Podcast
Questions and Answers
In autoimmune hemolytic anemia (AIHA), if a patient's red blood cells are destroyed due to antibodies formed against a drug that has bound to the RBC membrane, which mechanism is most likely the cause?
In autoimmune hemolytic anemia (AIHA), if a patient's red blood cells are destroyed due to antibodies formed against a drug that has bound to the RBC membrane, which mechanism is most likely the cause?
- Alloantibodies introduced from a donor reacting with normal RBC antigens.
- Autoantibodies directed against normal RBC constituents, such as Rh antigens.
- Genetic defects causing intrinsic erythrocyte disorders leading to increased RBC fragility inadvertently targeted by the immune system.
- Antibodies against antigens modified by drug haptenation to the RBC. (correct)
A patient with pyruvate kinase deficiency experiences early destruction of red blood cells. Which category does this cause of RBC destruction fall under?
A patient with pyruvate kinase deficiency experiences early destruction of red blood cells. Which category does this cause of RBC destruction fall under?
- Extrinsic due to trauma.
- Intrinsic due to enzyme defect. (correct)
- Extrinsic due to toxins.
- Immunologic due to autoimmune response.
Which of the following mechanisms leads to accelerated removal or destruction of red blood cells in immune hemolytic anemias?
Which of the following mechanisms leads to accelerated removal or destruction of red blood cells in immune hemolytic anemias?
- Increased synthesis of normal RBC constituents.
- Decreased production of RBC membrane antigens.
- Suppression of immune response against RBCs.
- Development of antibodies directed against RBC membrane antigens. (correct)
A patient develops hemolytic anemia after receiving a blood transfusion. Testing reveals the presence of antibodies in the patient's serum that are reactive against the donor's red blood cells. What is the most likely cause of this anemia?
A patient develops hemolytic anemia after receiving a blood transfusion. Testing reveals the presence of antibodies in the patient's serum that are reactive against the donor's red blood cells. What is the most likely cause of this anemia?
Which of the following conditions is least likely to be classified as an intrinsic cause of early red blood cell destruction?
Which of the following conditions is least likely to be classified as an intrinsic cause of early red blood cell destruction?
In the context of autoimmune diseases, what is the primary distinction between agonistic and antagonistic autoantibodies?
In the context of autoimmune diseases, what is the primary distinction between agonistic and antagonistic autoantibodies?
How does the chronic nature of autoimmune responses typically impact the progression and severity of autoimmune diseases?
How does the chronic nature of autoimmune responses typically impact the progression and severity of autoimmune diseases?
Which scenario exemplifies a failure in central tolerance leading to autoimmune disease?
Which scenario exemplifies a failure in central tolerance leading to autoimmune disease?
What is the most likely outcome of a mutation that impairs the function of FoxP3 in T regulatory cells?
What is the most likely outcome of a mutation that impairs the function of FoxP3 in T regulatory cells?
How do genetic predispositions typically contribute to the development of autoimmune diseases, considering the requirement for environmental triggers?
How do genetic predispositions typically contribute to the development of autoimmune diseases, considering the requirement for environmental triggers?
Autoimmune diseases can arise from a breakdown in immune tolerance. Which scenario exemplifies a failure of central tolerance?
Autoimmune diseases can arise from a breakdown in immune tolerance. Which scenario exemplifies a failure of central tolerance?
Molecular mimicry is implicated in the pathogenesis of autoimmune diseases. How does this mechanism contribute to autoimmunity?
Molecular mimicry is implicated in the pathogenesis of autoimmune diseases. How does this mechanism contribute to autoimmunity?
While most individuals possess circulating autoreactive lymphocytes, only a small percentage develop autoimmune diseases. Which factor is LEAST likely to contribute to the development of an autoimmune disease in an individual with autoreactive lymphocytes?
While most individuals possess circulating autoreactive lymphocytes, only a small percentage develop autoimmune diseases. Which factor is LEAST likely to contribute to the development of an autoimmune disease in an individual with autoreactive lymphocytes?
Superantigens can induce widespread T cell activation. What is the mechanism by which superantigens activate T cells?
Superantigens can induce widespread T cell activation. What is the mechanism by which superantigens activate T cells?
Autoimmune diseases exhibit a notable gender bias, with women being more frequently affected than men. Which of the following is the LEAST likely contributing factor to this observed gender disparity?
