Immunology Basics

Question 1

What is the clinical significance of CD34 cells?

Answer 1

CD34 is a marker of haematopoietic stem cells and may be used in clinical monitoring of bone marrow transplantation

Question 2

Which cell type is CD3 associated with?

Answer 2

T lymphocytes

Question 3

True or false?

VDJ (variable, diversity, joining) segment rearrangement (or somatic rearrangement) occurs in B cells but not T cells

Answer 3

False
T cells do somatic rearrangement to generate T cell receptors

Question 4

In T cell maturation, what is positive selection?

Answer 4

Takes place in medullary thymus
Positive selection:
Epithelial cells express MHC
If the T cell does not recognise this is undergoes apoptosis

Negative selection

Epithelial cells express self MHC from peripheral site
If autoreactive –> apoptosis

5% of thymocytes survive this process

Question 5

Which cells express CD3 and CD8?

Answer 5

Cytotoxic T cells
These perform the immune response against intracellular pathogens (such as viruses)
Recognise antigens presented on MHC I
Induce apoptosis

Question 6

Which cells express CD4?

Answer 6

Helper T cells
They recognise antigen presented by MHC II
Role depends on subtype

Question 7

True or false?

TH1 cells are associated with humoral immunity

Answer 7

False

TH1 = cell mediated response
APC secretes IL-12 and drives differentiation from Th to Th1 cell
Also stimulates NK cells to release ifn-gamma
Encourages macrophages and neutrophils to be more efficient killers
IL-2 - induces number of effector T cells

TH2 = humoral response

IL4,5
Il 4 = promotes B cell activation and class switching to IgE
IL - 5 - mobilisation of eosinophils

Question 8

Which of the following is not a B cell surface marker?

a. CD19
b. MHC I
c. CD20
d. CD40
e. MHC II

Answer 8

MHC I not a B cell marker - this is expressed on normal (non-professional) antigen presenting cells
B cells are professional antigen presenting cells (in addition to immunoglobulin secretion)

Question 9

Which antigens tend to provoke a T cell dependant response?

Answer 9

Proteins and glycoproteins
T cell dependant has isotope switching –> higher affinity IgM

Polysaccharides, lipopolysaccharides and polymeric proteins - T cell independent
Response is quicker, but lower affinity for antigen, poor memory B cell response

Question 10

Which of the following immunoglobulins has the highest levels in serum?

a. IgG
b. IgA
c. IgM
d. IgE
e. IgD

Answer 10

b = IgG

Question 10

Which of the following immunoglobulins has the highest levels in serum?

a. IgG
b. IgA
c. IgM
d. IgE
e. IgD

Answer 10

b = IgG

Question 11

True or false?

IgM is able to cross the placenta

Answer 11

False
IgG only class capable of this

Question 12

Name the classes associated with HLA class I

Answer 12

HLA-A, B and C

Question 13

Name the HLA types associated with HLA class II

Answer 13

HLA-DP, DQ, DR

Question 14

Which cell type uses the NADPH oxidase pathway to destroy bacteria?

Answer 14

Neutrophil

NADPH oxidase generates large amount of superoxide from molecular oxygen –> hydrogen peroxide
Myeloperoxidas catalyses reaction of H202 to create hypochlorous acid

Question 15

Which type of hypersensitivity reaction involves insoluble antigen-antibody complexes depositing in tissues and causing complement activation?

Answer 15

Type 3 reaction

Type 1 reaction: IgE antibodies bind to mast cells and cause degranulation (asthma, food allergies, hayfever).

Type 2 hypersensitivity reaction: an antibody dependent reaction seen in conditions such as haemolytic disease of the newborn and transfusion reactions.

correct - Type 3 reaction: insoluble antibody-antigen complexes are deposited in tissues which triggers complement activation causing causing tissue damage (e.g. RA, SLE, serum sickness).

Type 4 reaction: Cell mediated reaction involving CD8+ cytotoxic T cells and CD4+ helper T cells. (contact dermatitis, type 1 DM).

