Allergy and Hypersensitivity Flashcards
What is an allergy?
- response from immune system
- immune response damages the body
- can be non pathogenic (dust, food)
What is hypersensitivity?
- inappropriate activation of immune response
- response is due to none pathogenic antigens
What are the 2 most common immune responses that occur in the body that are triggered by an allergy?
- ⬆️ vascular permeability (vascular stage)
- inflammation (damages tissue, unnecessarily) which are neutrophili followed by macrophage stage
What are local allergic reactions?
- antigen interacts with a specific body site
- allergic response is confined to specific site or tissue
What are a few examples of a local allergic reaction?
- asthma (lungs)
- food allergy (GI tract)
- atopic dermatitis (skin)
What does anaphylaxis mean?
- system wide response
- antigen causing allergy needs to be systemic circulated
Why could an intravenous injection like penicillin cause a systemic response as seen in anaphylaxis instead of a local response?
- if allergic to penicilin
- intravenous means it can enter anywhere in the body
What is anaphylactic shock?
- dangerous system wide response to antigen
- can be fatal
Is hypersensitivity specific to the innate or adaptive immune system?
- it can affect both
What are allergans?
- antigens that initiate an allergic reaction
- allergic reactions are immune responses
How many classifications of hypersensitivity are there?
- 4
- types I, II, III and IV
- always written as roman numerals
What antibody is involved in type I hypersensitivity?
- IgE
How quickly do type I hypersensitivity reactions take to occur?
- almost immediately
Which classification of hypersensitivity are most allergic reactions?
- type I
What other names is type I hypersensitivity called?
- antibody mediated
- immediate
Which part of the IgE antibody binds with the antigen?
- variable region
- also known as the Fab (fragment antigen binding)
Which part of the IgE antibody binds with the cells of the immune system?
- Fc region
- referred to as the constant region
Which cells of the immune system does the Fc portion of the antibody bind to in allergic reactions?
- mast cells
- basophils
- eosinophils
What is the FcεRI, commonly referred to as the epsilon Fc receptor?
- specific Fc receptor located on
- mast cells, basophils and eosinophils
What type of transmembrane receptors are Fc receptors on cell surface?
- receptor tyrosine kinase
- enzyme induced receptors
Once bound to the Fc receptors of mast cells, basophils and eosinophils, what do the receptor tyrosine kinase do intracelluarly?
- cause signalling cascade
- facilitated by phosphorylation
- kinase phosphorylates
What is the purpose of the signalling cascade inside mast cells, basophils and eosinophils once the Fc portion of the antibody has bound to the Fc receptors?
- degranulation
- release of inflammatory mediators
Is the release of IgE antibodies only released during type I hypersensitivity?
- no
- IgE is important for parasitic infections
What classification of hypersensitivity are all allergies?
- type I
What are epitopes?
- part of antigen that binds to antibody
Do antigens have just one epitope?
- no
- pollen has lot of epitopes
When exposed to an allergen (antigen causing allergic reaction) for the first time what happens to the B cells of the adaptive immune response?
- become sensitised to antigen
- B cells present antigen on cell surface via MHC-II
When exposed to an allergen (antigen causing allergic reaction) for the first time. How do T helper cells bind to the antigen presenting cell as part of the adaptive immune system?
- T helper cells receptors bind to MHC-II
- CD4 check MHC-II
- CD40L (ligand) binds to CD40 on B cell to check cell
- 3 checks in total
When exposed to an allergen (antigen causing allergic reaction) for the first time, and after being activated by T helper cells, what do B cells then do as part of the adaptive immune response?
- differentiate into plasma and memory cells
When exposed to an allergen (antigen causing allergic reaction) for the first time, and after differentiating into memory and plasma cells, what do B plasma cells do?
- secrete antibodies
- antibodies bind to mast cells, basophils and eosinophils
Do you automatically have an allergic reaction when exposed to an allergen the first time?
- no as it takes 1-2 weeks to occur
- 2nd time exposed it will be fast acting
What are some common examples that can cause type I hypersensitivity?
