Immuno: Hypersensitivity Flashcards
What is the primary mediator of Type 1 Hypersensitivity?
IgE dependent Mast cells
What is the primary mediator of Type II Hypersensitivity?
IgG Abs that react with cell-surface or matrix antigens
What is the primary mediator of Type III Hypersensitivity?
Immune complexes
What is the primary mediator of Type IV Hypersensitivity?
T-cells
Why is Type IV also called delayed-type?
Because it takes a little while for effector T cells to proliferate.
Arthus reaction happens during what type of hypersensitivity reaction?
Type III - immune complex
Most human allergic responses are elicited by what route?
Inhalation of PROTEIN allergens
Name some properties common to most antigens
- Protein
2. HIghly soluble
How do soluble inhaled allergens get onto our system?
Inhale their carriers - most allergens are carried on desiccated particles (pollen, mite feces)
Upon contact with the mucosa of airways, soluble antigens elute from the delivery particles and diffuse into the mucosa.
What kind of T cell response do soluble inhaled antigens elicit?
Th2 cell response.
Soluble inhaled antigens are presented to the immune system at very low doses. Remember: Low doses of antigen cause Th0 –> Th2.
How do Th2 cells promote B-cells to class switch their antibodies to IgE?
Once Th2 cell binds its antigen via MHC-II, it secretes Il-4,5, and 13. These upregulate the T cell’s expression of CD40L and CD23 (low affinity IgE receptor)
CD40L and CD23 molecules bind to their match on B cells: CD40 and CD2 (respectively)
This combo of signals induces class switching to IgE by that B cell.
T/F : All people exposed to allergens will have an immune response.
False.
May be first exposure (allergic response occurs only after 2nd exposure) or an individual may not have innate reaction to that particular antigen.
Parasites produce many _____________, which elicit what kind of immune response? What kind of hypersensitivity?
proteolytic enzymes (proteases) are strong inducers of Th2 responses, therefore IgE response.
Type 1 Hypersensitivity
What 3 types of cells express the high affinity IgE receptor? What is the receptor called?
Mast cells, basophils, and eosinophils all express FceR1.
What causes degranulaton of mast cells, eosinophils, and basophils?
Antigen binding to and cross-linking IgE bound to the cells. (serving as a hijacked receptor since granulocytes don’t have specific receptors of their own)
During Type 1 hypersensitivity, mast cells degranulate, and what is the result?
The chemicals released are inflammatory mediators. They recruit eosinophils and basophils to the area, and contribute to the inflammatory response.
What demographic is most likely to have IgE responses to common environmental agents? What is this predisposed state called?
White people of N. America and Europe.
Atopy is the term for a predisposition to type 1 hypersensitivity evoked by common allergens.
What do Atopic individuals have that others don’t, that makes them more susceptible to IgE mediated hypersensitivity?
Higher levels of soluble IgE and more circulating eosinophils than normal people
How do you tell an individual’s sensitivity to a particular antigen?
There is a 2 step response if a person has an allergy to an injected allergen.
1st step of response: Wheal and flare caused by immediate mast cell degranulation. Histamine from the mast cell granules causes the wheal (increases vascular permeability in the area) and flare (redness caused by increased blood flow).
2nd step of response: 6-8 hours post-injection (late phase reaction) More widespread inflammatory response mediated by granule contents (chemokines, leukotrienes…etc..)
Airborne allergens will cause mast cell degranulation where?
In the bronchial mucosa.
Food-borne allergens will cause mast cell degranulation where?
GI tract.
Mast cell degranulation in the gut causes what to happen?
Increased mucosal secretion and increased peristalsis. Vomiting, diarrhea possibly
Mast cell degranulation in the airway causes what to happen?
Decreased diameter of bronchi (bronchioconstriction)
Increased mucus production
Violent cough, sneezing, wheezing.
Mast cell degranulation in the bloodstream causes what immediate effects?
Edema, inflammation, increased blood flow, vascular permeability, increased lymph flow and carriage of antigens to lymph nodes, creating more of a memory response.
What causes systemic anaphylaxis?
Wide-spread activation of mast cells. Degranulation causes INCREASED VASCULAR PERMEABILITY and widespread CONTRACTION OF SMOOTH MUSCLE.
Describe the effects of systemic anaphylaxis.
