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Transcript
The immune system and anaphylaxis
[email protected]
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
4
•
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
Antigens
5
•
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
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
Tetanus
Whole cell pertussis
Acellular pertussis
Offitt (2002) Pediatrics 109 124-129
1
1
3 000
5
Active antigens,
may contain
others such as
antibiotics and
preservatives
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
Innate (non-specific)
Acquired (specific)
Neutrophils
T lymphocytes
Macrophages
T helper cells (CD4)
Natural killer cells
T cyototoxic (CD8)
Acute phase proteins
B lymphocytes
Complement
Plasma cells
Dendritic cells
10
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
IgD
IgE
IgG
IgM
mucosal, no maternal transfer but found in
breast milk
bound to B cells
general inflammation, macroparasites
main serum antibody, maternally
transferred
produced by naive plasma cells
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
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
42
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
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
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
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