Question 16

Which of the following is a pro-inflammatory cytokine produced by basophils?

a. IL-7
b. IL-1
c. IL-10
d. IL-5

Answer 16

IL-7

Question 17

Which of the following interleukins is released by CD8 T cells in response to viral illness to increase MHC I expression and anti viral response?

a. IL-10
b. IL-5
c. IL-2
d. TNF-gamma

Answer 17

d. INF-gamma

Question 18

Which of the following is released by T-reg cells to decrease the TH1 immune response as an anti-inflammatory?

a. IL-5
b. TNA-alpha
c. IL-2
d. IL-10
e. TNF-gamma

Answer 18

d. IL-10

Question 19

Which of the following is released by T cells to promote T, B and NK cell growth?

a. IL-2
b. IL-10
c. IL-7
d. TNF-beta

Answer 19

a. IL-2

Question 20

Which of the following describes the alternative pathway for complement activation?

a. antigen-antibody complexes activating C1
b. direct recognition of microbial components by C3
c. recognition of mannose by MASP1 and 2
d. antigen antibody complexes activating C3
e. direct recognition of microbial components by C1

Answer 20

b.

Question 21

Which of the following describes the function of C5a and C3b

a. Are the initial building blocks of the membrane attack complex
b. Are the initial messengers in the MBL pathway
c. Opsonise pathogens and encourage phagocytosis by macrophages
d. Promote inflammation

Answer 21

c

Question 22

Which of the following correctly describes activation of the classical pathway of complement activation?

a. Microbes directly activate C3
b. IgM or IgG sequentially activates C1 –> C4 –> C2
c. Microbes directly activate C4
d. IgM or IgG sequentially activates C1 –> C2 –> C4

Answer 22

b

Question 23

You observe a Nitroblue Tetrazolium (NBT) test.

On observation, there are no blue granules in the cytoplasm of the neutrophils.

What disorder does this suggest?

Answer 23

Chronic granulomatous disease

In this test neutrophils are incubated with Nitroblue tetrazolium
They are then stimulated with either LPS or PMA
Normal neutrophils will undergo an oxidative burst, leads to reduction of NBT to a blue insoluble formazan - blue granules in cytoplasm
CGB neutrophils unable to do this
In carriers - 50% can, 50% can’t

Question 24

Which is the following is an appropriate test for the classical pathway of complement activation? a. C3/4 b. CH50 or THC c. Flow cytometry d. AP50

Answer 24

Correct: CH50 or THC - this is a screen for homozygous deficiency in an integral component of the classical pathway Measures the capacity of patient's serum to lyse sheep erythrocytes coated with IgG All components of the classical pathway (C1-9) are required for CH50 C3/4 - if both low suggests classical pathway. Normal C4 low C3 - suggests alternative pathway Could be used but not best test AP50 - alternative pathway

Question 25

You review a 2 year old boy you suspect has a primary immune deficiency. The have the following constellation of symptoms: Poor wound healing, oral/mucosal ulcerations, history of lymphadenitis and soft tissue infections. Which component of the immune system is most likely affected? a. Complement b. T cells c. B cells d. Phagocytic

Answer 25

Answer = D, phagocytic

Question 26

You review a 2 year old female who you suspect has primary immunodeficiency. They had the onset of recurrent infections from approximately 7 months of age with primarily severe pulmonary infections. Organisms isolated included streptococcus pneumonia and haemophilus pneumoniae. Which component of the immune system is most likely affected? a. phagocytic b. B cell c. T cell d. complement deficiency

Answer 26

Answer is B Onset after loss of maternal antibodies Tendency towards sinopulmonary infections with encapsulated bacteria

Question 27

You see a patient with the following features: They are a 3 years old male and present with recurrent sinopulmonary infections. They have also had one previous illness with enterovirus meningitis. On physical examination you find some scattered pulmonary crepitations and a complete absence of lymph nodes. Which of the following would you be most likely to see on investigation? a. Absence of circulating B-cells on flow cytometry b. Absolute neutropenia c. Normal IgG but low IgA and IgM d. Positive EBV pcr

Answer 27

A = A This stem suggests X-linked agammaglobulinemia The underlying defect is in Xq22 - the XLA gene. This codes of the B-cell protein tyrosine kinase (Bruton tyrosine kinase) BTK is responsible for B-cell expansion and maturation They will typically develop infections with encapsulated bacteria and CNS infection with echo, entero and coxsackie, fungal infection and mycoplasma Classically they have an absence of lymphoid tissue Investigations show peripheral B lymphocytes <1%, preBs present in bone marrow, increased T cells percentage and global low immunoglobulins They are managed with lifelong IVIG and antibiotic prophylaxis

Question 28

You see an 17 year old who has had two recent severe pneumonias is reviewed for possible immunodeficiencies. They have normal circulating B-cells on initial investigation, however immunoglobulins are globally decreased. Lymphoid tissue is normal and the patient is female. What disorder are you most suspicious of?

