Immunology

Question 1

Which one of the following vaccines is most likely to be damaged by freezing?

Answer 1

Hepatitis B vaccine

Question 2

A seven-year-old boy has trodden on a bee and presents to the emergency department with swelling and redness of the foot spreading to mid-calf. He has been stung on one previous occasion with only minor redness and swelling. He has a history of mild intermittent asthma. There are no other symptoms. His mother is concerned about the size of the present reaction, its treatment and about consequences of future bee stings.

Which of the following is the most appropriate advice about the management of the current reaction and prognosis for future stings?

Answer 2

large local reaction and treatment with oral corticosteroids could be considered as would any future similar reactions.

Question 3

The mechanism responsible for sporadic influenza virus pandemics includes which of the following?

Answer 3

Antigenic shift involves genetic reassortment and is associated with pandemics, such as the emergence of SARS-Cov2.

Antigenic drift involving point mutations of viral haemagglutinin or neuraminidase are associated with the epidemics typically associated with Flu and necessitate updating vaccine antigen composition; e.g. the emergence of variants of SARS-Cov2.

Question 4

One of the first immune cells recruited to the site of inflammation. Kills pathogens by phagocytosis and secreted molecules.

Answer 4

Neutrophils are one of the earliest cell types recruited to areas of inflammation. The complement components C3a and C5a and the cytokines Il-1b and IL-6 are chemotactic molecules for neutrophil migration and activation. Killing of pathogens is by both phagocytosis and secreted proteins.

Question 5

This cell patrols tissues playing a critical role in antiviral and cancer immunity. The multiple modes of action include the ability to recognise cells that are displaying reduced or no cell surface MHC Class I.

Answer 5

Natural Killer cells are innate cells of the lymphocyte lineage. Unlike other lymphocytes they do not express either a T-cell receptor or B-cell receptor. Some intracellular pathogens and cancerous cells attempt to evade immune detection by down-regulating MHC Class I on the surface of infected/cancerous cells. This allows evasion of T-cells. NK cells however are able to recognise these cells and kill them using perforin and granzyme proteases

Question 6

This cell resides in the tissues where it constantly samples its surroundings. When activated by pro-inflammatory cytokines or the direct detection of danger signals, these cells migrate to lymph organs where they are expert antigen-presenting cells.

Answer 6

Dendritic cells of the macrophage lineage. They display antigens on both MHC class I and class II in their activated state. The nature of the activating signal directly affects the types of cytokines secreted by these dendritic cells during antigen presentation, guiding the subsequent adaptive immune response towards the correct spectrum. For example, a dendritic cell activated by a virus-associated danger signal will secrete cytokines that promote C4+ T cells to differentiate into Th1 cells rather than Th2 cells.

Question 7

A boy with a history of easy bruising, and recurrent S.aureus infection, and was noted to have large lysosomal granules in the WBC on film.

Answer 7

Patients with Chediak Higashi are associated with oculocutaneous albinism, easy bruising, recurrent infections. It is a result of abnormal function of natural killer cells due to mutation in the lysosomal trafficking regulator gene. There are large lysosomal granules noted in the WBC and bone marrow on biopsy.

Question 8

A three-month old infant presents with pneumocystis pneumonia. Genetic testing demonstrates a mutation in a gene which encodes the CD40 ligand protein.

Answer 8

Patients with Hyper-IgM syndrome lack functional CD40 ligand which is situated on the surfaces of activated hyper T cells and is responsible for interacting with B cells to switch from producing IgM to IgA, IgG and IgE. These patients have elevated IgM with neutropenia and often presents in infancy with PCP.

Question 9

A four-week-old boy who presents with a perianal abscess requiring incision and drainage. There is positivity on dihydrorhodamine and nitroblue tetrazolium testing.

Answer 9

Chronic granulomatous disease is investigated for by performing nitroblue tetrazolium and dihydrorhodamine test which demonstrates defective neutrophil oxidative burst. These patients recurrent catalase positive bacterial infections and abscesses are characteristic of CGD.

Question 10

Hyperimmunoglobulin M syndromes are a heterogenous group of primary immune deficiencies that affect Ig class-switching. CD40L mutations are the most common cause.

Answer 10

IgM levels may be in the normal range, however, all other Ig isotypes will be deficient.

