Hypersensitivity Flashcards
What is hypersensitivity ?
a state of heightened reactivity to antigen
Describe hypersensitivity reactions
immune responses to innocuous antigens that lead to symptomatic reactions upon re-exposure
Describe Hypersensitivity disease
damage to host tissue caused by hypersensitivity reactions to typically innocuous antigens
Type antigen do I hypersensitivity Reactions involve
involve IgE-dependent triggering of mast cells (commonly referred to as allergy)
What antigens do Type II hypersensitivity reactions involve
involves IgG antibody that is reactive with cell-surface or matrix antigens
Describe Type III hypersensitivity
involves the production of antigen:antibody complexes
Describe Type IV hypersensitivity
T cell-mediated hypersensitivity
Type type of T cells promote a Type 1 Hypersensitivity
TH2 CD4 cells can induce class switching from IgM to IgE; antigens that selectively stimulate TH2 cells that drive an IgE response are known as allergens
What are the properties common to allergens?
What happens when soluble antigens strike mucosal membranes ?
•• most allergens are small proteins
•• most are highly soluble
•• most are carried on desiccated particles (pollen, mite feces)
•• upon contact with mucosa of airways, soluble antigens elute from the delivery particles and
diffuse into the mucosa
Do all allergens have enzymatic activity ?
How is IgE effective against parasites ?
many common allergens have enzymatic activity but not all of them •• many parasites produce and secrete proteolytic enzymes that break down connective tissues to gain access to the host; These proteases activate Th2 responses that will drive class switching from IgM ---> IgGG
What is a prerequisite for a Type 1 hypersensitivity reaction
the initial response to an allergen must be an IgE response because degranulation of Mast cells ( and neurophils and basophils ) drive the type 1 reaction
How do TH2 cells stimulate class switching to IgE?
How exactly does TH2 carry out its job ?
I would get creative on these but they are just to review…
effector TH2 cells deliver several molecular signals that favor class switching in B lymphocytes to IgE; once the TCR of a TH2 cell becomes ligated (by specific peptide antigen presented via MHC class II molecules on the B cell), the TH2 cell:
•• produces and secretes IL-4, IL-5 and IL-13
•• upregulates surface expression of CD40 ligand (CD40L) and CD23 (low affinity receptor for
IgE); these costimulatory molecules can bind to their counter receptors (CD40 and CR2)
on the presenting B cell
•• the combination of these signals induces class switching to IgE
Who initiates type 1 hypersensitivities?
How are these cells activated?
What do they do once they are activated?
mast cells (eosinophils and basophils are also involved)
• all 3 of these cell types express the high affinity IgE receptor (Fc RI)
•• when the IgE bound to these cells is crosslinked by specific antigen, they degranulate; their
granules contain a variety of inflammatory mediators that initiate
inflammatory responses
How do Th2 cells induce class switching from IgM to IgE
Activated Th2 cells…
- secretes ( IL-4, IL-5, and IL-13)
- Up-regulate CD40 and CD 23
- These co-stimulatory molecules bind to B cells and induce class switching.
How are Type 1 hypersensitivenes initiated ?
When IgE binds to the high affinity IgE receptors on Mast Cells, Basophils
Describe the genetic basis of predisposition to an allergy
In regard to IgE genetic predisposition there are two chromosomes involved, name them and try to list some of the genes they encode for
Different races of people can be more or less sensitive to a particular antigen
•• chromosome 11 encodes a gene for the subunit of FcRI (high affinity IgE receptor)
***chromosome 5 encodes a cluster of genes that encode IL-3, IL-4, IL-5, IL-9, IL-13, and GM-CSF; all of these proteins are involved in isotype switching, eosinophil survival, and mast cell proliferation
How does the HLA Class II Polymorphism affect the IgE response to certain allergins
IgE response to several pollen antigens of ragweed correlate with the expression of HLA class II allotype DRB1*1501; this suggests that a certain HLA class II:peptide combination predisposes to stimulation of a TH2 response
What is Atopy ?
Predisposition of common antibody responses to an environmental allergen
How do you test sensitivity to an allergen ?
