Autoimmunity Flashcards
your _____ immune system has 2 receptors ____ and _____, responsible for recognizing _______ of antigens
adaptive, immunoglobulin, TCR, 10^9 or more
there are ___ antigen receptor genes, ___ responsible for immunoglobulins _____, and ____ responsible for t cell receptor
7, 3, heavy, kappa lamda, 4 TCR: alpha, beta, gamma, delta
when apc presents to a naive tcell, it secretes ____ to turn it into a Th17 ____ to turn it into a Th1, and ____ to turn it into a Th2
TGFB, IL-6, IFN-gamma, IL-12, IL-4
Th17 cells turn on ____, Th1 cells turn on ____, Th2 cells turn on____
neutrophils, macrophages+mast cells, eosinophils
hypersensitivity is defined as:
injurious immune reactions (tissue injury as a direct result of your immune system)
definition of Type I hypersensitivity:
immediate, rapid immunologic reaction that occurs from previous sensitization, triggered by binding of antigen to IgE on mast cells
Type I Hypersensitivity pathogenesis:
initiated by introduction of allergen, stimulate Th2 responses and IgE production in genetically susceptible individuals (IgE class switching in B cells), re-exposure to allergen cross-links IgE and activates mast cells to secrete mediators
Cells associated with Type 1 Hypersensitivity
Mast cells (look like basophils deep blueish color) A in ACID mnemonic
in a slide of a type I hypersensitivity response, you see:
initially mast cells, later you see eosinophils
In a Type II hypersensitivity reaction:
antibodies react with antigens on cell surface or in the extracellular matrix causing disease by destroying cell, triggering inflammation, or interfering with normal functions (C in ACID, cy-TWO-toxic T cells)
pathogenesis of type II hs:
3 types: opsonization (direct coating of cell with antibodies and complement components, ingestion by phagocyte), inflammation (induced antibody deposition in fixed tissues i.e. basement membrane and extracellular matrix and by complement breakdown products i.e. glomerularnephritis, Cellular dysfunction from antireceptor antibodies that disturb the normal function of receptors i.e. myasthenia gravis, anti-TSH receptor activating TSH receptor in Graves causing hyperthyroidism
define Type III HS:
immune complex-mediated, antigen-antibody complex produces tissue damage by eliciting inflammation at the sites of deposition (I in ACID mnemonic “think 3 parts, antigen, antibody and complement protein”).
immune complexes are____ and _____ causing_____
insoluble, deposit in tissues, tissue damage via inflammation at the sites of deposition (usually at a site with lots of blood vessels), i.e. lupus- causing glomerular nephritis, complex gets lodged in the kidney
pathogenesis of Type 3 HS:
formation of immune complex (protein antigen triggers immune response, formation of antibodies) deposition of immune complex (deposited in blood vessels or tissues, organs where blood is filtered at high pressure, i.e. kidney), inflammation and tissue injury (activates complement system with release of breakdown products or engaging Tc receptors of leukocytes) this all results in vasculitis glomerulonephritis, and arthritis
Type 3, immune complex-mediated hypersensitivity, acute vasculitis, associated with necrosis of the vessel wall and intense neutrophilic infiltration
fibrinoid necrosis: necrotic tissue and deposits of immune complexes (the pink rink around vessel), inflamation. complement, and plasma protein area of tisue destruction, an apearance termed
Type 4 hypersensitivity is:
T-cell mediated
ACID: delayed (t-cell mediated)
inflammation resulting from cytokines produeced by CD4+T cells and cell killing CD8+T cells
RA, MS, Type 1 Diabetes, IBD,
type 1: immune system has turned on cytotoxic T cells to kill Beta islet cells in pancreas
Pathogenesis of Type 4 HS:
depends on type of cell turned on: 1 cytokine mediated: CD4+ t cells activated by exposure to antigen and differentiate into Th1 and Th17 effector cells
subsequent exposure results in cytokine secretion e.i. IFN-gamma activates macrophages to produce substances that cause tissue damage
2: cytotoxic reaciton: CD8+ cytotoxic T lymphocytes CTLs directly kill tissue cell (type 1 DM)
TB is a _____ hypersensitivity related to _____ cells
delayed-type, CD4 (Tuberculin PPD reaction)
ON TEST!
