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What is the primary consequence of autoantibodies and autoreactive T cells in pernicious anemia?
In Hashimoto thyroiditis, what role do autoantibodies play?
Which immune cells are primarily involved in the direct cellular damage seen in Hashimoto thyroiditis?
What is a potential underlying factor linked to autoimmune reactions in pernicious anemia?
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What is the result of the damage caused by autoantibodies in Hashimoto thyroiditis?
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What is the primary mechanism of cytotoxicity in Type 1 Diabetes Mellitus?
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Which type of immune response is primarily involved in Multiple Sclerosis?
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What triggers the entry of self-reactive T cells into the CNS in Multiple Sclerosis?
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Which autoantigen is commonly targeted in Multiple Sclerosis?
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Which therapy is a type of S1P receptor modulator used for Multiple Sclerosis?
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What role do autoantibodies play in Type 1 Diabetes Mellitus?
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What is the relationship between viral infections and Type 1 Diabetes Mellitus?
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Which of the following is NOT a component of the immune response in Multiple Sclerosis?
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Which of the following describes the role of Effector TH1 cytokines in T1DM?
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What type of immune response primarily contributes to the damage in the central nervous system in Multiple Sclerosis?
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Which autoantibody is classified as an IgM anti-IgG antibody commonly found in rheumatoid arthritis patients?
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What is the primary function of TNF inhibitors in the treatment of rheumatoid arthritis?
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Which of the following is a CTLA-4 fusion protein that inhibits T cell activation?
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Which cytokine is directly inhibited by Anakinra (Kineret®)?
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What critical change occurs during the citrullination of proteins that stimulates an immune response in rheumatoid arthritis?
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Which type of cytokines are found to be increased in rheumatoid arthritis due to the activation of TH1 and TH17 cells?
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What is the mechanism by which autoantibodies contribute to tissue damage in rheumatoid arthritis?
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Which treatment for rheumatoid arthritis targets and blocks the IL-6 receptor?
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What is the primary effect of anti-TSHR antibodies in Graves disease?
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In Myasthenia Gravis, how do autoantibodies affect neuromuscular transmission?
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What specific mechanism leads to megaloblastic anemia in pernicious anemia?
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Which of the following is a common early sign of Myasthenia Gravis?
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What is the role of intrinsic factor in vitamin B12 absorption?
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Which condition is characterized by autoantibodies acting as agonists?
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What is the expected effect of autoantibodies in organ-specific autoimmunities?
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What is a possible consequence of anti-AChR antibodies in Myasthenia Gravis?
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Which autoimmune disease is associated with inflammation of the orbit and periorbital tissues?
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What happens when intrinsic factor is blocked by autoantibodies in pernicious anemia?
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What is the primary mechanism by which Rituximab leads to B cell depletion?
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In systemic lupus erythematosus (SLE), which type of antibodies are most commonly found?
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What role do anti-nuclear antibodies (ANAs) play in the pathology of SLE?
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What consequence does the deposition of immune complexes in the vasculature have in SLE?
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What happens after the immune complexes are endocytosed by B cells and dendritic cells?
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What are the factors contributing to the breakdown of tolerance to self-antigens in SLE?
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What is the result of defective clearance of apoptotic bodies in SLE?
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Which component is primarily targeted by anti-Sm antibodies in SLE?
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Study Notes
Graves Disease
- Autoantibodies overstimulate the thyroid stimulating hormone receptor (TSHR)
- Unregulated activation and overproduction of thyroid hormones result in hyperthyroidism
- Patients may present with proptosis, inflammation of the orbit, and periorbital tissues
Myasthenia Gravis (MG)
- Autoantibodies block acetylcholine (ACh) from binding to acetylcholine receptors (AChR) on the neuromuscular junction
- Anti-AChR antibodies act as competitive receptor antagonists
