Tolerance and Autoimmune Disorders
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Questions and Answers

What are the general features of autoimmune diseases?

Autoimmune diseases are chronic, often progressive, have overlapping clinical manifestations, and may target either cellular or organ-specific self-antigens.

Name two examples of organ-specific autoimmune diseases and their affected organs.

Grave's disease affects the thyroid gland and Type 1 Diabetes Mellitus affects the pancreas.

How do systemic autoimmune diseases differ from organ-specific autoimmune diseases?

Systemic autoimmune diseases affect multiple organs and systems throughout the body, while organ-specific diseases target a specific organ.

What factors can influence the signs and symptoms of autoimmune diseases?

<p>Age, hormones, and environmental factors can all influence the presentation of autoimmune diseases.</p> Signup and view all the answers

Describe the impact of autoreceptor antibodies in autoimmune diseases, giving an example.

<p>Autoreceptor antibodies, such as those found in Myasthenia gravis, interfere with normal receptor function leading to muscle weakness.</p> Signup and view all the answers

What is a common feature of the immune responses in autoimmune diseases?

<p>Immune responses in autoimmune diseases often target self-antigens, leading to tissue damage.</p> Signup and view all the answers

Why is classification of autoimmune diseases often difficult?

<p>Classification is difficult due to similar symptoms presented by various types and overlapping clinical manifestations.</p> Signup and view all the answers

What happens to individuals with multiple autoimmune diseases?

<p>They may display symptoms from each disease simultaneously, complicating their clinical picture.</p> Signup and view all the answers

Give an example of a Type II hypersensitivity reaction in autoimmune disease.

<p>An example is autoimmune hemolytic anemia, where antibodies destroy red blood cells.</p> Signup and view all the answers

List two systemic autoimmune diseases and their potential symptoms.

<p>Systemic Lupus Erythematosus may cause fatigue and joint pain, while Rheumatoid Arthritis may lead to joint swelling and stiffness.</p> Signup and view all the answers

What is immunologic tolerance and why is it important for maintaining health?

<p>Immunologic tolerance is the inability of the immune system to mount a response against specific antigens, essential for preventing autoimmunity and maintaining homeostasis.</p> Signup and view all the answers

Explain the difference between central tolerance and peripheral tolerance.

<p>Central tolerance involves the clonal deletion of autoreactive lymphocytes during development in the thymus or bone marrow, while peripheral tolerance regulates or eliminates these cells after they have entered circulation.</p> Signup and view all the answers

Describe the role of anergy in peripheral tolerance.

<p>Anergy is the irreversible functional inactivation of autoreactive T and B lymphocytes that escape central tolerance, preventing them from functioning and causing autoimmunity.</p> Signup and view all the answers

What is the role of costimulatory molecules on antigen-presenting cells in T cell activation?

<p>Costimulatory molecules on APCs are essential for breaking T cell anergy, leading to the activation of T cells specific for self-antigens.</p> Signup and view all the answers

What mechanisms contribute to the suppression of autoreactive lymphocytes by regulatory T cells?

<p>Regulatory T cells suppress autoreactive lymphocytes primarily through the secretion of cytokines like IL-10, which inhibit their activation.</p> Signup and view all the answers

How does molecular mimicry contribute to autoimmune diseases?

<p>Molecular mimicry occurs when microbial antigens share amino acid sequences with self-antigens, leading to cross-reactivity and autoimmune responses.</p> Signup and view all the answers

How does antigen sequestration contribute to immunologic tolerance?

<p>Antigen sequestration involves hiding self-antigens behind blood-tissue barriers, such as those in the brain and eyes, preventing autoreactive lymphocytes from engaging with them.</p> Signup and view all the answers

What is the significance of the HLA-B27 allele in autoimmune diseases?

<p>HLA-B27 is strongly associated with ankylosing spondylitis, increasing the risk of developing the disease by 100-200 times.</p> Signup and view all the answers

Identify key factors that can lead to the breakdown of self-tolerance.

<p>Key factors include genetic predisposition, environmental triggers such as infections, and inherited susceptibility genes that disrupt tolerance mechanisms.</p> Signup and view all the answers

What are the potential outcomes of the failure of self-tolerance?

<p>The failure of self-tolerance can result in autoimmune diseases, where the immune system incorrectly targets and attacks the body's own tissues.</p> Signup and view all the answers

Describe the effect of viral infections on the development of autoimmune diseases.

<p>Viral infections can modify self-antigens, induce cross-reaction with shared epitopes, and cause necrosis and inflammation that promotes autoimmunity.</p> Signup and view all the answers

Explain how traumatic injury can lead to autoimmune reactions.

<p>Traumatic injury can expose previously sequestered antigens to autoreactive lymphocytes, potentially triggering an autoimmune response as the immune system mistakenly recognizes these antigens as foreign.</p> Signup and view all the answers

What mechanisms lead to the release of sequestered self-antigens?

<p>Sequestered self-antigens are released due to tissue trauma or inflammatory destruction, exposing hidden epitopes.</p> Signup and view all the answers

What is polyclonal B cell activation and its relevance to autoimmunity?