Answer 28

CVID = common variable immunodeficiency They have normal numbers of circulating lymphocytes, however, they do not differentiate into IgG producing cells when stimulated Same infections as XLA however M = F, less likely to have parachovirus/meningitis and onset is later in life Have normal lymphoid tissue

Question 29

You review a patient in immunology clinic. They have a medical history significant for coeliac disease and frequent respiratory viral illnesses. They have never been hospitalised for an infection and are growing and developing normally. If you were to perform immunoglobulins, which would you most expect to be abnormal a. IgA b. IgM c. IgG d. IgE

Answer 29

This stem suggests IgA deficiency

Question 30

You see a 2 year old infant in immunology clinic. They have had normal IgM and IgA, but low IgG They have not had any infections in addition to those expected for their age/stage IgG return to normal levels at 4 years of age without intervention. What is the diagnosis?

Answer 30

Transient hypogammaglobulinemia of infancy

Question 31

A 2 year old child is infected with EBV and develops a fulminant, life-threatening illness What is the diagnosis?

Answer 31

X-linked lymphoproliferative disease 3 possible manifestations 1. Fulminant EBV, often deadly - 60% 2. Lymphomas - 30% 3. Acquired hypogammaglobulinaemia - 20-30% Genetic defect in Xq25 --> defect in SLAM (signalling lymphocyte associated molecule) associated protein (SAP) Leads to excessive T cell response to EBV infection

Question 32

You review a child for immune deficiency. They have had cardiac surgery at a young age, hypocalcaemia and distinctive facial features. What diagnosis is suggested?

Answer 32

A = DiGeorge syndrome Microdeletions of sequences from 22q11 Dysmorphogenesis of the 3rd and 4th pharyngeal pouches leads to hypoplasia/aplasia of the thymus + parathyroid glands From an immune perspective can be complete/partial Complete - resembles SCID. Opportunistic infections such as PJP, GVHD from nonirradiated blood products Partial DiGeorge associated with fewer infections and often normal growth

Question 33

You see a young adult in immunodeficiency clinic. They have had chronic candida infections of their mouth and nails. They are also on oral calcium and magnesium replacement. They also have vitiligo and alopecia areata. What underlying condition are you most suspicious of? a. SCID b. APECED/APS1 c. IgA deficiency d. CVID

Answer 33

Answer is B - APECED (autoimmune polyendocrinopathy candiasis ectodermal dystrophy) Mutation ins AIRE (autoimmune regulator gene) Responsible for presentation of auto-antigens in thymus during T cell maturation Causes immune deficiency, endocrinological problems, autoimmune

Question 34

Which of the following correctly describes the most common genetic/inheritance pattern of SCID? a. autosomal recessive mutation of IL2RG b. X-linked mutation of JAK3 c. X linked recessive inheritance of IL2RG d. autosomal recessive mutation of JAK3

Answer 34

The correct answer is C SCID most commonly caused by defect in IL2RG (encodes IL-2 receptor) JAK3 is another cause, it is an autosomal recessive trait

Question 35

Which of the following is NOT suggestive of a diagnosis of SCID? a. absent thymic shadow on CXR b. Lymphopenia c. Low/negative TREC d. Chronic diarrhoea, FTT e. IgE in the 1000s

Answer 35

Answer = e

Question 36

You review a patient in immunology clinic. 2.5 year old child. They have been referred to the clinic after an admission with PJP pneumonia. They have mad numerous previous pneumonias and ear infections. They were noted to be profoundly neutropenic during their inpatient admission. This has persisted at follow up. Further immunological testing has shown normal B lymphocytes, high IgM and low IgG and IgA Which of the following diagnoses is suggested? a. Wiskott Aldrich b. Ataxia-telangiectasia c. Hyper IgM syndrome d. DiGeorge e. Nijmegen breakage syndrome

Answer 36

c (Hyper IgM) Defect is class switching recombination process - can't change to B cell producing IgG or IgA This particular stem suggests hyper IgM type 1, which is associated with profound neutropenia, susceptibility to pyogenic infection, PJP and cryptosporidium

Question 37

An Amish child with frequent infections, short pudgy hands, hyperextensible joints, fine, light hair and abnormalities of metaphyseal parts of bone What is the diagnosis?

