal infection * onset in childhood * affects skin, nails and mucosa (oesophageal and pulmonary) * other infections eg HSV Investigations * Lack Th17 cells

Answer 2

* Aetiology: lack of a component essential for T cell function * most common is defect on gene for gamma chanin (common to multiple cytokine receptors), X-linked * second most common is ADA deficiency (salvage pathyway of purine metabolism, required for DNA synthesis (lymphocytes are unable to divide appropriately), AR * AR other types * JAK3 deficiency- signalling cell from gamma chain * IL-7R aloha deficiency * ZAP70 deificency- tyrosine kinase essential for TCR signalling * CD3 deficiency * bare lymphocyte syndrome- MHC Class II deficiency * RAG1, RAG2 deficiency- genes for VDJ recombination * myeloid or reticular dysgenesis (defective maturation) * Clinical features * failure to thrive * chronic diarrhoea * recurrent opportunistic infections: fungal, viral, protozoal (eg PJP pneumonia), no B cell function secondary to lack of "help" * risk of malignancy and autoimmunity * absent lymphoid tissue (thymus) * ADA def associated with skeletal abnormalities * Treatment * BMT * enzyme replacement for ADA deficiency

Answer 3

* Clinical: triad of recurrent staphylococcal infections ("cold" skin with minimal incr CRP, pneumonia), candida infections, elevated IgE (usually \>2000) * Pathogenesis * AD-HIES patients have a Stat-3 mutation (signalling molecule in the cutokine response pathway (especially involved in Th17 development)--\> Th17 deficiency * Investigations * raised IgE \>2000 in most cases, tends to fall with age * other Igs normal * sometimes blunted specific antibody responses * eosinophilia in 60-93% (marked in AR, less in AD) * Treatment * Skin care- cleach bathes x3 per week * Ab prophylaxis (co-trim and antifungals) * surgical drainage of abscesses/excision of pneumatoceles * IVIG possible if poor Ab responses * Prognosis * AD survive to adulthood, AR lethal in childhood

Answer 4

* Molecular defect * deficiency of i of the 4 subunits of NADPH oxidase (gp91 on the X chromosome) * respiratory burst of neutrophils is generally necessary to kill intracellular organisms * neutrophil recognises pathogen--\> phagocytosis and fusion of pathogen and cellular granules--\> cellular activation--\> oxidative burst with generation of O2, H2O2 and NO * Clinical features * recurrent infection of: skin, lungs and other tissues, coag negative bacteria and fungi * staph infections of skin esp ears and nose, liver abscess (CGD until proven otherwise) * purulent dermatitis * lymphadenitis, often granulomatous * recurrent bronchopneumonia: hilar lymphadenoapthy, empyema, lung abscess * intestinal obstruction * Crohn's like syndrome: perianal abscess/fistula, hepatosplenomegaly * osteomyelitis * aspergillus pneumonia, osteomyelitis, other tissues\ * Investigations * tests ability of activated granulocytes to generate reactive oxygen species for microbicidal action * NBT test * chemiluminescence * flow cytometry for dihydrorhodamine reduction * Treatment * chronic Abs * Immunisation * interferon gamma

Answer 5

* Aetiology * failure of development of the 3rd and 4th pharyngeal arches * Immunodeficiency * Variable degree of T cell immunodeficiency: most moderate, rarely severe * Clinical features * Cardiac abnormalitis * Abnormal facies * Thymic hypoplasia/aplasia * Cleft palate * Hypocalcaemia * 22q11-pter deletion

Answer 6

* Aetiology * complex AR multisystem disorder * immunodeficiency and chromosomal instability * molecular defect * defect in the ATM (ataxia telangiectasia mutated gene), critical in cell cycle control and DNA damage response * chromosomal deletion or translocation--\> Ig/TCR loci disrupted * Clinical features * cerebellar ataxia * oculomotor signs * telangiectasia * sinopulmonary infections: bronchiectasis * mental retardation * growth retardation * increased malignancy risk (lymphoid and other solid tumours) * radiation sensitivity * Investigation findings * low T cells, normal B cells * thymic hypoplasia * variable low Igs, especially IgA * Treatment * supportive

Answer 7

* Inheritance: X-linked * Aetiology * defective WASP gene- involved in cytoskeletal reorganisation (during T cell activation) * Clinical features * thrombocytopenia with SMALL platelets (bleeding and bruising) * eczema, eosinophilia and food allergies * recurrent infections * respiratory tract * severe viral illnesses

Answer 8

* Clincal presentation * Fulminant EBV infection * uncontrolled expansion of EBV infection B cells and CD8 cells * haemophagocytic lymphohistiocytosis * Hypopgammaglobulinaemia +/- EBV infection * Lymphoma predisposition (mostly B cell in origin) +/- EBV infection * Aetiology * arises due to mutation in gene for SAP (SLAM associated protein) * adapter protein involved in intracellular signalling pathways * deficiency leads to increased survival of EBV infected/transformed B cells

Answer 9

* Aetiology * defect in beta subunit of beta-2 integrins (CD18) * Clincal features * onset at birth, delayed cord separation, omphalitis * failure to thrive * recurrent bacterial infection of the skin, mucous membranes, absence of pus formation * severe gingivitis and periodontitis * poor wound healing * Investigation findings * defective adhesion dependant neutrophil functions * defective expression of CD18 * Treatment * BMT * Abs * granulocyte transfusions

Answer 10

* Aetiology * defect in fucose metabolism * deficienct expression of fucosylated carbohydrates including SLeX * failure of selectin function * leukocytes fail to roll * Clinical features * severe mental retardation * Bombay blood group (hh) * short stature and characteristic facial features * Similar immunodeficiency to LAD-1 * onset at birth, delayed cord separation, omphalitis * failure to thrive * recurrent bacterial infection of the skin, mucous membranes, absence of pus formation * severe gingivitis and periodontitis * poor wound healing * Treatment * Abs * May become less severe with age

Immunodeficiency Flashcards

(34 cards)