- blood fluid depletion leading to ANAPHYLACTIC SHOCK
- Connective tissue swelling
- Constriction of airways and epiglottis swelling = ASPHYXIATION
What does anaphylaxis mean, literally?
“Anti-protection”
Makes sense. Prophylactic means “protective.”
What are some methods by which allergens can be introduced directly into the bloodstream?
- Insect sting
- Drug injection/ingestion
- Food intake - if GI absorption into the blood is rapid (peanuts)
What is the most common cause of anaphylaxis in the USA?
Drug injection/ingestion. Primarily IgE mediated allergy to PENICILLIN.
What is a reaction that resembles anaphylaxis, but doesn’t involve interaction between allergen and IgE called?
Anaphylactoid reaction.
“Anaphylaxis-like”
How do you treat anaphylaxis and anaphylactoid reactions? How does this treatment fix the problem?
Epinephrine injection stimulates reformation of tight junctions in between endothelial cells.
- reduce vessel permeability and tissue swelling
- raise BP
- Relax bronchial smooth muscle
- Kick start the heart
The formal name for hay fever is….. What is hay fever?
Allergic Rhinitis. mild allergic response. Violent bursts of coughing, sneezing, and runny nose in response to an inhaled allergen.
WHat are the characteristic traits of hay fever?
Local edema obstructing the nasal passages.
Nasal discharge that’s rich in eosinophils.
What other complications can arise from hay fever? (mild…)
Ear/throat infections due to accumulation of fluid in sinuses and eustachian tubes.
Conjunctival inflammation. (allergic conjunctivitis)
Which is more serious, rhinitis or asthma?
Asthma. You can’t die from hay fever.
Asthma involves the triggering of mast cell degranulation where, primarily?
the lower respiratory tract.
If a person with asthma inhales a common allergen that triggers mast cell degranulation, what happens next, physiologically?
Mucus secretion increases, and smooth muscle surrounding the bronchial airways constricts.
What type of leukocytes are found in the chronic inflammation found in the lungs of an asthma patient?
Th2s, eosinophils, neurophils.
What kind of hypersensitivity reaction is Asthma?
Type IV
What 2 reactions can occur from food or drug allergens that get carried to the skin via the bloodstream?
Urticaria (hives) - wheal and flare
Angioedema - mast cells degranulate in deep subcutaneous tissue. - more diffuse swelling than urticaria
What is the pathology behind ingestion of mild food antigens that affect the GI tract?
Individual ingests food allergen (ex: milk), and allergen passes through the gut wall, causing mast cell degranulation by binding to IgE.
Triggers vascular permeability, leading to fluid accumulation in the gut lumen
Smooth muscle contraction increases peristalsis in stomach and GI tract.
VOMITING and DIARRHEA
How does having a parasite prevent allergic responses?
In the presence of parasites, parasite-specific IgE is synthesized. THis is different from the normal IgE bound to mast cells usually. The normal IgE and parasite-specific IgE compete for the FceRI receptors on mast cells. Fewer cross links between receptors occur, due to difference in antigen specificity, so allergic reactions are abated.
What causes Type II hypersensitivity?
IgG antibodies specific for altered components of human cells.
What usually causes type II hypersensitivity?
Drugs and autoimmunity.
Describe the mechanism by which certain drugs cause Type II hypersensitivity reactions. What are examples of such drugs?
Drugs bind to RBC or platelet surface and create new epitopes. Immune system is not tolerant of these altered surface antigens.
Describe the mechanism of Penicillin-induced Type II hypersensitivity.
- Penicillin binds RBCs and creates altered surface antigens.
- Complement binds new antigens and the RBC is phagocytosed by MACs that bind complement receptors.
- MACs process RBCs and present new epitopes to naive CD4+ T’s, inducing a Th2 response.
- Th2s supply 2nd activation signal to B-cells, causing production of IgG and IgM specific for altered RBC epitopes.
- Abs coat altered RBCs and activate complement or induce phagocytosis.
- RBC depletion = ANEMIA
What causes Type III Hypersensitivity?
The accumulation of Immune complexes formed from IgG and soluble antigens. Once they accumulate, circulating leukocytes recognize their Fc receptors and activate inflammatory response.
Do antibody complexes (immune complexes) always cause damage?
