Immunology

Question 1

What is allergy?

Answer 1

Hypersensitivity of immune system to allergens (proteins that immune system recognises as foreign & potentially harmful). Not all proteins/antigens will cause hypersensitivity reaction

Question 2

The skin sensitisation theory is one of leading theories for allergy at present; describe the skin sensitisation theory

Answer 2

• Break in child’s skin that allows allergens to enter body and react with immune system
• Child does not have contact with the allergen in the GI tract/there is an absence of GI exposure to the allergen
• If, when weaned a baby regularly eats foods containing that allergen their GI tract is regularly exposed to the allergen and hence GI tract will recognise the allergen as food and not as a foreign or harmful protein
• Hence, theory is that regularly exposure to allergen through food and preventing exposure to allergen through skin can help prevent food allergies developing

Question 3

Coombs & Gell classification has 4 types of hypersensitivity reactions; describe each

Answer 3

• Type 1: IgE antibodies to allergen trigger mast cells & basophils to release histamine & other cytokines. Immediate reaction. Allergy.
• Type 2: IgG and IgM react to allergen and activate complement system leading to direct damange to local cells (e.g. haemolytic disease newborn)
• Type 3: immune complexes accumulate & cause damage to cells (e.g. SLE, RA, HSP)
• Type 4: cell mediated; inappropriate activation of T cells resulting in inflammation & damage to local tissues (e.g. organ transplant rejection, contact dermatitis)

Question 4

State some key aspects of potential allergy history

Answer 4

• Timing of reaction after exposure
• Previous & subsequent exposure to allergen
• Symptoms: rash, swelling, breathing difficulty, wheeze, cough
• Personal or FH of atopic conditions & alle

Question 5

Allergies can be diagnosed on history alone; true or false?

Answer 5

True; is most important part; investigations can support diagnosis (and help determine exact allergies if uncertain)

Question 6

State 3 investigations we can do for allergy

What is the gold standard and why?

Answer 6

• Skin prick testing (hypersensitivity)
• RAST testing (hypersensitivity
• Food challenge test

Food challenge test is the gold standard. Skin prick and RAST testing test for hypersensitivity; just because a child is sensitised it does not mean foods are unsafe to eat and child has allergy (i.e. a person can have IgE bound to mast cells but never experience allergy in their life). Food challenge test requires a lot of resources, time and is only available in certain places.

Question 7

Explain how skin prick testing is done

Answer 7

• Draw grid on child’s forearm
• Put allergen solutions (that you want to test for) on squares alongside a histamine and water control
• Using fresh needle for each, make a break in skin at site of each allergen
• Assess after 15 minutes comparing size of wheals to the control#
• *NOTE: size of wheal does not indicate severity of allergy; it indicates sensitisation*
• **NOTE: must advise pts not to take antihistamine 72hrs before test*

Question 8

Explain how RAST testing is done

Answer 8

• Take blood sample and measure total and allergen specific IgE

Question 9

Explain how food challenges are done

Answer 9

• Done in specialist unit with close monitoring
• Gradually give child increasing quantities of allergen
• Monitor child after each exposure

Question 10

Discuss the management of allergies (in general- not looking for anaphylaxis management)

Answer 10

• Establish/diagnose correct allergen
• Avoid the allergen
  
  • E.g. avoiding certain foods
  • E.g. regular hoovering, changing sheets & pillows if allergic house dust mites
  • E.g. stay inside when pollen count high
• Prophylactic antihistamines if contact inevitable
• If at risk of anaphylaxis should be given adrenaline autoinjector
• May be offered immunotherapy (gradually expose to allergen over months)

Question 11

Why should children be admitted after anaphylactic reaction?