Chronic liver disease is caused by unabated CMV and Cryptosporidium infection is common. Liver transplant carries a very high risk of mortality.

Class switching refers to the replacement of the heavy chain (mu in IgM) with another heavy chain (gamma in IgG etc).

CD40L deficiency is inherited in an X-linked fashion.

Question 11

An eight-year-old girl presents to ED with increased work of breathing. She is diagnosed with pneumonia and a blood culture reveal pneumococcus. She has a history of recurrent chest and ear infections. She is under investigation for failure to thrive and persistent diarrhoea. She takes no regular medication, has no known allergies and is up to date with immunisations.

On examination, she is febrile. Her right tympanic membrane is dull and bulging and her left ear appears normal. She is coryzal. Her tonsils are red but otherwise normal and she has generalised cervical lymphadenopathy. She has widespread crepitations and wheeze and her saturations are 94% on 2L oxygen (90% on air).

Full blood count reveals low Hb, high WCC (neutrophilia), normal platelets. Previous results include Iow IgG, IgA and IgM.

Which of the following is the most likely diagnosis?

Answer 11

Diagnosis of CVID requires low IgG levels plus low IgA and/or IgM, the presence of B cells and an absent (or poor) vaccine response. Other immunodeficiency disorders should be excluded. Unlike many Primary Immunodeficiency Disorders, CVID is not rare but is usually diagnosed after puberty. However, if it is diagnosed in childhood, the peak age is 8. Most children start to exhibit symptoms and seek medical attention from the age of two.

Agammaglobulinaemia are X linked (XLA) which makes the diagnosis less likely in a girl. There is also an autosomal recessive form of agammaglobulinaemia but these children usually present in infancy and the clinical course is severe enough that they are diagnosed in the pre school years. There is usually absent lymphoid tissue on examination. It is also not as common, and therefore less likely, than CVID.

Transient hypogammaglobulinaemia usually resolves by two years of age.

SDS can also present with recurrent infections, failure to thrive and steatorrhoea (due to pancreatic dysfunction) but will have a cytopaenia (usually neutropenia), rather than low immunoglobulins.

Question 12

An 8-year-old boy has a history of recurrent sinopulmonary infections. His serum IgA is low. IgG and IgM are normal. Which of the following is true?

Answer 12

Many medications can cause reversible IgA deficiency (e.g. phenytoin, lamotrigine, carbamazepine, captopril, thyroxine). Cyclosporin A can cause permanent IgA deficiency which persists even after the drug has been stopped.

IgA accounts for <20% of total immunoglobulin.

Monomeric IgA is involved with phagocytosis. Dimeric secretory IgA is important to mucosal immunity.

> 2/3 children with low levels of IgA are asymptomatic

Question 13

A mother develops chickenpox two days after delivery of a normal healthy baby boy. She caught the chickenpox from her five-year-old daughter. The baby is breastfed. Which of the following would be the most appropriate action with respect to the baby?

Answer 13

Give him zoster immunoglobulin

There is a high risk of developing severe neonatal varicella if mum displays signs and symptoms of acute VZV infection 5 days prior to 2 days after delivery as there is not enough time for mum to produce IgG that will protect baby.

Hence the need to cover with VariZIG.

Needs to be given ASAP, therefore don’t wait for serology to come back to commence VariZIG.

Aciclovir is only used to treat severe neonatal varicella.

Question 14

Bernard-Soulier disease

Answer 14

Severe congenital platelet disorder
Absence or severe deficiency of VWF receptor on platelet membrane
Inherited autosomal recessive
Features: thrombocytopaenia, giant platelets, prolonged bleeding time (> 20 mins)

Question 15

Chronic ITP

Answer 15

20% patients with acute ITP
Need to evaluate for associated disorders, especially autoimmune e.g. SLE, HIV, CVIS (common variable immunodeficiency syndrome, X-linked thrombocytopenia, Wiskott –Aldrich syndrome)
Treat with a splenectomy and/or medical therapy (IVIG, steroids, rituximab, IV anti D

Question 16

Fanconi anaemia

Answer 16

This is the most common inherited form of aplastic anaemia (bone marrow failure leading to panycytopaenia) and is autosomal recessive.

