Term
| If the antigen is localized to a given organ, the autoimmune disease is ______ specific |
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Definition
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Term
| If the antigen is widespread throughout the body, the autoimmune disease is _______ specific |
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Definition
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Term
| If there is a lesion, and the antigen in organ is target of immune attack, the autoimmune disease is _______ specific |
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Definition
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Term
| If there is a lesion, and there is an immune complex deposition in many tissues (skin, joints, kidney), the autoimmune disease is _____ specific |
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Definition
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Term
| Do Organ specific autoimmune diseases overlap with other (organ or non-organ ) specific diseases? |
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Definition
| organ (and non-organ specific overlap with other non-organ specific diseases) |
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Term
| Is tolerance and autoimmunity the same? |
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Definition
No
The normal status of organisms is that there is tolerance to self-antigens.
The development of autoimmunity is breaking the rule of tolerance. |
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Term
| What are some experimental induction models of anti-self responses (breaking tolerance)? |
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Definition
-Conjugation of self epitopes to immunogenic determinants (immunogenic epitopes starts process, covalent linkage between those epitopes induce self-antigen response)
-Localization with another vigorous immune response (adjuvant [mycobacterial CW] stimulate TLR receptors and non-specific/innate immune response to develop autoimmune response if antigen is included at sufficient amount)
-Exposure of "Hidden" self antigens (ex: cells don't see uvea in the eye, if injure one eye-uveitis affects both eyes)
-Genetic patterns of responsiveness
(2 classes: major histocompatibility (HLA) complex and) |
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Term
| What are the 2 classes of genetic patterns of responsiveness? |
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Definition
1. molecules of HLA complex or major histocompatibility complex where some alleles result in higher frequency in particular autoimmune diseases
2. single nucleotide polymorphisms (snips) (ex: snip in promoter of TNF-alpha propels inflammatory lesions that result in slight up regulation in TNF-alpha leading to an increased frequency of rheumatoid arthritis) |
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Term
| What is the general scheme of induction of organ specific autoimmune disease? |
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Definition
-Induction of local immune response (due to Infection, Drug Rx, Trauma, etc)
-Malfunction of immune regulation (Genetic predisposition and environmental factors increase likelihood to occur)
-Progressive immune response to tissue Ag --> Epitope Spreading (You promote the activation of normally suppressed self-reactive cells)
-Tissue destruction and loss of function (different tissues have different sensitivities) |
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Term
What disease is the immune destruction of the CNS by killing the oligodendrocytes?
The histopathology of this disease is dependent on? |
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Definition
Multiple sclerosis (=multiple scars)
dependent on the stage of lesion |
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Term
| What do some people think multiple sclerosis is caused by, other than an autoimmune disease? |
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Definition
| Viral infection as Antecedent |
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Term
| What is the animal model that is similar to multiple sclerosis? |
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Definition
Animal Models - experimental allergic encephalomyelitis (EAE)-paralytic disease involving hind limbs and spinal cord
Purified reactive T cells transfer disease, not antibodies |
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Term
What disease is caused by an immune mediated destruction of Islet beta cells (small nests in pancreas that make insulin)
What is the histopathology of this disease dependent on? |
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Definition
Insulin Dependent Diabetes Mellitus (can receive insulin, but have complications)
dependent on stage of lesion (when you look at disease) |
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Term
| What are 2 possible causes of insulin dependent diabetes mellitus? |
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Definition
viral infection (ex: coxsackie virus) kicks off immune response to get rid of virus in the beta cells
MHC linkage-immune response progresses and destroys all islets |
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Term
| What are the 2 animal models for Insulin Depedent Diabetes Mellitus? |
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Definition
BB rat (BioBreeding)
NOD mouse (non-obese diabetic), develop 10-12 weeks of age, can be used to look at islet transplant when deletion is due to an immune mechanisms |
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Term
| What is the disease where there is a chronic inflammatory lesion that results in destruction (shrink) of thyroid follicles (synthesize thryoglobulin and phagocytize thyroglobulin to release thyroid hormone) and ultimately hypothyriodism? |
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Definition
| Lymphocytic (Hasimoto’s) Thyroiditis |
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Term
| What is the disease where there is an antibody to TSH Receptor that stimulates receptor function and results in hyperthyroidism symptoms (but the result of the destruction of the thyroid is hypothyroidism). Can take ~20 years to go to completion. |
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Definition
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Term
| What are the 2 ways to treat Graves' Disease? |
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Definition
1. Surgically, without taking the parathyroid gland
2. giving high radioactive iodine (thyroid follicular cells take up iodine and die so stop producing antigen that's driving the immune response) |
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Term
What is the disease that is muscle weakness due to autoantibody to acetylcholine receptor of neuromuscular junction?