Answer 37

Cartilage hair hypoplasia

Question 38

Child with short stature, frequent infections and steroid resistant nephrotic syndrome What is the diagnosis?

Answer 38

Schimke Immune Osseous dysplasia

Question 39

You review a child in immunology clinic. They have had numerous infections with organisms with polysaccharide capsules (such as strept pneumo). They are noted to have numerous bruises and smaller petechiae and lichenification due to severe eczema over the cubital fossae. What is the diagnosis? a. Wiskott Aldrich b. Ataxia-telangiectasia c. Hyper IgM syndrome d. DiGeorge e. Nijmegen breakage syndrome

Answer 39

Answer is A, Wiskott Aldrich

Question 40

A child presents with hepatomegaly, splenomegaly and coombs positive haemolytic anaemia. Immunological investigations show hypergammaglobulinemia and proliferation of double negative T cells. ' What is the diagnosis?

Answer 40

Autoimmune lymphoproliferative syndrome

Question 41

You review a child who has chronic watery diarrhoea, eczema and type 1 diabetes mellitus with very early onset at 10 months of age. What is the diagnosis?

Answer 41

A = IPEX (immunodysregulation polyendocrinopathy enteropathy X-linked) Mutations in the gene for transcription factor FOXP3 - needed for T-reg function Only option for treatment is HSCT

Question 42

You see a patient in immunology clinic who has a positive DHR assay. Which if the following organisms would they NOT be susceptible to? a. Aspergillus b. Nocardia c. Staphylococcus aureus d. Streptococcus pyogenes e. Listeria

Answer 42

DHR assay = test for chronic granulomatous disease These patients are susceptible to infections with catalase positive organisms Catalase is an enzyme produced by aerobic organisms to protect themselves from the toxic by products of oxygen metabolism It allows the release of oxygen from H2O2 Streptococci are facultative anaerobes only ferment and do not respire using oxygen as a terminal electron acceptor

Question 43

You see a patient in clinic with the following features: - Poor wound healing - History of delayed umbilical cord separation and consequent omphalitis - Pyogenic infections - Peripheral leucocytosis with raised neutrophils Which is the following is the most likely disorder? a. Chediak-Higashi syndrome b. Leukocyte adhesion disorder c. MPO deficiency d. Chronic granulomatous disease e. Hyper IgE syndrome

Answer 43

A = Leukocyte adhesion disorder

Question 44

You review a patient in clinic with the following features: - Light hair - Frequent staphylococcal infections - Easy bruising - Peripheral neuropathy Which is the following is the most likely diagnosis? a. Chediak-Higashi syndrome b. Leukocyte adhesion disorder c. MPO deficiency d. Chronic granulomatous disease e. Hyper IgE syndrome

Answer 44

Answer = A Essentially a defect of cellular granule formation/degranulation

Question 45

A 1 month old infant presents with a skin infection. Investigation shows profound neutropenia, which does not improve despite serial testing over weeks and months. They have extensive further testing of renal, liver and pancreatic function which does not reveal any abnormalities. Detailed clinical examination and basic imaging for midline abnormalities does not show any dysmorphism. Which of the following diagnoses is most likely? a. cyclical neutropenia b. Schwachman-Diamond Syndrome c. Glycogen storage disorder 1b d. Kostmann syndrome

Answer 45

The correct answer is D = Kostmann syndrome AKA severe congenital neutropenia

Question 45

A 1 month old infant presents with a skin infection. Investigation shows profound neutropenia, which does not improve despite serial testing over weeks and months. They have extensive further testing of renal, liver and pancreatic function which does not reveal any abnormalities. Detailed clinical examination and basic imaging for midline abnormalities does not show any dysmorphism. Which of the following diagnoses is most likely? a. cyclical neutropenia b. Schwachman-Diamond Syndrome c. Glycogen storage disorder 1b d. Kostmann syndrome

