Immuno 2nd Year Flashcards
What is a type 1 hypersensitivity?
Allergic reaction
What are the immediate reactions with a type 1 hypersensitivity?
Local reactions: Ingested - GI symptoms, Inhaled - respiratory symptoms
Systemic reaction: agioedema, hypotension, tachycardia, broncho-constriction, haematochezia
What cells are involved in the type 1 hypersensitivity?
Mast cells - (IgE related)
What is the medical term for year round exposure to allergens?
Perennial exposure
What 3 interleukins are responsible for Type 1 hypersensitivity in the TH2 (T helper cells) response?
IL-4, IL-5, IL-13
What is the hygiene hypothesis and what does it mean?
Western lifestyle associated with a reduced infectious burden - hygiene hypothesis. Children exposed to animals, pets and microbes in the early postnatal period appeared to be protected against certain allergic diseases
Why are mucosal membranes and blood vessels affected in a type 1 hypersensitivity reaction?
The location of mast cells is in these areas and they have IgE on their surface so allergic reactions will cause local effects in these areas
What are the 4 mast cell mediators and what do they each do?
Tryptase - remodel connective tissue matrix but measured in the anaphylactic response
Histamine - toxic to parasites, increase vascular permeability, cause smooth muscle contraction
Leukotrienes C4, D4, E4 - cause smooth muscle contraction, increase vascular permeability, stimulate mucus secretion
Platelet-activating factor - attracts leukocytes, amplified production of lipid mediators, activates neutrophils, eosinophils and platelets.
What is happens on the 1st and subsequent exposures of an allergen causing an allergic response
Allergen 1st exposure - TH2 response
IgE - mediated triggering of mast cell - antigen specific IgE
No immediate response - sensitisation reaction here
Allergen 2nd exposure - IgE cross-linking = degranulation of mast cells, systemic exposure - systemic response
Allergic reaction leading to facial manifestations are called?
Angioedema
What are the systemic manifestations of allergic reaction and what symptoms are characterised by them?
Systemic: Hypotension/ cardiovascular collapse/ generalised urticaria - increased vascular permeability,
Angiodema - generalised vasodilation,
Breathing problems - bronchial constriction
How would you treat the abnormal adaptive immune response against the allergen (TH2 response, IgE, mast cell activation)?
TH2 response = allergen desensitisation (oral immunotherapy)
IgE = anti-IgE monoclonal antibody - good for chronic asthmatics and chronic urticaria
Mast cell activation = antihistamines, leukotriene receptor antagonists, corticosteroids
Define hypersensitivity
The antigen specific immune responses that are either inappropriate or excessive and result in harm to the host
Change in function or damage to the function of the host
What are the types of hypersensitivities and the causes of the response?
Type 1 - allergy
Type 2 - antibody mediated
Type 3 - immune complexes mediated
Type 4 - cell mediated (delayed) - environmental infectious agents and self antigens
What immunoglobulins are responsible for the 4 hypersensitivities?
Type 1 - IgE
Type 2 and 3 - IgG or IgM
Type 4 - IgM
Type 2 is organ specific disease - membrane bound
Type 3 IgG is soluble but when they complex they can get caught up in particular parts of the body and causes problems there
What are the 2 phases of hypersensitivity reactions?
Sensitisation phase - first encounter with antigen
Activation of APCs and memory effector cells.
Effector phase - pathologic reaction upon re-exposure to the same antigen and activation of the memory cells of the adaptive immunity
What happens in type 2 hypersensitivity within the following parameters:
Development time, Antibody involvement, Antigen location, Outcomes.
Development time: 5-12hours Antibody: IgG or IgM Antigens: cell bound antigens Exogenous: blood group antigens, rhesus D antigens Endogenous: self antigen
Outcomes:
Tissue/ cell damage, physiological change
What antigen can cause haemolytic disease of the newborn?
Rhesus D
What antigens cause transfusion reactions?
ABO blood group system
What 2 mechanisms drive type 2 hypersensitivity?
Complement activation and antibody-dependent cell cytotoxicity
Name the 3 antibody-dependent cell cytotoxic diseases of type 2 hypersensitivity
1- Autoimmune haemolytic anaemia
2- Immune thrombocytopenia Purpura
3- Goodpasture’s syndrome
What immunoglobulin is responsible for the RBC lysis in incompatible blood transfusions?
IgM
Explain what happens in Rhesus D positive pregnant mothers and what is the treatment?
In Rhesus D negative pregnancy the problems are not immediate but in further pregnancies miscarriage occurs if the foetus also has rhesus positive RBC due to the antigen on the foetuses RBC.
