Immunology SBAs Flashcards
A 10-year-old boy is seen by a paediatrician after suffering recurrent chestinfections. His mother reports purulent sputum production and cough for theprevious 2 years. Genetic testing reveals the child has a ΔF508 mutation onchromosome 7. Which physical barrier to infection is most likely to be affectedby the child’s condition?A SkinB Gastric acidC Mucociliary clearanceD TearsE Gut flora
C Mucociliary clearancePhysical barriers to infection which form part of the innate immunesystem provide initial protection against disease-causing organisms.Impaired mucociliary clearance (C) may arise secondary to cystic fibrosis,which is the most likely answer in this scenario. Cystic fibrosis isan autosomal dominant disease which primarily affects the lungs butalso the pancreas, liver and gastrointestinal system. The most commonmutation is the ΔF508 mutation on chromosome 7, which codes for thecystic fibrosis transmembrane conductance regulator (CFTR). Defectivesodium and chloride ion transport across epithelial cells leads to the formationof viscous secretions. In the respiratory tract increased viscoussecretions produced by goblet cells cause damage to the cilia, as well asdiffuse lung injury, which can result in bronchiectasis.
A 62-year-old woman sees her GP for a regular check-up. On examination, shehas notable deformities of her hands, including swan-neck and Boutonnieredeformities of her fingers. Blood tests reveal a raised CRP. Which of the followinginvestigation results will most likely feature?A Reduced AH50 and normal CH50B Reduced C1 inhibitorC Reduced C3 and C4D Reduced C3 and normal C4E High CH50
E High CH50The complement system is composed of the classical, lectin and alternativepathways. These individual pathways culminate in the formation ofthe membrane attack complex (MAC), which traverses cell surface membranesof pathogens, causing cell lysis. Components of the complementsystem can be quantified in order to differentiate possible diagnoses.CH50 (total complement activity) measures the level of factors of theclassical and final pathways (C1–C9). As complement factors are acutephase proteins, a high CH50 (E) indicates acute or chronic inflammation.Together with the raised CRP and clinical features, this patient is likelyto suffer from rheumatoid arthritis. Systemic lupus erythematosus (SLE)is a systemic autoimmune disease characterized by antibody-immune complex formation and deposition.
A 25-year-old woman, who has a history of allergy to nuts, is taken to accidentand emergency after eating a dessert containing peanuts. She has an evidentwheeze with an increased respiratory rate, swelling of her lips and itchy skin.Which cell of the innate immune system is most likely to be responsible for hersymptoms?A Natural-killer cellsB Dendritic cellsC EosinophilsD Mast cellsE Neutrophils
D Mast cellsMast cells (D) are involved in the inflammatory process that occurs inallergy and anaphylaxis (the diagnosis in this case), but also providea protective function against pathogens. Mast cells are activated byone of three mechanisms: direct injury (toxins or drugs), cross-linkingof IgE receptors or by activated complement proteins. Once activated,mast cells release granules containing histamine and heparin. Histaminecauses vasodilatation leading to the characteristic features of inflammation(oedema, warmth and redness of the skin). The ‘flare and wheal’skin reaction is a feature of histamine release by mast cells. Mast cellsplay a role in diseases such as asthma, eczema and allergic rhinitis.
A 35-year-old man develops diarrhoea with fever and malaise 24 hours after eatinga take-away meal. Stool cultures reveal the source of the infection is Salmonellaspp. Which antibody is responsible for protecting against gastrointestinal infections?A IgAB IgDC IgGD IgME IgE
A IgAIgA (A) can exist as a monomer or a dimer (joined by a short peptideknown as the J chain). Its role is primarily related to the protection ofmucosal surfaces via salivary, respiratory, gastrointestinal and lacrimalsecretions. IgA is also present in breast milk, providing passive immunityin neonates.
A 23-year-old man presents to his GP with recent onset diarrhoea, fatigue andweight loss. The patient suggests that his symptoms are worsened after eatingbread or rice. Which human leukocyte antigen is most likely to be associatedwith his disease process?A HLA B27B HLA DR2C HLA DR3D HLA DR4E HLA DQ2
E HLA DQ2HLA DQ2 (E) represents a risk factor for coeliac disease (HLA DQ8is also a risk factor but to a lesser extent). The cell surface receptorsformed by HLA DQ2 bind with greater affinity to α-gliadin, a proteinpresent in wheat, barley and rye which is responsible for the pathogenesisof coeliac disease. Therefore, receptors formed from HLA DQ2are more likely to recruit T cells and initiate an autoimmune responsecompared to other HLAs. HLA B27 (A) is associated with ankylosingspondylitis. The association with HLA B27 suggests the involvement ofCD8+ T cells in the pathogenesis of ankylosing spondylitis. HLA DR2(B) is associated with Goodpasture’s syndrome, an autoimmune diseasetriggered by a type II hypersensitivity reaction. It is characterized byglomerulonephritis and haemoptysis. HLA DR3 (C) is associated withGraves’ disease, systemic lupus erythematosus (SLE) and myastheniagravis. HLA DR4 (D) is associated with type I diabetes mellitus andrheumatoid arthritis; in these diseases, HLA DR4 recruits T cells withsubsequent production of islet cell antibodies.
