Immunology 3 Hypersensitivity Flashcards
Hypersensitivity reactions = __________ immune responses that cause damage
Excessive
Response to different types of antigens such as what?
- Infectious agents
- Environmental substances
- Self antigens
are all infections are capable of causing hypersensitivity reactions?
no
Do infections that elicit hypersensitivity do so in every case?
no
How does Influenza viruses can cause hypersensitivity?
- Influenza virus damages epithelial cells in the respiratory tract
- Can sometimes elicit an exaggerated immune response
- Can trigger high levels of cytokine secretion (cytokine storm)
- The cytokines attract leukocytes to the lungs and trigger vascular changes that lead to hypotension and coagulation
- In severe influenza, inflammatory cytokines also spill out into the systemic circulation, causing ill effects in remote parts of the body, such as the brain
Hypersensitivity to Environmental Substances - how can dust trigger a response?
- Dust triggers responses because it is able to enter the lower extremities of the respiratory tract, an area rich in adaptive immune response cells
- Dust can mimic parasites and may stimulate an antibody response
- If the dominant antibody is IgE, it may subsequently trigger immediate hypersensitivity, which manifests as allergy symptoms such as asthma or rhinitis
- If the dust stimulates IgG antibodies, it may trigger a different kind of hypersensitivity, such as farmer’s lung
Hypersensitivity to Environmental Substances:
- Smaller molecules sometimes diffuse into the skin and may act as ________, triggering a delayed hypersensitivity reaction
- _______ are small molecule irritants that bind to proteins and elicit an immune response
haptens
Haptens
Types of Hypersensitivity Reactions
Different type of hypersensitivity reactions - 4 different types
Main difference is the immune mechanism involved and because of this there is a difference in onset
Type 1 and 2 are very quick - Type 1 almost immediate
Type 3 caused by immune complexes
Type 4 is delayed, cell mediated, T cells and macrophages are involved, some type 4 are autoimmune diseases
Type I hypersensitivity is mediated through degranulation of what cells?
•Mediated through the degranulation of mast cells and eosinophils
how quick are the effects of Type I hypersensitivity felt after exposure?
- The effects are felt within minutes of exposure.
- Immediate hypersensitivity, allergy (or atopy)
Tend to have some genetic traits and once exposed environmentally the have IgE against certain antigens
what is atopy?
- Immediate hypersensitivity reaction to environmental antigens mediated by IgE
- Develops within minutes of exposure
- Family history with atopy traits.
- Atopy = allergy:
- Anaphylaxis, Angioedema, Urticaria, Rhinitis, Asthma and Dermatitis, eczema
Allergic march
how is atopy familial?
Doesn’t mean they have same allergy as family but increased risk of having an allergy in general
- Antigens that trigger allergic reactions are called _________
- They gain access to the ____ through inhalation, ingestion, contact or administered as drugs
allergens
body
•IgE is required for type I hypersensitivity:
what produces it?
•B cells produce it when co-stimulated with IL-4 (secreted by TH2 cells)
IgE made by B cells like any antibody
In people with allergies they produce more Th2 than Th1 whereas they should be equal
IL-4 suppresses Th1
IL-4 induces production of IgE by B cells
what causes the allergic symptoms?
Degranulating cells
Release of mediators that cause allergic symptoms
what cells degranulate causing allergic symptoms?
- Mast cells are resident in many tissues.
- Eosinophils migrate to tissues where type I hypersensitivity reaction is. (attracted to site of inflammation)
what is the process of mast cells degraulating and causing an immune repsonse?
- Mast cells initiate allergic symptoms after allergen and IgE interact
- Mast cells have receptors for IgE and FcεRI (high affinity IgE receptor)
Mast cells already attached to IgE so as soon as exposed to antigen then degranulate their components and cause an immune response
what are the different symptoms of an allergy?
Depends on system effected
anaphylaxis most serious
what is the Epidemiology of Allergies?
- Very common, up to 40% of the population affected
- Runs in families
- Prevalence on the rise globally
Inheritance is of the risk of allergies, not of the actual allergy
Genetic predisposition is multifactorial and doesn’t depend on a single gene
This is one example – genes relating to filaggrin
Filaggrin important for maintain skin
Genetics of Allergies:
- Filaggrin is expressed by keratinocytes and involved in maintaining epithelial barriers and moisturizing surfaces and controlling pH
- Polymorphisms in the gene encoding is established as a cause of allergy and implicated in 50% of severe eczema
- Exposure to environmental factors adds the risk of developing allergies
- Timing is important
Role of Environmental Factors:
•Effect of urbanization
what is the hygiene hypothesis
- Effect of urbanization
- Hygiene hypothesis: increase in allergies in the developed world is caused by reduced exposure to microorganisms in early life
- However, infections can either increase or decrease the risk of allergies depending on the timing of exposure and the genetic makeup
what envornmental factors play a role in allergy?
Many of the risk factors for allergic disease affect the microbiome of the skin, nasopharynx, lung and gut, particularly in a critical window in the early postnatal period when these organs, as well as the immune system, are still developing. Infections can have both protective and detrimental effects on allergy. Often these factors occur together, so the absence of one protective factor does not necessarily mean that allergic disease will ensue.
Also, many risk factors are associated. Antibiotic use is hard to disentangle from infection history.
(examples of antigens a baby can be exposed to)
•Anaphylaxis is the most serious type of allergy - what is the process and the effects of anaphylaxis?
- Mast cells produce prostaglandins and leukotrienes through the cyclooxygenase and lipoxygenase pathways
- The result is vasodilation and increased vascular permeability
- Shift of fluids from the vascular to the extra-vascular space resulting in a fall in vascular tone
- Severe drop in blood pressure
- IN the skin, mast cells release histamine further contributing to welling and fluid shift
what happens in allergic rhinitis?
- inhaled allergens stimulate mast cells in the nasal mucosa
- Subsequent vasodilation and oedema in the nose causes nasal stuffiness and sneezing
- Leukotrienes increase mucus secretion, which causes the discharge characteristic of allergic rhinitis
- Increased _____ secretion in asthma and contributes to the airflow obstruction
- In the lungs, _________ cause smooth muscle __________, which has the most dramatic effects on airflow reduction
mucus
leukotrienes
contraction