- Most frequent early sign of MG is ptosis (drooping eyelids)
- Autoantibodies can cause complement-mediated destruction of the muscle fibers
Pernicious Anemia
- Autoantibodies block absorption of vitamin B12
- Dietary vitamin B12 is absorbed when bound to intrinsic factor (IF)
- IF is secreted by gastric parietal cells
- Anti-intrinsic factor antibodies block IF binding to B12 and IF-B12 binding to the IF receptor
- Decreased vitamin B12 absorption leads to decreased erythropoiesis, resulting in megaloblastic anemia
- Hypersegmented polymorphonuclear neutrophils (PMNs) are often seen in pernicious anemia
Autoimmune-Mediated Damage
- Organ-specific autoimmunities can damage tissues in two main ways:
- Autoantibodies and/or autoreactive T cells can cause direct cellular damage
- Autoantibodies and/or autoreactive T cells can trigger inflammation and tissue damage
- Cellular lysis and/or inflammatory responses result in the replacement of normal tissue with connective tissue (fibrosis)
- Examples of diseases with direct cellular damage are:
- Pernicious anemia
- Hashimoto thyroiditis
- Type 1 diabetes mellitus
- Multiple sclerosis
Pernicious Anemia - Direct Cellular Damage
- Autoantibodies and cytotoxic T lymphocytes (CTLs) can cause direct cellular damage to gastric parietal cells
- Anti-parietal cell antibodies and autoreactive CTLs target the H+,K+-ATPase pump
- This results in killing of parietal cells, reduced intrinsic factor production, and ultimately, pernicious anemia
- Possible link to Helicobacter pylori infection
Hashimoto Thyroiditis - Direct Cellular Damage
- Autoantibodies and autoreactive T cells cause direct cellular damage to the thyroid gland
- CTLs and TH1 cells cause inflammation and damage to the thyroid, resulting in a goiter
- Anti-thyroid peroxidase (TPO) and/or anti-thyroglobulin (Tg) antibodies inhibit production of iodine, activate complement, and induce antibody-dependent cellular cytotoxicity (ADCC)
- Results in hypothyroidism
Type 1 Diabetes Mellitus (T1DM) - Direct Cellular Damage
- Autoantibodies and autoreactive T cells cause direct cellular damage to the pancreas
- Possible link to viral infections
- Delayed-type hypersensitivity (DTH) response (a type of cell-mediated immunity) destroys pancreatic beta cells
- Effector CTLs directly destroy beta cells
- Effector TH1 cytokines stimulate local inflammation
- Several autoantibodies can be found in patients with T1DM, which activate complement or induce ADCC
Multiple Sclerosis (MS) - Direct Cellular Damage
- Autoantibodies and autoreactive T cells cause direct cellular damage to the central nervous system (CNS)
- Infections and/or tissue damage may cause a disruption of the blood-brain barrier (BBB), leading to the release of CNS antigens
- This allows self-reactive T cells to enter the CNS
- Cell-mediated immune (CMI) response: T cells and macrophages infiltrate the CNS and attack myelin proteins
- Humoral response: autoantibodies to myelin proteins can activate complement or induce ADCC
Systemic: Rheumatoid Arthritis (RA)
- Autoreactive T and B cells are activated, leading to increased levels of TH1 and TH17 cytokines, as well as macrophage inflammatory cytokines
- Autoantibodies form immune complexes that can deposit into tissues, causing tissue damage
Rheumatoid Arthritis (RA) - Common Autoantibodies
- Rheumatoid Factor (RF): IgM anti-IgG antibody
- May be caused by exposure of hidden carbohydrates on IgG (cryptic epitopes)
- Anti-citrullinated peptide antibodies (ACPA):
- Anti-CCP and anti-MCV antibodies target citrullinated proteins (altered self), stimulating an immune response
Immunotherapies for RA
- Block the effects of proinflammatory cytokines:
- TNF inhibitors: bind and neutralize TNF
- Anakinra (Kineret®): IL-1R antagonist
- Tocilizumab (Actemra®): anti-IL-6R
- Tofacitinib (Xeljanz®): JAK1/3 inhibitor
- Inhibit T cell activation: Abatacept (Orencia®): CTLA-4 fusion protein that binds B7; blocks the T cell costimulatory signal
- Deplete B cells: Rituximab (Rituxan®): anti-CD20 antibody that binds to B cells, resulting in B cell destruction (depletion)
Systemic: Systemic Lupus Erythematosus (SLE)
- Genetic, hormonal, and environmental factors contribute to a breakdown of tolerance to self-antigens, mainly nuclear antigens
- Defective clearance of apoptotic bodies and/or the release of neutrophil extracellular traps (NETs) can lead to the release of nuclear antigens
- This stimulates self-reactive T and B cells against these nuclear antigens, resulting in the generation of antinuclear antibodies (ANAs)
Systemic: Systemic Lupus Erythematosus (SLE) - Common ANAs
- Most common ANAs are anti-dsDNA and anti-Sm antibodies
- Anti-dsDNA target double-stranded DNA
- Anti-Sm target the Sm ribonucleoprotein (an antigen found in the nucleus)
- ANAs form immune complexes that bind to nuclear antigens
- These immune complexes are endocytosed by B cells and dendritic cells
- Plasmacytoid dendritic cells (pDCs) secrete IFN-α, which triggers continued ANA production
Systemic: Systemic Lupus Erythematosus (SLE) - Consequences of Immune Complexes
- Immune complexes deposit in the vasculature/joints, activating complement and leading to tissue damage
- The result is inflammation, tissue damage, and various SLE symptoms
Immunotherapies For MS
- S1P receptor modulators:
- Fingolimod (Gilenya®) and Ozanimod (Zeposia®) are S1P receptor agonists
- They downregulate S1PR1, retaining lymphocytes within the lymphatic tissues, reducing inflammation in the CNS
- There are other S1P receptor modulators available on the market for MS treatment
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Description
This quiz covers key autoimmune diseases, including Graves' disease, Myasthenia Gravis, and Pernicious Anemia. It explores their mechanisms, symptoms, and the role of autoantibodies in these conditions. Gain insights into the clinical presentations and implications of these autoimmune disorders.
