Term
| True or False: Much of the damage in the diseases we encounter results from the actions of the immune response itself, rather than the invading organism. |
|
Definition
|
|
Term
| Give an example of an immunosuppressive class of drugs. Anti-inflammatory? |
|
Definition
-immunosuppressive: corticosteroids
-anti-inflammatory: aspirin, steroids, NSAIDS |
|
|
Term
| Disorders of the immunity can be thought of in three ways. What are they? |
|
Definition
1) a failure f the immune system to respond to foreign antigens= immune deficiencies (AIDS)
2) a failure to differentiate b/n self and non-self= autoimmune diseases
3) an exaggerated form of a normal immune response= hypersensitivity disorders |
|
|
Term
| In what three ways do the types of hypersensitivity differ? |
|
Definition
1) the component of the immune system that stimulates the rxn
2) the cells that are responsible for doing the damage or releasing the chemicals that do the damage
3) the pathologic manifestations of disease that they produce |
|
|
Term
| Give a general definition of type I hypersensitivity |
|
Definition
-aka "immediate" hypersensitivities
-clinical signs can be seen within seconds to minutes after exposure to the appropriate antigen |
|
|
Term
| What is the immune reactant in type I hypersensitivity disorders? What cells are involved? |
|
Definition
-IgE
-mast cells, basophils, eosinophils, and neutrophils |
|
|
Term
| What is the layman's term for type I hypersensitivity? What if it is systemic? |
|
Definition
-allergic rxn
-systemic= anaphylactic rxn |
|
|
Term
| Definition: Anaphylactoid |
|
Definition
| -a term used to describe the clinical manifestations of cellular events that happen in anaphylaxis that are triggered by non-immunolic factors |
|
|
Term
| What kind(s) of cell(s) does IgE bind(s) to? |
|
Definition
| -mast cells, basophils, activated eosinophils, and neutrophils |
|
|
Term
| What is special about IgE binding? |
|
Definition
| -it can bind to Fc receptor WITHOUT having to first bind to a specific antigen |
|
|
Term
| Where do mast cells originate? |
|
Definition
|
|
Term
| What is the delineation b/n the two kinds of mast cells? |
|
Definition
-one lives in CT
-one lives in mucosal tissues |
|
|
Term
| How can you identify mast cells? |
|
Definition
| -cytoplasm of the cell is packed with pink to purple staining granules with a round nucleus |
|
|
Term
| What is inside the granules of a mast cell? |
|
Definition
| -mediators responsible for Type I hypersensitivity rxns |
|
|
Term
| Basophils originate in the _________ and are most commonly found in the _________. |
|
Definition
|
|
Term
| How do we identify basophils? |
|
Definition
| -cytoplasmic granules are blue with a segmented nucleus |
|
|
Term
| Eosinophils are born where? Where are they most commonly found? |
|
Definition
|
|
Term
| How do we identify eosinophils? |
|
Definition
| -segmented nuclei with orange-sih granules |
|
|
Term
| Eosinophils are specifically designed to kill _________. |
|
Definition
|
|
Term
| True or False regarding Sensitization: The first step in any type I rxn is tat an animal responds to a particular antigen by producing IgG. |
|
Definition
|
|
Term
| What is the role of IgE in type I hypersensitivity rxns? What is its half-life? |
|
Definition
-binds to mast cells to prime them for action
-serum IgE has a half life of 2d but it is 12d when bound to mast cells |
|
|
Term
| If the same antigen is encountered again and makes it through circulation and into the tissues, it can now bind to the mast cell bound IgE, _____-ing the Fc receptors. |
|
Definition
|
|
Term
| What is the point of cross-linking the Fc receptors on the mast cells during a type I hypersensitivity rxn? |
|
Definition
1) second messenger systems are activated, causing the release of the cytoplasmic granules
-phospholipase A is activated, releasing arachidonic acid to produce prostaglandins and leukotrienes |
|
|
Term
| What are some of the major granule consitituents used in a type I hypersensitivity rxn? |
|
Definition
| -histamine, heparin, serotonin, kallikriens, and proteases |
|
|
Term
| What are the combined major effects of the mediators of a type I hypersensitivity rxn? |
|
Definition
1) inc vascular perm: causes edema, swelling, and hypotension
2) vasodilation mostly (some vasoconstriction)
3) smooth muscle contraction: prominent in airways, bladder, and intestines
