Autoimmune Diseases (complete) Flashcards
What happens in a normal immune response to a microbe
you have proliferation and differentiation of lymphocytes, an immune response
what happens in a normal response to self-antigens
you have anergy, deletion, or change in specificity of the lymphocyte
microbes are tolerogenic and self antigens are immunogenic. T or F
False, microbes are immunogenic and self antigens are tolerogenic
what are autoimmune diseases
diseases caused by failure of self tolerance and the subsequent immune responses against self antigens
what are the three things that combine to lead to the breakdown of self tolerance, and autoimmunity
Genetic factors (HLA)
Infections
Environmental factors
What is immune tolerance
the lack of a response to an antigen that is induced by a previous exposure to that antigen
how do normal individuals achieve self-tolerance
via self/non-self descrimination
When do we induce immune tolerance (when is immune activity too high)
- organ transplantation
- autoimmune diseases
- allergic diseases
What is central tolerance
immunological tolerance to self antigens induced in immature lymphocytes in the central lymphoid organs
What are the mechanisms of central tolerance
Deletion
receptor editing in B-cells (change in BCR)
development of Treg cells
what are the levels of Treg like in many autoimmune diseases
low levels of Treg cells are often found in autoimmune responses
What is the positive selection in thymus portion of central tolerance for T-cells
T-cells with low-affinity interactions of TCR with self MHC molecule positively selects, and saves thymocytes from apoptosis
What is the negative selection in thymus portion of central tolerance for T-cells
thymocytes that bind self MHC too tightly undergo apoptotic death
what is peripheral tolerance
immune tolerance to self-antigens encountered in peripheral tissues by mature lymphocytes
What are the mechanisms of peripheral tolerance
- clonal anergy (lacking second signal)
- Deletion (cell death)
- supression (via Treg secretions of IL-10 and TGF-beta)
What are the three mechanisms of mucosal intolerance
- ignorance of the antigen by immune system (anergy)
- Deletion of T-cells that respond to inhaled/ingested antigen.
- Tregs supress inflammatory response
is self tolerance learned/acquired or innate to lymphocytes
learned/acquired
do all lymphocytes have the potential to become autoreactive
yes
what usually leads to autoreactive lymphocytes
failure in central and peripheral tolerance mechanisms
what leads to autoimmune diseases
- breakdown of central and or peripheral tolerance
- failure of immune system to distinguish between self and non-self
- autoreactive T and B cells
- auto Abs or autoreactive T-cells attack the body
what do autoimmune diseases all cause
inflammation and tissue damage (through hypersensitivities 2,3, and 4 and uncontrolled compliment activation)
what are the three methods by which complement activation clears infection
- C3b opsonization-phagocytosis and killing of microbes
- cytolysis or killing of microbes
- activation of inflammation
what does the lack of complement proteins C1q, C2 or C4 lead to
defective clearance of immune complexes and apoptotic cells which is often found in autoimmune disease development
what are the mediators of type 2 hypersensitivity
IgG and IgM
what does the binding of IgG or IgM to an antigen cause
a cytotoxic immune response that kills the antigenic target cell
what are the three mechanisms of cytotoxicity
- complement mediated cell lysis
- cell injury by inflammatory cells
- phagocytosis of antibody coated cells
what type of hypersensitivity is caused by immune complexes
type 3
what usually removes immune complexes
phagocytes and complement activation
what determines whether an immune complex is likely to persist and deposit into the tissues
its size, there is an optimum size, medium and small complexes are more likely to deposit than large ones.