- pollens (rye grass, ragweed, timothy and birch trees)
- foods (nuts, eggs, seafood, peas, beans and milk)
- drugs (penicillin, sulphonamides, anaesthetics)
- insects (bee, cockroaches, ants, dust mites)
- miscellaneous (mold, animal hair, latex, vaccines, serum)
What are some common examples of type I hypersensitivity?
- asthma
- hay fever
- hives
- food allergies
- eczema
Asthma is an example of type I hypersensitivity, what is released by mast cells during degranulation that causes asthma?
- histamine
- initiates an immune response
Where is histamine located?
- inside granules of mast cells
What does histamine bind with?
- histamine receptor or H1 receptor
Where are histamine or H1 receptors located in the lungs?
- smooth muscle on tunica media
Once histamine has been released and bound to the H1 receptors on smooth muscle, what happens in asthma?
- vascular permeability ⬆️
- mucus production ⬆️
- smooth muscle vasoconstriction ⬆️
In addition to histamine, what 2 other molecules are released that are 1000 fold more active than histamines?
- leukotrienes
- prostoglandins
What type of cell surface receptor are histamine or H1 receptors?
- GPCR - specifically Gaq - ⬆️ Ca2+ released causing bronchoconstriction
How many stages are there in asthma?
- 2
What are the 2 stages in asthma?
- early response - late phase reaction
During early response in asthma, how is this treated effectively?
- inhalers
In the late phase response, in order for immune cells to bind onto the endotheial cells in blood vessels what is increased on the surface of endothelial cells?
- adhesion molecules
- ⬆️ binding of immune cells
What is the hygiene hypothesis?
- no exposure to non harmful antigens when younger - ⬆️ risk of body identifying harmless allergens as dangerous
What is type II hypersensitivity?
- antibodies bind to cells containing antigen
- these are host cells that appear infected
- cells are lysed even though they are not infected
Which antibodies are involved in type II hypersensitivity?
- generally IgG
- sometimes IgM
Once bound the antigen-antibody complex has been formed on host tissue, what are the 3 ways these host cells are killed?
1 - compliment system (C3B)
2 - antibody-dependent cell-mediated cytotoxicity (ADCC)
3 - opsonisation
What is the antibody-dependent cell-mediated cytotoxicity (ADCC) involved in type II hypersensitivity?
- antibodies (IgG and IgM) bind to antigens
- natural killer cells (NKC) bind to antibodies on cells
- NKC lyse cells using toxic granules
Transfusion reactions are an example of II hypersensitivity, what can happen if the wrong blood is transfused?
- blood contains specific antigens A, B or H
- determines our blood type
- if blood with wrong antigen is present the body will attack and kill red blood cells as they do not have self antigens (correct A, B or H antigen)
What is intravascular haemolysis?
- rupture of red blood cells - can happen if wrong blood is transfused
What are Rhesus antigens as an example of type II hypersensitivity?
- antigens on blood
- if mother is Rh- and father is Rh+ this is bad
- mothers IgG cross placenta and destroy fetal blood cells
- only occurs in second baby though
How does Malaria trigger type II hypersensitivity?
- antigen from P. falciparum parasite binds to blood
- antibodies trigger haemolysis (rupture of red blood cells)
What is drug induced haemolytic anaemia as an example of type II hypersensitivity?
- drug bind to proteins in the blood
- drug recognised as foreign antigen and antibodies bind
- immune cells attack the drug
- penicillin is an example
What is type III hypersensitivity?
- extensive immune complexes form
- immune complexes cannot be cleared and aggregate
- generally IgM antibodies, that then switch to IgG antibodies
What are immune complexes?
- multiple antibodies bind with multiple epitopes on antigens
- forms aggregates of antibody-antigen complexes
- insoluble so get stuck to blood vessels
What are the 2 most common causes why immune complexes cannot be cleared?
1 - disorder of phagocytic machinery
2 - phagocytes cannot access antigens to phagocytise
If immune complexes are not cleared what will they create at the site where they are present?
- create aggregates
- induce granulation from mast cells
- inflammation follows
- complement system activated
Do the immune complexes form from soluble antibodies or those bound to host cells?
- soluble antibodies
Where do immune complexes get deposited in tissue?