A foetuses RBC can sometimes leak out of the foetal circulation and enter the maternal circulation. This results in the mother in the first ever rhesus positive pregnancy producing anti-rhesus antibodies due to the sensitisation process. If the woman becomes pregnant again with another rhesus positive foetus then her anti-Rh antibodies will cross the placenta and damage foetal RBC causing haemolytic disease of the newborn
What 2 diseases result from receptor blockade and stimulation that are part of type 2 hypersensitivity?
Graves disease - receptor stimulation - antibodies against the TSH receptor causing hyperthyroidism
Myasthenia gravis - receptor blockade - antibody against the ACh receptor causing reduced signal transmission
How could type 2 hypersensitivity be treated?
Plasmaphoresis - removal of circulating antibodies and inflammatory mediators
Anti-inflammatory drugs - complement activation
Splenectomy - reduced opsonisation and phagocytosis
IVIG - IgG degradation
Antithyriod surgery or drugs to block the TSH receptor
Replacement therapy - pyridostigmine - AChE blocker to increase amount of ACh in synaptic cleft
What is a type 3 hypersensitivity?
Complex mediated IgG soluble therefore when complexes are made this causes damage in the organ they end up in
How quickly can T3 hypersensitivity reactions occur?
3-8 hours
What immunoglobulins are responsible for T3 hypersensitivity?
IgG or IgM and antigens
What are the causes (antigens) for T3 hypersensitivity?
Soluble antigens - foreign (infection) or endogenous (self antigen)
What 3 factors affect T3 hypersensitivity immune complex pathogenesis and why?
Complex size - small and large are not a problem to deal with but intermediate sized ones can’t be cleared effectively
Host response - low affinity antibody and complement deficiency
Local tissue factors - haemodynamic factors and physicochemical factors
What are 3 diseases that are type 3 hypersensitivity reactions?
Rheumatoid arthritis - antigen is the Fc portion of IgG with articular and extraarticular features. Intertwined with episodes of inflammation and remission
Glomerulonephritis (infectious) - bacterial endocarditis or hepatitis B infection - immune complexes have a sustained production of antibodies leading to glomerulonephritis
SLE - antigen is the double stranded DNA in cells. Most prevalent immune complexes disease. Mainly women affected 9:1
What is a type 4 hypersensitivity?
Cell mediated or delayed - environmental infectious agents and self antigens. Involves lymphocytes and macrophages
How long does it take for type 4 hypersensitivity to react?
24-72 hours - delayed
What are the different subtypes of type 4 hypersensitivity reactions?
Contact hypersensitivity
Tuberculin hypersensitivity
Granulomatous hypersensitivity
What is the pathophysiology of type 4 hypersensitivity?
Sensitisation phase - bacteria are seen by APCs and macrophages. They then inform the TH1 cells and the DTH cells.
Effector phase - TH1 cells inform the resting macrophages by TNF-beta and IFN-gamma which then causes them to become activated and then cause the local effects
What is contact hypersensitivity and what is an example of it?
On skin contact with the antigen a reaction occurs 48-72hours post exposure with an epidermal reaction and requires endogenous proteins
Nickel, poison ivy, organic chemicals are examples
What is granulomatous hypersensitivity?
Occurs 21-48 DAYS post exposure with resultant tissue damage. It is usually due to the inability for the body to remove the foreign material/ bacteria and so closes it off from the rest of the body. A granuloma is formed as a result. Central necrotic cord, surrounded by lots of Giant cells and T-cells.
Examples - TB, Leprosy, Schistosomiasis, Sarcoidosis
What are examples of T4 hypersensitivity reactions to endogenous proteins?
Pancreatic beta cells - insulin dependent DM
Thyroid gland - hashimoto’s thyroiditis
Fc portion of IgG = rheumatoid arthritis
Explain Hashimoto’s disease vs Grave’s disease immunologically?
Hashimoto’s disease - CD4 T-cells react with B cells and CD8 T cells to lead to necrosis and apoptosis of thyroid cells - leading to hypothyroidism. Plasma cells are activated by the CD4 cells and the CTL are activated CD8 T cells.
Grave’s disease - CD4 T cells activating B cells to produce antibodies against the TSH receptor causing activation
How do we treat T3 and T4 hypersensitivity?
Anti-inflammatory drugs - NSAIDs, Corticosteroids, Steroid-sparing drugs - AZA, Mycophenolate, cyclophosphamide.
Monoclonal antibodies - B -cells and T-cells, cytokine network, APCs.
What is allergy defined as?
Immunological hypersensitivity that can lead to a variety of different diseases via different pathomechanisms. This can be IgE mediated (e.g. peanut allergy) or non-IgE mediated (e.g. milk protein)
What is an allergen?