<p>Polyclonal B cell activation occurs when microorganisms stimulate multiple B cell clones, some of which may be autoreactive.</p> Signup and view all the answers

Discuss the interplay between genetic and environmental factors in the development of autoimmunity.

<p>The development of autoimmune diseases often involves a combination of genetic susceptibility and environmental factors, like infections, that trigger immune responses against self-antigens.</p> Signup and view all the answers

What is the significance of mutation of apoptosis genes in the context of autoimmune lymphoproliferative disorders?

<p>Mutations in apoptosis genes can lead to a failure in deleting autoreactive lymphocytes, resulting in autoimmune lymphoproliferative disorders characterized by uncontrolled immune cell proliferation.</p> Signup and view all the answers

Explain the importance of genetic factors in autoimmune diseases.

<p>Genetic factors, including mutations in apoptotic pathways and familial patterns of incidence, contribute significantly to the susceptibility of autoimmune diseases.</p> Signup and view all the answers

What role do defective regulatory T cells play in autoimmunity?

<p>Defective development of regulatory T cells can impair tolerance in the immune system, facilitating autoimmune disease progression.</p> Signup and view all the answers

How does inflammatory destruction expose cryptic epitopes?

<p>Inflammatory destruction can lead to tissue injury, which reveals cryptic epitopes previously hidden from the immune system.</p> Signup and view all the answers

What is the relationship between antibody reactions to streptococcal proteins and myocarditis?

<p>Antibodies produced against streptococcal proteins can cross-react with myocardial proteins, leading to myocarditis.</p> Signup and view all the answers

Flashcards

Immunologic Tolerance

The immune system's ability to distinguish between self and non-self antigens, preventing attacks on the body's own cells and tissues.

Self-tolerance

A specific type of immunologic tolerance where the immune system does not react against the individual's own antigens.

Central Tolerance

The process of eliminating or inactivating autoreactive lymphocytes (T and B cells) within the thymus or bone marrow, preventing them from reaching the periphery.

Anergy

A state of irreversible functional inactivation of autoreactive cells that escape central tolerance, preventing them from attacking self-antigens.

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Antigen Sequestration

A process where certain tissues, such as the brain and eye, hide their antigens behind barriers, preventing autoreactive lymphocytes from accessing them.

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Autoimmune Disease

A type of immune response where the immune system attacks the body's own tissues. This occurs when the mechanisms of tolerance fail, causing an immune response against self-antigens.

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Failure of Self-Tolerance

A breakdown in the balance between lymphocyte activation (fighting pathogens) and tolerance (accepting self), leading to autoimmune responses.

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Susceptibility Genes

Genes that increase the likelihood of developing autoimmune diseases by contributing to the breakdown of self-tolerance or regulation of immune responses.

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Environmental Triggers

Factors, such as infections, that can trigger autoimmune reactions, especially in individuals with genetic predisposition.

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Mechanisms of Autoimmunity

Autoimmune reactions that primarily occur through the failure of self-tolerance, involving abnormal immune responses to self-antigens.

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T cell anergy breakdown

T cell anergy can be broken down when antigen presenting cells (APCs) upregulate costimulatory molecules, leading to activation of T cells that are specific to self-antigens.

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T cell suppression in AIDS

In AIDS, T cell mediated suppression is impaired, contributing to the weakening of the immune system.

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Molecular mimicry

Molecular mimicry occurs when a microbe shares amino acid sequences with a self-antigen. The immune system might cross-react with the pathogen and attack the self-antigen, causing tissue damage.

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Rheumatic heart disease

Rheumatic heart disease is a classic example of molecular mimicry. Antibodies against streptococcal proteins cross-react with heart proteins, causing myocarditis.

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Polyclonal B cell activation

Certain microorganisms, like EBV, can cause polyclonal activation of B cells. Some of these activated B cells may be autoreactive and trigger autoimmune responses.

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Exposure of hidden self-antigens

Trauma or inflammation can expose hidden self-antigens (like lens proteins in the eye), leading to autoimmune responses.

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Familial autoimmune disease

Increased incidence of autoimmune diseases in families suggests a genetic component.

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HLA alleles and autoimmunity

Specific HLA alleles are associated with autoimmune diseases. For example, HLA-B27 is strongly linked to ankylosing spondylitis.

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Apoptotic pathway defects and autoimmunity

Genetic defects in apoptotic pathways may contribute to autoimmunity by disrupting tolerance mechanisms.

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Infection and autoimmunity

Infections, particularly viral infections, can trigger autoimmune responses through multiple mechanisms like modification of self-antigens, molecular mimicry, and exposure of hidden antigens due to inflammation.

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Organ or Cell-Specific Autoimmunity

Immune responses in autoimmune diseases may target specific organs or cells within the body. Examples include thyroiditis targeting the thyroid gland or autoimmune hemolytic anemia targeting red blood cells.

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Chronicity and Progressiveness in Autoimmune Diseases

Autoimmune diseases often have a chronic course with periods of activity and remission, and the damage caused by the immune system can worsen over time.

