Immunology Flashcards
What is an allergy?
Hypersensitivity of the immune system to allergens
What are allergens?
Proteins that the immune system recognises as foreign and potentially harmful
What is atopy?
Predisposition to having hypersensitivity reactions to allergens
What are the atopic conditions?
Eczema Asthma Hayfever Allergic rhinitis Food allergies
What is the leading theory for the origin of allergies?
The skin sensitisation theory
What is the skin sensitisation theory?
That there is a break in an infants skin (from eczema or infection) that allows allergens to cross the skin and react with the immune system. If there is then consequent lack of exposure to the allergen in the GI tract, it causes the immune system to become sensitised to the antigen.
What is Type 1 hypersensitivity?
Antibodies trigger mast cells and basophils to release histamines and cytokines, leading to immediate reaction
What kind of allergy is type 1 hypersensitivity?
Food allergy
What is the normal presentation of a type 1 hypersensitivity reaction?
Acute itching, facial swelling, urticaria
What antibodies are involved in a type 1 reaction?
IgE
What happens in a type 2 hypersensitivity reaction?
Antibodies react to an allergen and activate the complement system, leading to direct damage to local cells (cytotoxic)
What antibodies are involved in type 2 hypersensitivity reactions?
IgG and IgM
What are some examples of type 2 hypersensitivity reactions?
Haemolytic disease of the newborn
Transfusion reactions
What happens in Type 3 hypersensitivity reactions?
Immune complexes accumulate and cause damage to local tissues
What are some examples of type 3 hypersensitivity reactions?
SLE
Rheumatoid arthritis
HSP
What happens in type 4 hypersensitivity reactions?
Cell mediated hypersensitivity reactions caused by T-cells being inappropriately activated, causing inflammation and damage to local tissues
What are some examples of type 4 hypersensitivity reactions?
Organ transplant rejection
Contact dermatitis
What acronym helps remember hypersensitivity reactions?
ACID: Anaphylaxis Cytotoxic Immune complex Delayed type
How are allergies usually diagnosed?
Detailed history
What are the 3 main ways to test for allergy?
Skin prick testing
RAST testing
Food challenge testing
Why are skin prick and RAST test unreliable and misleading?
They test for sensitisation and not allergy
What is RAST testing?
Blood tests for total and specific IgE
Why should you be cautious when performing an allergy test?
Often come back showing patient is sensitised to many things you have tested for, but they don’t necessarily need to avoid these things
What is the gold standard test for diagnosing allergy?
Food challenge testing
How is skin prick testing performed?
Drops of different allergen solutions are applied to a patch of skin, along with a water and histamine control. After 15 minutest the size of the wheals of each allergens are assessed
What is patch testing?
Patch containing allergen is placed on skin. After 2-3 days the reaction is assessed
What allergies can patch testing help diagnose?
Allergic contact dermatitis (latex, perfumes, cosmetics or plants)
What happens during food challenge testing?
Child given increasing quantities of an allergen to assess reaction
How are allergies managed?
Avoid allergen
Prophylactic antihistamines
Epipen
How can you treat allergic reactions?
Antihistamines
Steroids
IM adrenaline for anaphylaxis
What is anaphylaxis?
Life threatening type-1 hypersensitivity reaction
What happens during anaphylaxis?
IgE stimulates mast cells to rapidly release histamine and other pro-inflammatories, causing rapid onset of symptoms
What is mast cell degranulation?
When mast cells rapidly release their contents (histamine and pro-inflammatory chemicals0
What are the key features that differentiate anaphylaxis from a non-anaphylactic allergic reaction?
Compromise of the airways, breathing or circulation
What symptoms may be present in anaphylaxis?
Urticaria Itching Andio-oedema (face swelling) Abdominal pain SOB Wheeze Larynx swelling Tachycardia Lightheadedness Collapse
What is urticaria?
Hives- red, itchy welts
What are the principles of anaphylaxis management?
ABCDE
Im adrenaline
Antihistamines
Steroids
What should happen after an anaphylactic reaction and why?
Period of observation and assessment in cause a biphasic reaction occurs
How can anaphylaxis be confirmed retrospectively?
Measuring serum mast cell tryptase within 6 hours of the event
What are the indications for an adrenalin auto-injector?
All children and adolescents with anaphylactic reactions
May be given to those with generalised allergic reactions with specific risk factors: (steroid inhalers, poor access to medical treatment, nut or sting allergies, significant co-morbidities)
What kind of reaction is allergic rhinitis?