Any substance stimulating the production of IgE or a cellular immune response. Usually a protein, but can be carbohydrates
Define sensitivity
Normal response to a stimulus
Define hypersensitivity
Abnormally strong response to a stimulus
Define sensitisation
Production of IgE antibodies (detected by serum IgE assay or SPT) after repeated exposure to an allergen
Define atopy
A tendency to produce IgE antibodies in response to ordinary exposure to potential allergens. Strongly associated with asthma, rhinitis, eczema and food allergy
Define anaphylaxis
A serious allergic reaction with bronchial, laryngeal and cardiovascular involvement that is rapid in onset and can cause death
Define food allergy
Immunologically mediated adverse reaction to food
How does allergic rhinitis present?
Blocked/ runny nose, itchy nose, sneezing
What is the trigger of allergic rhinitis?
Pollen, pets or HDM
How does allergic conjunctivitis present?
Red, swollen, itchy, watery eyes
How does asthma present?
Chest symptoms of wheeze, cough, SOB and tight chest
How does atopic dermatitis eczema present?
Commonest chronic inflammatory skin disease with itch and excoriation
How does urticaria (hives) present?
Acute/ chronic maculo-papular pruritic rash without or with angioedema
How does insect allergy present?
Mainly to bee or wasp stings. Mild (local), Moderate (urticaria), Severe (anaphylaxis)
How do drug allergies present?
Especially to antibiotics - anaphylaxis or hives or angioedema, rashes
How does eczema prevalence change with age?
As age increases prevalence of asthma decreases
How does food allergy prevalence change with age?
As age increases prevalence of food allergy decreases
How does asthma prevalence change with age?
As age increases prevalence of asthma increases up until 26 when prevalence decreases
How does rhino conjunctivitis prevalence change with age?
Increases rapidly with age
What two allergies help predict future asthma prevalence?
Food allergy and eczema
Before what age do milk allergies always present by?
12 months
What are the 3 most common major allergens?
Celery, Cereals containing gluten, Crustaceans
How can blood tests be used to determine food allergies?
IgE levels and levels of allergens can be detected in the blood
What is the difference in symptom onset with IgE- mediated and non IgE-mediated food allergies?
IgE-mediated = immediate 5 to 30mins
Non IgE-mediated = delayed hours to days
What is the difference in presenting age with IgE- mediated and non IgE-mediated food allergies?
IgE-mediated = variable - age of contact, all milk allergy by 1 year
Non IgE-mediated = infancy and early childhood, all milk allergy by 1 year
What is the difference in natural history with IgE- mediated and non IgE-mediated food allergies?
IgE-mediated = milk and egg allergy can resolve, others persistent into adulthood
Non IgE-mediated = Resolve earlier than IgE and many by school age
How does temperature affect cows milk allergy?
Casein is more heat resistant than whey
Forms bonds in food matrix to reduce availability and allergenicity
Up to 70% milk-allergic can tolerate baked milk (in wheat)
How does temperature affect egg white allergy?
4 major proteins in egg white, all except ovomucoid heat labile
Well cooked eggs are much less allergenic than raw egg
Up to 70% of egg-allergic can tolerate baked egg (in wheat)
How does temperature affect peanut allergy?
Allergenicity increased if dry roasted, decreased if boiled/fried
How does temperature affect fish allergy?
Fish protein is very heat stable but canned tuna and salmon are significantly less allergenic
How does temperature affect allergies to apples?
Apple proteins are very heat sensitive therefore patients with pollen food syndrome can eat processed apple
What is another term for IgE mediated allergy?
Immediate-onset
What is another term for Non-IgE mediated allergy?
Delayed-onset
How does diagnosis verification work in allergy diagnosis?
Controlled oral food challenges
How can immunoassays be used for detection of specific IgE?
ELISA-Plates, Western blots
1 - Allergen is adsorbed and immobilised to a solid phase
2 - Patient’s serum is added followed by incubation for 30-60minutes followed by several washing steps
3 - Allergen-bound IgE is detected by an enzymatically labelled anti-human IgE monoclonal antibody
What are typical symptoms of lactose intolerance?
Bloating, flatulence, explosive diarrhoea
How early can lactase be detected in the jejunal brush border and when do the levels rise then decrease?
Detection from 8 weeks gestation
Rise from 32 weeks to peak at birth
Activity decreases within months
How many stages are there on the milk ladder?
4 stages
On the milk ladder what stage has the most denatured/ lower protein dose and which has the least denatured/ higher protein dose?
Stage 1 - more denatured / lower protein dose - less allergenic
Stage 4 - less denatured / higher protein dose - more allergenic
How are food induced anaphylaxis treated?
Adrenaline - EpiPen / Emerade
What causes angioedema in allergic reactions?
Non-itchy swelling as histamine and bradykinin are released in the deep dermis - causing vasodilation and inc vascular permeability.
How do you treat mast cell activation in allergies?
Antihistamines, leukotriene receptor antagonists, corticosteroids