TB skin test is an example of:
Type 4, delayed-type hypersensitivity
positive PPD reaction,
during the Tuberculin PPD test, as the innoculation grows larger there are CD4 helper T cells that cause the inflammatory response
type I HS
ACID, A for allergy, anaphalaxis, bronchial Asthma
Immediate response,
production of IgE
autoimmune diseases def:, clinical features:
immune mediated damage of self tissues, clinical features: progressive with relapse and remission
Type 2 HS
ACID-C is for complement
antibody-mediated response
IgG, IgM, phagocytosis or lysis of target cell by activated comlement receptor,
autoimmune hemolytic anemia, myasthenia gravis, graves
Type 3 HS
ACID: I is for inflammation, Immune complex mediated
deposition of antigen-antibody comples into tissue, necrotizing vasculitis
SLE, Glomerulonephritis, serum sickness and arthus reaction
Type 4 HS:
ACID: D is for Delayed, activated T lymphocytes,
CD4 Tcell is making too much IFN-gamma recruites neutrophils or IL17 recruits macrophages
TB test, granuloma formulation, perivascular infiltrates,
MS, Type 1 diabetes, TB, Hashimoto’s thyroiditis
Difference between type 2 and 3 hs
type 2, the antibody is causing the response,
type 3, the antibody is combining with something else that is being deposited in the tissues that is causing the damage
type 3 is usually systemic, where as type 2 is localized
Increased metabolic state, protusion of eyes,
thyroid test shows:
elevated total and free T4
elevated T3
decreased TSH
suggests?
Thyrotoxicosis, hyperthyroidism
pituitary gland is trying to shut it off
hyperplasia, graves disease, hypertrophic thyroid, hyperthyroidism
what is the etiology of granves?
pathogenesis?
(Probably TEST)
patients have autobodies to TSH receptors that cause mitogenesis of thyroid epithelial cells
path: 1. IgG autoantibodies to the TSH receptor
2. Bind to thyroid follicular cells
3. Thyroid hypertrophy/hyperplasia
4. increased secretion of T3 and T4
what kind of hypersensitivity is this?
2, Classic, type 2, antibody mediated hypersensitivity, autoimmune disease
Increased total and free T4, decreased TSH
lab results for hypothyroid?
decreased total and free T4
elevated TSH
pathogenesis of autoimmunity includes:
- susceptibility genes (HLA genes, i.e. HLA-B27)
- Environmental triggers (antigens)
- Lymphocytes enter tissues
- Activation of self-reactive lymphocytes-tissue damage (too many turned on and can’t get turned off)
why is the thyroid enlarged?
what kind of hypersensitivity?
hypothyroidism from direct damage from the inflammation
enlarged thyroid
lymphocytes are destroying the thyroid follicles
type 4, t-cell mediated HS, not systemic (like type 3) localized, and includes both T and B cells
continued inflammation leads to scarring and ceased function
Hashimoto’s thyroiditis is the most common cause of hypothyroidism
decreased T4, increased TSH
lymphocytes are directly damaging the thyroid follicles
Hashimoto’s Thyroiditis
leads to fibrosis and scarring
most common cause of hypothyroidism
elevated T4 and decreased TSH
what labs do you look for in SLE?
ANA positive (not specific) for the diagnosis of SLE
anti-dsDNA and anti-Smith antigen (specific for lupus)
note:ANA and anti-dsDNA antigens are in the nucleus and are released to provoke an immune response
when cells of the epidermis die, they release toxins that get deposited into the basement membrane of the skin (immune complex in the skin, kidneys, joints, etc)
classic for Type 3, complex deposits in skin, joints, kidneys
SLE: kidney, lupus nephritis, deposition of immune complexes on basement membrane
type 3: Immune complex
Antinuclear Antibodies
anti-dsDNA
Antigen-antibody complex generated at higher level and deposited in multiple tissues/organs
autoimmune disease associated with salivary glands:
Sjogren syndrome
type 4 HSR
Destruction of lacrimal/salivary glands
antibodies: anti-SSA anti-SSB RF
Autoimmune disease?
RA
Rheumatoid Factor: affects joints extraarticular tissues
cellular and humoral immune response against self-antigens
synovitis
autoimmune disease?
systemic sclerosis (scleroderma)
activation of fibroblasts by cytokines produced by cd4 T cells
immense collagen build up
classic autoimmune disease
