Lecture 20 Cytokines part 3

What is the role of cytokines in disease?

Cytokines and their receptors play a significant role in various diseases by either overexpression or underexpression. These imbalances can lead to conditions such as autoimmune diseases, cancers, and toxic shock syndrome.

What is toxic shock syndrome, and what causes it?

Toxic shock syndrome is initiated by the release of superantigens from bacteria like Staphylococcus aureus and Streptococcus pyogenes. These superantigens cause an overproduction of cytokines, leading to systemic reactions like fever, hypotension, and shock, which can be fatal.

How does bacterial septic shock occur?

Bacterial septic shock occurs due to the overproduction of cytokines, particularly IL-1 and TNF-α, in response to Gram-negative bacterial endotoxins. This can result in fatal outcomes if untreated.

What is the connection between cytokines and certain cancers?

Elevated levels of cytokines or their receptors are associated with cancers such as Adult T-cell Leukemia (autocrine IL-2 stimulation) and Hodgkin lymphoma (autocrine IL-5).

What therapeutic strategies are used to modulate cytokine function?

Therapeutic strategies include neutralizing antibodies, soluble cytokine receptors, cytokine antagonists, and cytokine analogs. These methods aim to regulate or inhibit cytokine activity to treat diseases like autoimmune conditions and cancers.

What are cytokine inhibitors, and give examples?

Cytokine inhibitors are naturally occurring or synthetic agents that block cytokine activity. Examples include
-IL-1Ra
-IL-6Ra
-IFN-γRa
-TNF-αRa
-which inhibit cytokine signaling to reduce inflammation.

How do biologics help in immune-based diseases?

Biologics, like monoclonal antibodies and immune modulators, target specific cytokines or receptors to manage autoimmune diseases, cancers, and other immune-related conditions.

What role do cytokines play in allergies and asthma?

Cytokines like IL-4 and IL-13 promote Ig class switching, contributing to allergies and asthma. Therapies targeting these cytokines aim to reduce IgE production and manage allergic responses.

What is Age-Related Macular Degeneration (AMD), and how is it related to immune regulation?

AMD results from the failure of regulatory proteins to clear waste in the macula, leading to vision loss. The immune system's inability to manage this waste contributes to the condition.

What are lymphokine-activated killer (LAK) cells, and how are they used therapeutically?

LAK cells, generated by exposing NK or T-cells to high concentrations of IL-2, are used in passive immunotherapy to target and destroy cancer cells.

How does recombinant IL-2 contribute to LAK cell therapy?

Recombinant IL-2 is used to stimulate the production and activity of LAK cells, enhancing their ability to target and destroy cancer cells in immunotherapy.

What is the role of IL-2R Inhibitors (IL-2Ri) in immune responses?

IL-2Ri is formed by the proteolytic release of a portion of the IL-2R α chain and is associated with chronic T-cell activation. It serves as a clinical marker for diseases like Adult T-cell Leukemia (ATLL).

How does IL-1Ra function as a cytokine antagonist?

IL-1Ra binds to the IL-1 receptor on CD4+ T-cells, preventing their activation and thereby regulating the intensity of inflammatory responses.

What are the common bacterial causes of keratitis?

The two most common bacterial causes of keratitis are Staphylococcus aureus and Pseudomonas aeruginosa, often linked to contact lens misuse or ocular trauma.

What are biologics, and how are they classified?

Biologics are a diverse group of medications, including vaccines, immune modulators, monoclonal antibodies, and growth factors. They are classified based on their origin, such as chimeric human-mouse (-ximab), humanized mouse (-zumab), and fully human (-mumab) drugs.Fb

How is IFN-α used therapeutically?

IFN-α is used to treat viral infections like Hepatitis B and C by enhancing the immune system's ability to fight the virus and increasing the expression of tumor-associated antigens.

What is the significance of IL-10 in systemic lupus erythematosus (SLE)?

Elevated levels of IL-10 are associated with SLE. TH2 cells, which primarily express IL-10, are believed to contribute to disease initiation or progression.

What is the therapeutic potential of targeting TH2 cells in allergies and asthma?

Targeting TH2 cells and their cytokines (e.g., IL-4, IL-13) can help control the production of IgE and IgG, potentially leading to treatments for allergies and asthma by skewing the immune response toward TH1 cells instead of TH2.

How do soluble cytokine receptors work as therapeutic agents?

Soluble cytokine receptors bind to extracellular cytokines, neutralizing them by removing their signal from the environment, thereby reducing inflammation or preventing disease progression.

How does the immune system distinguish between innate and adaptive immunity?

Innate immunity is nonspecific and provides a quick defense, while adaptive immunity is antigen-specific, slower to develop, and generates memory responses for future protection.

What role do biologics play in treating age-related macular degeneration (AMD)?

Biologics can be used to address immune dysregulation in AMD by targeting proteins involved in waste clearance in the macula, potentially slowing the progression of vision loss.

What causes adult T-cell leukemia (ATLL), and what cytokine is involved in its progression?

Adult T-cell leukemia is caused by infection with Human T-cell Lymphotropic Virus type 1 (HTLV-1). The infected T-cells express high levels of IL-2, which leads to autocrine stimulation and uncontrolled cell proliferation.

What are the clinical implications of elevated IL-6 in myelomas?

In myelomas, autocrine production of IL-6 supports the survival and proliferation of malignant plasma cells, contributing to the progression of the disease.

How are TNF inhibitors used in the treatment of rheumatoid arthritis?

TNF inhibitors are used to compete with cell-bound TNF receptors, reducing the levels of TNF-α in inflamed joints. This helps alleviate the pain, swelling, and stiffness in rheumatoid arthritis patients.

What is the role of IFN-γ in cancer immunotherapy?

IFN-γ enhances the expression of MHC molecules and tumor-associated antigens on cancer cells, making them more recognizable to the immune system for destruction.

How do biologics affect eye care, particularly in conditions like keratitis?

The use of biologics, especially those that suppress the immune system, has been linked to an increased risk of opportunistic infections like bacterial keratitis, which can lead to vision loss if untreated.

What is the mechanism of action for soluble IL-2 receptors in immune regulation?

Soluble IL-2 receptors (sIL-2R) circulate in the bloodstream and bind free IL-2, preventing it from interacting with cell-bound receptors. This reduces T-cell activation in conditions such as adult T-cell leukemia.

What are the key cytokines involved in autoimmunity regulation, and how do they affect disease progression?

Key cytokines involved in autoimmunity regulation include:
-IL-4
-IL-10
-IL-12
-IFN-γ
-Dysregulation of these cytokines can lead to autoimmune diseases, as they influence the generation of autoantibodies and immune responses.

What is the therapeutic use of IL-4-specific antibodies in asthma treatment?

IL-4-specific antibodies reduce IL-4 production, which decreases the B-cell class switching to IgE, thus reducing allergic responses and helping manage asthma.

How does systemic lupus erythematosus (SLE) relate to cytokine dysregulation?

In SLE, elevated IL-10 levels are a hallmark of the disease, contributing to abnormal immune regulation and the generation of autoantibodies that attack the body's own tissues.

What are the potential side effects of biologics in treating autoimmune diseases?

While biologics can be effective in treating autoimmune diseases, they may cause severe adverse effects, including increased susceptibility to infections, due to immune system suppression.