- move around in circulation - become deposited in capillary beds
If immune complexes become deposited in capillary beds, what can this cause to the capillary beds?
- inflammation - vasculitis
What are the 2 most common chronic problems immune complex deposition can cause in the body?
1 - arthritis 2 - glomerulonephritis (inflammation of kidneys)
What is arthus reaction when caused by an insect bite?
- type III hypersensitivity
- immune complexes form with antigen
What are some common autoimmune disease examples of type III hypersensitivity?
1 - rheumatoid arthritis 2 - multiple sclerosis 3 - systemic lupus erythematosus
What are some common infection disease examples of type III hypersensitivity?
1 - meningitis 2 - hepatitis 3 - mononucleosis 4 - malaria 5 - trypanosomiasis 6 - poststreptococcal glomerulonephritis
What are some common drug reactions as examples of type III hypersensitivity?
1 - penicillin 2 - sulphonamides
What are some common arthus reactions as examples of type III hypersensitivity?
1 - farmers lung (actinomycetes (bacteria) in hay) 2 - pigeon fanciers disease (faeces)
What is type IV hypersensitivity?
- a cell mediated response to antigens
In type IV hypersensitivity are antibodies involves?
- no
- only hypersensitivity classification with no antibodies
What cells are involved in type IV hypersensitivity?
- antigen presenting cells (macrophages+Langerhans)
- T helper cells
What are the 2 stages of type IV hypersensitivity?
1 - sensitisation
2 - effector phase
What is the sensitisation phase of type IV hypersensitivity?
- antigen presenting cells present antigen
- T helper cells bind to MHC-II complex
- T helper cells are activated by cytokines
Once T helper cells are activated in type IV hypersensitivity, what do they differentiate into?
- T helper effector cells - T helper memory cells
How long does sensitisation in type IV hypersensitivity generally take?
- 1-2 weeks similar to normal immune response
What is type IV hypersensitivity also referred to as?
- delayed type hypersensitivity
Once sensitised to the antigen how long, how long does the effector phase of type IV hypersensitivity take to initiate?
- 24-48 hours
Once sensitised, what do T helper cells do in the effector phase of type IV hypersensitivity?
- produce cytokines
- cytokines activate macrophages and immune cells
- macrophages are responsible for most tissue damage
In type IV hypersensitivity is the inflammatory response local or regional?
- generally local - like poison ivy on specific skin that touched it
What are a few intracellular bacteria that can cause type IV hypersensitivity?
1 - mycobacterium tuberculosis
2 - mycobacterium leprae
3 - brucella abortus
4 - listeria monocytogenes
What are a few intracellular viruses that can cause type IV hypersensitivity?
1 - herpes simplex virus
2 - variola (smallpox)
3 - measles
What are a few intracellular fungi that can cause type IV hypersensitivity?
1 - pneumocystis carinii 2 - candida albicans 3 - histoplasma capsulatum 4 - cryptococcus neoformans
What is an intracellular parasite that can cause type IV hypersensitivity?
- leishmania sepsis
What are a few contact antigens that can cause type IV hypersensitivity?
1 - hair dyes 2 - nickel salts 3 - poison ivy 4 - poison oak 5 - picryl chloride
What are 2 of the most common causes of a type IV hypersensitivity?
- graft rejection
- contact dermatitis
Which classification is most commonly associated with a cough?
- type 1 hypersensitivity
Although coughs are generally not serious there are some occasions when they may be a red flag for a serious pathology. What duration of a cough with a wheeze would be classed as a red flag?
- >3 weeks
Although coughs are generally not serious there are some occasions when they may be a red flag for a serious pathology. What may recurrent chest infections be a sign of and a red flag?
- inflammation of the pleural of lungs and thoracic cavity - chest pain is also common
Although coughs are generally not serious there are some occasions when they may be a red flag for a serious pathology. Dyspnoea is laboured breathing, when can this be classed as serious and classed as a red flag?
- when the patient coughs up phlegm every morning - >3 months
Although coughs are generally not serious there are some occasions when they may be a red flag for a serious pathology. Why is a persistent nocturnal cough a red flag?
- could be underlining pathology - infection - cancer - lung disease