what diseases are associated with immune complex deposition
autoimmune disease
SLE
RA
what is it called when immune complexes deposit into vessels
vasculitis
what are the factors that lead to vasculitis
platelet aggregation and complement activation
microthrombi formation
C5a, C3a recruitment of PMN that damage the cell wall
which type of hypersensitivity is associated with idopathic thrombocytopenia purpura, and autoimmune hemolytic anemia
type 2 Ab-induced
which type of hypersensitivity is associated with grave’s disease, myasthenia gravis, and insulin receptorAb syndrome
type 2 Ab-induced receptor stimulation or blockade
which type of hypersensitivity is associated with SLE and vasculiitis
type 3
which type of hypersensitivity is associated with Insulin-dependent diabetes mellitus, hasimoto’s thyroiditis, (rheumatoid arthritis?), multiple sclerosis
type 4
what are the four different types of autoantibodies
Anti-DNA antibody
complement fixing autoantibodies
tissue specific autoantibodies
autoantibodies to cell-surface receptors
what type of auto antibody is seen in lupus nephritis
anti DNA autoantibody
what type of auto antibody is seen in autoimmune anemias and thrombocytopenia
complement fixing autoantibodies
what type of auto-antibody is seen in SLE, RA, and type 1 diabetes mellitus
tissue specific autoantibodies
what type of auto-antibody is seen in graves disease and myasthenia gravis
autoantibodies to cell surface receptors
what does the pathogenic role of autoantibodies depend on
concentration and charge of the auto-antigen
affinity and charge of the auto-antibody
which is more pathogenic auto-antibodies with high or low affinity for auto-antigens
high (they form more stable complexes and activate complement more effectively)
what kind of charge do anti-dna antibodies have, and what does it cause
weak positive charge that causes it to bind to the negatively charged glomerular basement membrane
what is glomerulonephritis
inflammation of the glomeruli caused by uncleared immune complexes
what causes grave’s disease
autoantibodies binding to the TSH receptor on thyroid cells. this causes the cell to secrete unregulated amounts of thyroid hormones (hyperthyroidism)
what causes myasthenia gravis
autoantibodies binding to the ACH receptor, inhibits binding of ACH, causes muscle weakness and paralysis
what are cross reactive antigens
autoreactive B-cells that recognize both a self-antigen and a forgein antigen
what happens when a cross-reactive B-cell binds a self antigen
you get no Th cell help via cytokine secretion
what happens when a cross reactive B-cell binds a non-self antigen
you get Th cell help via cytokine secretion. this leads to B-cell proliferation
secretion of antibodie to control infection
what is a so bad about cross-reactive antigens if they don’t illicit an immune response when the B-cell binds a self antigen, but only when it binds a non-self antigen
because the remaining/residual auto antibodies that are produced can go on and bind to self antigens
what causes rheumatic fever
the auto-antibodies that were created in response to an antigen on group A strep infection, that antigen is cross-reactive with the self-antigen on the heart valves. so those auto-antibodies attack the heart valves
what can be a similar cause of insulin dependent diabetes mellitus and guillan-barre syndrome
a cross reactive antigen reaction
What are the signs of Grave’s disease
exophthalmos
enlarged thyroid gland
What are the T-cell mediated autoimmune diseases
Type 1 diabetes (attacks islet cell Ag)
RA (attacks synovial fluid Ag)
MS (attacks myelin protein)
Hasimoto’s thyroiditis (attacks thyroglobin)
what is the link between RA and periodontitis
citruillination of proteins.
how does periodontitis lead to RA
p. gingivalis creates CCPs, which are also found in the patients gingiva. so as you create an immune response against the CCPs, you also lose self-tolerance, and those anti-CCP antibodies can get to the synovial fluid and break down the citruillinated proteins there. causing RA
what is CCP
cyclic citruillinated protein
Heat shock protein comes from p. gingivalis and is implicated in
periodontitis and autoimmune atherosclerosis
what does the link between RA and periodontitis mean clinically
it means that treatments for one may benefit the other condition as well
how are autoimmune diseases normally diagnosed
determining the auto-Antibody participating
what are the 4 treatments of autoimmune diseases
- NSAIDs/COX inhibitors to reduce inflammation
- cyclophosphamid prevents B-cell proliferation
- Anti-TNF-a mAb (infliximab/remicade) controls inflammation
- anti-CD20 mAb (Rituximab) eliminates B-cells in RA, SLE
what is ADCC that occurs in patients treated with mAb drugs
antibody dependent cellular cytotoxicity
how do mAb drugs work
the target cells are coated/marked with the mAb, and the NK cells kill them
how is allergen immunotherapy done
a series of injections of an allergen with the attempt of densensitizing the patient to the allergen (chaning from IgE to IgG and TH2 to TH1)
