16/05/2016

1

The immune system and anaphylaxis

edward.purssell@kcl.ac.uk

About the immune system

The immune system

Protects the body from infectious

organisms, foreign bodies and malignancies

Surface barriers

Innate immunity

Acquired immunity

3

Key issues

• Discrimination between self and non-self

• Sufficient but not excessive immunity

• The right kind of response

• A response in the right place at the right time

• Sufficiently quick to prevent damage

4

Antigens

• Immune system works by identifying antigens

• Antigen is anything recognised by the immune

system; immunogen provokes immune response

• A bacterium will contain many antigens

• Immune system does not have to recognise them

all

5

Antigens

An antigen is a molecule that is recognised by the immune system; an immunogen provokes an immune response A single bacteria will contain many hundreds of individual antigens Vaccines contain differing numbers depending upon their formulation Sometimes referred to as the valency Diphtheria 1 Tetanus 1 Whole cell pertussis 3 000 Acellular pertussis 5

Active antigens, may contain others such as antibiotics and preservatives

Offitt (2002) Pediatrics 109 124-129

16/05/2016

2

Influenza Vaccine components 2014/5

A/California/7/2009 (H1N1)pdm09-like virus

A/Texas/50/2012 (H3N2)-like virus

B/Massachusetts/2/2012-like virus

Quadrivalent vaccine

B/Brisbane/60/2008-like virus

Vaccines for use in the 2015/2016 influenza season (northern hemisphere winter)

A/California/7/2009 (H1N1)pdm09-like virus

A/Switzerland/9715293/2013 (H3N2)-like virus

B/Phuket/3073/2013-like virus

Quadrivalent vaccine

B/Brisbane/60/2008-like virus

WHO (2015) WER 90, 97–108

Overview

10

Innate (non-specific) Acquired (specific)

Neutrophils

Macrophages

Natural killer cells

Acute phase proteins

Complement

Dendritic cells

T lymphocytes

T helper cells (CD4)

T cyototoxic (CD8)

B lymphocytes

Plasma cells

Memory cells

Lymphocytes

Four main classes

1. B (plasma cell)

2. T cell

Helper (CD4)

Cytotoxic (CD8)

3. Natural regulatory (nTreg)

4. Natural killer cells (NK) - innate

11

Antibody classes

IgA mucosal, no maternal transfer but found in

breast milk

IgD bound to B cells

IgE general inflammation, macroparasites

IgG main serum antibody, maternally

transferred

IgM produced by naive plasma cells

16/05/2016

3

Immunoglobulins and infants

• IgG transferred maternally

• The process is active, but immunity is passive

• Provides immunity to everything the mother has

immunity to

• Declines over first 6 months of life, all gone by 18

months

• No IgA which is important for mucosal immunity

• IgA from breast milk

Primary and secondary immune responses

The ‘problem’ of immunity

• Balancing the need to rid the body of a

foreign body with the avoidance of damage

• May result in hypersensitivity, damage

caused by an immune respsonse

• Gell and Coombs (1963) suggested 4 types

1. Allergic/anaphylactic

2. Antibody dependent cytotoxic

3. Immune complex

4. Delayed type

About anaphylaxis

Anaphylaxis

Allergy - a hypersensitivity reaction initiated by specific immunologic mechanisms

Atopy - a personal and/or familial tendency, usually in childhood or adolescence, to become sensitized and produce IgE antibodies in response to ordinary exposures to allergens, usually proteins

Anaphylaxis - a severe, life-threatening generalized or systemic hypersensitivity reaction

Revised nomenclature for allergy for global use: Report of the Nomenclature Review

Committee of the World Allergy Organization J Allergy Clin Immunol 113-832-836

Pathology

IgE-mediated

Initial sensitization stage

Subsequent anaphylactic response

16/05/2016

4

Sensitisation stage

Exposure to antigen (allergen)

Plasma cells (B cells) produce specific IgE in

response to allergen

Circulating IgE antibodies attach to mast cells and

basophils

Anaphylactic response

Subsequent dose of same allergen invades body

Allergen binds to IgE attached to mast cells and

basophils

This triggers degranulation and release of

histamine/other chemical mediators

Type 1 hypersensitivity - allergy

Antigen acts as allergen

B cell produces large amounts IgE

IgE binds to mast cell

Subsequent exposure allergen cross links bound IgE leading to degranulation

Rochester Institute of Technology

Substances released during degranulation

Histamine Capillary dilation and permeability Oedema Chemoattraction Nerve irritation Proteoglycans, mainly heparin Serine proteases Prostaglandin D2 Leukotriene C4 Various cytokines