IgE-mediated type 1 hypersensitivity reaction
What happens in allergic rhinitis?
Environmental allergens cause allergic inflammatory response in nasal mucosa
What are the different types of allergic rhinitis?
Seasonal
Perennial
Occupational
What is an example of seasonal allergic rhinitis?
Hayfever
What is an example of perennial allergic rhinitis?
House dust mite allergy
What are the symptoms of allergic rhinitis?
Runny, blocked and itchy nose
Sneezing
Itchy, red, swollen eyes
What are the common triggers of allergic rhinitis?
Tree pollen Grass House dust mites Pets Mould
How is allergic rhinitis managed?
Avoid trigger: Cleaning (hoovering, changing sheets regularly) Stay inside during summer Minimise contact with pets Medications
What can be taken prior to exposure to reduce allergic symptoms?
Oral antihistamines
What are some examples of non-sedating antihistamines?
Cetirizine
Loratidine
Fexodenadine
What are some examples of sedating antihistamies?
Chlorphenamine
Promethazine
What can be given to help allergic rhinitis?
Nasal corticosteroid sprays
Nasal antihistamines
What age range is most typically affected by cow’s milk protein allergy?
Infants and children under 3
What is cow’s milk protein allergy?
Hypersensitivity to the protein in cow’s milk
What are the two types of cow’s milk protein allergy?
IgE mediated (rapid) Non-IgE mediated (slower reaction time)
What is the difference between lactose intolerance and cows milk protein allergy?
Lactose is a sugar not a protein and intolerance is not an immune reaction
What are the risk factors for developing a cows milk protein allergy?
Formula fed
Personal or family history of atopic conditions
When does cows milk protein allergy usually become apparent?
When babies are weaned from breast milk to formula milk or food containing milk
What are the common symptoms of cows milk protein allergy?
Bloating Wind Abdominal pain Diarrhoea Vomiting Allergic symptoms (swelling, hives, cough, sneezing, eczema)
How is cows milk protein allergy diagnosed?
Full history
Skin prick testing
How is cows milk protein allergy managed?
Avoid cows milk:
Breast feeding mothers avoid dairy products
Replace formula with hydrolysed formulas
What are hydrolysed formulas?
Formulas that contain cow’s milk but the proteins have been broken down to avoid an immune response
By what age do most children outgrow cow’s milk protein allergy?
3
How are children with cows milk protein allergy reintroduced to milk?
Milk ladder (slowly progress up ladder until they develop symptoms)
What is the difference between cow’s milk intolerance and cow’s milk allergy?
Cow’s milk intolerance has same GI symptoms but no allergic features
Up to how may respiratory infections is it normal for a healthy child to have per year?
4-8
What associated features would cause you to initiate further assessment in a child with recurrent infections?
Chronic diarrhoea
Failure to thrive
Appearing unusually well with severe infection
Significantly more infections than expected
Unusual or persistent infections
What investigations may be done into recurrent infections in children?
FBC Immunoglobulins Complement proteins Antibody responses HIV test CXR Sweat test CT chest
What is SCID?
Severe combined immunodeficiency
What causes SCID?
Genetic disorders that result in absent or dysfunctioning T and B cells
How will SCID present?
Persistent severe diarrhoea Failure to thrive Opportunistic infections Unwell after live vaccines Omenn syndrome
What is the most common cause of SCID?
Mutations in common gamma chain on X chromosome that codes for interleukin receptors on T & B cells.
What is the inheritance pattern of the most common cause of SCID?
X-linked recessive
What is Omenn syndrome?
Rare cause of SCID caused by mutation in RAG gene that codes for proteins in T & B cells
What is the inheritance pattern of Omenn syndrome?
Autosomal recessive
What causes the symptoms in Omenn syndrome?
Abnormally functioning and deregulated T cells that attack the tissues in the fetus or neonate
What are the classic symptoms of Omenn syndrome?
Erythroderma (rash) Alopecia Diarrhoea Failure to thrive Lymphadenopathy Hepatosplenomegaly
How is SCID managed?
Specialist immunology centre Treat underlying infections Immunoglobulin therapy Sterile environment Haematopoietic stem cell transplantation
What is the action of B cells?
Produce antibodies
What is hypogammaglobulinemia?
Deficiency in immunoglobulins caused by abnormal B cells
What does hypogammaglobulinemia lead to?
Susceptibility to recurrent infections
What is the most common immunoglobulin deficiency?
