HRR: hypersensitivity Flashcards
Define hypersensitivity reaction
Hypersensitivity occurs when the immune response is triggered and maintained inappropriately.
What are some immune reactions associated with hypersensitivity
-Immune response is inadequately controlled
-Immune response is directed against normally harmless antigens
-Immune response inappropriately targets host tissues
What are the 4 types of hypersensitivity reactions?
-Immediate hypersensitivity (type I)
-Antibody-mediated hypersensitivity (type II)
-Immune complex-mediated hypersensitivity (type III)
-Cell mediated hypersensitivity (type IV)
Describe immediate hypersensitivity
Also known as an allergic reaction or allergy, these occur rapidly, and clinical manifestations may be seen locally or systemically
What interaction triggers immediate hypersensitivity
Antigen interacts with IgE on mast cells
Describe the mechanism of developing an immediate hypersensitivity reaction
-An allergen enters the mucosal lining and is taken up by a dendritic cell or B cell
-Antigen presentation occurs. A dendritic cell will present to a naïve T cell, and a B cell will present to a Th2 helper cell. If it is a dendritic cell, the T cell matures to Th2 and interacts with a B cell
-B cell becomes a plasma cell that produces IgE
-IgE binds to FceRI on mast cells
-Repeat exposure occurs between IgE on mast cells and the antigen
-The mast cell is activated and releases various vasoactive amines (immediate reaction) and cytokines (late-phase reaction) that lead to reaction.
Explain how allergen binding to IgE on mast cells results in release of various chemicals
Binding of an allergen with cross-linking of IgE results in phosphorylation of ITAMs. This then initiates several signaling pathways that lead to the release of mast cell granules.
what is the histiopathology of type I hypersensitivity reactions
vascular dilation, edema, smooth muscle contraction, mucus production, tissue injury, inflammation
What do vasoactive amines lead to?
Vascular dilation and smooth muscle contraction
What do proteases lead to?
Tissue damage
What do prostaglandins lead to?
Vascular dilation
What do leukotrienes lead to?
Smooth muscle contraction
What to cytokines lead to?
Inflammation/ leukocyte recruitment; part of the late response
What factors cause smooth muscle spasm
Leukotrienes C4 and D4, histamine, prostaglandin D2, and PAF
Describe chronic allergic disease
-Upon epithelial barrier injury, epithelial cells secrete IL-25, IL-33, and TSLP
-These drive T cells to differentiate into Th2 and Tfh helper cells
-The Th cells produce IL-5 and IL-13 upon repeat exposure to antigen
-These stimulate eosinophils and chronic allergic inflammation
Name the prototypes and basic pathology associated with immediate hypersensitivity reaction
-Hay fever: inflamed airways and mucous secretion
-Food allergies: contraction of intestinal muscle
-Asthma: bronchial smooth muscle hyperactivity causes airway obstruction
-Anaphylaxis: vascular dilation leads to shock; edema leads to airway obstruction
Describe the general mechanism of antibody-mediated hypersensitivity
IgG and IgM antibodies bind to antigens on target cells or tissues and lead to phagocytosis/lysis via activated complement or Fc receptors
What are the three major mechanisms involved in antibody mediated disease
-Opsonization and phagocytosis
-Activating complement
-Interfering with normal cellular function
what is the histopathology of type II hypersensitivity reactions
phagocytosis and lysis of cells, inflammation, and sometimes functional derangements without cell or tissue injury
Describe immune complex hypersensitivity
Antigen-antibody complexes formed in circulation deposit in blood vessels, leading to complement activation and acute inflammation. These tend to be systemic.
Which tissues/organs are typically impacted by immune complex hypersensitivity
Kidney, joints, small blood vessels
Describe the general mechanism of immune complex hypersensitivity
-Complexes form in a blood vessel
-Complexes deposit into the wall of the vessel. Here, they fix complement and activate neutrophils
-Inflammation and tissue injury occur. Platelets aggregate and vasculitis happens.
What are the two types of cell reactions in T cell mediated hypersensitivity
-Cytokine mediated inflammation in which cytokines are produced by CD4+ T cells
-Direct cell cytotoxicity mediated by CD8+ T cells
CD4+ T cell mediated hypersensitivity reactions: general characteristics and main example
They’re chronic and destructive; the big example is delayed-type hypersensitivity. This is when antigens are introduced into the skin of a previously immunized individual, and there is a detectable reaction in 24-48 hours. Biggest example is a TB test.
Autoimmune hemolytic anemia: type of reaction, mechanism, pathology
-Type II
-Opsonization and phagocytosis
-Hemolysis and anemia
autoimmune thrombocytopenic purpura
-Type II
-Opsonization and phagocytosis
-Bleeding
Goodpasture syndrome: type of reaction, mechanism, pathology
-Type II
-Complement and Fc receptor mediated inflammation
-Nephritis and lung hemorrhage
Graves’ disease: type of reaction, mechanism, pathology
-Type II
-Antibody-mediated TSH receptor stimulus
-Hyperthyroidism
Myasthenia gravis: type of reaction, mechanism, pathology
-Type II
-Antibody inhibits Ach binding
-Muscle weakness and paralysis
Pemphigus vulgaris: type of reaction, mechanism, pathology
-Type II
-Antibody-mediated disruption of intracellular adhesion
-Skin vesicles
Pernicious anemia: type of reaction, mechanism, pathology
-Type II
-Neutralization of intrinsic factor and decreased absorption of B12
-Anemia due to abnormal erythropoiesis and nerve damage
Rheumatic fever: type of reaction, mechanism, pathology
-Type II
-Inflammation and macrophage activation
-Myocarditis and arthritis
Lupus erythematous: type of reaction, pathology
-Type III
-Nephritis, arthritis, vasculitis
Polyarteritis nodosa: type of reaction, pathology
-Type III
-Vasculitis
Post-streptococcal glomerulonephritis: type of reaction, pathology
-Type III
-Nephritis
Serum sickness: type of reaction, pathology, cause
-Type III
-Systemic vasculitis
-Receiving antibodies from other individuals or species
Describe the arthus reaction
Type III reaction; repeated injections of a protein into the same site leads to a hemorrhagic and necrotic reaction. A localized immune complex mediated vasculitis
Granulomatous inflammation is seen in what kind of hypersensitivity?
CD4+ T cell mediated hypersensitivity; specifically, prolonged DTH reaction
Contact dermatitis is an example of what kind of hypersensitivity
Delayed hypersensitivity aka T cell mediated hypersensitivity
Describe CD8+ T cell mediated cytotoxicity
CD8+ CTLs kill antigen-expressing target cells directly
What are two examples of CD8+ T cell mediated hypersensitivity
Type I diabetes and graft rejections