Clinical manifestations:

Hyperpigmentation of trunk, neck, intertriginous areas
Café-au-lait spots, vitiligo
Short stature (growth failure can be associated with: abnormal growth hormone secretion, hypothyroidism)
Upper limb abnormalities (absent radii, hypoplastic, supernumery, bifid or absent thumbs)
Lower limb abnormalities (feet, congenital hip dislocation, leg)
Males: penis underdeveloped, undescended or atrophic or absent testes, hypospadias, phimosis
Females: abnormal genitalia
Fanconi “facies”: microcephaly, small eyes, epicanthal folds, abnormal ears
Renal malformations
10% intellectual disability
Gastrointesital, cardiopulmonary malformations

Question 17

Wiskott-Aldrich syndrome

Answer 17

Thrombocytopaenia with tiny platelets, eczema, recurrent infection due to immune deficiency
Inherited X linked
5% patients develop lymphoreticular malignancies
Splenectomy corrects thrombocytopaenia
Bone marrow transplant cures
The abnormal gene, located on the Wiskott-Aldrich syndrome protein arm on XP11

Question 18

Selective IgA deficiency

Answer 18

Most common of the primary immunodeficiencies.

Phenotypically normal B cells are present, however B lymphocytes are unable to mature into IgA producing plasma cells. Autosomal dominant inheritance. IgG and

IgM present in normal or increased levels. Normal or new normal T cell,

phagocytic cell and complement system function. Associated with HLA-B8, DR3.

Question 19

SCID

Answer 19

Results from mutations in any one of the 12 known genes that encode components of the immune system crucial for lymphoid cell development.

Abnormal genes in SCID: cytokine receptor gene; IL-2RG; Jak3; IL-7Ralpha; antigen receptor genes; RAG1; RAG2; Artemis; CD3delta; other genes; ADA; CD45.

Question 20

X linked agammaglobulinaemia

Answer 20

Also called XLA, Bruton XLA.
X linked recessive

Very low or absent B cells, IgA, IgM, IgG, IgD, IgE levels ALL low. Mutation in the Bruton tyrosine kinase (btk) gene at Xq22.3-22 causing absence of B cells cytoplasmic tyrosine kinase.

Question 21

A child with eczema, recurrent infections and recombinase activating gene 1 defect.

Answer 21

Recombinase activating gene 1 defect and recombinase activating gene 2 defect (RAG1 and 2) are associated with Omenn syndrome. Omenn syndrome is a variant of SCID (severe combined immunodeficiency). Children present with recurrent infections, exudative erythroderma, lymphadenopathy, hepatosplenomegaly, chronic persistent diarrhoea, and failure to thrive.

Question 22

A child with eczema, recurrent infections, raised serum immunoglobulin E (IgE) and trichorrhexis invaginat

Answer 22

Trichorrhexis invaginata of hair is also known as “bamboo hair” and is pathognomonic of Netherton syndrome. Netherton syndrome is a severe disorder of cornification caused by (SPINK5) mutations. Menkes disease is also known as ‘kinky hair disease’ but is not associated with eczema, recurrent infections or raised IgE. Children present with seizures and development delay due to genetic disorder leading to severe copper deficiency.

Question 23

Churg-Strauss syndrome

Answer 23

Vasculitis, accompanied by asthma and eosinophilia
considered a disease of adults; occurrence in children has been reported infrequently.

Question 24

Lymphocytic interstitial pneumonia (LIP)

Answer 24

yndrome of fever, cough, and dyspnea, with bibasilar pulmonary infiltrates consisting of dense interstitial accumulations of lymphocytes and plasma cells
fibrosis is not a typical feature
LIP is the most common form of classically described pediatric interstitial lung disease.

LIP most often occurs in association with underlying conditions, such as autoimmune disease and immunodeficiencies, but also occurs in familial and idiopathic forms.
LIP occurs in 25 to 40 percent of children with perinatally acquired HIV, and usually presents in the second or third year of life. LIP is an AIDS-defining condition in HIV-infected children, but not in adults.

LIP may result from an exaggerated immunologic response to inhaled or circulating antigens and/or caused by a primary infection with Epstein-Barr virus (EBV), HIV, or an unknown source . Immune dysregulation may play a role in the pathogenesis of LIP, and in some cases, LIP may be a premalignant state.

Laboratory test results are nonspecific for lymphocytic interstitial pneumonia (LIP). Serum protein electrophoresis commonly shows polyclonal hypergammaglobulinemia.