Selective IgA deficiency
Where is IgA present?
Secretions of mucous membranes (saliva, resp/GI tract secretions, tears, sweat)
What does IgA protect against?
Opportunistic infections
How does IgA deficiency usually present?
Often asymptomatic
Recurrent mucous membrane infections
When is IgA deficiency commonly tested for?
When testing for coeliac disease (anti-TTG and anti-EMA are IgA antibodies)
What is common variable immunodeficiency?
IgG and IgA +/- IgM deficiency
What causes common variable immunodeficiency?
Genetic mutation in genes coding for components of B cells
What does common variable immunodeficiency lead to?
Recurrent respiratory tract infections, leading to chronic lung disease
What are patients with common variable immunodeficiency more prone to?
Infections
Immune disorders (RA)
Cancers (Non-hodgkins lymphoma)
How is common variable immunodeficiency managed?
Regular immunoglobulin infusions
Treat infections as they occur
What is X-linked agammaglobulinaemia?
X-linked recessive condition that results in abnormal B cell development and deficiency in all classes of immunoglobulins
What are some different T cell disorders?
DiGeorge syndrome Purine nucleoside phosphorlyase deficiency Wiskott-Aldrich syndrome Ataxic telangiectasia Acquired immunodeficiency syndrome
What causes DiGeorge syndrome?
Microdeletion in a portion of chromosome 22, leading to developmenal defect in third pharyngeal pouch and third brachial cleft
What is the main complication of DiGeorge syndrome?
Leads to underdeveloped thymus gland that is unable to make functional T cells
What are the key features of DiGeorge syndrome?
CATCH-22: Congenital heart disease Abnormal facial features Thymus gland underdevelopment Cleft palate Hypoparathyroidism + Hypocalcaemia 22nd chromosome affected
What is Purine nucleoside phosphorylase deficiency?
Autosomal recessive condition that causes reduction in enzyme that protects against T-cell breakdown
What is PNPase?
Enzyme that helps breakdown purines
What builds up without the presence of PNPase?
dGTP metabolite
What cells is dGTP toxic to?
Exclusively T cells
What is WAS?
Wiskott-Aldrich syndrome
What kind of genetic inheritance is Wiskott-Aldrich syndrome?
X-linked recessive
What are the features of Wiskott-Aldrich syndrome?
Abnormal T cells Thrombocyopenia Immunodeficiency Neutropenia Eczema Recurrent infections Chronic bloody diarrhoea
What is ataxic telangiectasia?
Autosomal recessive condition affecting the gene that codes for a protein that plays an important part in DNA coding
What are the features of ataxic telangiectasia?
Low T-cells and immunoglobulins Ataxia Telangiectasia Predisposition to cancers Slow growth Accelerated ageing Liver failure
What causes acquired immunodeficiency syndrome?
HIV leading to reduced numbers of CD4 T-cells
What is the complement system most effective in dealing with?
Encapsulated organisms:
Haemophilus influenza B
Strep. pneumonia
Niesseria meningitidis
What do complement deficiencies make children particularly susceptible to?
Infections of the respiratory tract, ears and throat
What are complement deficiencies associated with?
Immune complex disorders (SLE)–> incomplete complement cascade leads to immune complexes building up and being deposited in tissues, leading to chronic inflammation
What is the most common complement deficiency?
C2 deficiency
What is a very important management step in patients with complement disorders?
Vaccinate against encapsulated organisms
What is the action of Bradykinin?
Responsible for promoting blood vessel dilation and increased vascular permeability in the inflammatory response
What does bradykinin cause?
Angioedema (swelling underneath skin)
What is the action of C1 esterase?
Inhibits bradykinin
What does an absence of C1 esterase cause?
Intermittent angioedema in response to minor triggers
Where does angioedema most commonly occur?
Lips and face but can occur anywhere, including the resp and GI tract
What are the complications of angioedema?
May last several days
Can occur in he larynx and compromise the airway
What is Hereditary angioedema?
C1 Esterase inhibitor deficiency–> condition causing excess bradykinin leading to angioedema
How are patients with C1 esterase inhibitor deficiency treated?
IV C1-esterase inhibitor
How is hereditary angioedema tested for?
Check levels of C4, will be low in this condition
What does mannose-binding lectin deficiency lead to?
Inhibition of the alternative pathway of the complement system
What is the complication of mannose-binding lectin insufficiency?
In patients who are susceptible to infection, can lead to a more severe disease