Answer 11

Can have biphasic reaction therefore need admitting for period of observation

Question 12

Discuss which children are given adrenaline autoinjectors

Answer 12

• All those with anaphylactic reactions
• Children with generalised allergic reactions with risk factors such as:
  
  • Asthma requiring ICS
  • Poor access to medical treatment (e.g. rural location)
  • Adolescents (higher risk)
  • Nut or insect sting allergies
  • Significant co-morbidities

Question 13

Different adrenaline autoinjectors exist and are to be used differently; summarise key points

Answer 13

• Remove safety cap
• Grip with fist with needle pointing down
• Inject into outer portion of mid thigh (can be done through clothing)
• Hold for up to 10 secs (3 secs in Epipen, 10 secs Jext)
• Remove injector
• Massage site for 10 seconds
• Phone ambulance
• Repeat in 5 mins if required

Question 14

Remind yourself of treatment options for allergic rhinitis

Answer 14

• Avoid trigger (e.g. avoid outdoors in high pollen count, avoid pets, change pillows etc…)
• Oral antihistamines:
  
  • Non-sedating: loratadine, cetirizine, fexofenadine
  • Sedating: chlorphenamine (piriton), promethazine
• Nasal corticosteroids (e.g. fluticasone, mometasone)
• Nasal antihistamines

Question 15

What age does cow’s milk protein allergy typically occur in?

Answer 15

Occurs in children <3yrs

Question 16

Cow’s milk protein allergy can be IgE and non-IgE mediated; what is the difference between IgE and non-IgE mediated?

Answer 16

IgE mediated: rapid reaction (usually within 2hrs)

Non-IgE mediated: slower reaction (over several days)

See table for differences in symptoms

Question 17

Describe presentation of cow’s milk allergy

Answer 17

Usually presents <1yr of age:

GI symptoms

• Bloating & wind
• Abdo pain
• Diarrhoea
• Vomiting

General allergic symptoms

• Urticarial rash
• Angio-oedema
• Cough
• Wheeze
• Sneezing
• Watery eyes
• Eczema

*in severe cases anaphylaxis may occur

Question 18

Discuss the management of cow’s milk allergy

Answer 18

Management is centred around avoiding cow’s milk:

• Breastfeeding mum avoiding dairy
• Replacing formula with special hydrolysed formulas for cow’s milk allergy (still contain cow’s milk protein but proteins broken down so don’t trigger immune response)
• Replace with elemental (amino acid) formulas (if severe and cannot tolerate hydrolysed. Example is neocate)

Over time, about ~6 months try infant on first step of milk ladder then slowly progress up until develop symptoms; as time goes on should eventually be able to progress to normal diet containing milk. Most children grow out of milk allergy by age of 3-5yrs (IgE ~5yrs, non-IgE ~3yrs)

Question 19

Explain the difference between cow’s milk intolerance & cow’s milk allergy

Answer 19

• Cow’s milk protein intolerance is not an allergic reaction.
• Cow’s milk protein intolerance will present with same GI symptoms as cow’s milk allergy but without allergic features (rash, angioedema etc..)
• Infants with cow’s milk intolerance will be able to tolerate cow’s milk & continue to grow & develop (but have GI symptoms when consume the milk) however those with allergy will not

Question 20

Discuss the management of cow’s milk intolerance

Answer 20

• Avoid cow’s milk (e.g. breastfeed with mum avoiding dairy, hydrolysed formula, wean to foods not containing cow’s milk)
• After 1yr of age start on milk ladder

Question 21

Which children with recurrent infections should be sent for further specialist assessment?

Answer 21

• Chronic diarrhoea since infancy
• Failure to thrive
• Appearing unusually well with quite severe infection (e.g. afebrile with large pneumonia)
• Significantly more infections than expected (particularly bacterial LRTIs)
• Unusual or persistent infections (e.g. CMV, PCP, candida)

Question 22

What investigations would you consider in children who recurrent infections?

Answer 22

• Full blood count: low neutrophils suggest a phagocytic disorder and low lymphocytes suggest a T cell disorder
• Immunoglobulins: abnormalities suggest a B cell disorders
• Complement proteins: abnormalities suggest a complement disorder
• Antibody responses to vaccines, specifically pneumococcal and haemophilus vaccines
• HIV test if clinically relevant
• Chest xray for scarring from previous chest infections
• Sweat test for cystic fibrosis
• CT chest for bronchiectasis

Question 23

What are primary immunodeficiency disorders?

