BLD 434 - Quiz 6 Flashcards
Explain the immune system mechanism responsible for each of the 4 types of hypersensitivity reactions, including the isotype of the antibody involved (as appropriate) and/or effector cell types acting in each.
Type I: IgE mediated, mast cell degranulation (FceRI cross linking). Ex: asthma, hay fever
Type II: IgG response, antibody mediated cell surface rations that cause cytotoxicity, complement activation. Ex) hemolytic anemia, HDFN
Type III: IgG response immune complex mediated, complement activation Ex: arthus reaction
Type IV: cell mediated, sensitized T cells (mostly Tc (CD8) but some Th1 (CD4)), activated macrophages. Ex: contact dermatitis
Explain how an “immediate hypersensitivity” differs from a “delayed-type hypersensitivity (DTH)” response, and what type of hypersensitivity (I – IV) is being tested for by each.
Delayed response hypersensitivity reaction occurs 1-3 after contact with the antigen while immediate hypersensitivity reactions occur immediately
Immediate hypersensitivity = Type I hypersensitivity
Delayed response hypersensitivity = Type IV hypersensitivity
Identify which hypersensitivity is associated with histamine release.
Type 1
Describe the utility of total serum IgE testing, skin prick testing, and allergen-specific laboratory testing, listing the advantages and disadvantages of each.
Total serum IgE testing: RIST. Elevated total serum IgE. Advantage: inexpensive and suggests further testing Disadvantage: not sensitive and doesn’t identify allergen
Skin prick testing: Wheal reaction. Advantage: positive test is clinically significant Disadvantage: danger of systemic reaction, traumatic to the patient, and only tests limited individual allergens
Allergen-specific laboratory testing: RAST. Advantage can be taken with antihistamines and only require single skin puncture to draw blood for serum testing. Disadvantage: lower specificity than skin testing and only tells if IgE is present not if its responsible for current allergic symptoms
Identify common examples of type II hypersensitivities.
Type II hypersensitivities occur following administration of certain types of drugs and are responsible for blood transfusion reactions, HDN, some autoimmune diseases including Goodpasture’s syndrome, Grave’s disease, and myasthenia gravis.
For the following illnesses/diseases, identify the type of hypersensitivity responsible: “serum sickness”, celiac disease, poison ivy hypersensitivity, allergic asthma, food allergy such as shellfish allergy.
Serum sickness: type III hypersensitivity
Celiac disease: type IV hypersensitivity
Poison ivy hypersensitivity: Type IV hypersensitivity
Allergic asthma: Type I hypersensitivity
Food allergy such as shellfish allergy: type I hypersensitivity
Identify which hypersensitivity responses involve complement activation.
Type II and Type III hypersensitivity responses
Identify whether CD4+ T cells, CD8+ T cells, and/or B cells are responsible for autoimmune disease.
All are responsible for autoimmune disease – CD4, CD8, and B cells – Both autoimmune antibodies and T cells (Tc) have been found to be responsible for eliciting autoimmunity.
Ultimately, because of the requirement for T cell help in antibody production, all persistent autoimmunity must be due to breach in T cell tolerance – hence the link of autoimmunity to HLA genes, esp. MHC class II, but also MHC class I.
Identify two proteins involved in T lymphocyte self-tolerance that when defective in humans lead to generalized autoimmune disease.
Defects in tolerance development or maintenance itself lead to more generalize autoimmunity are AIRE and FoxP3
Define “relative risk” and the ultimate effect that it has on an individual’s likelihood to develop any given autoimmune disease. Be able to interpret a relative risk score.
Relative risk: if you have the associated HLA gene, relative risk is the increased risk you have over the general population to get the disease.
However, just because you have HLA susceptibility does not mean that you will get the disease. Divide total risk by the total risk to get the actual risk of getting the disease.
Explain the role of HLA alleles in development of autoimmunity (i.e. what are the HLA molecules doing exactly to trigger autoimmunity?).
Linked more commonly to increased susceptibility to autoimmunity to due their ability to present self-antigen
List and define/explain the mechanisms of several factors described in the textbook reading that have been proposed to be risk factors for autoimmune disease development.
- Release of sequestered antigens by tissue damage: Intracellular proteins and nucleic acids that are released by traumatic damage into extracellular fluid and elicit an inflammatory response at the same time
- Inflammation causing ectopic expression of MHC Class II on cells that would not normally express it: IFN-y can cause several types of cell types to express MHC Class II in a cell-mediated response to a virus. These cells may express a protein that is not made in the thymus and hence there is no T cell tolerance to that protein.
- Molecular mimicry: An immune response to a pathogen triggers a TCR/BCR that cross-reacts with the self-antigen. Infections causing inflammation (such as Strep A, chlamydia, Lyme disease, Coxsackie virus, etc.) can lead to molecular mimicry.
- Polyclonal B cell activation: Triggers antibody synthesis to many self-antigens. Antibodies produced are all IgM due to no T cell help.
- Inhibitory FcyR polymorphisms: A defect in the immune system itself that leads to inability to inhibit B cell responses even antibody is present in adequate amount
- Genetic mutations in C1-C4: A defect in the immune system itself that leads to C1-C4 and complement receptors that bind to C1q predispose to Lupus. This is caused from ineffective clearance of immune complexes that eventually activates complement and lyses cells and spews out proteins which are processed and presented in MHC Class II. These proteins are the target of autoimmunity in Lupus.
CHECK: Define epitope spreading (in the context of autoimmune disease) and how linked recognition is responsible for epitope spreading.
Epitope spreading is a common feature of autoimmune disease that refers to the amount of autoantigen that is recognized by the immune system. When a patient is first diagnosed, the number of auto-antibodies detected is limited therefore the number of auto-antigens is also limited. However, as the autoimmune disease progresses the patient will develop more auto-antibodies against more auto-antigens. This is all caused by the sloppiness of T cell help to B cells. Ex: in Lupus, CD4 T cells that are specific for one epitope of a macromolecular complex can provide help to B cells specific for other accessible epitopes of the complex
Discuss the general usefulness of IVIg, RhoGAM, and other antibody preparations used in the therapeutic treatment of humans.
IVIg is intravenous immunoglobulin that is concentrated human IgG that is pooled from healthy human donors to treat primary antibody immune deficiencies, but now it can be used as an interfering anti-idiotypic antibody to block autoantibodies, inhibit naïve B cells, and overwhelm FcgR.
RhoGAM is used in the prevention of hemolytic disease of the newborn in which polyclonal antibody is purified from pooled Rh-negative mother who has Rh antibody Monoclonal antibody treatments are used to target and kill tumor cells or as immunosuppressants.
CHECK: Describe how monoclonal antibody preparations differ from polyclonal antibody preparations (aka, antiserum).
Monoclonal antibodies are antibody preparations in which antibody is all identical and is produced by a cell clone called a hybridoma