Answer 45

The correct answer is D = Kostmann syndrome AKA severe congenital neutropenia a = cyclical neutropenia have a neutropenia that recurs every 14 - 35 days, most have a cycle lasting approximately 21 days Assoc with ELANE mutations like Kostmann b. Schwachman-Diamond syndrome is neutropenia + pancreatic insufficiency and metaphyseal dysplasia c. Glycogen storage - expect other features, particularly hepatomegaly d. D is correct

Question 46

You review a patient with the following features: - recurrent, severe eczema - multiple previous staphylococcal infections, including progression to abscess - coarse facial features with thieckening of the soft tissues of the face - retention of primary teeth - IgE levels >3000, blood film shows eosinophilia but no other diagnostic features What is the diagnosis?

Answer 46

Likely Job syndrome Wiskott Aldrich can also have eczema and elevated IgE but would also expect platelet abnormality

Question 47

Which of the following is NOT TRUE in regards to deficiency of factors in the classical pathway of complement activation (C1, C4, C2, C3) a. This predisposes to SLE b. higher rates of encapsulated bacterial infections c. trouble clearing immune complexes d. associated with hereditary angio-oedema

Answer 47

Answer = D All others are true Hereditary angio-oedema is associated with C1 INHIBITOR deficiency

Question 48

A 9 month old infant tries peanut for the first time and immediately develops a maculopapular rash, lip swelling and wheeze. Which type of hypersensitivity is suggested? a. Type 1 b. Type 2 c. Type 3 d. Type 4

Answer 48

Answer = A, Type 1 (IgE mediated)

Question 49

A 5 year old receiving a blood transfusion develops fever and haemolysis. Which type of hypersensitivity reaction would you suspect? a. Type 1 b. Type 2 c. Type 3 d. Type 4

Answer 49

Answer is B - type 2, antibody dependant cytotoxic

Question 50

Following a viral illness a child develops signs and symptoms of Henoch Schoenlein Purpura What type of hypersensitivity reaction is this? a. Type 1 b. Type 2 c. Type 3 d. Type 4

Answer 50

Answer = C, Type 3 (immune complex) reaction

Question 51

A patient undergoing post travel screening has a positive Mantoux test. Which type of hypersensitivity is this?

Answer 51

a. Type 1 b. Type 2 c. Type 3 d. Type 4

Question 52

A commercial allergen is pricked under the skin on the volar aspect of the arm. The average of the length and width is calculated (L + W / 2) True or false - a wheal >2 mm would be considered positive

Answer 52

A = false. Needs to be >3 mm larger than saline control Read afer 15 minutes

Question 53

Which of the following medications is NOT contraindicated prior to skin testing? a. Cetirizine b. Ranitidine c. Ventolin d. Amitriptyline

Answer 53

Answer = C, ventolin

Question 54

Describe the appropriate therapy for allergic rhinitis in a 4 year old child a. Nasonex (mometasone furorate) for 3-6 months, allergen avoidance and anti-histamines as needed b. Rhinocourt (budesonide) for 2-4 weeks, allergen avoidance and antihistamines as needed c. Fluticasone (Avamys) for 3-6 months, allergen avoidance and antihistamines as needed d. Beclomethasone dipropionate (Qvar) 2-4 weeks, allergen avoidance and antihistamine as needed

Answer 54

Answer = A Nasonex due to age brakcet First line treatment for perennial and seasonal allergic rhinitis. Take for 2-4 weeks before maximum benefit is achieved. Continue for a minimum 3-6 months. This should be continuous treatment. Preparations (in no particular order): Mometasone furorate - children over 3 years (eg. Nasonex, on private prescription). Budesonide - children over 6 years (eg. Budamax, Rhinocort, 32mcq over the counter or 64mcq on PBS prescription). Fluticasone fluroate -children over 12 years (eg: Avamys - on private prescription). Beclomethasone dipropionate-children over 6 years (eg: QVar, on PBS script) Triamcinolone acetonide-children over 12 years (eg: Telnase- over the coucnter) These newer topical corticosteroids have low systemic bioavailability and are generally not associated with systemic effects on the adrenal axis. Emphasize correct spray technique (away from septum). - video of how to use a nasal spray - written information on nasal spray technique In seasonal rhinitis, commence spray one month prior to relevant pollen season and continue over the syptomatic period. Contraindications for INCS include severe nasal infections, haemorrhagic diatheses or a history of recurrent nasal bleeding.

