Hypersensitivity - Toka Flashcards
What is Type I hypersensitivity mediated by?
IgE
What is Type II hypersensitivity mediated by?
IgG and IgM
What is Type III hypersensitivity mediated by?
Ab-Ag complexes
What is Type IV hypersensitivity mediated by?
T-lymphocytes
What is atopy?
Excessive production of IgE
What is phase 1 of hypersensitivity Type I? How does it work?
Phase 1: Sensitization
APCs present to CD4+ T cells
CD4+ T cells differentiate into Th2 cells
Th2 cells promote humoral response of B cells by secreting IL-4 and IL-13
B cells make alot of IgE
IgE then binds to BASOPHILS and MAST CELLS in tissues where Ag first entered
Then Mast cell makes more IL-4 following degranulation which stimulates Th2 cells
How does IgE bind to mast cells?
Through Fc receptor - FcERI (most commonly)
Or by IgG using FcYRI
How does FcERI help with hypersensitivity Type I?
high affinity for IgE - binding is irreversible
IgG4
plays a role in atopic dermatitis in dogs
What is phase 2 of hypersensitivity Type I? How does it work?
Phase 2: Hypersensitivity rxn
** inflamm. occurs rapidly
Re-encounters Ag (allergen)
Binds to 2 IgE molecules (cross linking)
This leads to degranulation of mast cells and release of inflamm. mediators
= acute inflammation
What is the result of Phase 2, Type 1 hypersensitivity?
acute inflamm, results in URTICARIA, LACRIMATION, or SNEEZING
Edema, pruritis and hyperemia occur within 6-12 hours
What happens to mast cells after Type 1 Hypersensitivity?
They dont die
They regenerate contents of cytoplasmic granules
What is the clinical presentation of Type I Hypersensitivity?
Depends on:
- Dose of Ag
- Route of Admin of Ag
- # and location of mast cells
How does anaphylaxis occur?
When large doses of Ag are admin rapidly (intravenously)
What are symptoms of anaphylaxis?
- Difficulty breathing and talking
- Loss of consciousness
- Wheezing/ coughing
- Swelling of throat and tounge
Anaphylaxis in Horses
Shock organ: Resp tract + intestines
Symptoms: Cough, dyspnea
Pathology: Emphysema
Mediators: Histamine + Serotonin
Anaphylaxis in Dogs
Shock organ: HEPATIC VEIN
Symptoms: Collapse, dyspnea, diarrhea, vomiting
Pathology: Hemmorhage
Mediators: Histamine, Leukotrienes, Prostaglandins
Anaphylaxis in Swine
Shock organ: Resp tract + intestines
Symptoms: Cyanosis, pruritis
Pathology: Hypotension
Mediators: Histamine
Anaphylaxis in Ruminants
Shock organ: Resp Tract
Symptoms: cough, dyspnea, collapse
Pathology: lung edema, hemorrhage
Mediators: Serotonin, Leukotrienes, Kinins, Dopamine
Anaphylaxis in Cats
Shock organ: Resp tract
Symptoms: Dyspnea, vomiting, diarrhea, pluritis
Pathology: lung edema, intestinal hemorrhage
Mediators: Histamine, leukotrienes
Anaphylaxis in chickens
Shock organ: Resp. Tract
Symptoms: Dyspnea, convulsions
Pathology: lung edema
Mediators: Histamine, Serotonin, Leukotrienes
What are the routes of entry of an allergy?
- Inhalation
- Eyes
- Ingestion
- Intradermal
- Intravenous
What symptoms could you see from an allergen that entered the body through INHALATION?
Rxn in the resp tract
Sneezing, coughing, asthma
What symptoms could you see from an allergen that entered the body through the eyes?
Lacrimation, conjunctivitis
What symptoms could you see from an allergen that entered the body through INGESTION?
Colic, diarrhea, hemorrhage
What symptoms could you see from an allergen that entered the body INTRADERMALLY?
Urticaria, pruritus, hyperemia, dermatitis
What symptoms could you see from an allergen that entered the body INTRAVENOUSLY?
Systemic rxns
A dog got stung by wasps, what is the route of entry and what symptoms would you see?
Entered intradermally through bee sting, causes urticaria (hives)
What is an example of Type I Hypersensitivity in dairy cows?
Allergy to their own milk - common in dairy cows
Caused by lack of milking @ appropriate times
Allergic to A-casein in milk
These milk proteins are absorbed into blood and leads to allergic rxn causing skin lesions, anaphylaxis and death
Avoid by milking regularly
Food allergy is an example of Type _____ hypersensitivity rxn
Type I
Ag can reach the skin and bind to IgE on mast cells causing skin lesions and diarrhea
30% of skin problems are from food allergies in dogs
Food intolerance
Does NOT involve IR
results from toxic metabolites in food
Ex: Grapes, Chocolate
Atopic dermatitis is an example of Type ____ hypersensitivity
Type I
Through Ag (allergens) ingested, inhaled, or penetrated through skin
Penicillin
can lead to allergic or anaphylactic rxn (Type I Hypersensitivity)
metabolized to haptens which binds to host proteins and becomes immunogenic
Flea allergy dermatitis is an example of Type ___ Hypersensitivity?