State some examples

Answer 23

Rare, genetic disorders in which part of the body’s immune system is missing or functions improperly.

Question 24

What is SCID?

Answer 24

Severe combined immunodeficiency (SCID) is the name given to a group of rare, inherited disorders that cause major abnormalities of the immune system. There are many different types of SCID, each with different genetic causes. Have almost no immunity. Have absent or dysfunctioning T and B cells

Question 25

Describe how SCID will present

Answer 25

Present in first few months of life with:

• Persistent or severe diarrhoea
• Failure to thrive
• Opportunistic infections (tat are more frequent or more severe than in other healthy children e.g. Pneumocystis jiroveci, CMV, near fatal chickenpox)
• Unwell after live vaccinations (e.g. MMR, BCG, nasal flu)
• Omenn syndrome

Question 26

There are many different types of SCID, each with different genetic causes; however, more than 50% of mutations are caused by a mutation in _____ on _______ that codes for _______; _____ inheritance pattern

Answer 26

>50% caused by mutation in common gamma chain on x-chromosome that codes for interleukin receptors on B & T cells; x-linked recessive inheritance pattern

Question 27

What is Omenn syndrome?

Answer 27

• Rare cause of SCID due to mutation in recombination-activating gene (RAG 1 or RAG 2) that codes for proteins in T and B cells
• Autosomal recessive inheritance
• Dysfunctional and dysregulated T cells attack tissues in fetus or neonate leading to classic features:
  
  • Red, scaly, dry rash (erythroderma)
  • Hair loss
  • Diarrhoea
  • Failure to thrive
  • Lymphadenopathy
  • Hepatosplenomegaly

Question 28

Discuss the management of SCID

Answer 28

• Fatal if not treated sucessfully
• Management involves:
  
  • Treating underlying infections
  • Immunoglobulin therapy
  • Minimising risk of new infections (e.g. sterile environments)
  • Avoiding live vaccines
  • Haematopoietic stem cell transplant

Question 29

B cell/immunoglobin (antibody) disorders (like all immunodeficiencies) leads to increased susceptibility to infections; what infections are those with immunoglobulin deficiencies particularly prone to?

Answer 29

LRTIs

Question 30

For selective immunoglobulin A deficiency, discuss:

• Whether it is common
• Levels of immunoglobulins
• Where IgA is usually found/present
• Whether it is symptomatic

Answer 30

• Most common immunoglobulin deficiency
• Low IgA, normal IgG and IgM
• IgA present in secretions of mucous membranes (e.g. saliva, resp tract, GI tract, tears, sweat) hence get opportunistic infections of these membranes
• Mil immunodeficiency hence often asymptomatic and never diagnosed

*Most likely to come across this when testing for coeliac disease as anti-TTG and anti-EMA are IgA hence you also test for IgA

Question 31

For common variable immunodeficiency, discuss:

• Mutation
• Which immunoglobulins are deficient
• Management
• Complications

Answer 31

• Mutation in genes coding for components of B cells
• Deficiency in IgG AND IgA +/- IgM
• Regular immunoglobulin infusions & treating infections/complications
• Increased risk of RA, cancers (e.g. Non-Hodgkins lymphoma)

Question 32

For common variable immunodeficiency, discuss:

• Mutation
• Which immunoglobulins are deficient
• Management
• Complications

Answer 32

• Mutation in genes coding for components of B cells
• Deficiency in IgG AND IgA +/- IgM
• Regular immunoglobulin infusions & treating infections/complications
• Increased risk of RA, cancers (e.g. Non-Hodgkins lymphoma)

Question 33

For x-linked agammaglobulinaemia, discuss:

