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Questions and Answers
What occurs when mature T cells recognize self-antigens in peripheral tissues?
What occurs when mature T cells recognize self-antigens in peripheral tissues?
What is a major factor determining whether T cells are activated or tolerized?
What is a major factor determining whether T cells are activated or tolerized?
What does anergy in T cells indicate?
What does anergy in T cells indicate?
Which receptor is primarily associated with terminating T cell activation?
Which receptor is primarily associated with terminating T cell activation?
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What is the role of PD-1 on T cells?
What is the role of PD-1 on T cells?
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What happens when CTLA-4 binds to B7 on APCs?
What happens when CTLA-4 binds to B7 on APCs?
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Which mechanism is NOT involved in T cell anergy?
Which mechanism is NOT involved in T cell anergy?
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How can checkpoint blockade be utilized in cancer treatment?
How can checkpoint blockade be utilized in cancer treatment?
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What is the probability that two siblings will have the same MHC alleles?
What is the probability that two siblings will have the same MHC alleles?
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Why do T cells exhibit strong reactions to allogenic MHC molecules?
Why do T cells exhibit strong reactions to allogenic MHC molecules?
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What role do dendritic cells play in the induction of immune responses against transplants?
What role do dendritic cells play in the induction of immune responses against transplants?
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Which of the following statements about direct allorecognition is correct?
Which of the following statements about direct allorecognition is correct?
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How do recipient T cells recognize graft alloantigens in indirect allorecognition?
How do recipient T cells recognize graft alloantigens in indirect allorecognition?
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What distinguishes minor histocompatibility antigens from MHC reactions in graft rejection?
What distinguishes minor histocompatibility antigens from MHC reactions in graft rejection?
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Which immune system cells are primarily responsible for mediating graft rejection?
Which immune system cells are primarily responsible for mediating graft rejection?
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What is the primary reason why a single allogeneic graft cell can elicit a strong immune response?
What is the primary reason why a single allogeneic graft cell can elicit a strong immune response?
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What is a characteristic of antigen loss variants in tumors?
What is a characteristic of antigen loss variants in tumors?
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Which mechanism is NOT commonly adopted by tumors to evade the immune response?
Which mechanism is NOT commonly adopted by tumors to evade the immune response?
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How do monoclonal antibodies function in passive immunotherapy?
How do monoclonal antibodies function in passive immunotherapy?
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What type of therapy utilizes T lymphocytes with tumor-specific CTLs?
What type of therapy utilizes T lymphocytes with tumor-specific CTLs?
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What is the primary goal of vaccination in cancer immunotherapy?
What is the primary goal of vaccination in cancer immunotherapy?
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Which of the following is a characteristic feature of the Chimeric Antigen Receptor (CAR) therapy?
Which of the following is a characteristic feature of the Chimeric Antigen Receptor (CAR) therapy?
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What role do immunosuppressive cytokines like TGF-beta play in tumor biology?
What role do immunosuppressive cytokines like TGF-beta play in tumor biology?
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What is a potential consequence of tumors losing class I MHC molecules?
What is a potential consequence of tumors losing class I MHC molecules?
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What is the main method used for therapy in congenital immunodeficiencies?
What is the main method used for therapy in congenital immunodeficiencies?
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Which immunodeficiency is characterized by being acquired during life and not genetic?
Which immunodeficiency is characterized by being acquired during life and not genetic?
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Which cell type is primarily targeted by the HIV virus?
Which cell type is primarily targeted by the HIV virus?
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What process allows HIV to integrate its genetic material into the host's genome?
What process allows HIV to integrate its genetic material into the host's genome?
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What is the primary component of the HIV envelope that enables it to bind to host cells?
What is the primary component of the HIV envelope that enables it to bind to host cells?
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Which of the following is NOT a method mentioned for treating congenital immunodeficiencies?
Which of the following is NOT a method mentioned for treating congenital immunodeficiencies?
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What occurs during the life cycle of HIV after the infection of host cells?
What occurs during the life cycle of HIV after the infection of host cells?