4) increased glandular secretions: runny eyes and watery nose |
|
|
Term
| Describe the "second wave" evident in type I hypersensitivity rxns |
|
Definition
-occurs due to the recruitment of eosinophils several hrs after exposure
-many of the eosinophil granule products are capable of killing parasites |
|
|
Term
| IgE is produced under the influence of what type of T-helper cell? In response to what cytokine(s)? |
|
Definition
-Th2
-in response to IL-4: induces class switching to IgE in B-cells AND stims naïve T-cells to becme Th2 cells |
|
|
Term
| True or False: Antigens that are presented in very high concentrations across mucosal surfaces tend to induce IgE responses, an example being parasite antigens or antigens that are enzymes. |
|
Definition
|
|
Term
|
Definition
| -a predisposition to producing IgE and htus having allergies |
|
|
Term
| What is the biological activity of histamines in type I hypersensitivity rxns? |
|
Definition
| -vasodilation, smooth muscle contraction, inc vascular perm |
|
|
Term
| What is the biological activity of serotonin in type I hypersensitivity rxns? |
|
Definition
| -vasoconstriction or dilation dep on spp, smooth muscle contration |
|
|
Term
| What is the biological activity of heparin in type I hypersensitivity rxns? |
|
Definition
| -protects mast cells from proteases, anticoagulant |
|
|
Term
| What is the biological activity of eosinophil chemotactic factor in type I hypersensitivity rxns? |
|
Definition
|
|
Term
| What is the biological activity of proteases in type I hypersensitivity rxns? |
|
Definition
| -activates complement to form anaphylotoxincs (C3a, C5a) |
|
|
Term
| What are the two types of arachidonic acid metabolites? What do they do? |
|
Definition
-Prostaglandin D2: bronchospasm, vasodilation, mucus secretion
-LTC4/LTD4/LTE4: vasodilation, smooth muscle contraction, inc vascular perm |
|
|
Term
| What are the 4 eosinophil mediators? What do they do? |
|
Definition
-eosinophil peroxidase: kill microorganisms, toxic to host cells, triggers histamine release from mast cells
-Major basic protein: toxic to parasites and host cells, triggers histamine release from mast cells
-eosinophil cationic protein: toxic to parasites, neurotoxin
-eosinophil derived neurotoxin: neurotoxin (shocker) |
|
|
Term
| What are the visible dermatologic changes that occur in a type I hypersensitivity rxn in response to histamine? |
|
Definition
-inc in vascular perm with extravasation of fluid
-utricaria: red, edematous swelling in the skin
-Angioedema: diffuse swelling due to fluid accumulation in loose CT |
|
|
Term
| True or False: In type I hypersensitivity rxns, the skin often becomes intensely pruritic in the location the antigen was absorbed. |
|
Definition
| FALSE, occurs where the mast cells are, not where the antigen was absorbed |
|
|
Term
| What are the GI clinical signs that occur during a type I hypersensitivity rxns? |
|
Definition
-smooth muscle contraction leads to vomiting and/or diarrhea
-possibly urination |
|
|
Term
| What are the respiratory clinical signs that occur in a type I hypersensitivity rxn? |
|
Definition
-smooth muscle contraction can cause bronchoconstriction and dyspnea
-possibly inc mucus production |
|
|
Term
| What are the systemic affects of a type I hypersensitivity rxn? |
|
Definition
-profound hypotension from widespread vasodilation, leading to collapse
-dyspnea and coughing
-in dogs: liver is shock organ thus liver is often massively engorged with blood |
|
|
Term
| What are a few examples of triggers of type I hypersensitivity rxns? |
|
Definition
-Vaccines: especially those containing adjuvant or those that are multivalent
-Drugs: often act as haptens (ex: Penecillin)
-Parasites: parasitic infections can make the rxns go overboard sometimes (cysts can be ruptures and this will cause anaphylaxis)
-inhaled allergens: often cause prurtitic dermatitis in animals
-Dietary allergans: abnormal consistency of feces, vomiting, cramping, etc |
|
|
Term
| What are the 3 most popular courses of treatment of type I hypersensitivity rxns? Describe them. |
|
Definition
-Avoidance: most affective with drugs and food allergies, but not plausible with inhaled allergens
-Drug therapy: epinephrine is the most important, antihistamines, and corticosteroids |
|
|
Term
| Describe how epinephrine is helpful in the treatment of type I hypersensitivity rxns. |
|
Definition