Can these symptoms be transferred in people and mouse models? |
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Definition
Myasthenia Gravis (similar to Graves' disease-related to Thymus)
Symptoms can be transferred with antibody to AchR |
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Term
| In Myasthenia Gravis, what are the two things that autoantibodies do? |
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Definition
1. it clears the receptor from the cell surface, so you have fewer molecules of acetylcholine receptors there so that the muscle is less responsive (dominant)
2. It can block the ability of acetylcholine to get into the active site of the receptor and also block the function of the receptor. |
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Term
| What kind of muscles are affected greatly by blocking auto-antibodies in Myasthenia Gravis? |
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Definition
| muscles that require very tight neuromuscular control (ex: extra ocular eye muscles, tongue NOT back, hips, or legs = no problem walking) |
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Term
| Crohn's Disease and Ulcerative Colitis are two examples of what kind of disease? |
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Definition
| Inflammatory Bowel Disease |
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Term
| If a patient had transmural inflammation (in mucosa, submucosa, muscularous, and serousal side) throughout the GI tract (especially common in terminal ileum) with "skip lesions" (same inflammatory in different parts of GI that can come at different times) and granulomas. What disease might this person have? |
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Definition
| Crohn's Disease (Regional Enteritis) |
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Term
| If a patient as inflammation restricted to mucosa (doesn't penetrate into muscle) and involves contiguous areas in colon (may extend into ileum) with little bits of normal tissue stuck inside (pseudopolyps), what disease do you expect this person to have? |
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Definition
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Term
| Can Crohn's Disease or Ulcerative Colitis be treated with anti-TMF alpha agents (as can rheumatoid arthritis) |
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Definition
| Crohn's (ulcerative colitis is not susceptible) |
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Term
| What disease is chronic inflammatory disease of joint synovium (lining) that leads to erosive lesions of cartilage and bone result from inflammatory “pannus” (granulomatous tissue), it can involve other organs besides joint, and occasionally associated with other autoimmune syndromes? |
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Definition
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Term
What is the antibody in Rheumatoid Arthritis that bind to the Fc portion of IgG and is usually of IgM class?
It forms immune complexes but rarely results in _______ (the hallmark lesion of immune complex disease) |
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Definition
Rheumatoid factor
glomerulonephritis |
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Term
| What is the lesion developed over time in rheumatoid arthritis that involves a necrotic core and big granuloma? |
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Definition
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Term
| In a lesion of pannus tissue in rheumatoid arthritis, sometimes they fill up with _____ cells making __________ |
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Definition
plasma cells
rheumatoid factor antibody |
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Term
| What is the Classic “Systemic” Autoimmune Disease that is mediated by immune complex injury (DNA/anti-DNA immune complexes often implicated in tissue injury) |
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Definition
| Systemic Lupus Erythematosis |
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Term
In Lupus, what cells are increased?
What is the worst lesion in Lupus? |
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Definition
B cells (makes antibodies --> start to develop autoantibodies)
glomerular nephritis |
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Term
If you notice a patient with a "butterfly" rash, what disease would you expect them to have?
Why does the butterfly rash occur? |
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Definition
Lupus
Exposure to sunlight increases the sensitivity of the skin to have the immune complexes deposit in that spot |
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Term
| What are the contributors to control infection and hypersensitivity? |
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Definition
Dynamics of infectious organism
Frequencies and function of autoreactive T cells
Cytokine milieu - TGFb + IL-10 (wound healing) versus IL-6, TNFa, IFNg (stimulate immune response)
Amount and kinetic course of auto-Ag |
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