Immunology of Beta Cells and Inflammation

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Questions and Answers

What is the role of chemokines CCL2 and CXCL10 in the context of beta cells?

They promote the destruction of beta cells by NK cells.

They stimulate the proliferation of beta cells.

They induce the recruitment of neutrophils and monocytes. (correct)

They inhibit the activation of T cells.

Which cells are primarily recruited and activated due to the expression of stress ligands by beta cells?

Neutrophils and B cells

Macrophages and CD8 T cells

NK cells and TH1 T cells (correct)

Monocytes and CD4 T cells

What is the consequence of epitope spreading in the immune response against beta cells?

It prevents macrophage infiltration into the tissue.

It leads to the rapid recovery of beta cell function.

It decreases the recruitment of neutrophils.

It results in activation of additional T helper and cytotoxic T cell clones. (correct)

What happens to monocytes once they are recruited to the tissue in this context?

They differentiate into macrophages. Signup and view all the answers

Which receptors are involved in recognizing the stress ligands expressed by beta cells?

Activating receptors of NK cells Signup and view all the answers

What is the role of phagocytes during an infection?

They migrate to lymph nodes to activate autoreactive T cell clones. Signup and view all the answers

Why are regulatory T cells not activated during an infection?

Pro-inflammatory cytokines impair their function. Signup and view all the answers

What effect does inflammation have on the potential for autoimmune diseases?

It creates an optimal environment for autoimmune disease induction. Signup and view all the answers

Which type of cells are primarily involved in the inflammation seen in autoimmune diseases?

Macrophages and dendritic cells. Signup and view all the answers

What is the relationship between dendritic cells in the joint and autoimmune disease symptoms?

The presence of dendritic cells correlates with symptom worsening. Signup and view all the answers

During the inflammation response after an infection, which cytokines are inhibited in their release by T regulatory cells?

TGFβ, IL10, IL35. Signup and view all the answers

What is primarily responsible for the bystander activation of neighboring T cells in lymph nodes?

Cytokines released by activated phagocytes. Signup and view all the answers

What happens when dendritic cells are targeted and eliminated during an autoimmune response?

The symptoms of autoimmune diseases improve. Signup and view all the answers

What mechanism is primarily involved in the activity of therapeutic monoclonal antibodies against tumor cells?

Activation of the complement system Signup and view all the answers

Which process is specifically described as being enhanced by antibodies to promote tumor cell destruction?

Antibody-dependent cellular cytotoxicity (ADCC) Signup and view all the answers

What specific role does trastuzumab play in relation to Her2-positive breast cancer cells?

Blocks the binding of Her2 to its growth factors Signup and view all the answers

What effect does the binding of therapeutic monoclonal antibodies have on tumor cell receptors?

Induces internalization of the receptor Signup and view all the answers

What is a potential approach for developing new monoclonal antibodies targeted at tumor cells?

Targeting and conjugating with specific bacterial toxins Signup and view all the answers

What process is involved in the destruction of tumor cells after antibody binding?

Internalization of toxins Signup and view all the answers

What is the consequence of opsonization of tumor cells by antibodies?

Facilitation of phagocytosis by macrophages Signup and view all the answers

What therapeutic effect is associated with complement-mediated cytotoxicity (CMC)?

Lysis of tumor cells Signup and view all the answers

What is the primary reason for the persistence of immunocomplexes in circulation during self-antigen release?

Ineffective complement activation due to low inflammation Signup and view all the answers

What is meant by epitope spreading in the context of autoimmune diseases?

Activation of additional T or B cell clones against cryptic epitopes Signup and view all the answers

In the case of pemphigus, what triggers the activation of antibodies against α-desmoglein1?

Initial destruction of α-desmoglein3 due to immune response Signup and view all the answers

What happens to the number of epitopes recognized by the immune system after the first immune reaction?

The number of epitopes increases as new ones become visible Signup and view all the answers

What is a key example of epitope spreading observed in diabetes type 1?

Activation of T cells against insulin due to GAD destruction Signup and view all the answers

Which of the following statements is true regarding the effector mechanism in autoimmune diseases?

It refers to the mechanism inducing autoreactive disease Signup and view all the answers

What is a potential trigger for the immune response in pemphigus at the cellular level?

Recognition of α-desmoglein3 by antibodies Signup and view all the answers

During self-antigen release, what characteristic of inflammation is notably different compared to an infection?

Minimal inflammation and immune response Signup and view all the answers

What role do dendritic cells play in the context of inflammation?

They activate autoreactive T cells by presenting self-antigens. Signup and view all the answers

Which cytokine is primarily associated with the response to viral infections?

Interferon type 1 Signup and view all the answers

What is a consequence of cytotoxic T cells destroying infected cells?

They release self-antigens that can activate other immune cells. Signup and view all the answers

How does interferon gamma influence B cells and macrophages?

It enhances the expression of HLA class II molecules. Signup and view all the answers

What does the term 'molecular mimicry' refer to in immunology?

The similarity between pathogen peptides and self-antigens. Signup and view all the answers

What is the primary result of increased expression of peptide-HLA complexes on epithelial cells due to interferon?

Enhanced recognition by CD8 T cells. Signup and view all the answers

What happens when B cells encounter self-antigens in an inflammatory context?

They begin to produce autoantibodies against self-proteins. Signup and view all the answers

What initiates the activation of dendritic cells during inflammation?

Danger signals released during tissue damage. Signup and view all the answers

What factor primarily causes the T cells to recognize tumor cells in the described experiment?

Altered expression of normal proteins Signup and view all the answers

Which of the following best describes tumor-associated antigens (TAA)?

