Immunology EMQs Flashcards
A Kostmann syndromeB Severe combined immunodeficiencyC Hyper IgM syndromeD Leukocyte adhesion deficiencyE Protein-losing enteropathyF Cyclic neutropeniaG Bruton’s agammaglobulinaemiaH Di George’s syndromeI AIDSA 4-month-old girl is referred to a paediatrician with failure to thrive, aftersuffering from recurrent infections since birth, especially recurrent candidainfections of her skin and mouth. Blood tests reveal a diminished T-cell count;further lymphocyte testing demonstrates non-functional B cells.
B Severe combined immunodeficiencySevere combined immunodeficiency (SCID; B) causes defects in bothT cells and B cells. The most common subtypes can be categorized intoan X-linked disease (mutation of IL-2 receptor) or an autosomal recessivecondition (mutation of adenosine deaminase gene which leads toa build-up of toxins and hence compromised proliferation of lymphocytes).Characteristically, there is hypoplasia and atrophy of the thymusand mucosa-associated lymphoid tissue (MALT). Clinical featuresinclude diarrhoea, failure to thrive and skin disease (graft-versus-hostinduced, secondary to transplacental maternal T cells or blood transfusion-related caused by donor T cells).
A Kostmann syndromeB Severe combined immunodeficiencyC Hyper IgM syndromeD Leukocyte adhesion deficiencyE Protein-losing enteropathyF Cyclic neutropeniaG Bruton’s agammaglobulinaemiaH Di George’s syndromeI AIDSA 5-month-old boy is referred to a paediatrician after suffering with recurrentinfections since his birth. His mother has noticed increased irritability. Bloodtests reveal a neutrophil count of 350/μL. NBT test is normal.
A Kostmann syndromeKostmann syndrome (severe congenital neutropenia; A) is a congenitalneutropenia as a result of failure of neutrophil maturation. This resultsin a very low neutrophil count (less than 500/μL indicates severe neutropenia)and no pus formation. Kostmann syndrome is usually detectedsoon after birth. Presenting features may be non-specific in infants,including fever, irritability and infection. The nitro-blue-tetrazolium(NBT) test can help with diagnosis; the liquid turns blue due to the normalpresence of NADPH. In Kostmann syndrome, NBT test is positiveand therefore normal.
A Kostmann syndromeB Severe combined immunodeficiencyC Hyper IgM syndromeD Leukocyte adhesion deficiencyE Protein-losing enteropathyF Cyclic neutropeniaG Bruton’s agammaglobulinaemiaH Di George’s syndromeI AIDSA 4-year-old girl is referred to a paediatrician after experiencing recurrentchest infections. Blood tests demonstrate a reduced B-cell count as well as lowIgA, IgM and IgG levels.
G Bruton’s agammaglobulinaemiaBruton’s agammaglobulinaemia (G) is an X-linked disease that presentsin childhood. It is caused by a mutation of the BTK gene, whichexpresses a tyrosine kinase. This mutation inhibits B-cell maturationand therefore B-cell and immunoglobulin levels are diminished. Bloodtests will reveal a normal T-cell count, but diminished B-cell count aswell as IgA, IgM and IgG levels. Plasma cells will also be absent fromthe bone marrow and lymphatics.
A Kostmann syndromeB Severe combined immunodeficiencyC Hyper IgM syndromeD Leukocyte adhesion deficiencyE Protein-losing enteropathyF Cyclic neutropeniaG Bruton’s agammaglobulinaemiaH Di George’s syndromeI AIDSA 48-year-old woman presents to her GP with a history of diarrhoea for3 weeks, which occasionally contains blood. She has felt increasingly tired andfeverish. The patient has had similar episodes in the past which were treatedwith mesalazine. She also reports recurrent chest infections since her first episodeof diarrhoea.
E Protein-losing enteropathyProtein-losing enteropathy (E) is defined as the severe loss of proteinsvia the gastrointestinal tract. The underlying pathophysiology mayrelate to mucosal disease, lymphatic obstruction or cell death leading toincreased permeability to proteins. If more proteins are lost than synthesizedin the body, hypoproteinaemia will result. Causes include Crohn’sdisease, coeliac disease and rarely, Menetrier’s disease. Hypoproteinaemiasecondary to such conditions results in fewer immunoglobulins beingformed which diminishes the adaptive immune response.
