HYPERSENSITIVITY REACTIONS Flashcards
how many CLASSES OF HYPERSENSITIVITY REACTIONS and name them
4
type 1
type 2
type 3
type 4
hypersensitivity reactions
reactions are exaggerated or inappropriate immune responses to harmless substances, leading to tissue damage
type 1 hypersensitivity reactions
aka immediate hypersensitivity
caused by IgE antibodies binding to allergens, triggering mast cells and basophils to release histamine.
Examples: Allergies, asthma, anaphylaxis.
note that in some cases people with this type lose it as they get older
type 2 hypersensitivity reactions
aka cytotoxic hypersensitivity
caused by IgG or IgM antibodies targeting antigens on cells, thereby activating the complement system, leading to cell destruction.
Examples: Hemolytic anemia, transfusion reactions.
type 3 hypersensitivity reactions
aka immune complex hypersensitivity
caused by Antigen-antibody complexes deposit in tissues, causing inflammation.
Examples: Lupus, rheumatoid arthritis
involves IgM, IgG and sometimes IgA antibodies
the most common hypersensitivity reactions
type 1 and 4
type 4 hypersensitivity reactions
aka delayed-type hypersensitivty
caused by T-cell mediated response, usually 24-72 hours after exposure.
Examples: Contact dermatitis, tuberculosis skin test.
allergens that cause type 1 hypersensitivity can be harmless and more harzadous, true or false
true
pollen, dust, drugs, or insect venoms etc could all cause it
anaphalyxis vs prophalyxis
A severe, life-threatening allergic reaction that occurs rapidly after exposure to an allergen, causing symptoms like difficulty breathing, swelling, and a drop in blood pressure
while
A preventive treatment or measure taken to prevent disease or a medical condition, such as vaccines or medications to prevent infections or allergic reactions.
some of the effects of type 1 hypersensitivity(what could it lead to)
Nasal allergic rhinitis or hay fever
Ocular allergic conjunctivitis, potentially due to seasonal allergens such as pollen or mould spores
Dermatological hives, atopic eczema, or erythema
Soft tissue angioedema
Pulmonary reactions, such as allergic asthma or hypoxia
Systemic reaction, which is a life-threatening medical emergency, and also known as anaphylaxis.
some of the risk factors for type 1 hypersensitivity
geographical distribution
environmental risks such as pollution
socioeconomic status
genetic predisposition
“hygiene hypothesis”.
hygiene hypothesis suggests that our modern society practices of good hygiene
and the lack of early exposure to many microbes or antigens may result in failures of
the immune system functionality.
the two stages in the response to an antigen exposure
the sensitization stage: host experiences an
asymptomatic contact with the antigen
the effect stage: the pre-sensitized host is re- introduced to the antigen, which then leads to a type I anaphylactic or atopic immune response.
describe IgE mediated mast cell activation and degranulation
Sensitization: Upon first exposure to an allergen (e.g., pollen, dust), B cells produce IgE antibodies specific to that allergen. These IgE antibodies bind to FcεR receptors on the surface of mast cells and basophils, which become “sensitized.”
Re-exposure to Allergen: During subsequent exposure to the same allergen, the allergen cross-links the IgE antibodies bound on the mast cell surface.
Mast Cell Activation: The cross-linking of IgE receptors triggers mast cell activation, leading to intracellular signaling.
Degranulation: Activated mast cells release pre-stored granules containing histamine, cytokines, and other inflammatory mediators into the surrounding tissue.
Allergic Reaction: The released mediators cause vasodilation, increased vascular permeability, smooth muscle contraction, and mucus production, leading to symptoms like itching, swelling, and in severe cases, anaphylaxis.
eicosanoids
lipid-based signaling molecules that regulate a variety of physiological responses, including inflammation, tissue homeostasis, and host defense
examples are prostaglandins, thromboxanes and Leukotrienes
atopy
the tendency to produce an exaggerated IgE immune response to otherwise harmless substances in the environment.
normal IgE levels precludes(preevents) atopy, true or false
false
even though atopy is characterised by elevated igE levels, it does not normal levels means there is no atopy
risk factors for atopy
family history
high IgE levels
genetics
activation of mast cells may lead to some diseases, name some
Hayfever
Allergic Rhinitis
Asthma
Conjunctivitis
Eczema
Dermatitis
Vomiting
Diarrhoea
the nasal discharge from allergic rhinitis is often rich in which type of WBC
eisinophils
eisinophil function
Eosinophils are released during infections, allergic reactions, and asthma. They consume harmful matter, and swarm inflamed sites to fight disease
food allergies are characterised by
activation of mucosal mast cells in the GI tract
Transepithelial fluid loss and increased smooth muscle contraction
causes nausea and diarrhoea in food allergies
acute urticaria
a skin condition that causes itchy, raised, red, and swollen areas on the skin
it Follows the subcutaneous
administration of allergen
eg. Insect bite
does the route of entry of an allergen define it’s clinical effect on the person?