Physical examination findings in children may include the following: generalized lymphadenopathy, hepatosplenomegaly, parotid enlargement, clubbing, & wheezing (occasional).

Question 25

Mycoplasma infection

Answer 25

Most common clinical syndrome is bronchopneumonia. Onset characterised by headache, malaise, fever, and pharyngitis, followed by progression to LRTI. Radiographic findings are generally non-specific but include interstitial or bronchopneumonic infiltrates, unilateral and centrally dense in 75% of cases, hilar lymphadenopathy in 33%.

Lab tests are generally non-specific, cold agglutinins and mild degrees of haemolysis may occur.

Question 26

Sarcoidosis

Answer 26

a chronic multisystem granulomatous disease of unknown cause. It occurs most frequently in young adults but can occur during childhood.

relatively rare in children. Infants and children younger than 4 years present with the triad of skin, joint, and eye involvement without typical pulmonary disease; in older children, involvement of the lungs, lymph nodes, and eyes predominates.

Non-caseating epitheliod granulomas can occur in almost any organ of the body. The lungs and thoracic lymph nodes are involved at some point in almost all patients, causing ILD.

Manifestations in children commonly involve fatigue, anorexia, weight loss, bone and joint pain, and anemia. The lungs are most frequently affected causing cough, CP and exertional dyspnoea. Extrathoracic lymphadenopathy, eye changes (uveitis, iritis), skin lesions (red-brown to purple maculopapular lesions), hepatic lesions and bone marrow involvement also occur frequently.

Parotid gland enlargement is a frequent finding in children with sarcoidosis. In early onset sarcoidosis, involvement of the parotid gland is reported in 13% of cases.

Neurologic involvement is rare but may cause seizures, CN or hypothalamic dysfunction.

The course is variable, treatment is supportive/symptomatic +/- corticosteroids to suppress acute manifestations.

Question 27

Sjögren syndrome

Answer 27

chronic, inflammatory, auto-immune disease characterised by progressive lymphocytic and plasma cell infiltration of the salivary and lacrimal glands.

The primary disorder is most common in women 35-45, it is uncommon in the pediatric age group. Sjögren syndrome may overlap with other pediatric autoimmune disorders (e.g. SLE, scleroderma) and, less commonly, may present as a primary condition.

Commonly children present with recurrent parotid gland enlargement. Extraglandular manifestations may mimic these other autoimmune disorders.

Question 28

Boys with X-linked lymphoproliferative disorder are at highest risk of the development of severe illness or lymphoma following infection with which of the following pathogens?

Answer 28

This is an x-linked recessive trait characterised by an inadequate immune response to infection with EBV. There is an underlying genetic defect, which causes a T and NK cell defect and an uncontrolled cytotoxic T-cell immune response to EBV can occur.
Clinical manifestations - patients are usually healthy until EBV infection is acquired; mean age of presentation is <5 yrs

Fulminant: fatal infectious mononucleosis (50% of cases)
Lymphomas: predominantly involving B-lineage cells (25%)
There is marked impairment in the production of antibodies to EBV nuclear antigen and 70% die by 10 years of age.

Question 29

IgE antibodies bind to mast cells and cause degranulation (asthma, food allergies, hayfever).

Answer 29

Type 1 reaction

Question 30

IgG or IgM bind to a cellular antigen and activate complement and cell lysis?

Answer 30

Type 2 reaction

Question 31

Insoluble antibody-antigen complexes are deposited in tissues which triggers complement activation causing causing tissue damage (e.g. RA, SLE, serum sickness).

Answer 31

Type 3 reaction

Question 32

Cell mediated reaction involving CD8+ cytotoxic T cells and CD4+ helper T cells. (contact dermatitis, type 1 DM).

Answer 32

Type 4 reaction

Question 33

A 6-year-old girl with ataxia, recurrent sinopulmonary infections and nystagmus is seen in clinic

Answer 33

Ataxia Telangiectasia (AT).

Children with AT are at increased risk of developing malignancies so should not be exposed to radiation unless absolutely necessary. While it may be reasonable to request a chest x-ray in the acute setting, MRI should be used to monitor pulmonary disease.

Vaccines should be given to children with AT if they are able to produce antibodies. Antibiotic prophylaxis should be considered in children with recurrent sinopulmonary infections. Those with hypogammaglobulinemia or impaired specific antibody production, or who do not tolerate or fail therapy with antibiotics, should be given gamma globulin infusions.

