Cytokines Intro and Immune Responses - Study Flashcards

QA flashcards covering the key concepts from the lecture notes on cytokines, their signaling, cellular differentiation, and therapeutic applications.

What is a cytokine?

A chemical messenger that regulates immunity, produced by many immune and nonimmune cells, and binds to receptors on target cells.

What does autocrine signaling mean in cytokine action?

Cytokines act on the cell that secreted them.

What does paracrine signaling mean in cytokine action?

Cytokines act on cells in the tissue region surrounding their source.

What does endocrine signaling mean in cytokine action?

Cytokines diffuse into the bloodstream and influence distant cells.

What does pleiotropy mean in cytokine biology?

A single cytokine can have many different actions.

What does redundancy mean in cytokine biology?

Different cytokines activate some of the same pathways and genes, often because they share receptor subunits.

How are cytokines classified by distance of action?

Some act locally (autocrine/paracrine) while others act systemically (endocrine).

What is a cytokine cascade?

One cytokine induces production of additional cytokines, amplifying the response.

What is a cytokine storm?

Massive overproduction and dysregulation of cytokines leading to shock, multiorgan failure, or death.

Name major proinflammatory cytokines.

TNF-α, IL-1, and IL-6.

Name major anti-inflammatory cytokines.

IL-10 and TGF-β (and IL-1 receptor antagonist IL-1RA).

Which cytokine is historically known as endogenous pyrogen?

IL-1β (IL-1α is also proinflammatory; IL-1β induces fever via the hypothalamus).

What are the major roles of IL-1β in inflammation?

Recruitment of immune cells to inflamed tissues, induction of chemokines, fever, and production of acute-phase proteins and CSFs.

What is the active form of IL-6?

IL-6 functions as a homodimer; two IL-6 polypeptide chains form the active form.

What is the IL-6 receptor signaling complex?

IL-6 binds IL-6R and gp130; gp130 transduces signals to activate IL-6–mediated gene expression.

What are chemokines and their primary function?

A subgroup of cytokines that influence the motility and migration of immune cells, directing leukocyte recruitment to sites of infection or inflammation.

What are the four chemokine families and how are they named?

CC, CXC, CX3C, and C; classification based on the arrangement of cysteines in the N-terminus.

Why are chemokine receptors important for leukocyte migration?

Leukocytes detect chemokine gradients via receptors, triggering cytoskeletal changes and directed movement toward the source.

What are CSFs and name examples?

Colony-stimulating factors stimulate bone marrow progenitors; examples include IL-3, erythropoietin (EPO), G-CSF, M-CSF, GM-CSF.

Where is erythropoietin (EPO) primarily produced and what is its clinical use?

Primarily produced in the kidneys; recombinant EPO is used to treat anemia and support RBC production during cancer therapy.

Which cytokines promote Th1 differentiation and what do Th1 cells produce?

IL-12 from dendritic cells promotes Th1 differentiation; Th1 cells produce IL-2 and IFN-γ and support cell-mediated immunity.

Which cytokines drive Th2 differentiation and function?

IL-4 promotes Th2 differentiation; Th2 cells produce IL-4 and IL-10 and drive antibody responses, including IgE.

What are Treg cells and how are they characterized?

CD4+, CD25+, FoxP3+ T cells that suppress immune responses and maintain peripheral tolerance; can be thymic (natural) or induced (iTregs).

What are Th17 cells and what do they secrete?

Th17 cells secrete IL-17 family cytokines and require TGF-β and IL-6 (with IL-23 involvement) for development; they recruit neutrophils and drive inflammation.

What are the hematopoietic CSFs and their general roles?

CSFs (IL-3, EPO, G-CSF, M-CSF, GM-CSF) stimulate bone marrow progenitors to differentiate into various blood cell lineages.

Where is EPO produced and what is its effect on RBCs?

Produced mainly in the kidneys; stimulates RBC production in bone marrow to improve oxygen delivery; levels rise in anemia.

What signals direct Th1 vs Th2 differentiation during T-cell activation?

DC-derived cytokines: IL-12 promotes Th1, IL-4 promotes Th2; the cytokine milieu during activation directs polarization.

What are the key cytokines produced by Th1 cells?

IL-2 and IFN-γ; also promote IgG1/IgG3 and activate macrophages and cytotoxic T cells.

What are the key cytokines produced by Th2 cells?

IL-4 and IL-10; IL-4 drives Th2 responses and IgG2a/IgE; IL-5 promotes eosinophils; IL-13 has overlapping roles and anti-inflammatory effects.

What marks Treg cells and their main function?

CD4, CD25, and FoxP3 expression; suppress immune responses to maintain tolerance and limit autoimmunity.

What is the role of IL-17 in the immune response?

Th17–derived IL-17 cytokines recruit neutrophils and induce proinflammatory mediators (TNF-α, IL-1β, IL-6); implicated in autoimmune diseases.

What is IL-2’s alternate name and how is the IL-2 receptor expressed?

IL-2 is the T-cell growth factor; naive T cells express a low-affinity IL-2R (βγ); activation induces IL-2 and upregulation of the α subunit to form high-affinity IL-2R (αβγ).

What are Type I interferons and their primary antiviral roles?

IFN-α and IFN-β; inhibit viral replication, recruit NK cells, and increase MHC class I expression to enhance antigen presentation.

What is the main function of IFN-γ in immunity?

The key Th1 cytokine; activates macrophages, increases antigen presentation via MHC I/II, and supports CD4+/CD8+ T cells and NK cells.

What are inflammasomes and what is the role of caspase-1?

Inflammasomes are cytoplasmic complexes that activate caspase-1, which cleaves pro-IL-1β to active IL-1β for secretion (driven by DAMPs).

What are TNF-α and TNF-β (lymphotoxin) in brief?

TNF-α is the major soluble TNF involved in inflammation; TNF-β is produced by lymphocytes and has roles in cytotoxicity and lymphoid tissue development.

How do TNF receptors signal to affect target cells?

TNFR1 and TNFR2; if TNF-α trimer concentration is high, receptor signaling alters adhesion molecule expression and other downstream responses.

What is the clinical significance of anti-cytokine therapies?

Therapies like infliximab (anti-TNF-α) and etanercept (TNF receptor fusion) block cytokines to reduce inflammation in diseases like RA, Crohn’s, and psoriasis.

What does ELISpot measure and how is it performed?

Detects and counts individual cytokine-secreting cells by capturing secreted cytokines on antibody-coated plates and quantifying spots.

How do multiplexed ELISAs and microbead assays differ from ELISpot?

Multiplexed ELISAs and microbead assays measure multiple cytokines in a single sample; ELISpot identifies cytokine-secreting cells, not the source.

What is the T-SPOT.TB ELISpot used for?

An ELISpot test to evaluate cell-mediated response to Mycobacterium tuberculosis by counting IFN-γ–secreting cells.

What is the role of anti-cytokine therapies in autoimmune diseases?

Block specific cytokines or receptors to disrupt inflammatory cycles in diseases such as RA, Crohn’s disease, and psoriasis.