A 3-year-old Afro-Caribbean boy is referred to a paediatrician after concernsabout his recurrent chest infections. The child’s hair slowly fell out and there isevidence of depigmentation of his skin. Blood tests reveal hypocalcaemia andhigh TSH levels. Which component of the immune tolerance system is likely tobe dysfunctional?A Regulatory T cellB TGF-βC Autoimmune regulatorD Dendritic cellsE IL-10
C Autoimmune regulatorCentral tolerance is the induction of tolerance to self, which is integratedinto T-cell development in the thymus, a major site for the maturationof T cells. Within the thymus, T-cell receptors are exposed toself major histocompatibility complexes (MHC). Those binding to theseMHCs with some affinity are positively selected, whereas those with noaffinity (unable to recognize MHC) are neglected and removed. T cellsbinding with high affinity are removed by apoptosis, as these cells posean autoimmune risk. The autoimmune regulator (AIRE; C) is also presentwithin the thymus and presents T-cell receptors with a range oforgan-specific antigens. If T-cell receptors bind to such antigens, theyswiftly die via apoptosis. Autoimmune polyendocrine syndrome type 1(APECED; associated with mild immune deficiency, dysfunctional parathyroidgland/adrenal gland, hypothyroidism, gonadal failure, alopeciaand vitiligo) results from mutations in the AIRE gene. The child in thisscenario has features of APECED.
A 34-year-old man presents to his GP with fever, joint pain and a rash on histrunk. On examination, a new murmur is auscultated. Blood investigations reveala raised anti-streptolysin O titre. What is the most likely mechanism for thisdisease process?A Defective immunoregulationB Molecular mimicryC T-cell bypassD Release of hidden self antigensE Cytokines
B Molecular mimicryMolecular mimicry is the term used to describe the phenomenonwhereby pathogens produce antigens that are molecularly very similarto self antigens.The immune response to this pathogenic antigen generatesT cells and B cells which are both anti-pathogen and anti-self;this process is known as immunological cross-reactivity. In the case ofpost-streptococcal rheumatic fever, antibodies to M-proteins present onthe surface of group A streptococci cross-react with cardiac myosin; thisresults in the inflammatory features of rheumatic fever (fever, raisedESR/CRP, leukocytosis, carditis).
A 2-year-old girl is seen by an infectious disease paediatrician after sufferingrecurrent infections since she was born. Her neutrophil count is normal. A nitroblue-tetrazolium (NBT) test is performed, which remains colourless. What is thediagnosis?A Kostmann syndromeB Cyclic neutropeniaC Leukocyte adhesion deficiencyD Chronic granulomatous diseaseE Von Gierke’s disease
D Chronic granulomatous diseaseChronic granulomatous disease (CGD; D) is an X-linked disorder causingdeficiency of NADPH oxidase. As a result, neutrophils cannot producethe respiratory burst required to clear pathogens. The disease ischaracterized by chronic inflammation with non-caseating granulomas.Clinical features include recurrent skin infections (bacterial) as wellas recurrent fungal infections including Candida spp. and Aspergillusspp. The disease is usually detected by the age of 5 and is diagnosedusing the nitro-blue-tetrazolium (NBT) test, which remains colourlessdue to NADPH deficiency (if NADPH is present the solution turns blue).The NBT test distinguishes CGD from other phagocyte deficiencies. Thepatient will have a normal neutrophil count as there is no defect inneutrophil production. Treatment involves the use of prophylactic antibioticsand interferon-gamma
A 29-year-old woman presents to her GP with recent onset joint pain and tiredness.On examination she has a malar rash. Further blood tests reveal she is antinuclearantibody and anti-double stranded DNA positive. Which component ofthe complement system is she most likely to be deficient in?A C3B C4C C6D C9E C1 inhibitor
B C4This patient demonstrates symptoms, signs and diagnostic features consistentwith systemic lupus erythematosus (SLE) and is therefore mostlikely to have a deficiency of the classical pathway such as C4 deficiency(B). Other possible deficiencies in this pathway include C1q, C1r andC1s and C2. The classical pathway is responsible for clearing immunecomplexes and apoptotic cells; patients who have deficiencies in thispathway therefore have a greater risk of developing immune complexdisease such as SLE.
A 4-year-old girl is seen by a paediatrician to investigate possible developmentaldelay and learning difficulties. Initial blood tests reveal hypocalcaemia, reducedCD4+ and CD8+ T-cell counts as well as deficiency in IgG and IgA. FISH analysisreveals the child has a deletion of 22q11. What is the diagnosis?A Di George’s syndromeB Severe combined immunodeficiencyC Bare lymphocyte syndromeD Wiskott–Aldrich syndromeE Interferon-gamma receptor deficiency
A Di George’s syndromeDi George’s syndrome (A) is caused by an embryological abnormalityin the third and fourth branchial arches (pharyngeal pouches) due to a22q11 deletion. The result is an absent or hypoplastic thymus, as wellas a deficiency in T cells. There is a reduced level or absence of CD4+and CD8+ T cells as well as decreased production of IgG and IgA. B-celland IgM levels are normal. The features of Di George’s syndrome canbe remembered by the mnemonic ‘CATCH’: cardiac abnormalities, atresia(oesophageal), thymic aplasia, cleft palate and hypocalcaemia
