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36 Cards in this Set
- Front
- Back
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What are the 3 phases of autoimmune disease pathogenesis?
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1. Induction phase - innate immune system activated. Cells recruited.
2. Inflammatory phase - antigen-specific immune response. 3. Destructive phase - tissue injury occurs. clinical manifestation of disease. |
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How are auto-reactive T cells eliminated?
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If they encounter high affinity self-antigen in the thymus, they are killed
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How many signals are needed to activate mature T cells?
What are they? |
2 signals needed
Signal 1: Stimulation of TCR by antigen (from APC) Signal 2: Co-stimulation from B7/CD28 on B cell/APC |
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What happens if T cells get Signal 1 without 2 or vice a versa?
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ANERGY
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What is the role of CTLA4 in T cells?
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Inhibition (prevents Signal 2 - binding of B7 to CD28)
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What are the 3 steps that need to be broken to get autoimmunity?
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1. Auto reactive T cells need to escape thymus
2. Receive stimulation from activated APCs 3. Avoid regulatory T cells that would suppress |
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What type of receptor is key to innate immunity?
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Toll-Like Receptors (TLR)
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What specific structures on AB's make them specific to an antigen?
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Hypervariable regions
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How many antibody hypervariable loops does it take to bind an antigen?
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ONLY ONE!
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What is cross-reactivity?
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When an antibody binds more than 1 antigen
This is possible bc hay 6 hypervariable regions but only 1 is needed to bind an antigen |
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What is it when an external antigen "looks like" an autoantigen?
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Molecular Mimicry
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How does molecular mimicry cause autoimmunity?
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External antigen stimulates B cell AB production of AB that will also attack endogenous cells
Ex: Rheumatic fever after Strep (attacks cardiac myosin) |
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What are the 4 main ways that AutoAbs can cause disease?
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1. Attack self cells - cause direct damage
2. Produce abnormal cell activation (ie Graves disease) 3. Block normal ligand (ACh in myasthenia gravis) 4. Form soluble immune complexes which deposit |
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What is it called when immunization with a foreign protein elicits an immune complex mediated disease?
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Serum Sickness
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What are 2 ways that certain HLA (MHC) types could be correlated with autoimmune disease?
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1. Certain HLA alleles bind autoantigens and present to T cells
2. Certain HLA allels bind cross reactive viral/bacterial antigens |
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MCH I and II often bind different peptides, how do they select which ones to bind?
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1. Bind the peptide backbone (predominate in MCH II)
2. Bind specificity pockets (predominate in MHC I) |
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What do MHC II molecules present?
Present to what cells? |
- Exogenous antigens
- Presented by APC's - Presents to CD4+ T cells |
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What do MHC I molecules present?
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- Endogenous peptides
- Present on ALL cells - Presents to CD8+ T cells |
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What type of pathogen would be associated with MHC I mediated autoimmunity?
MHC II? |
MHC I: intracellular pathogen
MHC II: extracellular pathogen |
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Which is specific in what they present, MHC or TCR?
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TCR, MHC present EVERYTHING
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What are the 2 ways that an antigen could act as a molecular mimic?
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1. Structural similarity
2. Sequence similarity |
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What are the roles of the following T cell types?
TH1 TH2 TH17 Treg |
TH1: DTH and cytotoxicity (cell mediated)
TH2: Humoral and allergic responses (Humoral) TH17: Bacteria, cancer, autoimmunity Treg: immunosuppression |
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What T cell type is often important in autoimmunity?
What cytokine does it produce? |
TH17
IL-17 |
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What is seen (with regard to T cell type) in SLE?
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Decreased Treg and increased TH17
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How many Antigens can an APC present?
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MULTIPLE
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What is epitope spreading?
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When antigens that are associated together are taken up and ALL are presented by an APC
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What are the 2 steps of T cell epitope spreading?
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1. APC's take up immune complexes and present multiple epitopes to T cells
2. Multiple T cells are stimulated with multiple epitopes contained within the immune complex |
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What is the key concept of B cell epitope spreading?
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A single epitope specific T cell will stimulate any B cell that presents that epitope
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What is the major cytokine in Rheumatoid Arthritis (RA)?
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Tumor Necrosis Factor (TNF)
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Does 1 gene necessarily mean you only get one autoimmune disease?
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No, overlapping therefore families can have multiple diseases
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What are the major pathogenic steps in Systemic Lupus Erythematosus (SLE)?
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1. Defects in thymic deletion/Treg cells lead to autoreactive T cells
2. T cells produce autoreactive B cells and Ab's 3. Auto Ab's form complexes and activate complement 4. Inflammation cascade initiated |
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What can immune complex deposition cause?
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1. Glomerulonephritis
2. Vasculitis 3. Dermatitis |
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What HLA molecule is linked to RA?
Why? |
- HLA-DR
- Perhas because specific peptide from type II collage (seen Win cartilage) binds HLA-DR |
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What finding suggested cross-reactivity at T cell level in RA?
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Dual TCR expression on T cells present in joint of RA patient
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How might environmental triggers play a role in RA?
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Oxidative stress (coffee, smoking, etc) causes vimentin mutation and this altered self antigen can trigger auto-immune response
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How could apoptotic blebs trigger autoimmunity?
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An APC that binds an antigen on an apoptotic bleb will process and present all of the antigens contained within the bleb
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