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What major consequence occurs due to the activation of HIV within the immune system?
What major consequence occurs due to the activation of HIV within the immune system?
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What is the primary consequence of a deficiency in c function related to T lymphocytes?
What is the primary consequence of a deficiency in c function related to T lymphocytes?
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Which condition is associated with mutations in the Bruton Tyrosine Kinase (BTK) gene?
Which condition is associated with mutations in the Bruton Tyrosine Kinase (BTK) gene?
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What role does JAK3 play in SCID related conditions?
What role does JAK3 play in SCID related conditions?
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How does adenosine deaminase (ADA) deficiency affect lymphocyte development?
How does adenosine deaminase (ADA) deficiency affect lymphocyte development?
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What characterizes X-linked Hyper-IgM Syndrome?
What characterizes X-linked Hyper-IgM Syndrome?
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Which syndrome results from an incomplete development of the thymus?
Which syndrome results from an incomplete development of the thymus?
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What is a common outcome in patients with common variable immunodeficiency (CVID)?
What is a common outcome in patients with common variable immunodeficiency (CVID)?
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Which of the following immune cells is most affected by defects in RAG1 or RAG2?
Which of the following immune cells is most affected by defects in RAG1 or RAG2?
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Which mediator is responsible for causing dilation of small blood vessels and increasing vascular permeability?
Which mediator is responsible for causing dilation of small blood vessels and increasing vascular permeability?
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What type of hypersensitivity is characterized by the involvement of IgG and IgM antibodies against tissue antigens?
What type of hypersensitivity is characterized by the involvement of IgG and IgM antibodies against tissue antigens?
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What is the primary component of the immune response in the case of delayed-type hypersensitivity?
What is the primary component of the immune response in the case of delayed-type hypersensitivity?
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Which condition is the most severe form of immediate hypersensitivity reaction?
Which condition is the most severe form of immediate hypersensitivity reaction?
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Which of the following therapies can be used to manage immediate hypersensitivity reactions?
Which of the following therapies can be used to manage immediate hypersensitivity reactions?
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What mechanism of injury is commonly associated with antibodies binding to acetylcholine receptors?
What mechanism of injury is commonly associated with antibodies binding to acetylcholine receptors?
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In chronic inflammation, what type of hypersensitivity disorder is associated with serum sickness?
In chronic inflammation, what type of hypersensitivity disorder is associated with serum sickness?
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Which type of lymphocyte deficiency is primarily responsible for Severe Combined Immunodeficiency (SCID)?
Which type of lymphocyte deficiency is primarily responsible for Severe Combined Immunodeficiency (SCID)?
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What triggers the release of mediators in bronchial asthma?
What triggers the release of mediators in bronchial asthma?
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Which type of hypersensitivity disorder is characterized by exaggerated responses to environmental antigens?
Which type of hypersensitivity disorder is characterized by exaggerated responses to environmental antigens?
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Which type of cytokine is mainly produced by Th2 cells and contributes to tissue injury?
Which type of cytokine is mainly produced by Th2 cells and contributes to tissue injury?
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What is the primary purpose of desensitization therapy in the context of allergies?
What is the primary purpose of desensitization therapy in the context of allergies?
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Which cytokines produced by Th1 cells predominantly activate macrophages?
Which cytokines produced by Th1 cells predominantly activate macrophages?
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How are Type 2 hypersensitivity disorders often triggered by infections, such as with streptococcal infections?
How are Type 2 hypersensitivity disorders often triggered by infections, such as with streptococcal infections?
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Study Notes
Immunological Tolerance and Autoimmunity
- Immunological tolerance is the unresponsiveness to self-antigens. It's a lack of response to antigens induced by lymphocyte exposure to those antigens.
- Immunogenic lymphocytes are activated, proliferating and differentiating into effector and memory cells (productive immune response) – usually for microbes.
- Tolerogenic lymphocytes are inactivated or killed resulting in tolerance – normally for self-antigens. Failure of self-tolerance causes autoimmune disease.