Question 55

You review a child in the emergency department who has presented after a bee sting. They have generalised swelling of their calf (where the sting occurred) which is greater than 5 cm There are no other skin manifestations distant to the calf and no other organ systems (GI, resp, CVS) with symptoms of allergy or anaphylaxis What treatments would be considered reasonable?

Answer 55

Reasonable - cold compress, antihistamine, simple analgesia, +/- single dose of steroids can be used in a large reaction Not indicated - EpiPen, venom immunotherapy Local reaction - <5 cm Large LR - >5 cm Generalised cutaneous reaction - generalised skin eruption w/o other systemic features Anaphylaxis/systemic reaction - GI symptoms more likely to progress to severe systemic reaction and should be treated as anaphylaxis

Question 56

You are referred a child in allergy clinic who has had a single episode of anaphylaxis after a sting from a wasp. They are aged 9. RAST has shown IgE positive to was venom. True or false - venom immunotherapy would be indicated

Answer 56

Answer is true - previous systemic reaction would be in indication for VIT

Question 57

Define urticaria

Answer 57

= swelling of the dermis Also called weals Appear as raised, well circumscribed lesions with a smooth Inner part and border may be erythematous or pale Typically lasts hours, max 24 hours

Question 58

Define angioedema

Answer 58

= swelling involving dermis and hypodermis Lips, eyes commonly involved due to lower skin tension

Question 59

what activates the classical pathway

Answer 59

IgG and IgM

Question 60

What activates the alternative pathway?

Answer 60

surfaces of microbes, IgA immune complexes, C3 nephritic factor

Question 61

Which components make up the classical pathway?

Answer 61

C1q, r, s C2, C4, C3

Question 62

Which components make up the alternative pathway?

Answer 62

C3, B, D, properdin

Question 63

Which components of complement make the membrane attack complex?

Answer 63

C5-9

Question 64

Explain the activation of the alternative pathway

Answer 64

C3 'tick over' Certain amount activated to C3b automatically Thio ester bond will bind to microbe cell surface if present (if not will just be degraded) Factor B cleaved by D --> Bb and Ba Forms C3bBb --> this goes on to release an anaphylatoxin and activate the MAC

Question 65

Explain the activation of the classical pathway of complement

Answer 65

C1q (in a complex with C1s and C1e) interacts with Fc portion of IgM and IgG C4 --> C2 C4bC2b is the classical pathway 'C3 convertase' - once C3 kicks off can join the convertase to make C4bC2bC3b and activate MAC

Question 66

Explain the activation of the MBL pathway of complement

Answer 66

MASP1 (mannose binding lectin) can bind organisms with high amounts of mannose glycoproteins --> C4 activated

Question 67

What are complement control proteins?

Answer 67

These are proteins expressed by 'self' They inhibit the uncontrolled activation of complement

Question 68

what is the inheritance of C1 esterase deficiency?

Answer 68

Autosomal dominant

Question 69

What are the typical skin manifestations of C1 esterase deficiency?

Answer 69

oedema - not urticaria/wheals, non pruritic Can affect skin, larynx, gut

Question 70

What are the typical lab findings in C1 esterase deficiency?

Answer 70

C4 reduced, C3 normal In type 1 low C1 esterase In type 2 normal C1 esterase but is dysfunctional so need functional assay

Question 71

acute treatment for C1 esterase deficiency

Answer 71

Berinert - synthetic C1 esterase

Question 72

what manifestations would you expect in a patient with MAC/terminal pathway deficiencies?

Answer 72

C5-9 = neisseria

Question 73

What manifestation would you expect in patients with early complement component deficiencies?