There are two steps be sure to describe both of them… We all took one of these tests before school started during orientation
1st step of response: injection of an allergen into the skin of a sensitive individual produces a characteristic inflammatory reaction known as a wheal and flare (you will describe what this is in 2 cards)
- *Localized redness and swelling**
- *Sub-Q Tb test where Tb protein is injected to see if you react to it
Describe the second step of response to the antigen response test
consists of more widespread swelling and is mediated by leukotrienes, chemokines,
and cytokines produced by mast cells following IgE-mediated activation from the injected foreign proteins
What is a wheal and Flare Response ?
he wheal and flare reaction is called an immediate reaction because it appears within a few minutes; it is the result of mast cell-degranulation in the skin; released histamine and other mediators cause increased permeability of local blood vessels (fluid enters tissue causing swelling or edema); the swelling produces the wheal; increased blood flow in the area causes redness (flare)
What is systemic anaphylaxis?
What causes the drop in blood pressure?
How is this different from prophylactics ?
wide-spread activation of mast cell degranulation causing both an increase
in vascular permeability and a widespread constriction of smooth muscle
•• fluid leaving the blood causes dramatic reduction of blood pressure (anaphylactic shock)
***called anaphylaxis (anti-protection) because instead of being protective, this immune response is
fatal; as opposed to prophylaxis (protection)
What are anaphylactoid reactions ?
resemble anaphylactic reactions, but do not involve interaction between allergen and IgE
What are the 4 ways epinephrine can ease the effects of an anaphylactic reaction
injection of epinephrine.
- This tightens the tight junctions between endothelial cells, (Decreases permeability)
- Diminishes swelling
- Raises Blood Pressure
- Relaxes bronchioles so you can breathe
What does the injected epinephrine do ?
- • epinephrine stimulates reformation of tight junctions between endothelial cells, thus reducing permeability of blood vessels, diminishing tissue swelling, and raising blood pressure; also relaxes constricted bronchial smooth muscle and stimulates the heart
- • patients with known anaphylactic sensitivity to insect venoms or food are encouraged to carry a syringe full of epinephrine at all times (EpiPen)
- What is allergic Rhinitis ?
- What causes it ?
- What are some general organ involvement?
( I listed a bunch of things just try and remember what you can )
- mild allergic response characterized by violent bursts of sneezing and
runny nose in response to inhaled allergens•• - caused by allergens that diffuse across the mucous membranes of nasal passages and activate mucosal mast cells beneath the nasal epithelium which release histamine
- histamine release causes a general irritation of the nasal passages as well as fluid accumulation in the nose and throat. (reasons why you would take antihistamine)
What is allergenic Asthma ?
Chronic breathing difficulties triggered by submucosal allergens. IgE activates submucosal mast cells and the histamine will cause bronchial constriction.
What type of hypersensitivity is chronic asthma?
Type 4
What is urticaria ?
(hives): itchy swellings caused by release of histamine by mast cells in the skin (following activation by allergen)
•• reaction is essentially a wheal and flare reaction
What is angioedema ?
inflammation caused by activation of mast cells in deep subcutaneous tissue •• swelling is more diffuse than observed for urticaria
What are the three common strategies to treat and prevent allergic reactions ?
Three main ones. With lots of details. Sorry in the future I will make them better
1) modification of patients behavior and environment to eliminate contact with the allergen
2) pharmacological approach: to use drugs that reduce the impact of contact with an allergen
•• drugs that block the effector pathways of the allergic response and limit inflammation that results
3) immunological treatment: to prevent the production of allergen-specific IgE
•• modulate the immune response so that it shifts from an IgE response to an IgG response
How do antihistamines help allergic reactions ?
reduces rhinitis and urticaria by preventing histamine from binding to H1 histamine receptors on vascular endothelium
How do corticosteroids help treat allergic reactions?
suppresses leukocyte function; used to treat chronic inflammation of asthma, rhinitis, or eczema
How is epinephrine used to treat allergic reactions ?
Reverses anaphylaxis
How do you moderate the immune response to switch it from IgE to IgG
••• desensitization: a series of injections of increasing doses of the allergen; gradually
changes a TH2 (IgE) response to a TH1 response in which no IgE is produced; can result
in anaphylaxis…must be careful!