-has both alpha and beta adrenergic actions
-alpha affects: constriction of peripheral vessels that reduces edema and raises blood pressure
-beta actions relax smooth muscle and promote bronchodilation
-Desensitization therapy |
|
|
Term
| How are corticosteroids helpful in treating type I hypersensitivity rxns? |
|
Definition
-they are both anti-inflammatory and immunosuppressive
-inhibit phospholipase A from releasing arachidonic acid from cell membranes, thus preventing the generation of prostaglandins and leukotrienes |
|
|
Term
| Describe Desensitization therapy |
|
Definition
-giving the animal a series of injections containing gradually increasing ocncentrations of the offending allergen over a number of weeks
-stimulates Th1 cells to produce gamma interferon and eventually a shift from a Th2 to Th1 response
-this will block the production of IgE, shutting down the Th2 response |
|
|
Term
| Type II hypersensitivity rxns are also termed ________ b/c the immune response is directed against cellular anitgnes. |
|
Definition
|
|
Term
| True or False: In a type II hypersensitivity rxn, the antigens present on the cells must be antigens intrinsic to that cell. |
|
Definition
| FALSE, the antigens can either be anitgens intricnic to that cell or an antigen that has absorbed onto the cell membrane |
|
|
Term
| If an intrinsic cell antigen is recognized in a hypersensitivity rxn, the disease is one of _________. |
|
Definition
|
|
Term
| The antibodies involved in autoimmunity are termed _________. |
|
Definition
|
|
Term
| What are the immune reactants in type II hypersensitivity disease? |
|
Definition
|
|
Term
| What cells are involved in type II hypersensitivity rxns? |
|
Definition
-RBCs most common, the platelets
-neutrophils are least common |
|
|
Term
| What ar the pathologic findings found with type II hypersensitivity rxns? |
|
Definition
-hemolytic anemia, thrombocytopenia (low platelet count), or neutropenia
-signs of hemolytic anemia result of lack of oxygen: weakness, collapse
-signs of thrombocytopenia resulf from agnormal coagulation: petechial hemorrhages, ecchymotic hemorrhages, bleeding from mucosal surfaces |
|
|
Term
| In a type II hypersensitivity rxn, once an IgG or IgM has formed against and bound to an erythrocyte Ag, there are 3 major effector mechanisms. What are they? |
|
Definition
1) Phagocytosis: RBS that have been opsonized are recognized by macrophages and phagocytized mainly in the spleen and liver (this is called extravascular hemolysis)
2) complement lysis: if sufficient complement activation occurs, cells are destroyed by the formation of a membrane attack complex (called intravascular RBC destruction)
-Antibody dependent cellular cytotoxicity (ADCC): NK cells bind ot the Fc fragments of IgG and results in cell lysis via perforin-granzyme patway |
|
|
Term
| What will you expect to see in the CBC of intravascular RBC destruction that you will NOT see in the CBC of extravascular hemolysis? |
|
Definition
| -hemolyzed serum (pink-red serum) and hemoglobinuria (red urin dur to free hemoglobin) |
|
|
Term
| What are three different examples of type II hypersensitivity rxns? |
|
Definition
1) blood transfusion rxns
2) hemolytic disease of newborn (HDN)
3) immune mediated hemolytic anemia (IMHA)/ immune mediated thrombocytopenia (ITP) |
|
|
Term
| What causes a blood transfusion rxn? |
|
Definition
-the donor red cells have an antigen that is not present on the red cells of the recipient
-a subsequent transfusion of red cells with the same antigen can result in a hemolytic transfusion rxn (type II hypersensitivity rxn) |
|
|
Term
| Why are blood transfusion rxns important? |
|
Definition
-you lost the transfused cells very quickly and the transfusion basically does no good
-more importantly, the destruction of the transfused red cells is associated with complement activation and a subsequent systemic inflammatory response |
|
|
Term
| In a blood transfusion rxn, the antibodies that form against transfused RBCs are termed _________. |
|
Definition
|
|
Term
| True or False: Blood transfusion rxns only occur after multiple transfusion from the same type of incompatible blood. |
|
Definition
| FALSE, only true for the most part, not true in animals like cats that have naturally occurring alloantibodies to certain blood antigens |
|
|
Term
Definition: neonatal isoerythrolysis (NI)
-what is this called in humans?