A Kostmann syndromeB Severe combined immunodeficiencyC Hyper IgM syndromeD Leukocyte adhesion deficiencyE Protein-losing enteropathyF Cyclic neutropeniaG Bruton’s agammaglobulinaemiaH Di George’s syndromeI AIDSA 3-year-old girl is seen by a GP due to recurrent mild chest infections. Thedoctor notices the girl has a cleft lip. Blood tests reveal a reduced T-cell countas well as hypocalcaemia.
H Di George’s syndromeDi George’s syndrome (H) is caused by an embryological abnormalityin the third and fourth branchial arches (pharyngeal pouches) due to a 22q11 deletion. The result is an absent or hypoplastic thymus, as wellas a deficiency in T cells. There is a reduction or absence of CD4+ andCD8+ T cells as well as decreased production of IgG and IgA. B cell andIgM levels are normal. The features of Di George’s syndrome can beremembered by the mnemonic ‘CATCH’: cardiac abnormalities, atresia(oesophageal), thymic aplasia, cleft palate and hypocalcaemia.
A Selective IgA deficiency diseaseB Common variable immunodeficiencyC Nephrotic syndromeD Bare lymphocyte syndromedeficiencyE Sickle cell anaemiaF Chronic granulomatousG Reticular dysgenesisH Wiskott–Aldrich syndromeI Interferon-gamma receptorA 4-year-old boy is referred to a paediatrician after suffering recurrent chestinfections over the preceding few months. The boy has a history of eczema aswell as recurrent nose bleeds. Blood tests reveal a reduced IgM level but raisedIgA and IgE levels.
H Wiskott–Aldrich syndromeWiskott–Aldrich syndrome (WAS; H) is an X-linked condition which iscaused by a mutation in the WASp gene; the WAS protein is expressedin developing haematopoietic stem cells. WAS is linked to the developmentof lymphomas, thrombocytopenia and eczema. Clinical featuresinclude easy bruising, nose bleeds and gastrointestinal bleeds secondaryto thrombocytopenia. Recurrent bacterial infections also result. Bloodtests reveal a reduced IgM level and raised IgA and IgE levels. IgG levelsmay be normal, reduced or elevated.
A Selective IgA deficiency diseaseB Common variable immunodeficiencyC Nephrotic syndromeD Bare lymphocyte syndromedeficiencyE Sickle cell anaemiaF Chronic granulomatousG Reticular dysgenesisH Wiskott–Aldrich syndromeI Interferon-gamma receptorA 20-year-old man presents to his GP with signs of a mild pneumonia. Thepatient states he has had several similar episodes in the past. Further investigationsby an immunologist reveal the patient has a genetic condition caused by amutation of MHC III.
B Common variable immunodeficiencyCommon variable immunodeficiency (CVID; B) presents in adulthood. Amutation of MHC III causes aberrant class switching, increasing the riskof lymphoma and granulomas. Patients with CVID also have a predispositionto developing autoimmune diseases. Recurrent infections causedby Haemophilus influenzae and Streptococcus pneumoniae are common.Clinical sequelae include bronchiectasis and sinusitis. Blood tests reveala reduced B-cell count, a normal/reduced IgM level and decreased levelsof IgA, IgG and IgE.
A Selective IgA deficiency diseaseB Common variable immunodeficiencyC Nephrotic syndromeD Bare lymphocyte syndromedeficiencyE Sickle cell anaemiaF Chronic granulomatousG Reticular dysgenesisH Wiskott–Aldrich syndromeI Interferon-gamma receptorA 3-year-old girl is referred to a paediatrician after concerns about recurrentskin infections she has suffered from since birth. A nitro-blue-tetrazolium testis negative (remains colourless).
F Chronic granulomatousChronic granulomatous disease (F) is an X-linked disorder causing deficiencyof NADPH oxidase. As a result, neutrophils cannot produce the respiratory burst required to clear pathogens. The disease is characterizedby chronic inflammation with non-caseating granulomas. Clinical featuresinclude recurrent skin infections (bacterial) as well as recurrentfungal infections. The disease is usually detected by the age of 5 and isdiagnosed using the nitro-blue-tetrazolium (NBT) test, which remainscolourless due to NADPH deficiency (if NADPH is present the solutionturns blue). The patient will have a normal neutrophil count as there isno defect in neutrophil production.