Question 34

Hypotonic hyporesponsive episode.

Answer 34

Classically associated with the vaccine for pertussis. It occurs in children less than two years old. There is sudden onset of muscle limpness, reduced responsiveness and pallor or cyanosis after vaccination. It can last from six minutes to several hours and is commonly mistaken for anaphylaxis or seizures.

Question 35

Muckle-Wells syndrome

Answer 35

differentiated by progressive hearing loss, and amyloidosis nephropathy

Question 36

Familial Mediterranean fever

Answer 36

Autosomal recessive disease resulting from biallelic pathogenic mutations in the MEFV gene, coding for pyrin.
It is understood that mutations in the MEFV gene cause gain of function of pyrin protein such that it propagates inflammation following a relatively insignificant trigger, and without needing an external toxin or infective agent.

Question 37

TRAPS

Answer 37

tumor necrosis factor (TNF) receptor-1 associated periodic syndrome (TRAPS), fever, myalgias and rash are typically accompanied by conjunctivitis and periorbital oedema. As the name suggests, it is associated with TNFR1.

Question 38

Hyper-IgE syndrome

Answer 38

Job syndrome. It is characterised by recurrent “cold” staphylococcal infections, eczema-like skin rashes, severe lung infections that result in pneumatoceles and very high levels of IgE.

Question 39

activating complement

Answer 39

IgG and IgM are capable of activating the classical complement pathway.

IgA molecules do not activate the classical complement pathway, but may activate the alternative complement pathway.

Question 40

Factor D deficiency

Answer 40

rare disorder which occurs in children of consanguineous parents and is associated with Meningococcal sepsis.

Question 41

CD56 is a glycoprotein predominantly expressed by which cell type?

Answer 41

NK cells

Question 42

severe congenital neutropaenia

Answer 42

rare – approximately two per million. Most cases of neutropenia are acquired and are due to increased destruction, granulocyte apoptosis, or decreased granulocyte production.

ELANE gene mutation is an autosomal dominant mutation which accounts for 60% of cases of severe congenital neutropaenia (SCN). It was discovered when multiple children who were born SCN as a result of sharing the same affected sperm donor.

Question 43

If Rubella vaccine is inadvertently given to a woman in the first four weeks of pregnancy the risk of vaccine related birth defects is closest to:

Answer 43

1%
pregnancy is contraindication to rubella vaccine administration
rubella vaccine virus may cross the placenta and infect fetus
however, there have been NO cases of congenital rubella syndrome reported in women inadvertently vaccinated in early pregnancy
given the theoretical risk, women are advised to avoid pregnancy for 28 days following vaccination

Question 44

A child with recurrent infections, short stature and an erythematous photosensitive facial rash.

Answer 44

Bloom syndrome, an autosomal recessive disorder which has increased risk of malignancy. Children have a characteristic appearance and develop an erythematous photosensitive rash in the first two years of life. Bloom syndrome is a rare disorder but especially prevalent among the Ashkenazi Jewish population. Although it is rare, it is common in exams.

Question 45

child with recurrent infections and metaphyseal dysplasia has mutations in the ribonuclease mitochondrial RNA processing gene.

Answer 45

Cartilage-hair hypoplasia is an autosomal recessive disorder where children have immunodeficiency, short limbed dwarfism and sparse, fine hair.

Hair may appear normal on clinical examination and only be detected as fine on microscopic examination.

Children have increased risk of Hirschsprung disease, haematological malignancies and autoimmune disorders.

Question 46

A child with recurrent infections, short stature, presents with peri-orbital oedema, proteinuria and has low albumin.

Answer 46

Schimke immuneouseous dysplasia is an autosomal recessive disorder which presents with short stature, spondyloepiphyseal dysplasia, immunodeficiency and progressive renal failure. Children may also have skin and eye abnormalities. Any child who presents with short stature and recurrent infections should have renal function tested. Children with Schimke immuneouseous dysplasia develop nephrotic syndrome secondary to focal segmental glomerulosclerosis and will progress to renal failure.

Question 47

Anaphylaxis

Answer 47

can be immune-mediated (requires allergen-specific antibodies) and non-immune mediated. Both mechanisms can lead to a similar clinical picture of multisystem dysfunction and cardiovascular collapse.