Autoimmune diseases exhibit a notable gender bias, with women being more frequently affected than men. Which of the following is the LEAST likely contributing factor to this observed gender disparity?
Rheumatic Heart Disease is an example of molecular mimicry. What is the mechanism of damage in Rheumatic Heart Disease?
Rheumatic Heart Disease is an example of molecular mimicry. What is the mechanism of damage in Rheumatic Heart Disease?
How does tissue injury contribute to autoimmunity?
How does tissue injury contribute to autoimmunity?
Which of the following autoimmune diseases is considered a systemic autoimmune disease rather than an organ-specific one?
Which of the following autoimmune diseases is considered a systemic autoimmune disease rather than an organ-specific one?
Which of the following is the best definition of tolerance?
Which of the following is the best definition of tolerance?
How would you classify Guillain-Barré syndrome?
How would you classify Guillain-Barré syndrome?
In autoimmune hemolytic anemia (AIHA), if IgG auto-antibodies induce Fc receptor-mediated opsonization, where is this process most likely to occur?
In autoimmune hemolytic anemia (AIHA), if IgG auto-antibodies induce Fc receptor-mediated opsonization, where is this process most likely to occur?
How does the mechanism of action of IgM auto-antibodies differ from IgG auto-antibodies in autoimmune hemolytic anemia (AIHA)?
How does the mechanism of action of IgM auto-antibodies differ from IgG auto-antibodies in autoimmune hemolytic anemia (AIHA)?
Why can drug-induced autoimmune hemolytic anemia (diAIHA) continue even after the offending drug is discontinued?
Why can drug-induced autoimmune hemolytic anemia (diAIHA) continue even after the offending drug is discontinued?
Which of the following best describes the mechanism by which penicillin causes drug-induced autoimmune hemolytic anemia (diAIHA)?
Which of the following best describes the mechanism by which penicillin causes drug-induced autoimmune hemolytic anemia (diAIHA)?
In hemolytic disease of the newborn, which immunoglobulin crosses the placenta to target fetal red blood cells?
In hemolytic disease of the newborn, which immunoglobulin crosses the placenta to target fetal red blood cells?
During blood transfusions, why are ABO incompatibilities primarily mediated by IgM alloantibodies from the donor rather than IgG alloantibodies?
During blood transfusions, why are ABO incompatibilities primarily mediated by IgM alloantibodies from the donor rather than IgG alloantibodies?
Autonomic dysfunction is a common manifestation in Guillain-Barré Syndrome (GBS). Which of the following is NOT a typical manifestation of this dysfunction during the progressive phase of GBS?
Autonomic dysfunction is a common manifestation in Guillain-Barré Syndrome (GBS). Which of the following is NOT a typical manifestation of this dysfunction during the progressive phase of GBS?
In Guillain-Barré Syndrome (GBS), if a patient's disease was triggered by Campylobacter jejuni, which immune cell type is characteristically more prominent compared to cases triggered by other pathogens?
In Guillain-Barré Syndrome (GBS), if a patient's disease was triggered by Campylobacter jejuni, which immune cell type is characteristically more prominent compared to cases triggered by other pathogens?
Which statement best explains the role of MadCAM-1 in the inflammatory process of ulcerative colitis?
Which statement best explains the role of MadCAM-1 in the inflammatory process of ulcerative colitis?
A patient presents with rectal bleeding and intermittent abdominal pain associated with bowel movements. Imaging reveals inflammation limited to the mucosa and submucosa of the colon and rectum. Which of the following treatments would be most appropriate, considering the information provided?
A patient presents with rectal bleeding and intermittent abdominal pain associated with bowel movements. Imaging reveals inflammation limited to the mucosa and submucosa of the colon and rectum. Which of the following treatments would be most appropriate, considering the information provided?
What is the primary distinction between Crohn's disease and ulcerative colitis regarding the layers of the gastrointestinal (GI) tract affected by inflammation?
What is the primary distinction between Crohn's disease and ulcerative colitis regarding the layers of the gastrointestinal (GI) tract affected by inflammation?
A patient experiencing continuous abdominal pain, coupled with a diagnosis of transmural inflammation affecting multiple regions from the mouth to the anus, would most likely be suffering from which condition?