Normal proteins that are up-regulated or mis-expressed in tumor cells Signup and view all the answers

How are cancer testis antigens like MAGE and TRP-1 aberrantly expressed?

In cells that usually do not express them, like epithelial cells Signup and view all the answers

What is a common characteristic of tumor antigens expressed as a result of viral infections?

They may lead to transformation of healthy cells into tumor cells Signup and view all the answers

What is the role of the major histocompatibility complex (MHC) in the context of tumor antigens?

Presents tumor antigens for T cell recognition Signup and view all the answers

What method is commonly used to identify specific antigens from tumor cells?

Co-culturing tumor cells with patient's isolated T cells Signup and view all the answers

What was an initial misconception regarding tumor-specific antigens?

They are always completely different from normal proteins Signup and view all the answers

Which of the following best illustrates the expression of embryonic antigens in adult cells?

They normally appear during fetal development but can re-emerge in adults Signup and view all the answers

Study Notes

Autoimmune Reaction

Autoimmune reactions are closely linked to hypersensitivity reactions. Type 1, 2, 3, and 4 hypersensitivity reactions can lead to autoimmune diseases.
An autoimmune response is an immune response directed against self-antigens and self-cells.
Paul Ehrlich first described this response as "horror auto-toxic" in the early 1900s.
Lupus erythematosus and multiple sclerosis were the first clinically recognized autoimmune diseases (1950s and 1960s, respectively).
For a disease to be considered autoimmune, it must involve tissue damage and resulting clinical symptoms.

Noel Rose

Noel Rose was a pioneer in autoimmune disease research.
He worked with animal models (mice and rabbits) to study thyroiditis (Hashimoto's disease).
His early work was initially rejected for lack of clinical evidence.
His subsequent research led to the description of Hashimoto's disease in humans.

Autoimmune Mechanisms

Autoimmune reactions can be triggered by autoantibodies or T cells.
Autoantibodies can activate type 2 and type 3 hypersensitivity responses.
Autoreactive T cells usually trigger type 4 hypersensitivity and tissue damage.
These responses can lead to the development of autoimmune diseases.

Mechanisms of Autoimmune Disease

Central tolerance failure: Autoreactive T cells escape from the thymus and are released into the periphery, where they encounter self-antigens. This is a rare cause of autoimmune disease, as mechanisms are tightly regulated.
Peripheral tolerance failure: Failure of mechanisms intended to maintain tolerance via various cells (Treg cells, cytokine production, etc.) can lead to autoimmunity. This allows self-reactive lymphocytes to cause tissue damage.
Inflammation: Chronic inflammation is necessary for several autoimmune diseases; this can arise from infections or other sources. Inflammation release danger signals activating dendritic cells and other lymphocytes..
Molecular mimicry: Pathogen antigens can have similar structures to self-antigens; this can trigger an autoimmune response.
Defects in immune system: Immune system components (B cells, T cells, cytokines, etc.) can have defects leading to autoimmune problems. Defects in the immune system can result from chronic inflammation.

Inflammation and Autoimmunity

Inflammation often triggers or exacerbates autoimmune diseases.
Danger signals, released during inflammation, activate antigen-presenting cells (APCs).
Pro-inflammatory cytokines impair regulatory T (Treg) cell function.
Treg cells normally release inhibitory cytokines, such as TGF-β, IL-10, and IL-35. The failing of immune tolerance related to impaired Treg activity can lead to autoimmunity.
This inflammatory environment can contribute to or induce autoimmune disease.

Immune Response and Autoimmunity

Many autoimmune diseases are characterized by the presence of autoantibodies and/or autoreactive T cells. These cells can trigger immune responses that damage tissues and lead to clinical symptoms.
Some autoimmune diseases manifest with only one specific kind of response by B or T-cells. Sometimes the immune response involves many molecules that induce other inflammatory cells.
The virus, bacteria, or chronic infections can be a trigger for autoimmune diseases because they induce a high level of inflammation which can lead to activate the regulatory T cells, leading to an immune response and autoimmunity.

Epitope Spreading

Epitope spreading means the reaction against a specific antigen that leads to the amplification of the reaction in response to other related antigens.
During the immune response to a specific antigen, autoreactive T-cells or B-cells may become activated against other antigens.

Effector Mechanisms

Antibody-mediated effects: Antibodies can activate complement, leading to phagocytosis of cells, and cause tissue damage by activating various inflammatory cells.
Lymphocyte-mediated effects: T cells attack, and damage cells, tissues, or organs as a result of the reaction to an antigen.
Macrophages are an immune cell activated by and related to the inflammation and are crucial in the pathogenesis of inflammatory diseases.
Molecular mimicry: Pathogen antigens can have similar structures to self-antigens, triggering an autoimmune reaction.

Abnormalities and Autoimmunity

Defects in regulatory T cells (Treg cells) can cause autoimmune diseases.
Defects in antigen-presenting cells (APCs) such as dendritic cells can result in immune dysfunction that causes autoimmune disorders.
Lack of factors required for immune responses or other immune components cause disease.

Autoimmune Diseases - Examples

Graves' disease (hyperthyroidism) and Hashimoto's thyroiditis (hypothyroidism) are common thyroid diseases.
Multiple sclerosis results in demyelination of the nerves.
Rheumatoid arthritis is associated with the destruction of joints.
Myasthenia gravis is a disease in which the neuromuscular junction is affected, leading to muscle weakness.

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Description

This quiz explores the intricate roles of chemokines CCL2 and CXCL10 in beta cell function and their implications for autoimmunity. It delves into the cellular responses triggered by stress ligands and the dynamics of immune cell activation and inflammation. Understand the interactions between various immune cells and their contributions to autoimmune diseases.