Type I
How can you diagnose Type I Hypersensitivity?
- Direct skin test - inject dilute solutions of suspect allergens INTRADERMALLY, look for rxn
** not used in cats
** dogs cant be on steroids during testing
- Serology - Western Blot, ELISA
** neg result EXCLUDES atopy
How to manage Type I Hypersensitivity?
- Avoid allergen
- Corticosteroids - inhibits prostaglandin, leukotrienes - immunosupression
- Cyclosporines - treats symptoms of atopic dermatitis but does not solve it
- Histamine inhibitors - Benadryl
Desensitization of Type I Hypersensitivity
by reintroducing allergens to host
Giving IV injections of increasing amounts of allergen (Allergy shots)
Leads to decrease in IgE and increase in IgG
Activates T regs to secrete IL-10 and block IgE and mast cell degranulation
Reverses IR from Th2 to Th1
Type II Hypersensitivity is mediated by
IgG or IgM
How does Type II Hypersensitivity start?
By destruction of a target cell, leading to release of Antigens that sensitive the host
Leads to production of IgG and IgM Ab
What are the 3 pathways of Type II Hypersensitivity?
- Ab-Ag complex - complement binds + leads to tissue damage via Classical pathway
- Ab-Ag complex on cell surface - NK cells with Fc receptors bind and activate ADCC pathway
- Ab on cell surface act as OPSONINS which allows phagocytosis through Fc Receptors
Hemolytic Disease of Newborns (HDN) is an example of ____________
Type II Hypersensitivity
How does Hemolytic Disease of the Newborn (HDN) occur?
- Ag of fetus RBCs are introduced to moms blood
- Mom makes Ab against fetus RBCs + concentrates them in colostrum
- Mom transfers Ab to newborn through colostrum
- Baby has an anti-RBC rxn leading to haemolysis of RBCs
occurs if: mom is sensitized to fetus Ag, if mom has repeated placental bleeding, if mom breeds with the same sire, and if the newborn drinks the colostrum from mom who has anti-RBC AB
Type II hypersensitivity due to medications
- Drugs may bind to RBCs (Ex: penicillin) - RBCs recognized as non-self and get killed
- Drugs may modify RBC membranes and expose self Ag to which AB bind and opsonize for phagocytosis
- Drug + Ab activates complement and kill RBCs
Antigens from infectious agents cause Type II Hypersensitivity by
Modifying RBC membranes and making them look foreign so they are removed by complement or macrophages
Hypersensitivity Type III
Mediated by too many Ab-Ag complexes
Deposited in tissues leading to damage by neutrophils
What are examples of Type III Hypersensitivity?
- Glomerulonephritis
- Rheumatoid arthritis
- Serum sickness
- Arthus Rxn
- Malaria
What are the 2 forms of Type III Hypersensitivity?
- Localized
- Generalized
Localized Type III Hypersensitivity
Ag-Ab complexes deposited in tissues -
ANTIBODY EXCESS
Ex: Arthus rxn
Generalized Type III Hypersensitivity
Ag-Ab complexes formed in BLOOD during IV Ag administration.
Ag-Ab complexes deposited in glomerulus (kidney)
ANTIGEN EXCESS
Ex: Serum sickness - Ex Anti venom serum
What conditions lead to Arthus reaction?
- occurs in host who has alot of precipitating antibodies
- occurs when large amount of antibodies are administered to host who already has antigens
- occurs when already formed complexes with excess antibody are administered
Blue eye is an example of
Type III Hypersensitivity
How does blue eye occur?
In dogs following adenovirus infection or vaccination of live vaccine against adenovirus
Causes edema and opacity of cornea
What is serum sickness?
A disease that happens after IV admin of large amounts of ANTIGEN
Reacts by making Ab against serum
Causes GLOMERULONEPHRITIS
Type I Serum Sickness
Ag-Ab complexes deposited in endothelium of glomerulus
leads to production of TGF beta which stimulates production of collagen, fibronectin, and proteoglycan
these cause thickening of the glomerulus BM
Type II Serum sickness
proliferation of vascular endothelium and mesangial cells
Type III serum sickness
Deposition of Ag-Ab complexes on both sides of glomerular BM
results in kidney failure
IgA nephropathy
Deposition of Ag-Ab complexes in the kidneys
in dogs 4-7 yrs old
causes renal failure
Purpura hemorrhagica
in horses
after streptococcus equi infection
causes edema, hemorrhage on limbs and mucosa
A TYPE III Hypersensitivity
Type IV Hypersensitivity is mediated by?
T-cells
How long does it take for Type IV Hypersensitivity to occur?
72 hours
What is the difference between Type I-III hypersensitivity vs Type IV?
Type I-III mediated by Ab-Ag complexes
Type IV mediated by T cells
The tuberculin reaction is an example of _______
Type IV hypersensitivity