- Immunological ignorance refers to antigen-specific lymphocytes that do not react, ignoring the presence of an antigen.
- Central tolerance occurs in generative lymphoid organs (bone marrow and thymus) where immature lymphocytes specific to self-antigens are deleted.
- Peripheral (secondary) tolerance involves mature lymphocytes encountering self-antigens in peripheral lymphoid organs/tissues.
- CD4+ T cells mediate responses to protein antigens. They can induce tolerance, preventing both cell-mediated and humoral immune responses against self-proteins.
- Autoimmunity is when the immune system attacks the individual's own cells and tissues.
- Central T cell tolerance involves the removal of immature T cells that react with self-antigens.
- Negative selection occurs when immature T-lymphocytes interact with a self-antigen triggering apoptosis, preventing the T-cell becoming functionally competent.
- Self-proteins are crucial in thymic expression.
- Peripheral T cell tolerance involves mature T cells recognizing self-antigens, leading to functional inactivation (anergy) or death, or suppression by regulatory cells.
- Antigen recognition without costimulation leads to T-cell anergy or death, enhancing sensitivity to suppression by regulatory T cells.
- Anergy is a long-lived functional unresponsiveness in T cells due to abnormal TCR complex signaling or inhibitory signals from other receptors like CTLA-4, CD152, or PD-1.
- CTLA-4 and PD-1 are inhibitory receptors that regulate T-cell responses. CTLA-4 reduces costimulation and suppresses regulatory T-cell activity, while PD-1 terminates T-cell responses to self-antigens and chronic infections via ITIM.
- Checkpoint blockade is a cancer treatment that involves blocking inhibitory receptors such as CTLA-4 or PD-1, potentially causing autoimmune responses against one's own tissues.
- Regulatory T cells (Tregs), CD4+ cells expressing CD25 and FoxP3, suppress harmful lymphocytes specific to self-antigens.
- FoxP3 is a transcription factor essential for Treg development and function.
Mutations and Survival
- Mutations can cause multiorgan autoimmune disease (IPEX).
- Survival and function of regulatory T cells are dependent on the cytokine IL-2.
- TGF-beta stimulates FoxP3, a regulatory T cell-stimulating cytokine.
- Regulatory T cells suppress immune responses by producing cytokines (IL-10 and TGF-beta), blocking B7 on APCs using CTLA-4, and consuming T-cell growth factors.
Deletion and Antigen Recognition
- Deletion of mature lymphocytes occurs when they recognise self-antigens.
- Two mechanisms involve pro-apoptotic protein activation and co-expression of death receptors and their ligands which activate downstream caspases and apoptosis of the lymphocytes
B Cell Tolerance
- B lymphocytes prevent autoantibody production by self-polysaccharides, lipids, and nucleic acids (T-independent).
- Central B cell tolerance occurs when immature B lymphocytes interact with self-antigens leading to receptor editing or deletion.
- Receptor editing is the process where B cells modify Ig light chain genes to produce new receptors not specific for self-antigens.
- Anergy can affect B-cells, similarly to T cells.
Tolerance to Commensal Microbes and Fetal Antigens
- Commensal microbes and fetal antigens require tolerance to co-exist.
- Microbes in the intestines, skin, or respiratory tract are tolerated by mature cells.
- Paternal antigens in the placenta are typically tolerated by the mother.
Autoimmunity: Pathogenesis and Genetic Factors
- Genetic factors, mainly MHC genes, influence autoimmune disease susceptibility.
- HLA alleles can increase the risk of autoimmune diseases by influencing self-tolerance/immune response.
- Polymorphisms (variations in genes) can contribute to autoimmune diseases.
- Infections may trigger or influence autoimmunity as molecules might mimic self-antigens (molecular mimicry).
Immune Surveillance and Responses Against Tumors
- Immune surveillance is the immune system's role in controlling and eliminating malignant cells.
- Evidence for this includes lymphocyte infiltrates around tumors, rapid rejection of transplants if exposed previously to the tumor, and immunodeficiencies associated with increased tumor incidence.