Answer 73

C1, 2, 4 = IC disease SLE, vasculitis

Question 74

Which of the following interactions underpins neutrophil rolling? a. sialyl lewis X and selectins b. integrins and CAM

Answer 74

Sialyl lewis X and integrins underpin normal neutrophil rolling on endothelium Release of chemokines activates integrins on neutrophil surface which bind to CAM (firm adhesion), this is followed by diapedesis Mnemonic Lewis selects rolling CAM is integral

Question 75

Spot diagnosis: severe eczema, prominent forehead and recurrent staphylococcus abscesses

Answer 75

Hyper IgE syndrome (Job's)

Question 76

Spot diagnosis: severe eczema, frequent viral illnesses including EBV/CMV

Answer 76

DOK8 deficiency

Question 77

What is the most common cause of IgE levels above 2000 IU/L a. Job's syndrome (Hyper IgE) b. eczema c. asthma d. allergic rhinitis

Answer 77

b = eczema

Question 78

What is the approximate half-life of serum immunoglobulin M (IgM)?

Answer 78

IgM has a half-life of 5-8 days. IgA has a half-life of 5-8 days. IgG has a half-life of 21 days.

Question 79

Which of the following is NOT part of the criteria for the diagnosis of hemophagocytic lymphangiohistiocytosis? a. soluble CD25 markedly raised b. ALT >200 c. cytopenias in at least 2 cells lines d. hypertryglyceridaemia or hypofibrinogenaemia e. perforin1 mutation

Answer 79

a. soluble CD25 markedly raised b. ALT >200 c. cytopenias in at least 2 cells lines d. hypertryglyceridaemia or hypofibrinogenaemia e. perforin1 mutation B - ALT is suggestive but is not part of the criteria

Question 79

Which of the following is NOT part of the criteria for the diagnosis of hemophagocytic lymphangiohistiocytosis? a. soluble CD25 markedly raised b. ALT >200 c. cytopenias in at least 2 cells lines d. hypertryglyceridaemia or hypofibrinogenaemia e. perforin1 mutation

Answer 79

a. soluble CD25 markedly raised b. ALT >200 c. cytopenias in at least 2 cells lines d. hypertryglyceridaemia or hypofibrinogenaemia e. perforin1 mutation B - ALT is suggestive but is not part of the criteria

Question 80

At what aged infant will immunoglobulin levels reach their physiological nadir?

Answer 80

3-6 months

Question 81

Which immunoglobulin has the longest serum half life?

Answer 81

IgG

Question 82

Which PID is associated with a lack of the CD40L?

Answer 82

HyperIgM, not able to class switch

Question 83

In a patient with a large local reaction to was sting, what is the risk of progression to anaphylaxis?

Answer 83

<10% https://www.allergy.org.au/patients/insect-allergy-bites-and-stings/allergic-reactions-to-bites-and-stings

Question 84

Management of generalised urticaria after bee sting

Answer 84

<10% chance of anaphylaxis 20% according to JPCH article refer to allergy/immunology AIT in adult but not child

Question 85

patients deficient in C2 are most likely to be infection with organism....

Answer 85

streptococcus pneumoniae Complement deficiencies are rare and often underdiagnosed primary immunodeficiencies that may be associated with invasive bacterial diseases. Serious infections with encapsulated organisms (mainly Streptococcus pneumoniae, but also Neisseria meningitides and Haemophilus influenzae type B) are frequent in patients with a deficiency of the second component of complement (C2), but no data are available on long-term follow-up. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143546/

Question 86

Which recurrent fever syndrome is characterised by rash, abdominal pain, periorbital oedema, migratory myalgias and fever > 14 days? Cryopyrin associated periodic fever syndrome TRAPS FMF HIDS