A Selective IgA deficiency diseaseB Common variable immunodeficiencyC Nephrotic syndromeD Bare lymphocyte syndromedeficiencyE Sickle cell anaemiaF Chronic granulomatousG Reticular dysgenesisH Wiskott–Aldrich syndromeI Interferon-gamma receptorA 4-year-old boy is referred to a paediatrician after a period of mild butchronicdiarrhoea. On examination the child is found to have icteric sclera andhepatomegaly. Following blood tests, the doctor has a high suspicion that thechild could have a defect in MHC I.
D Bare lymphocyte syndromeBare lymphocyte syndrome (D) is caused by either deficiency in MHC I(type 1; all T cells become CD4+ T cells) or MHC II (type 2; all T cellsbecome CD8+ T cells). Clinical manifestations include sclerosing cholangitiswith hepatomegaly and jaundice.
A Selective IgA deficiency diseaseB Common variable immunodeficiencyC Nephrotic syndromeD Bare lymphocyte syndromedeficiencyE Sickle cell anaemiaF Chronic granulomatousG Reticular dysgenesisH Wiskott–Aldrich syndromeI Interferon-gamma receptorA 22-year-old woman visits her GP after several chest infections in the past fewyears. As well as the chest infections, the patient reports that she has had severalbouts of diarrhoea over the same time period.
A Selective IgA deficiency diseaseSelective IgA deficiency (A): IgA specifically provides mucosal immunity,primarily to the respiratory and gastrointestinal systems. SelectiveIgA deficiency results from a genetic inability to produce IgA and ischaracterized by recurrent mild respiratory and gastrointestinal infections.Patients with selective IgA deficiency are also at risk of anaphylaxisto blood transfusions due to the presence of donor IgA. Thisoccurs especially after a second transfusion; antibodies having beencreated against IgA during the primary transfusion. Selective IgA deficiencyis also linked to autoimmune diseases such as rheumatoid arthritis,systemic lupus erythematosus and coeliac disease.
A HLA-matchingB CorticosteroidsC Cyclosporine AD AzathioprineE SirolimusF OKT3G IL-2 receptor antibodyH TacrolimusI Anti-lymphocyte antibodyA 48-year-old man has undergone a kidney transplant operation as a resultof renal failure caused by long-standing diabetes mellitus. However, despiteimmunosuppression,signs of organ rejection become evident just 1 hour afterthe procedure.
A HLA-matchingHLA-matching (tissue typing; A) is a preventative method of limitingthe risk of organ transplant rejection. It is impractical to match all HLA loci and hence tissue typing focuses on major HLA antigens such asHLA-A and HLA-B. HLA-DR is also now routinely typed due to its rolein activating recipient’s T-helper cells. HLA-matching greatly reducesthe chance of hyperacute rejection caused by the presence of preformedantibodies against the graft. Pre-formed antibodies may occur asa result of previous blood transfusion or pregnancy.
A HLA-matchingB CorticosteroidsC Cyclosporine AD AzathioprineE SirolimusF OKT3G IL-2 receptor antibodyH TacrolimusI Anti-lymphocyte antibodyA 45-year-old man undergoes a heart transplant due to end-stage heart failure.Seventy-two hours after the operation, the patient shows signs of organ rejectionwhich is resistant to corticosteroid therapy. A mouse monoclonal antibodyis administered to save the transplant.
F OKT3OKT3 (muromonab-CD3; F) is a mouse monoclonal antibody targetedat the human CD3 molecule used to treat rejection episodes in patientswho have undergone allograft transplantation. Administration of theantibody efficiently clears T cells from the recipient’s circulation, T cellsbeing the major mediator of acute organ rejection. Primary indicationsinclude the acute corticosteroid-resistant rejection of renal, heartand liver transplants. Anaphylaxis can result given a murine proteinis introduced to the recipient. OKT3 can also bind to CD3 on T cells,stimulating the release of TNF-α and IFN-γ causing cytokine releasesyndrome, which if severe, can be fatal.