-what species has this most commonly? |
|
Definition
-hemolysis that occurs when a newborn's RBCs are destroyed by Ab's made by the mother
-in humans this is called "erythroblastosis fetalis"
-occurs most commonly in horses |
|
|
Term
|
Definition
-occurs when a mare lacking a certain RBC Ag is bred to a stallion that has a RBC Ag, then the fetal RBCs have the Ag that is foreign to the mare
-when transferring of fetal RBS and mare RBCs occurs, the mare will mount an Ab response to the Ab on the fetal RBCs
-when maternal Ab's are transferred to the foal via colostrum ingestion, a hemolytic rxn occurs in the foal |
|
|
Term
| What is the easiest way to avid NI? |
|
Definition
|
|
Term
| Describe the general mechanism of IMHA/ITP. |
|
Definition
| -Ab's are developed to RBC antigens with subsequent phagocytosis or intravascular destruction bit it is NOT associated with transfusion |
|
|
Term
| Describe the mechanism of autoimmune hemolytic anemia. |
|
Definition
| -Ab's are mounted against normal RBC Ag's due to a breakdown of self-tolerance |
|
|
Term
| Give an type II hypersensitivity example of Ab's being directed against foreign Ag's absorbed to RBCs. |
|
Definition
| -when RBC's become infected with parasites |
|
|
Term
| Describe the effects of Hemobartonella felis in cats |
|
Definition
-common RBC parasite of cats
-extracellular parasite that lives on the outside of RBCs
-Ag's on surface of RBCs will incite IMHA
-also occurs with bacterial Ag's, viral Ag, and drug Ag |
|
|
Term
| During what season are IMHA/ITP more common? |
|
Definition
|
|
Term
| True or False: Most RBC antigens are either glycoproteins or glycolipids present on the surface of the cell, integral membrane components, but some are soluble Ag's that are present in circulation and just passively adhere to RBC membranes. |
|
Definition
|
|
Term
| Describe the blood system of cats. |
|
Definition
-AB system with A dom over B
-AB is extremely rare
-99% of cats are blood type A, 40% of British shorthairs are B
-rxns from mismatched blood are severe b/c most B cats have very strong natural Ab's agains A Ag's |
|
|
Term
| Is neonatal isoerythrolysis (NI) common in cats? |
|
Definition
| -not common, but likely to occur when a B queen is bred to an A male |
|
|
Term
| Describe the blood system of dogs. |
|
Definition
-DEA 1,3,4,5,6,7,8
-DEA 4= 98% of dogs
-DEA 1.1>1.2>1.3 (about 60% of dogs have one of those Ag's, the rest are negative)
-DEA 1 system produces the mostly clinically severe transfusion rxns thus universal donor= DEA 1 negative |
|
|
Term
| Describe the blood system of cows. |
|
Definition
|
|
Term
| Describe the blood system of horses. |
|
Definition
-7 different group systems
-NI is most common in horses
--two major Ags responsible for NI in horses are Aa and Qa (Aa is more severe)
-less blood transfusions in horses b/c the donor cells only last for 3-5 days |
|
|
Term
| What are the major tests done regarding transfusion medicine? |
|
Definition
| -blood typing and cross matching |
|
|
Term
| What does blood typing accomplish? |
|
Definition
| -determines the status of an individual animal for a given Ag |
|
|
Term
| What is the purpose of cross-match testing? |
|
Definition
| -helps to tell you if there are performed antibodies present that are likely to cause a rxn b/n a given patient and a given donor |
|
|
Term
|
Definition
-the donor's red cells are mixed with the patient's serum
-if the red cells agglutinate, then the patient has antibodies, then the patient has antibodies against the red cells and the transfusion should not be given from that donor |
|
|
Term
| Type III hypersensitivity responses are known as _________ diseases because they are caused by the deposition of immune complexes in various tissues. |
|
Definition
|
|
Term
| Briefly explain what happens in an immune complex disease. |
|
Definition
| -occurs when Ab's bind their specific Ag in high numbers and produce immune complexes (ICs), either in circulation or in tissues, these immune complexes get deposited into various tissues and cause issues |
|
|
Term
| What are the three major things that happen in response to the accumulation of immune complexes in type III hypersensitivity reactions? |
|
Definition
1) Immune complexes lead to the activation of complexes: formation of MAC will damage the surrounding tissues, prdn of anaphylotoxins (C5a)
2) macrophages are also activated by their interaction with ICs and respond by releasing IL-1 and TNF-alpha=> lead to the upregulation of selectins on vascular endothelium
c) accumulated neutrophils attempt to phagocytize immune complexes and if the complexes are too large to be phagocytosed, they undergo frustrated phagocytosis, producing oxygen free radicals and damaging the tissue |