A patient experiencing continuous abdominal pain, coupled with a diagnosis of transmural inflammation affecting multiple regions from the mouth to the anus, would most likely be suffering from which condition?
How does the nature of abdominal pain typically differ between Crohn's disease and ulcerative colitis, as described?
How does the nature of abdominal pain typically differ between Crohn's disease and ulcerative colitis, as described?
In rheumatoid arthritis (RA), the development of anti-cyclic citrullinated peptide antibodies (ACCPA) involves which specific chemical modification?
In rheumatoid arthritis (RA), the development of anti-cyclic citrullinated peptide antibodies (ACCPA) involves which specific chemical modification?
What is the primary mechanism by which rheumatoid factor (RF) contributes to the pathology of rheumatoid arthritis (RA)?
What is the primary mechanism by which rheumatoid factor (RF) contributes to the pathology of rheumatoid arthritis (RA)?
A patient tests positive for anti-cyclic citrullinated peptide antibodies (ACCPA). What is the most accurate interpretation of this result in the context of rheumatoid arthritis (RA)?
A patient tests positive for anti-cyclic citrullinated peptide antibodies (ACCPA). What is the most accurate interpretation of this result in the context of rheumatoid arthritis (RA)?
Which of the following accurately describes the combined influence of genetic predisposition and environmental factors in the etiology of rheumatoid arthritis (RA)?
Which of the following accurately describes the combined influence of genetic predisposition and environmental factors in the etiology of rheumatoid arthritis (RA)?
How do biologics like Humira and Remicade modulate the inflammatory response in rheumatoid arthritis (RA)?
How do biologics like Humira and Remicade modulate the inflammatory response in rheumatoid arthritis (RA)?
Janus kinase (JAK) inhibitors like Tofacitinib and Baricitinib are used in the treatment of rheumatoid arthritis (RA). What is their primary mechanism of action?
Janus kinase (JAK) inhibitors like Tofacitinib and Baricitinib are used in the treatment of rheumatoid arthritis (RA). What is their primary mechanism of action?
Methotrexate and hydroxychloroquine are commonly used as DMARDs in the treatment of RA. What is their primary mechanism of action?
Methotrexate and hydroxychloroquine are commonly used as DMARDs in the treatment of RA. What is their primary mechanism of action?
A patient with RA is experiencing inflammation and damage not only in the joints but also in the eyes, lungs, and skin. What percentage of patients experience symptoms in other parts of the body?
A patient with RA is experiencing inflammation and damage not only in the joints but also in the eyes, lungs, and skin. What percentage of patients experience symptoms in other parts of the body?
Enbrel is a soluble TNF-$α$ receptor used in treating rheumatoid arthritis (RA). How does it reduce inflammation?
Enbrel is a soluble TNF-$α$ receptor used in treating rheumatoid arthritis (RA). How does it reduce inflammation?
What is the primary characteristic of hemolytic anemias?
What is the primary characteristic of hemolytic anemias?
Flashcards
Autoimmune disease
Autoimmune disease
Disorders where antibodies or T cells attack the body’s own tissues.
Tolerance in immunity
Tolerance in immunity
The state where the immune system does not attack self-antigens.
Types of autoimmune diseases
Types of autoimmune diseases
Can be organ specific (like diabetes) or systemic (like SLE).