- Tumor antigens include products of mutated genes, oncogenes, or mutated tumor suppressor genes, and overexpressed or aberrantly expressed proteins.
- Cytotoxic T lymphocytes (CTLs) act to kill tumor cells specific for tumor antigens.
Evasion of Immune Responses by Tumors
- Tumors may evade detection or resistance to immune response by losing antigens, neglecting MHC molecules, inhibiting T cell activation, or producing immunosuppressive cytokines.
Cancer Immunotherapy
- Cancer immunotherapy focuses on activating anti-tumor effectors, actively immunizing against tumors, or activating the patient's antitumor immune response.
- Passive immunotherapy uses immune effectors (antibodies) specific for tumor antigens to activate host effector mechanisms.
- Adoptive cellular therapy involves isolating tumor-specific T lymphocytes and returning them to a patient.
Immune Responses Against Transplants
- Direct allorecognition refers to recipient T cells directly recognizing donor MHC molecules on graft dendritic cells and attacking them.
- Indirect allorecognition involves graft allo-antigens being processed and presented by recipient dendritic cells and recognized by alloreactive CD4+ T cells.
- Transplants can be rejected based on MHC antigens, leading to inflammatory reactions, damaging the transplanted tissue.
Prevention and Treatment of Graft Rejection
- Immunosuppression inhibits T-cell activation and effector functions to prevent graft rejection.
- FK506 and Rapamycin are immunosuppressive drugs that block immune responses.
Hypersensitivity Reactions
- Hypersensitivity reactions describe when immune responses to an antigen result in sensitivity to challenge with that antigen.
- Immediate hypersensitivity (Type 1) involves mast cells releasing mediators such as histamine against environmental antigens following IgE binding.
- Antibody-mediated (Type 2) involves antibodies (other than IgE)(IgM or IgG) attacking cell or tissue antigens.
- Immune complex-mediated (Type 3) involves soluble antigen and antibody complexes depositing in blood vessels and tissues leading to inflammation and tissue injury.
- T-cell mediated (Type 4) reactions occur via macrophage activation, cytokine-mediated inflammation, direct cytotoxicity, and damage.
Mechanisms of Tissue Injury and Disease
- Mediators such as proteases, arachidonic acid metabolites, and cytokines damage tissues.
Immunodeficiency Diseases
- Immunodeficiency diseases are disorders due to defective immunity.
- Congenital (primary) immunodeficiencies arise from genetic abnormalities affecting immune system components.
- Acquired (secondary) immunodeficiencies develop due to factors like infections, nutritional issues, or medical treatments altering functionality of immune components.
- Severe combined immunodeficiency (SCID) involves defects in both B and T lymphocytes.
- Chediak-Higashi syndrome or Ataxia-telangiectasia are diseases exhibiting impaired phagocyte and/or lymphocyte function.
- Therapy for deficiencies often involves hematopoietic stem cell transplantation or intravenous immunoglobulin (IVIG) injections.
Acquired Immune Deficiency Syndrome (AIDS)
- The Human immunodeficiency virus (HIV) largely affects CD4+ T lymphocytes, causing progressive destruction of immune cells and leading to opportunistic infections.
- HIV lifecycle includes infecting cells (using gp120), producing viral DNA copies, integration into host genome, and expression/production of viral particles.
- Clinical features of HIV show signs like acute HIV syndrome followed by latency- a period of viral suppression where HIV might cause mild symptoms or remain asymptomatic but continues to destroy the immune system. Symptoms of AIDS develop progressively as CD4+ T cells decline (below 200 cells/mm^3).
- Advanced AIDS is marked by characteristic opportunistic infections and cancerous tumors (Kaposi's sarcoma and B-cell lymphomas from Epstein Barr Virus).
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Description
Explore the complex concepts of immunological tolerance and autoimmunity in this quiz. Understand how the immune system distinguishes between self and non-self antigens, and learn about mechanisms like central and peripheral tolerance. Test your knowledge on the activation of lymphocytes and the implications of failure in self-tolerance.