Answer 86

TRAPS - Recurrent fevers >38°C/100.4°F over months or years in the absence of associated viral or bacterial infections are characteristic of TRAPS, Febrile episodes every five to six weeks are typical, Precipitating factors are generally not identified, though some patients or caregivers observe that physical and emotional stress.may tend to trigger attacks. Fever and associated symptoms commonly last at least five days and often continue for more than two weeks. Other features: Myalgias and limb pain, sometimes migratory. Abdominal symptoms including pain and vomiting, rash, LN, Chest pain, conj and periorbital oedema.The rash may take a relatively characteristic form, with single or multiple erythematous patches (picture 1) that may spread distally down an extremity over time. Familial Mediterranean fever — Familial Mediterranean fever (FMF) is a disorder characterized by episodic attacks of fever lasting one to three days and accompanied, in most cases, by abdominal pain, pleurisy, and arthralgias/arthritis secondary to serositis and synovitis. The diagnosis of FMF may be strongly suggested by patient ethnicity since this autoinflammatory disease is most commonly seen in certain ethnic groups including Sephardic Jews, Armenians, North Africans, and Turks and, to a lesser extent, Ashkenazi Jews, Greeks, and Italians [27]. Hyperimmunoglobulin D syndrome — Hyperimmunoglobulin D syndrome (HIDS) is an autosomal-recessive periodic fever syndrome most prevalent among patients of Dutch and French origin. Episodic attacks of fever lasting three to seven days are accompanied, in most cases, by chills, cervical lymphadenopathy, abdominal pain, vomiting, and/or diarrhea. Other symptoms include headache, arthralgias/arthritis, aphthous ulceration, a pleomorphic rash, and, occasionally, splenomegaly. Elevated levels of immunoglobulin D (IgD; >100 international units/mL) are often present, a finding that is not typically seen in TRAPS. Genetic testing is used to confirm the diagnosis of HIDS PFAPA syndrome — Periodic fever with aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a syndrome for which the underlying etiology and pathogenesis are uncertain. Febrile episodes of abrupt onset last three to six days and are typically, although not invariably, accompanied by one or more of the following: pharyngitis (exudative or nonexudative), mild aphthous ulcerations, and lymphadenopathy. Recurrences of fever generally occur with nearly clockwork regularity, and laboratory markers of inflammation return to normal between episodes. There are no confirmatory laboratory tests for PFAPA, but the ability to "abort" an attack with a dose or two of systemic glucocorticoids is highly suggestive of the diagnosis. CAPS - three clinically overlapping, interleukin (IL) 1-associated, autoinflammatory disorders are known collectively as the cryopyrin-associated periodic syndromes (CAPS) or cryopyrinopathies: familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disorder (NOMID, also known as chronic infantile neurologic cutaneous and articular [CINCA] syndrome). The cryopyrinopathies are rare, with an estimated prevalence of 1 in 360,000 in a French study [1]. A related but distinct autoinflammatory disorder is due to deficiency of the IL-1 receptor antagonist (DIRA).

Question 87

true or false - TRAPS may be associated with amyloidosis?

Answer 87

True

Question 88

Patient with intermittent episodes lasting 1-2 weeks characterised by fever, rash, abdominal pain, raised CRP No infective focus ever found Diagnosis? a. HyperIgE b. TRAPS c. FMF d. Leukaemia

Answer 88

TRAPS - duration of symptoms much more likely to be TRAPS

Question 89

what is the most common SCID variant and what is its cell T B NK status?

Answer 89

Deficiency of IL-2R-gamma X-linked T - B+ NK -

Question 90

what is the second most common SCID variant, what is the inheritance and the T B and NK status?

Answer 90

ADA deficiency Adenosine deaminase deficiency - causes accumulation of toxic purine analogues Autosomal recessive

Question 91

which form of SCID may be associated with Omenn syndrome?

Answer 91

• Omenn syndrome ○ T-B-NK+ phenotype ○ One defective RAG1 or 2 allele ○ Also referred to as leaky SCID or atypical SCID ○ These patients usually have varying degrees of lymphopenia with low numbers of T and B cells, inflammation, lymphadenopathy, low IgA, G and M and elevated IgE/eosinophils

Question 92

What is the target for treatment in CAPS? a. IL-1 b. IL-2 c. TNF-alpha d. TNF-alpha

Answer 92

a. IL-1 CAPS = cryopyrin associated periodic disorders Familial cold autoinflammatory Muckle Wells NOMID

Question 93

●Intermittent episodes of fever, headache, urticarial rash, and joint pain (arthralgias or arthritis) ●Progressive sensorineural hearing loss ●Secondary (AA) amyloidosis with nephropathy What is the diagnosis?

Answer 93

Muckle Wells one of the caps

Question 94

what does are the Fab and Fc regions of immunoglobulin molecules?

Answer 94

Represent investigations made by breaking down immunoglobulins with proteases Fab - fragment antigen binding Fc - fragment crystallisable (this is the constant region)

Question 95

what is the target of the monoclonal antibody eculizumab?

Answer 95

C5 Used in atypical HUS Meningococcal prophylaxis required