••• vaccinate patients with allergen-derived peptides that are known to be presented by
HLA class II molecules to TH2 CD4 cells in an attempt to induce anergy
Describe Type 2 hypersensitivities
type II hypersensitivity reactions are caused by antibodies specific for altered components of
human cells
•• common examples include hemolytic anemia and thrombocytopenia (caused by destruction
of red blood cells or platelets, respectively) following the administration of drugs
Can type 2 hypersensitivities be associated with the administration of drugs ?
Yes, type II hypersensitivity reactions can be associated with the administration of the drugs
penicillin, quinidine (used to treat cardiac arrhythmia), and methyldopa (used to treat high blood pressure)
••• in each case, the chemically active drug binds to the surface of red blood cells or platelets and creates new epitopes to which the immune system is not tolerant
Describe a penicillin induced Type 2 hypersensitivity
he new epitopes generated by penicillin stimulate the production of IgM and IgG antibody specific
for the new epitope(s)
•• penicillin-modified RBCs must be coated with complement (side effect of complement
activation by infection being treated with penicillin); facilitates phagocytosis by
macrophages via complement receptors
Characterize type 3 hypersensitivities
type III hypersensitivity reactions are caused by immune complexes formed from IgG and soluble antigens
What is serum sickness ?
results from immune responses to non-self material administered into the
bloodstream as a treatment for a variety of illnesses; serum sickness is caused by a systemic accumulation of immune complexes (and eventual systemic inflammatory responses), and is characterized by chills, fever, rash, arthritis, vasculitis, and sometimes glomerulonephritis
How can Type 3 hypersensitivities cause tissue damage?
tissue damage (type III hypersensitivity) occurs when sufficient immune complexes accumulate; once immune complexes accumulate, circulating leukocytes recognize the immune complexes thru their Fc and complement receptors, activating their inflammatory activities
Describe type 4 hypersensitivies ?
type IV hypersensitivity reactions are mediated by antigen-specific effector T cells
•• also called delayed-type hypersensitivity (DTH) reactions because they usually occur 1-3
days after contact with antigen; this is in stark contrast to Ab-mediated hypersensitivities which are usually apparent within minutes of antigen exposure
What type of hypersensitivity is poision ivy and how does it work ?
type IV hypersensitivity reaction produced against penadecacatechol upon initial contact with a poison ivy plant, penadecacatechol penetrates the outer layers of the skin and indiscriminately forms covalent bonds with extracellular proteins and skin cell surface proteins, forming new antigens that are recognized as non-self; local antigen presenting cells (macrophages and Langerhans’ cells) take up the new antigens, return to secondary lymphoid tissues, and present peptide antigens on MHC class II to naïve CD4 cells
Describe Contact Specificity
poison ivy is an example of contact sensitivity, because contact of the allergen with the skin is required to initiate the allergic response
What induces class switching from IgM to IgE ?
Cytokines secreted from TH2 cells
How do the Th2 cells induce class switching from IgM to IgE ?
They secrete IL-4, IL-5, IL-13 which up regulates CD-40 ligand and CD 23 ligand
What stimulates allergic asthma
IgE / Allergen interaction
What is allergic asthma characterized by ?
3 Things
- Increased fluid in muccosal secretions into the respiratory tract.
- Bronchial construction due to contraction of smooth muscle surrounding airways.
- Chronic inflammation of the airways involving persistent infiltration of leukocytes.
While the allergic asthma is initially driven by a response to an allergen what will the chronic inflammation do?
Do you need continuous stimulation to maintain the chronic inflammation ?
The chronic inflammation can persist even in the absence of further antigen.
- Mucous plugs will occlude the airways
- Hypersensitivity of the airway will develop. Making them succeptable to smoke and chemicals
What is another way asthma is triggered ?
Kyle’s Cousin in South Park… Dont throw the ball to Faaaaaast I have aaaaasthma..
Has anyone seen my Glaaaasses ?
What can exaborate asthma responses ?
Bacterial and viral infections