Most anaphylactic reactions are monophasic. ~20% of cases show a second delayed reaction in the absence of further allergen exposure

Question 48

A child with severe microcephaly who develops lymphoma. Radiation hypersensitivity is found in both lymphocytes and fibroblasts.

Answer 48

NBS is caused by mutations in the nibrin (NBN) gene on 8q21 that encodes the protein nibrin. Patients have progressive, severe microcephaly. They also have intrauterine growth retardation and short stature, immunodeficiency with recurrent sinopulmonary infections and are susceptible to developing lymphomas.

Radiation sensitivity is also a feature of ataxia telangiectasia but you would not expect severe microcephaly. You would also expect ataxia and nystagmus.

Question 49

A child with a biliary infection caused by cryptosporidium who develops cholangiocarcinoma.

Answer 49

CD40 ligand deficiency is also known as Hyper IgM and is known to be associated with cryptosporidium infection. Chronic infection and inflammation can lead to cholangiocarcinoma. They are also susceptible to peripheral neuroectodermal tumours of the gastrointestinal tract.

CD40 ligand deficiency is particularly at risk of cholangiocarcinoma.

failure to thrive, confirmed cryptosporidium infection and possible PJP. All immunoglobulins but IgM are low. In spite of the name, IgM is not always raised but, rather, is the only immunoglobulin that is not decreased. The most common type of Hyper IgM is X linked CD40 ligand deficiency. CD40L is transiently expressed upon CD4+ T cell activation. The T cells then interact with CD40 on B cells, resulting in B cell activation, proliferation, immunoglobulin class switch recombination, and affinity maturation. There may be a normal total number of B cells, but the B cells are not effective.

Question 50

A child with a history of fulminant infectious mononucleosis develops lymphoma.

Answer 50

X-linked lymphoproliferative disease (XLP) XLP is caused by mutations in the signalling lymphocyte activation molecule (SLAM)-associated protein (SAP) gene.

Children appear well until they are infected with EBV – they most commonly present with fulminant infectious mononucleosis during the preschool years but can also present with lymphoma or dysgammaglobulinaemia.

XMEN disease is also associated with EBV related lymphoma but patients have chronic infection rather than an acute episode. It is caused by a mutation of the gene encoding magnesium transporter

Question 51

Deficiency of which one of the following components of neutrophils is most likely to result in the development of granulomas?

Answer 51

NADPH oxidase – involved in chronic granulomatous disease

Question 52

A 12-month-old male admitted to PICU with their third episode of severe community acquired pneumonia. There is a history of recurrent sinopulmonary infections from six months of age. The adenoids and palatine tonsils are absent.

Answer 52

X-linked agammaglobulinaemia. It is caused by defects in Bruton tyrosine kinase, a protein critical for B cell maturation. Male infant, recurrent invasive infections since six months of age when passive immunity from maternally derived IgG was weaned and the characteristic physical finding of absent adenoids and palatine tonsils. Management involves regular Ig infusions and avoiding all live vaccines.

Question 53

A six-month-old male presents with a severe Streptococcus pneumoniae pneumonia. There is a history of easy bruising, mucosal bleeding and eczema with frequent bacterial superinfection.

Answer 53

classical Wiskott-Aldrich syndrome. It is caused by defects of Wiskott Aldrich syndrome protein; this protein is critical in inducing changes to the cytoskeleton in response to a variety of signally pathways. 90% of patients will have thrombocytopaenia at the time of diagnosis and bleeding diathesis is a common presentation. Up to 50% of patients will develop eczema with a course marked by recurrent bacterial superinfection

Question 54

A six-month-old infant is being assessed for failure to thrive. There is a history of foul oily stools. Full blood count shows significant neutropaenia.

Answer 54

Shwachman-Diamond syndrome. It is caused by biallelic defects in the SBDS gene. The protein of this gene is involved in ribosome biogenesis and mitosis and is expressed in all human tissues. These patients typically present with failure to thrive, have exocrine pancreatic insufficiency and cytopaenias with neutropaenia typically appearing first.

Question 55

Which one of the following is the most important in clearing an acute infection with an intracellular organism?

Answer 55

Intracellular organisms require cell-mediated immunity.

MHC class I molecules are found on every nucleated cell of the body. Their function is to display fragments of proteins from within the cell to T cells. When a cell expresses foreign proteins, such as after viral infection, a fraction of the class I MHC will display these peptides on the cell surface.