Mechanisms of autoimmunity
Mechanisms of autoimmunity
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Chronic responses in autoimmune disorders
Chronic responses in autoimmune disorders
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Causes of RBC destruction
Causes of RBC destruction
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Extrinsic causes
Extrinsic causes
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Intrinsic causes
Intrinsic causes
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Autoimmune Hemolytic Anemia (AIHA)
Autoimmune Hemolytic Anemia (AIHA)
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Types of antibodies in AIHA
Types of antibodies in AIHA
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Central Tolerance
Central Tolerance
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Peripheral Tolerance
Peripheral Tolerance
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Molecular Mimicry
Molecular Mimicry
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Superantigen Activation
Superantigen Activation
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Etiology of Autoimmune Diseases
Etiology of Autoimmune Diseases
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Common Autoimmune Disorders
Common Autoimmune Disorders
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Gender Bias in Autoimmune Diseases
Gender Bias in Autoimmune Diseases
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Systemic Autoimmune Diseases
Systemic Autoimmune Diseases
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Organ-Specific Autoimmune Diseases
Organ-Specific Autoimmune Diseases
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Rheumatoid Arthritis (RA)
Rheumatoid Arthritis (RA)
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Anti-cyclic citrullinated peptide antibodies (ACCPAs)
Anti-cyclic citrullinated peptide antibodies (ACCPAs)
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Citrullination
Citrullination
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Rheumatoid Factor (RF)
Rheumatoid Factor (RF)
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JAK inhibitors
JAK inhibitors
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Disease-Modifying Antirheumatic Drugs (DMARDs)
Disease-Modifying Antirheumatic Drugs (DMARDs)
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Biologics
Biologics
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Genetic predisposition
Genetic predisposition
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Environmental exposure
Environmental exposure
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Extra-articular symptoms of RA
Extra-articular symptoms of RA
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Idiopathic conditions
Idiopathic conditions
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Drug-induced AIHA
Drug-induced AIHA
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Common drugs causing diAIHA
Common drugs causing diAIHA
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Alloantibody targets
Alloantibody targets
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Hemolytic disease of the newborn
Hemolytic disease of the newborn
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Guillain-Barré Syndrome
Guillain-Barré Syndrome
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Autonomic dysfunction in GBS
Autonomic dysfunction in GBS
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Immune mechanisms in GBS
Immune mechanisms in GBS
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MadCAM-1
MadCAM-1
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Leukocyte extravasation
Leukocyte extravasation
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Vedolizumab (Entyvio)
Vedolizumab (Entyvio)
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Crohn's Disease vs. Ulcerative Colitis
Crohn's Disease vs. Ulcerative Colitis
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Rectal bleeding in Ulcerative Colitis
Rectal bleeding in Ulcerative Colitis
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Study Notes
Learning Objectives
- Explain how autoimmune disorders occur and their relationship to tolerance.
- Describe selected autoimmune disorders.
- Identify the key clinical features of specific autoimmune disorders.
- Explain the immune mechanisms contributing to clinical features.
- Describe treatments and therapeutic options for selected autoimmune disorders.
Autoimmune Diseases
- Generally mediated by antibodies or T cells, sometimes with other cells involved (e.g., macrophages, neutrophils, eosinophils).
- Antibodies can be agonistic (activating an improper response) or antagonistic (suppressing a normal response).
- Autoimmune diseases can be organ-specific (e.g., diabetes affecting the pancreas) or systemic (e.g., lupus).
Autoimmune Disease and Tolerance
- Autoimmune diseases can develop through failure of tolerance to self-antigens or immune system dysregulation.
- Responses are often chronic because the antigen is the body's own.
- Constant tissue insult can be fatal if the targeted antigen is in a vital organ (e.g., kidney).
- Lack of tolerance can be present at lymphocyte development or induced by mechanisms (like molecular mimicry).
- Aberrant activation of tissue antigen-presenting cells (APCs) which activate autoreactive T cells is one mechanism.
- Molecular mimicry happens when an infectious agent's epitope resembles self.
- Non-specific T cell activation by a pathogen superantigen can activate autoreactive T cells.
- Trauma or injury can expose self-antigens.
Autoimmune Disease - Contributing Factors
- Individuals possess autoreactive lymphocytes.
- Autoimmune disorders occur in about 3% of the population.
- Factors contributing to the development include genetics (HLA), anatomical alterations (injury, citrullination), infectious agents, and exposure to toxic chemicals.
Autoimmune Disease - Molecular Mimicry
- Explains how infection can lead to autoimmune disease.
- A specific example of this is Rheumatic Heart Disease.
- The bacteria Streptococcus pyogens infects a patient.
- The patient produces antibodies against a bacterial protein (M protein).
- If a human tissue protein (like a heart protein) resembles the bacterial protein, antibodies can mistakenly attack the self-protein.
- A specific example of this is Rheumatic Heart Disease.
Autoimmune Disease - Superantigen T Cell Activation
- Superantigens can activate many T cells (polyclonal activation) instead of just the correct/specific T cells to target an antigen.
- The superantigen from a pathogen holds the MHC II molecule to the T cell receptor (TCR), mimicking the correct presentation of the peptide.
- This leads to inappropriate activation and can trigger autoimmune responses.
Examples of Autoimmune Disorders
- The provided list includes numerous autoimmune disorders affecting various body systems.
- Women are more commonly affected by autoimmune disorders than men, often approximately a 2:1 ratio.