A HLA-matchingB CorticosteroidsC Cyclosporine AD AzathioprineE SirolimusF OKT3G IL-2 receptor antibodyH TacrolimusI Anti-lymphocyte antibodyA 32-year-old woman undergoes a bone marrow transplant for chronic lymphoblasticleukaemia. She is prescribed a medication that inhibits calcineurin. Onexamination, the patient has gum hyperplasia.
C Cyclosporine ACyclosporine A (C) is an important immunosuppressive agent in the organtransplant arena, which inhibits the protein phosphatase calcineurin. This inturn inhibits IL-2 secretion from T cells, a cytokine which stimulates T cellproliferation. Another proposed mechanism of action involves the stimulationof TGF-β production. TGF-β is a growth-inhibitory cytokine, theproduction of T cells is reduced, hence minimizing organ rejection. Adverseeffects include nephrotoxicity, hepatotoxicity, diarrhoea and pancreatitis.On examination, patients taking cyclosporine A may have gum hyperplasia.
A HLA-matchingB CorticosteroidsC Cyclosporine AD AzathioprineE SirolimusF OKT3G IL-2 receptor antibodyH TacrolimusI Anti-lymphocyte antibodyA 62-year-old man who has undergone a kidney transplant was started on animmunosuppressive agent prior to the operation. The patient is warned that hewill only be on the medication for a short period due to long-term side effectssuch as osteoporosis.
B CorticosteroidsCorticosteroids (B) are used as an immunosuppressive agent in both theprevention and treatment of transplant rejection. Corticosteroids inhibitphospholipase A2 thereby blocking prostaglandin formation as wellas a series of inflammatory mediators. The immunosuppressive effectsof corticosteroids are numerous and include reducing the number ofcirculating B cells, inhibiting monocyte trafficking, inhibiting T-cellproliferation and reducing the expression of a number of cytokines, forexample, IL-1, IL-2 and TNF-α. Prednisolone is used prophylacticallybefore transplantation to prevent rejection; methylprednisolone is usedin the treatment of rejection. Side effects are frequent, however, andinclude osteoporosis, diabetes mellitus and hypertension.
A HLA-matchingB CorticosteroidsC Cyclosporine AD AzathioprineE SirolimusF OKT3G IL-2 receptor antibodyH TacrolimusI Anti-lymphocyte antibodyA 62-year-old man who is undergoing a liver transplant as a result of cirrhosisis prescribed a medication that inhibits DNA synthesis in an attempt to preventproliferation of T cells.
D AzathioprineAzathioprine (D) is an antimetabolite agent used in immunosuppressivetherapy. Azathioprine is metabolized into 6-mercaptopurine (6-MP), apurine analogue that prevents DNA synthesis, thereby inhibiting theproliferation of cells; lymphocytes are most affected. Antigen presentingcells present non-self proteins (from the allograft) to T cells whichin turn produce IL-2 to stimulate T-cell proliferation. However, 6-MPinhibits this proliferation and so the reaction between T cells and theallograft is minimized. Important side effects include hepatotoxicity,hypersensitivity reactions and myelosuppression.
A Anti-smooth muscleB p-ANCAC Anti-Jo1D Anti-cyclic citrullinated proteinE Anti-centromereF Anti-double stranded DNAG Anti-parietal cellH Anti-thyroid stimulatinghormoneI Anti-topoisomeraseA 56-year-old woman presents to the rheumatologist with pain in her hands.On examination there are obvious deformities of her proximal interphalyngealjoints and metacarpophalyngeal joints. Swan-neck deformities are seen but thepatient has retained functionality of her fingers.
D Anti-cyclic citrullinated proteinAnti-cyclic citrullinated protein (anti-CCP; D) antibody is associatedwith rheumatoid arthritis. The antibody is directed at the filamentaggregating protein, filaggrin. Rheumatoid arthritis is a chronic systemicautoimmune disease that results in a symmetrical deforming polyarthritis.Clinical features include deformities of the hands (Boutonierre’sdeformity, swan-neck deformity, Z-thumb and ulnar deviation of thefingers). The proximal interphalangeal joints are affected more than thedistal interphalangeal joints. Extra-articular manifestations include pulmonaryfibrosis, pericardial effusion, rheumatoid nodules and splenomegaly(Felty’s syndrome). Rheumatoid factor is another antibody measuredin the investigation of rheumatoid arthritis, but is less sensitiveand specific in comparison to anti-CCP.