yes it does
how/when does systemic anaphalyxis occur
a severe, potentially fatal allergic reaction that affects multiple organ systems
after intravenous or rapid oral absorption or administration of allergen
the effects of systemic anaphalyxis
Connective tissue mast cells associated with all blood vessels become activated
Results in vascular permeability (loss of blood pressure, oedema)
airway constriction
swelling of epiglottis
suffocation
causes of systemic anaphalyxis
Foreign serum
Penicillin injection
Bee venom
Some foods
anaphalytic shock
a severe, potentially life-threatening allergic reaction that can affect the entire body
it is a response to allergens that** directly ** enter the blood. in this response, mast cells and basophils are enlisted throughout the body
treatment for anaphalytic shock
adrenaline
its the first line treatment, and causes bronchodilation, which helps with the wheezing..etc associated with A.S, and causes vasoconstriction, to counter the extreme low BPs in A.S
name some clinical tests for allergy
Skin prick tests
RASTs (Radio Allergo Sorbant Test)
how does the Radio Allergo Sorbant Test(RAST) work in testing for allergies
Blood sample collected
the potential allergen is attached to a solid phase, which could be a paper disk or a plastic surface
the blood sample is then added to the solid phase, if person allergic to the allergen, then IgE antibodies specific to that specific allergen will be produced
A secondary antibody tagged with a radioactive isotope is added. This secondary antibody binds to any IgE attached to the allergen
these are then counted to quantify the presence of IgE antibodies, indicating the severity of the allergy
note that this test is a bit old and has been largely replaced by tests like immunocap
name some treatments for allergies
avoiding the allergens
hyposensitization
corticosteroids
antihistamines
etc
Hyposensitization, also known as desensitization or allergen immunotherapy, is a medical treatment for asthma and environmental allergies. It involves gradually exposing a patient to larger and larger amounts of an allergen to change the immune system’s response
there’s loads, check workshop book, you’d have made notes about them in there
hyposensitization
a long term treatment for allergies, which works by gradually exposing the patient to increasing amounts of the allergen over time, which helps the immune system become less sensitive to it.
aka allergy immunotherapy
the two MAIN antibodies involved in hyposensitization, and what they do
IgG and IgE
IgE production is reduced, while IgG binds to the allergen before it reaches IgE, blocking it from causing a severe allergic response
type 2 hypersensitivity reactions
Antibody-mediated immune reaction in which antibodies (IgG or IgM) are
directed against cellular or extracellular matrix antigens.
Results in cellular destruction, functional loss, or tissue damage
name some common type of type 2 hypersensitivity reactions
Blood transfusion reactions
Hemolytic disease of the newborn (Rh disease; mother Rh- and infant Rh+)
Autoimmune hemolytic anaemias
Drug reactions
Drug-induced loss of self-tolerance
Hyperacute graft rejection
Myasthenia gravis (acetylcholine receptor)
name some ways/mechanisms in which damage to cells occur in type 2 hypersensitivity reactions
Antibody binding to cell surface receptors and altering its activity
Activation of the complement pathway
Antibody dependant cellular cytotoxicity
ADCC
(Antibody Dependent Cellular Cytotoxicity)
usually carried out by IgG
an immune response mechanism in which immune cells target and destroy infected or abnormal cells (like cancer cells) that have been marked or coated by specific antibodies.
key in getting rid of abnormal cells
main antibodies involved in blood group compatibility are
mainly IGM antibodies, but in some cases they could be IgG
what happens during incompatible blood transfusions , i.e where the blood of the donor and the receipient are not compatible
note this is in vivo
In an incompatible transfusion, IgM antibodies bind to the donor RBCs, activating the complement system, which leads to cell lysis (destruction). Simultaneously, antibody-antigen(ab-ag) complexes are recognized by tissue-fixed macrophages, leading to phagocytosis and further tissue damage.
the name of the in vitro test used to detect antibodies on the surface of RBCs before transfusion
these antibodies act agaisnt antigens on the surface of the RBCs, eg if a person with blood type A has in incompatible blood type tranfused to them, then specific antibodies are produced against the donor blood
the antoglobulin test or Coomb’s test
Direct Coomb’s Test (DCT): Uses Coomb’s reagent to detect antibodies already attached to red blood cells. Helps diagnose autoimmune hemolytic anemia, transfusion reactions, or hemolytic disease of the newborn.