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Classification Challenges in Autoimmune Diseases

Autoimmune diseases often involve a complex interplay of immune cells and molecules, making classification difficult.

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Shared Symptoms Across Autoimmune Diseases

While different autoimmune diseases may affect different organs, they share similar symptoms like fatigue, pain, and inflammation.

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Coexistence of Autoimmune Diseases

Individuals can have multiple autoimmune diseases simultaneously, leading to a combination of signs and symptoms.

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External Factors Influencing Autoimmune Disease

External factors like age, hormones, and environmental influences can affect the development and severity of autoimmune diseases.

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Commonly Affected Organs in Autoimmune Diseases

Autoimmune diseases commonly affect blood vessels, connective tissues, joints, muscles, red blood cells, skin, and endocrine glands.

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Organ-Specific Autoimmune Diseases

Autoimmune diseases where the immune response is directed at a specific organ or organ system.

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Systemic Autoimmune Diseases

Autoimmune diseases that affect multiple organs and systems throughout the body.

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Study Notes

Tolerance and Autoimmune Disorders

  • Tolerance is the inability of the immune system to mount an immune response against a specific antigen.
  • Self-tolerance is the lack of response to the body's own antigens, crucial for maintaining harmony between cells and tissues.
  • Tolerance mechanisms are broadly categorized as central and peripheral tolerance.

Central Tolerance

  • Clonal deletion (apoptosis) of autoreactive T and B lymphocytes occurs in the thymus (T cells) or bone marrow (B cells).
  • Post-thymic tolerance, includes mechanisms where self-reacting T cells ignore self-antigens, those antigens being sequestered (hidden), or in cells unable to respond (anergic) or by immune regulation.

Peripheral Tolerance

  • Mechanisms in the peripheral lymphoid organs (lymph nodes, spleen, mucosal lymphoid tissue) remove or deactivate autoreactive lymphocytes.
    • Anergy: irreversible functional inactivation of lymphocytes.
    • Suppression by regulatory T cells (inhibiting lymphocyte activation through cytokine secretion, e.g., IL-10).
    • Deletion by apoptosis, mutation of apoptosis genes can lead to autoimmune disorders.
    • Antigen sequestration: certain tissues have blood-tissue barriers that hide antigens from autoreactive lymphocytes.
    • Traumatic injury can expose these antigens and lead to autoimmune disorders.

Autoimmune Diseases

  • Autoimmune diseases result from a failure of tolerance, allowing immune responses against self-antigens.
  • These responses arise from interactions between abnormal susceptibility genes and environmental triggers, mainly infections.
  • Mechanisms of autoimmunity include failure of self-tolerance, genetic factors, and infectious factors.

Breakdown of Self-Tolerance

  • Breakdown of T cell anergy: upregulation of costimulatory molecules on antigen-presenting cells (APCs) leading to T cell activation against self-antigens.
  • Failure of T cell-mediated suppression (e.g., AIDS).
  • Molecular mimicry: microbial antigens sharing amino acid sequences with self-antigens triggering immune response against both.

Role of Susceptibility Genes

  • HLA alleles are associated with autoimmunity (e.g., HLA-B27 and ankylosing spondylitis, HLA association with type 1 diabetes).
  • Defective regulatory T-cell development is linked to some autoimmune disorders.
  • Autoimmune diseases frequently involve genetic susceptibility patterns rather than single mutations.

Role of Infection

  • Microbial agents (especially viruses) can modify self-antigens, lead to cross-reactions with microbial epitopes causing immune responses against self-antigens.
  • Microbial agents can induce necrosis and inflammation, potentially up-regulating co-stimulatory molecules and releasing hidden antigens.
  • Polyclonal activation of lymphocytes by microbial products can also contribute to autoimmune disorders.

Tissue Damage in Autoimmune Diseases

  • Tissue damage can result from type II (antibody-mediated) hypersensitivity reactions (e.g., autoimmune hemolytic anemia), Type III (immune complex deposition) hypersensitivity such as Systemic Lupus Erythematosus and Rheumatoid Arthritis, and anti-receptor antibodies (e.g., Myasthenia gravis).

General Features of Autoimmune Diseases

  • Immune responses target cellular or organ-specific self-antigens.
  • Autoimmune diseases are chronic, progressive, with relapses and remissions, and overlapping features which leads to difficult classification.
  • Similar symptoms can appear across various autoimmune diseases.
  • Symptoms are influenced by factors such as age, hormones, and environmental factors.

Classification of Autoimmune Diseases

  • Organ-specific autoimmune diseases (e.g., autoimmune thyroid disease [graves disease/Hashimoto], type 1 diabetes mellitus, myasthenia gravis).
  • Systemic autoimmune diseases (e.g., Systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease).

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Tolerance, Autoimmune Disorders PDF

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Explore the concepts of tolerance and autoimmune disorders, focusing on the mechanisms of central and peripheral tolerance. Understand how the immune system regulates responses to self-antigens and the role of lymphocytes in maintaining immune harmony.

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