Ch 6: Immunopathies (Part 2 - Hypersensitivity) Flashcards
What are the types of hypersensitivity reactions?
Type 1 = IgE-mediated hypersensitivity (allergies)
Type 2 = IgG-mediated cytotoxic
Type 3 = Immune-complex mediated
Type 4 = cell-mediated
What are the Type 1 hypersensitivity reactions?
Uticaria
Angioedema
Anaphylaxis
Seasonal allergies
Food allergies
Asthma
What is the process of a Type-1 hypersensitivity rxn?
DCs present Ag to T-cells
T cells differentials to TH2
B cells class switch to IgE
Mast bind IgE to FceRI - activation
Interleukins involved: IL-4 = class switching IL-5 = eosinophil activation IL-13 = enhanced IgE production
What happens when mast cells are activated?
Degranulation = histamine
Release of:
vasoactive amines and lipid mediators (leukotrienes B/C/D, Prostaglandin D2, PAF) = early phase
cytokines = late phase
What presentation can be seen with an immediate response (early phase)?
Vasodilation
Vascular leakage
Smooth muscle spasm
Characterized by vasodilation, congestion, edema
What presentation can be seen with an late phase response?
Infiltration of tissues with eosinophils, basophils, neutrophils
Epithelial damage
What cell dominated last phase rxn?
Eosinophils
Mast cells are for immediate rxn
What is eosinophilic esophagitis?
Food Ag-driven disease of childhood
Recurrent dysphagia Weight loss (couldn't swallow effectively, hurts to swallow)
What is a Type 2 Hypersensitivity Rxn?
Rxn where abs directly react with Ag present on cell surface or ECM
Autoabs
Exogenous Ag bound to cell surface
What are the 3 mechanisms of Type 2 hypersensitivity rxns?
Opsonization and phagocytosis
Complement and fc receptor-mediated inflammation
Ab mediated cellular dysfunction
Describe opsonization and phagocytosis in Type 2 hypersensitivity. What disease can you get?
Opsonization leads to phagocytosis - or direct lysis in case of Antibody dependent cellular cytotoxicity
Basic mechanism = No cells = anemia and thrombocytopenia
Dz:
Autoimmune hemolytic anemia
Autoimmune thrombocytopenia purpura
Describe complement and Fc receptor mediated inflammation in Type 2 hypersensitivity. What disease can you get?
Basic mechanism = damaged tissue + inflammation
Streptococcal proteins that cross-react with myocardium
Dz:
Vasculitis caused by ANCA
Goodpasture syndrome
Acute rheumatic fever
Describe what happens with vasculitis caused by ANCA.
Target ag = Neutrophil granule proteins, released from activated neutrophils
MOD = neutrophil degranulation and inflammation
Describe what happens with Goodpasture syndrome.
Target ag = noncollagenous protein in basement membrane of kidney glomeruli and lung alveoli
MOD = complement and Fc mediated inflammation
Describe what happens with acute rheumatic fever.
Target Ag = streptococcal cell wall ag; ab cross reacts with myocardial ag
MOD = inflammation, macrophage activation
Acute and chronic forms
Describe Ab-mediated cellular dysfunction in Type 2 hypersensitivity. What disease can you get?
Basic mechanism = dysfunction due to receptor blockade
Disrupted endocrine and neural signaling
Dz:
Myasthenia Gravis
Graves Disease
Insulin-resistant diabetes
Describe what happens with myasthenia gravis.
Target ag = acetylcholine receptor
MOD = Ab inhibits Ach biniding, down-modulates receptors
Describe what happens with Graves disease.
Target Ag = TSH receptor
MOD = Ab-mediated stimulation of TSH receptor
Describe what happens with insulin resistant DM.
Target Ag = Insulin receptor
MOD = Ab inhibits binding of insulin
What is Type 3 Hypersensitivity Rxn? What is the mechanism?
Ag-Ab complexes form and deposit causing damage
Mechanism:
Ab combines with Ag
Circulating immune complexes lodged in basement membrane of epithelia (kidney, lungs, joints, skin)
Fragments of complement cause release of histamine and other mediator substances
Neutrophils migrate to site of immune complex and release enzyme that cause severe damage
What type of diseases can you get with Type 3 hypersensitivity?
Serum sickness
Arthus reaction
What is serum sickness?
Acute form classically due to non-human protein Ag (diphtheria antitoxin)
Chronic form usually due to self antigen (LUPUS)
What is Arthus reaction?
It is a rare local effect of vaccination
Experimentally seen in rabbits inked with horse serum
How would immunofluorescence on kidney biopsies look different on Type 2 and 3 hypersensitivity diseases?
Type 2 = smooth and linear
Type 3 = grainy and granular
How do streptococcal proteins affect the heart and kidney differently?
Heart = cross-reactive Abs directly act on myocardium = Type 2
Kidney = cross-reactive abs are forming immune complexes that deposit in glomeruli = Type 3
What is characteristic of Type 4 hypersensitivity? What are the 2 mechanisms?
Uses T-cells
CD4 response = cytokine release + inflammation
CD8 = cytotoxic against Ag on surface of target cell
2 Mech:
Cytokine mediated inflammation
T-cell mediated killing of host cells
What is one hallmark of Type 4 hypersensitivity?
Immune granulomas = caused by variety of agents capable of inducing persistent T-cell mediated immune response
What are some Type 4 Hypersensitivity diseases?
Rheumatoid arthritis Multiple Sclerosis Type 1 DM IBD Psoriasis Contact sensitivity
What is the tuberculin skin test?
A tuberculin purified protein derivative (PPD) us injected intradermally
48-72 hrs later, rxn assessed
Sensitized T cells start inflammatory response
Local swelling (induration) results
Indicated prior or current TB exposure