Indirect Coomb’s Test (ICT): Uses Coomb’s reagent to detect free antibodies in the plasma. Used for blood compatibility testing before transfusions or organ transplants.
describe the ABO blood group system, and the main antigens involved in this system
The ABO blood group system is based on the presence or absence of certain antigens on the surface of red blood cells (RBCs). These antigens are carbohydrates that are attached to proteins or lipids on the RBC membrane.
the main antigens are A and B antigens
name the various blood types and their genotypes(i.e their alleles)
Blood group A-> AA or AO
Blood group B-> BB or BO
Blood group AB-> AB
Blood group O-> OO
the genotypes indicate the alleles they inherited from each parent
the antiodies contained in the serum of each of the blood types and what they indicate
for blood group A, it has anti-B antibodies, indicating that people with blood group A cannot not receive blood from those with B
for blood group B, they have anti-A antibodies, same implies
for blood group O, they have Anti-A and Anti-B antibodies.
AB blood group does not have any antibodies. O is the universal blood group, so can donate to any blood type. AB is the universal receipient
Giving a recipient blood with incompatible antigens can result in a hemolytic transfusion reaction, where the antibodies in the recipient’s blood attack the donor’s red blood cells, leading to cell lysis and serious complications
hypersensitivity reactions can be drug induced, for exmaple by drugs like penicillin, celphalosporin..etc
which antibodies or Immunoglobulins are produced when this happens?
note that
IgM and IgG
note that drug indced hypersensitivity occurs when the drugs to plasma proteins or red blood cells (RBCs)
describe what happens in type 2 hypersensitivity when;
- IGM is more abundant in drug induced hypersensitivity
- IgG is more abundant than IgM
- When IgM antibodies are more abundant, the immune system activates the complement system, which leads to direct lysis (destruction) of RBCs. This is common when large doses of the drug are given over a long period (several weeks).
- When IgG antibodies are more abundant, they coat the RBCs, marking them for destruction. The phagocytes (immune cells like macrophages) then recognize and remove these antibody-coated RBCs, causing hemolysis (destruction of red blood cells).
Antibodies can activate the complement pathway by binding to self-antigens, consequently leading to neutrophil activation.
how does the activation of neutrophils occur when this happens?
when antibodies bind to self antigens, it results to the formation of the complement components C3a and C5a
these act as chemotatic factors for neutrophils, bringing them in to the site
consequently, neutrophils are activated
here activated neutrophils release enzymes and reactive oxygen species to damage the tissues. this is A cause of autoimmunity
what happens in goodpasture syndrome
autoantibodies are directed against collagen in glomerular and alveolar basement membranes.
this leads to strong activation of the complement system, which recruits leukocytes, resulting in
inflammation
Autoantibodies are proteins produced by the immune system that attack the body’s own cells, tissues, and proteins
molecular mimicry meaning
a phenomenon where the immune system mistakenly targets the body’s own tissues because the structure of a foreign antigen (e.g., from a pathogen) closely resembles a self-antigen (e.g., a protein in our own body).
This similarity leads to cross-reactivity, which is when antibodies or T cells that are originally designed to fight the pathogen also attack the body’s own cells that have a similar structure.
a classic example of molecular mimicry, and how it occurs
a classic example is in acute rheumatic fever, a condition developped after infection with Group A Streptococcus, a bacteria. some of these bacteria share structural similarities with human proteins, specifically cardiac myosin. So the antibodies generated to fight against them also bind to cardiac myosin in the heart.
Complement system activated, which leads to inflammation and damage to the heart tissue, resulting in** rheumatic heart disease**
how does Grave’s disease happen, as a type 2 hypersensitivity reaction
mainly looking for the role that autoantibodies play in this
the autoantibodies bind to the thyrotropin receptor on
thyroid follicular cells resulting in the overproduction of thyroid hormones.
Normally the production of thyrotropin by the pituitary is regulated by levels of thyroid hormones in the blood, but these antibodies lead to autonomous production of thyroid hormones by the follicular cells, which
are not inhibited by high levels of thyroid hormones in the blood resulting in much higher levels than cause symptoms of thyrotoxicosis.
Thyrotropin, also known as thyroid-stimulating hormone (TSH), is a hormone that regulates the thyroid gland’s function
how myasthenia gravis happens, as a type 2 hypersensitivity reaction
Autoantibodies directed against the nicotinic
acetylcholine receptor do not allow acetylcholine to bind to its receptor on muscle cells, leading to muscle weakness.
some treatments for type 2 hypersensivity reaction
or complications arising from type 2 hypersensitivity reactions, as if you treat the complications, then you practically treat the reaction
Removing the causative agent where possible (drug, allergen etc.)
Antibiotics for acute rheumatic fever
Acute manifestations (reactive arthritis etc.) can be treated with NSAIDs
Graves’ disease anti-thyroid drugs like carbimazole, Propylthiouracil…etc
for Myesthenia Gravis, acetylcholinesterase inhibitors, general immunosuppressive therapy (e.g corticosteroids) and thymectomy is also sometimes considered
methimazole is the active metabolite of carbimazole(a pro drug)