Clinical signs

Skin

Flushing, pruritus, urticaria, angioedema

Upper respiratory

Congestion, rhinorrhea

Lower respiratory

Bronchospasm, throat or chest tightness,

hoarseness, wheezing, shortness of breath, cough

Gastrointestinal tract

Oral pruritus

Cramps, nausea, vomiting, diarrhea

Cardiovascular system

Tachycardia, bradycardia, hypotension/shock,

arrhythmias, ischemia, chest pain

16/05/2016

5

16/05/2016

6

16/05/2016

7

42

16/05/2016

8

How it looks in the Green Book

1. Send for additional health professional assistance

2. Send a responsible adult to dial 999 and state that there is a case

of suspected anaphylaxis

3. Stay with the patient at all times

4. Lie the patient down, ideally with the legs raised (unless the patient

has breathing difficulties)

5. Administer oxygen if available

6. If breathing stops, mouth to mouth/mask resuscitation should be

performed

7. If there is no pulse, start cardiopulmonary resuscitation

All patients with clinical signs of shock, airway swelling or definite

breathing difficulties should be given adrenaline 1:1000 IM

The preferred site is the mid-point of the anterolateral aspect of the

thigh

Doses

The intramuscular doses we recommend are for

healthcare staff who rarely deal with paediatric

emergencies

The doses have been chosen because they are easy

to draw up and administer and are within the safe

acceptable dose ranges for the particular age groups

Needles

IM injection - blue needle (25 mm 23 G)

Best site for IM adrenaline is the anterolateral aspect of

the middle third of the thigh

Needle needs to be long enough to ensure that the

adrenaline is injected into muscle

Current RC UK guidance states that a 25 mm length

needle is best and suitable for all ages

If obese a longer needle may be needed (38 mm)

Standard orange needle is only 16 mm in length which

can result in injecting the adrenaline SC

16/05/2016

9

Vaccine related anaphylaxis

Between 1997 and 2003, there were 130 reports to

the MHRA and no reported deaths

117 million doses of all vaccines were supplied to

hospitals and GPs

This equates to a rate of approximately

1:1 000 000 vaccine doses

Usually occurs in people without history

Risk of anaphylaxis after vaccination of children and

adolescents

4 HMOs USA, looked for ICD-9 codes suggestive of

anaphylaxis

Vaccinations administered n = 7 644 049

Initially reviewed 657 diagnoses of interest

6 probable or possible anaphylaxis

1 not vaccine related

= 5 cases = 0.65 per million doses (CI 0.21-1.53)

3 questionable regarding vaccine or outcome

=2 cases = 0.26 per million doses (CI 0.03-0.95) Bohlke (2003) Pediatrics 112 815-820

16/05/2016

10

Adrenaline shock packs

Check Dosage/resuscitation card

The expiry dates on adrenaline shock packs must

be checked regularly

Packs are sealed, if opened, do not use and do

not add anything to the pack

Protect from heat, light and moisture

Packs do not need to be refrigerated

Avoid prolonged exposure to heat

Return expired packs to pharmacy

Contents adrenaline shock packs

3 x 1 ml adrenaline injection 1:1000

3 x 1 ml syringes

3 x blue needles 23G

3 x green needles 21G

Dosage/resuscitation card

The ‘problem’ of immunity

• Balancing the need to rid the body of a

foreign body with the avoidance of damage

• May result in hypersensitivity, damage

caused by an immune respsonse

• Gell and Coombs (1963) suggested 4 types

1. Allergic/anaphylactic

2. Antibody dependent cytotoxic

3. Immune complex

4. Delayed type

The following conditions are contraindications to routine

immunisation

All vaccines are contraindicated in those who

have had:

• A confirmed anaphylactic reaction to a

previous dose of a vaccine containing the

same antigens, or

• A confirmed anaphylactic reaction to another

component contained in the relevant vaccine,

e.g. neomycin, streptomycin or polymyxin B

(which may be present in trace amounts in

some vaccines)

Egg allergy

Individuals with a confirmed anaphylactic reaction to

egg should not receive yellow fever vaccine

Individuals who have egg allergy may be at

increased risk of reaction to some influenza vaccines

All children with egg allergy should receive the MMR

vaccination as a routine procedure in primary care

Latex allergy

History of anaphylactic allergy to latex, vaccines

supplied in vials or syringes that contain latex should

not be administered, unless the benefit of vaccination

outweighs the risk of an allergic reaction to the

vaccine

16/05/2016

11

Immunesuppression

Live vaccines can, in some situations, cause severe

or fatal infections in immunosuppressed individuals

due to extensive replication of the vaccine strain. For

this reason, severely immunosuppressed individuals

should not be given live vaccines, and vaccination in

immunosuppressed individuals should only be

conducted in consultation with an appropriate

specialist

Pregnancy

There is a theoretical concern that vaccinating

pregnant women with live vaccines may infect the

foetus. There is no evidence that any live vaccine

(including rubella and MMR) causes birth defects.

However, since the theoretical possibility of foetal

infection exists, live vaccines should generally be

delayed until after delivery

Note injected influenza and pertussis are not live

vaccines

Timing

Observe patient for 10 minutes

Most reactions occur within 2 minutes

Another adult should be present

What to do if worried

Discuss with patient/parents

Don’t vaccinate

Refer to local vaccine co-ordinator

Most hospitals run vaccination clinics