No. They are made with essentially every immune response, and in normal cases cause no damage.
Which is the bigger problem: large or small immune complexes?
SMALL!
Large immune complexes can fix complement easily, and are readily taken up by MACs.
Small immune complexes don’t fix complement as easily, and tend to remain in circulation and deposit on blood vessel walls.
Immune response to non-self material administered directly into the bloodstream is called……
Serum sickness
What are the symptoms of serum sickness?
Chills fever Rash Arthritis Vasculitis Sometimes glomerulonephritis
What are the 2 most common Type III hypersensitivity reactions of the lung?
Bird-breeders disease
Farmer’s Lung
How do you get Type III hypersensitivity in the lungs?
Occupational hazards where workers constantly inhale the same airborne antigens.
How long after antigen exposure does a delayed-type hypersensitivity reaction occur?
1-3 days after exposure
What is the most well-studied Type IV hypersensitivity reaction?
Tuberculosis test.
What indicates a positive TB test?
If a person has antibodies to a TB test, it means they have been previously infected with TB.
They will produce an inflammatory reaction around the injection site within 24-72 hours.
What type of helper T’s are utilized in Type IV hypersensitivity?
Th1s - for macrophage recruitment. Think about how TB is cleared! Have to activate MACs!
What cytokines produced by Th2 cells cause B-cell Ab class switching to IgE?
Il-4 and Il-13
What substances release by mast cell degranulation are responsible for smooth muscle contraction?
Leukotrienes C4, D4, and E4
Describe the Arthus reaction.
Occurs in situations of Type III Hypersensitivity.
Soluble antigen floats in bloodstream and gets opsonized by IgG antibodies the host has previously generated to that antigen.
Classical complement pathway activated.
C5a binds receptors on Mast cells in surrounding tissues and cause degranulation.
Mast cells cause vascular permeability, vasodilation, and recruit MACs/neutrophils.
Macs and Neutrophils can bind immune complexes with their Fc receptors and secrete their inflammatory mediators as well.
Inflammation everywhere.
How is an Arthus reaction specifically defined? Hw long does it take to occur?
Systemic inflammation caused by immune complexes. Takes 1-2 hours to occur
WHere is the main site of immune complex deposition in the body?
Kidney Glomeruli
What do people inhale to get Farmer’s Lung? What type of sensitivity reaction is it?
Mold spores and allergens - chronic inhalation of an allergen produces Type IV sensitivity.
Poison ivy is what type of immune reaction? what cells is it mediated by?
Type IV. Mediated by Th1s and CTLs.
What’s the name of the oil in poison ivy that penetrates the skin and causes alteration of self-determinants?
Pentadecacatechol
If you see the words “happened in minutes” in a question stem, what type of antibody mediated the allergic reaction?
IgE - Type 1 hypersensitivity
What type of T cell is involved in Type 1 hypersensitivity? Why?
Th2 cells are needed for the activation of B-cells to produce IgE
“Modified self antigens” provoke what type of immune response?
Type 2 hypersensitivity
How long does it take for a Type 4 Hypersensitivity reaction to occur?
24-72 hours, sometimes even weeks. Anything before that is NOT TYPE 4
Antigens that selectively induce a Th2 cell response that causes IgE production are called….
Allergens
There are a lot of proteases floating around in the blood stream. What type of infection do you have and what hypersensitivity response will occur?
Proteases are secreted by parasites. Th2/IgE response will be the result.
Acute asthma is what type of hypersensitivity reaction? Chronic asthma?
Acute - Type 1 - mast cell degranulation in the lower bronchi
Chronic - Type 2 - chronic inflammation, triggered by random antigens
What type of reaction is Bird Breeder’s lung? Farmers lung?
Type 3 hy[ersensitivity- occurs due to chronic inhalation of antigens that elicit IgG responses rather than IgE. Accumulation of immune complexes in the lungs/alveoli - leads to inflammation
Delayed type hypersensitivity reactions have Th1 cell responses. What does this indicate about the sheer amount of antigen in the body?
100-1000 fold larger quantities of antigen are required to activate Type IV responses. Remember, large quantities of antigen = Th1 response. MAC recruitment.
An allergic reaction caused by contact of an allergen to the skin is called what?
Contact sensitivity.
Examples: Pentadecacatechol/nickel