Systemic Autoimmune Diseases
- Rheumatoid Arthritis (RA)
- Autoimmune Hemolytic Anemia (AIHA)
- Guillain-Barré syndrome
Organ-Specific Autoimmune Diseases
- Vitiligo
- Crohn's disease
- Ulcerative colitis
Arthritis Classifications
- Different types of arthritis exist, including inflammatory and non-inflammatory, infectious, and crystal-induced forms.
- A classification exists for rheumatoid arthritis, ACCPA+, ACCPA-, Lupus, Scleroderma, Ankylosing spondylitis, Psoriatic Arthritis, Reacctive Arthritis, Inflammatory Bowel Disease Arthritis ,Vasculitis, Sjogren's.
Rheumatoid Arthritis
- Two major subtypes: positive for anti-cyclic citrullinated peptide antibodies (ACCPAs) and negative for ACCPAs.
- ACCPAs develop when a positively charged arginine is replaced by a neutral citrulline.
- ACCPAs are in ~ 67% of patients with RA. + ACCPA's often link to a more severe disease.
- Etiology remains unclear, but may be linked to rheumatoid factor and the formation of immune complexes.
- Other diseases (e.g., SLE, HepC, sarcoidosis, MCTD) can also have positive tests for RF.
- Symptoms can affect other parts of the body beyond just joints in about 40% of RA patients (e.g., skin, eyes, lungs, heart, kidneys, salivary glands, blood vessels, bone marrow).
Hemolytic Anemias
- Disorders characterized by premature destruction of red blood cells.
- Causes can be immunologic (immune, autoimmune), trauma, toxins, infections, drugs, or genetic disorders.
Autoimmune Hemolytic Anemia (AIHA)
- Results from antibodies directed against red blood cell (RBC) membrane antigens.
- Antibodies can target normal RBC constituents (like Rh) or modified antigens (e.g., drugs bound to RBC).
- Sources of these antibodies can be autoantibodies (autoimmune AIHA) or alloantibodies introduced from a donor (alloimmune AIHA).
- Half of AIHA cases are idiopathic (unknown cause).
Guillain-Barré Syndrome
- An acute, progressive, and monophasic paralytic neuropathy triggered by aberrant autoimmunity—typically linked to infections.
- Campylobacter jejuni is the most common antecedent pathogen, though other pathogens can be involved.
- Immune response, involving T cells, B cells, macrophages and complements, is a component in the disease.
Organ-Specific Autoimmune Diseases
- Conditions where the immune system attacks specific cells in an organ, leading to tissue damage and dysfunction in organs that are targeted.
Vitiligo
- Characterized by the loss of skin pigment due to melanocyte destruction.
- Two main types are non-segmental and segmental, based on the affected skin area.
- Causes may include autoimmune attack of melanocytes and/or genetic mutations.
- Triggers, such as childbirth, skin damage (response known as Koebner), hormonal changes, liver or kidney problems, or exposure to chemicals can trigger or influence the course of the clinical presentation of vitiligo.
Crohn's Disease
- Type of inflammatory bowel disease.
- Inflammation can affect any part of the gastrointestinal tract, though is often localized in the lower part of the small intestine and the upper part of the large intestine.
- Can involve the development of ulcers called focal aphthoid ulcers and transmural inflammation, causing thickening of the bowel wall.
- Associated with a range of causes, including immune response against elements(antigens) from the gut microbiome, and genetic components).
Ulcerative Colitis
- A chronic inflammatory disorder of the colon. Typically begins in the rectum and can extend throughout the colon.
- Pathology may include reduced mucin production, damage to the epithelial barrier, altered regulation of tight junctions, and presence of certain T cell and cytokine responses, including an atypical TH2 response mediated by non-classic NKT-cells producing IL-4 & IL-13.
- Increased TNF-a is present.
Treatment Descriptions
- Specific treatments described for different autoimmune diseases, including DMARDs (for RA), biologic agents (for Crohn's and ulcerative colitis), plasmapheresis, immunosuppressants and corticosteroids.
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Description
Explore the mechanisms behind hemolytic anemia, including drug-induced, enzyme deficiencies, immune-mediated destruction, and transfusion reactions. Differentiate between intrinsic and extrinsic causes of red blood cell destruction. Understand the role of autoantibodies in autoimmune diseases.