|
|
Term
| True or False: Any antigen that stimulates an antibody response can initiate a type III response if there is lots of it. |
|
Definition
|
|
Term
| In what situations do you typically see type III disease? Why? |
|
Definition
-autoimmune disease, persistent or recurrent infections and repeatedly inhaled environmental antigens
-b/c it takes a lot of antigen to form enough ICs to cause clinical disease |
|
|
Term
| Give an example of an autoimmune disease that is a type III hypersensitivity disease. Why are autoimmune diseases potential causes of type II reactions? |
|
Definition
-systemic lupu erthematosis or SLE
-b/c self antigens will always be present and will continually promote the formation of more antibody |
|
|
Term
| True or False: Environmental antigens that are repeatedly inhaled over a long period of time can cause type III disease although this is usually localized ot the lungs rather than being systemic. |
|
Definition
|
|
Term
| The antibodies involved in type III hypersensitivity reactions must be precipitating and complement fixing. The are usually ___ or ___. |
|
Definition
|
|
Term
| What are they two basic types of IC disease? |
|
Definition
| -systemic/generalized and local |
|
|
Term
| Type III hypersensitivity diseases differ from type ___ hypersensitivity rxns in that there is no immunologic specificity involved as far as the tissues damaged. |
|
Definition
|
|
Term
| In a type III hypersensitivity rxn, the tissues affected by disease are dictated how? |
|
Definition
| -by where the immune complexes get deposited |
|
|
Term
| In systemic IC disease, circulating immune complexes get deposited in tissue in which there is ________. |
|
Definition
|
|
Term
| Where are some locations in the body that are common for systemic IC disease? |
|
Definition
| -glomerulus, synovial membrane, choroid plexus, and small vessels of the skin |
|
|
Term
| Glomerular deposition of immune complexes leads to a ______, one common manifestation of systemic IC disease. |
|
Definition
|
|
Term
| How does glomerulopathy present? |
|
Definition
| -loss of the ability of the glomerulus to selectively retain large molecular weight molecules in the blood, thus proteinuria that leads to hypoproteinemia |
|
|
Term
| Deposition of ICs in synovial membranes leads to a _________ (inflammation of multiple joints). |
|
Definition
|
|
Term
| Deposition of ICs in vessels of the skin lead to destruction of those vessles (_________). How does this manifest? |
|
Definition
-vasculitis
-this usually manifests as hemorrhages within the skin, termed purpura |
|
|
Term
| In localized type III disease, antigens are often deposited in the ________. This leads to IC deposition where? |
|
Definition
-skin
-as the Ag is heading into the vessels, Ab is heading out of vessels, thus ICs will form in the vessel wall, leading to vasculitis (Arthus rxn) |
|
|
Term
| How long does it take Arthus rxn to develop? Is this slower or faster than a type I rxn? |
|
Definition
-several hrs (about 8)
-slower than a type I rxn |
|
|
Term
| What is the pathologic hallmark of Type III IC disease? |
|
Definition
|
|
Term
| Name a few of the known causes of glomerulonephritis. |
|
Definition
-heartworm disease
-neoplasms
-ehrlichiosis
-chronic viral disease |
|
|
Term
|
Definition
-protein losing glomerulopthy=> roteinuria, edema, ascites secondary to te resultant loss of oncotic pressure
-if bad enough, the entire nephron dies, thus renal failure
-high BUN and creaitne on CBC |
|
|
Term
Definition: Passive immunization
-was it bad? |
|
Definition
-years ago, hyperimmune serum containing Ig's against a specific disease were commonly used against specific diseases (usually of horse origin)
-sometimes people would mount an immune response to the horse proteins and a type III hypersensitivity would develop 7-10 days later |
|
|
Term
| In passive immunization, why does the type III hypersensitivity develop after 7-10 days? |
|
Definition
| -for ICs to form you need the Ag and Ab to be in approx. equal amounts and it takes about 7-10 days for the concentrations to reach this point |
|
|
Term
| What are the clinical signs of a type III hypersensitivity rxn in response to passive immunization? |
|
Definition
| -arthralgia (joint pain), glomerular disease, and skin lesions (vasculitis) |
|
|
Term
| What is hypersensitivity pneumonitis? What type of animal is susceptible? |
|
Definition
-a localized type III disease that results from the repeated inhalation of foreign antigens
-animals housed indoores throughout the winter are susceptible |
|
|