A Anti-smooth muscleB p-ANCAC Anti-Jo1D Anti-cyclic citrullinated proteinE Anti-centromereF Anti-double stranded DNAG Anti-parietal cellH Anti-thyroid stimulatinghormoneI Anti-topoisomeraseA 45-year-old woman is referred to a hepatologist after suffering an episode ofjaundice, fatigue and fever. Liver function tests reveal an increased AST. Biopsyof the liver reveals cirrhosis and an autoimmune pathology is suspected.
A Anti-smooth muscleAnti-smooth muscle (A) antibody (anti-SMA) suggests the diagnosis ofautoimmune hepatitis, but can also be present in patients with primarysclerosing cholangitis. Autoimmune hepatitis is characterized by inflammation,hepatocellular necrosis, fibrosis, with cirrhosis in severe cases.Diagnosis requires histological confirmation together with the presenceof autoantibodies which may either be non-organ or liver-specific.Autoimmune hepatitis is classified into two major groups depending onthe autoantibody present: type 1 is defined by the presence of anti-SMAand/or anti-nuclear antibody, whilst type 2 is characterized by the presenceof anti-liver/kidney microsomal-1 antibody (anti-LKM-1).
A Anti-smooth muscleB p-ANCAC Anti-Jo1D Anti-cyclic citrullinated proteinE Anti-centromereF Anti-double stranded DNAG Anti-parietal cellH Anti-thyroid stimulatinghormoneI Anti-topoisomeraseA 42-year-old woman presents to the rheumatologist with weakness in herproximal muscles and describes how she is finding it difficult to climb stairs.On examination, a rash is observed surrounding both eyes. A high resolution CTscan reveals a pulmonary fibrosis picture.
C Anti-Jo1Anti-Jo1 (C) antibody is present in patients with dermatomyositis.Dermatomyositis is characterized by autoimmune inflammation of musclefibres and skin. Clinical features include a heliotrope rash aroundthe eyes, Gottron’s papules on the dorsum of finger joints as well as weaknessof the proximal limb muscles which causes difficulty inclimbing stairs and rising from a chair. Dermatomyositis is commonlyassociated with SLE and scleroderma. The presence of anti-Jo1 in dermatomyositistypically suggests interstitial pulmonary involvement.Blood tests reveal an increased ESR and raised creatine kinase level.
A Anti-smooth muscleB p-ANCAC Anti-Jo1D Anti-cyclic citrullinated proteinE Anti-centromereF Anti-double stranded DNAG Anti-parietal cellH Anti-thyroid stimulatinghormoneI Anti-topoisomeraseA 43-year-old man is referred to the rheumatologist after experiencing palenessin his fingers, especially when exposed to cold weather. The patient also complainsof recent onset difficulty in swallowing solid food.
E Anti-centromereAnti-centromere (E) antibody is associated with limited systemic scleroderma(CREST syndrome). CREST syndrome is characterized by calcinosis,Reynaud’s syndrome, oesophageal dysmotility, sclerodactyly and telangiectasia.The pathophysiology is defined by endothelial injury and chronicfibrosis (orchestrated by PDGF and TGF-β). Blood investigations will reveala raised ESR, anaemia and hypergammaglobulinaemia. Anti-centromereantibodies detected in the presence of primary biliary cirrhosis indicateportal hypertension.
A Anti-smooth muscleB p-ANCAC Anti-Jo1D Anti-cyclic citrullinated proteinE Anti-centromereF Anti-double stranded DNAG Anti-parietal cellH Anti-thyroid stimulatinghormoneI Anti-topoisomeraseA 42-year-old woman presents to the rheumatologist with joint pain and stiffness.On examination, the patient appears to have a tight mouth and fine endinspiratory crackles on auscultation of the lungs. The woman also has a widespreaditchy rash on her body.
I Anti-topoisomeraseAnti-topoisomerase (I) antibody is characteristic of diffuse systemicscleroderma. Diffuse systemic scleroderma shares some features of limitedsystemic scleroderma, however, it is more aggressive in its course,affecting large areas of the skin as well as involving the kidneys, heartand lungs. The pathogenesis of diffuse systemic scleroderma is similarto that of limited systemic scleroderma. The presence of anti-topoisomeraseantibodies in diffuse systemic sclerosis is associated withpulmonaryinterstitial fibrosis.