Consequently, CD8 cytotoxic T lymphocytes (CTLs) specific for the MHC:peptide complex will recognize and kill the presenting cell.

Class II molecules interact exclusively with CD4+ (“helper”) T cells. The helper T cells then help to trigger an appropriate immune response which may include localised inflammation and swelling due to recruitment of phagocytes or may lead to a full-force antibody immune response due to activation of B cells.

Question 56

Which of the following clinic scenarios is most characteristic of defects in the terminal classical complement components, C5-C9?

Answer 56

Factors C5-C9 form the membrane attack complex, the final common pathway of the complement cascade. This transmembrane complex forms non-selective pores in the surface of pathogenic cells, leading to their osmotic lysis

Recurrent Neisseria meningitidis infection is highly suspicious for a deficiency of factors C5-C9.

Early onset SLE associated with deficits in C1-C4.

Question 57

A couple come to see you for advice about the appropriate course of action to be taken after the birth of their baby, which is due in one month. They have had one other child, a boy, who died at three months of age of Pneumocystis carinii pneumonia secondary to severe combined immunodeficiency (SCID). Prenatal amniocentesis has revealed the sex of the expected baby to be male but no other genetic testing has been performed. The most appropriate investigation to be performed on a cord blood sample to be taken from the expected baby in the immediate neonatal period is:

Answer 57

Infants with SCID have lymphopaenia (<2000/mm3) that is present at birth. There are usually more than 4000 lymphocytes (per cubic millimeter) in normal infant blood in the first year of life, 70% of which are T-cells. Since SCID infants have no T-cells, they usually have many fewer lymphocytes than this. The average for all types of SCID is 1500 lymphocytes (per cubic millimeter).

Question 58

Severe combined immune deficiency

Answer 58

Absence or impaired function of T and or B cells from birth

Two groups:

T-B- SCID (lack T and B cells)
T- B+ (lack T cells, normal B cells) - profound lymphopoenia, hypogammaglobulinemia, small thymus
Clinical features:

Severe faltering growth, absent lymphoid tissue, diarrhoea, infections, GvH symptoms
Death by < 2 yrs unless SCT or gene therapy

Question 59

Hyper-IgM syndrome

Answer 59

Most cases are caused by mutations in a gene that is located on the X chromosome; this gene encodes a protein (CD40 ligand) on the surfaces of activated helper T cells. In the presence of cytokines, normal CD40 ligand interacts with B cells and thus signals them to switch from producing IgM to producing IgA, IgG, or IgE. In X-linked hyper-IgM syndrome, T cells lack functional CD40 ligand and cannot signal B cells to switch. Thus, B cells produce only IgM; IgM levels may be normal or elevated. Patients with this form may have severe neutropenia and often present during infancy with Pneumocystis jirovecii pneumonia. Otherwise, clinical presentation is similar to that of X-linked agammaglobulinemia and includes recurrent pyogenic bacterial sinopulmonary infections during the first 2 yr of life.

Question 60

Hypersensitivity reactions

Answer 60

Five different hypersensitivity types

Allergy:
Atopy, anaphylaxis, asthma
Mediators: IgE

Cytotoxic, antibody dependant:
Autoimmune haemolytic anaemia
Thrombocytopenia
Erythroblastosis fetalis
Goodpastures syndrome
Graves disease
Myasthenia Gravis
Mediators: IgM or IgG (complement)

Immune complex disease:
Serum sickness
SLE
Mediators:IgG

Delayed-type hypersensitivity:
Contact dermatitis
Mantoux test
Chronic transplant rejection
MS
Mediator: T cells

Autoimmune disease
Graves disease
Myasthenia gravis
Mediators: IgM or IgG

Question 61

Th2 cytokine profile in eczema

Answer 61

Interleukin 4 is produced by macrophages and Th2 cells. It stimulates the development of Th2 cells from naïve Th cells and it promotes the growth of differentiated Th2 cells resulting in the production of an antibody response. It also stimulates Ig class switching to the IgE isotype.

Question 62

Which immunoglobulin in human breast milk is the most immunoprotective?

Answer 62

IgA: serves as a first line of mucosal defense. Maternal supply of secretory IgA is important, as infant intestinal IgA production does not begin until several months of age; and even at one year of age serum IgA levels are only 20% of adult levels.