• What else it is known as
• Inheritance pattern
• Immunoglobulin deficiencies

Answer 33

• Bruton’s agammaglobulinaemia
• X-linked recessive
• Abnormal B cell development leading to deficiency in all classes of immunoglobulins
• Causes similar issues (e.g. RA, NHL) to common variable immunodeficiency

Question 34

State some examples of T cell disorders

Answer 34

• DiGeorge syndrome
• Purine Nucleoside Phosphorylase Deficiency
• Ataxic telangiectasia
• Acquired immunodeficiency syndrome

Question 35

For DiGeorge syndrome, discuss:

• Mutation
• How mutation leads to condition
• Features (CATCH-22 mnemonic)

Answer 35

• Microdeletion of portion of chromosome 22
• Developmental defect in 3rd pharyngeal pouch & 3rd branchial cleft which results in incomplete development of thymus gland leading to an ability to produce functional T cells
• Features:
  
  • C – Congenital heart disease
  • A – Abnormal facies (characteristic facial appearance)
  • T – Thymus gland incompletely developed
  • C – Cleft palate
  • H – Hypoparathyroidism and resulting Hypocalcaemia
  • 22nd chromosome affected

* Facial features: periorbital fulness, narrow upslanted palpebral fissures, prominent nose with large tip and hypoplastic nares, small mouth with everted upper lip and small dysmorphic ears ​

Question 36

For Purine Nucleoside Phosphorylase deficiency, discuss:

• Inheritance pattern
• Pathophysiology
• Presentation

Answer 36

• Autosomal recessive
• Deficiency of PNPase enzyme (enzyme which breaks down purines); without enzyme toxic dGTP accumulates. dGTP is toxic to T cells.
• Patients immunity to infections gradually gets worse over time and become more susceptible to infections

Question 37

For Wiskott-Aldrich syndrome, discuss:

• Inheritance pattern
• Mutation
• Other features other than immunodeficiency

Answer 37

• X-linked recessive
• Mutation in WAS gene resulting in abnormal functioning of T cells
• Other features:
  
  • Thrombocytopenia
  • Neutropenia
  • Eczema
  • Recurrent infections
  • Chronic bloody diarrhoea

Question 38

For ataxic telangiectasia, discuss:

• Inheritance pattern
• Mutation
• Features of condition

Answer 38

• Autosomal recessive
• Mutation in ATM serine/threonine kinase protein on chromosome 11 (involved in several functions of DNA coding)
• Features:
  
  • Low T cells & immunoglobulins
  • Ataxia
  • Telangiectasia (especially in sclera & damaged areas of skin)
  • Slow growth & delayed puberty
  • Predisposition to cancers
  • Accelerated ageing
  • Liver failure

Question 39

Complement proteins are most important in dealing with what organisms?

Answer 39

Encapsulated organisms (e.g. H.influenza B, S.pneumonia, N.meningitidis)

Hence, children are particularly susceptible to ENT infections.

Question 40

What is the most common complement deficiency?

Answer 40

C2 deficiency

*Complement deficiencies are associated with immune complex disorders e.g. SLE

Question 41

For C1 esterase inhibitor deficiency (also known as hereditary angioedema), discuss:

• Pathophysiology
• Presentation
• Key investigation

Answer 41

• C1 esterase inhibits bradykinin; bradykinin is an inflammatory mediator which causes vasodilation & increased vascular permeability leading to angioedema.
• Get intermittent angioedema in response to minor triggers (e.g. viral infection, stress, no clear trigger). Often affects lips or face but can occur anywhere (including respiratory tract which may lead to airway compromise)
• C4 (low)
• IV C-1 esterase inhibitor as prophylaxis before dental or surgical procedures or as treatment for angioedema

Question 42

For mannose-binding lectin deficiency, discuss:

• Pathophysiology
• Whether it causes problems

Answer 42

• Deficiency in mannose-binding lectin which leads to inhibition of alternative pathway of complement system
• Quite common and in otherwise healthy individuals it does not cause any major problems; however, in pts who are already susceptible to infection (e.g. CF) can lead to more severe variant of disease