Cytokines (class 2) Flashcards
What is chemotaxis?
The migration of types of WBCs toward the source of the chemokine
Describe the process of chemoattraction in action
Recognition of/activation by pathogens/PAMPs –> resident MACs in tissue –> cytokine release (IL-1, TNFa, chemokines)
- IL-1/TNFa –> endothelial cells to express cellular adhesion molecules (CAMs) and selectins
- chemokines –> leukocytes to site of inflammation
Initiation of extravasation
How is IL-6 an example of cytokines acting in both the innate and adaptive immune response?
IL-6 is a single protein produced by both lymphoid and nonlymphoid cells: T cells, B cells, monocytes and macrophages, fibroblasts, hepatocytes, keratinocytes, astrocytes, vascular endothelial cells, and various tumor cells.
- IL-1 primarily triggers secretion of IL-6.
- IL-6 is a pleiotropic cytokine, affecting inflammation, acute phase reactions, immunoglobulin synthesis, and the activation states of B cells and T cells.
- IL-6 stimulates B cells to proliferate and differentiate into plasma cells and induces CD4+ T cells to produce greater quantities of both pro- and anti-inflammatory cytokines.
How are cytokines involved with the Adaptive immune response?
Cytokines involved in the adaptive immune response are mainly secreted by T cells, especially T helper (Th) cells, and affect T- and B-cell function more directly than was the case with cytokines in the innate immune response.
How are the subclasses of helper T cells stimulated/expanded?
There are three main subclasses of Th cells: TH1, TH2, TH17, and Treg (T regulatory cells).
Once the T-cell receptor (TCR) recognizes antigen, clonal expansion of those particular CD4+ T helper cells occurs.
Differentiation into Th1, Th2, or Treg cell lineages is influenced by the spectrum of cytokines expressed in the initial response
Th1 cells function
produce IL-2 (cell proliferation), interferon gamma (IFN-γ) and tumor necrosis factor-beta (TNF-β), which protect cells against intracellular pathogens.
Th2 cells function
produce a variety of interleukins, including IL-4, IL-5, IL-10, and IL-13.
The essential role of the Th2 cells is to help B cells produce antibody against extracellular pathogens.
What is the importance of IFN-gamma to Th1 cytokines?
IFN-γ is the principal molecule produced by Th1 cells, and it affects the RNA expression levels of more than 200 genes.
These genes are involved in regulation and activation of CD4+ Th1 cells, CD8+ cytotoxic lymphocytes, NK cells, bactericidal activities, IL-12R, and IL-18R are all regulated by IFN-γ.
IFN-γ also stimulates antigen presentation by MHC I and MHC II molecules.
Type II IFN (IFN-γ) is involved in regulation of cell function….typically NOT direct inhibition of viral replication
What is the importance of IL-2 to Th1 cytokines?
Th1 cells also secrete IL-2 in addition to IFN-γ. IL-2 is also known as the T-cell growth factor.
IL-2 drives the growth and differentiation of both T and B cells and induces lytic activity in NK cells.
IL-2 alone can activate proliferation of Th2 cells and helps to generate IgG1- and IgE-producing cells.
What is the function of IL-7 and where is it found?
IL-7 is another cytokine that can induce proliferation or help to maintain the “memory pool” of lymphocytes. It can be found in the lymph nodes, so as cells migrate around the periphery, they can get “pro-survival” signals from IL-7 in the lymph nodes
What is the relation of Th2 cytokines to IL-4?
Th2 cells are primarily responsible for antibody-mediated immunity.
(B cell activation and antibody class switching)
IL-4 is one of the key cytokines regulating Th2 immune activities and helps drive antibody responses in a variety of diseases.
The IL-4 receptor is expressed on lymphocytes and on numerous nonhematopoietic cell types.
How do TH1 and TH2 impact Leprosy
(Mycobaterium leprae)
- Bacterium infects and lives inside macrophages
Two main forms of disease:
- Tuberculoid (Primarily induces a cell mediated response (TH1)/Forms granulomas and clear bacterium from macrophage)
- Lepromatous (Primarily induces a humoral response (TH2)/ Bacteria cannot be controlled and lead to systemic disease)
What are Tregs and their function?
CD4+ CD25+ T cells that are selected in the thymus.
- They play a key role in establishing peripheral tolerance to a wide variety of self-antigens, allergens, tumor antigens, transplant antigens, and infectious agents.
- Inhibit immune response by direct contact or by cytokines
- They produce IL-10 and TGF- beta
What is TGF-beta and its function?
The transforming growth factor beta (TGF-β) superfamily is composed of three isoforms: TGF-β1, β2, and β3.
TGF-β was originally characterized as a factor that induced growth arrest in tumor cells.
Later, it was identified as a factor that induces antiproliferative activity in a wide variety of cell types.
Active TGF-β is primarily a regulator of cell growth, differentiation, apoptosis, migration, and the inflammatory response.
Thus, it acts as a control to help
down-regulate the inflammatory response
when no longer needed.
TGF-β inhibits the activation of macrophages and the growth of many different somatic cell types.
It also functions as an anti-inflammatory factor for mature T cells.
In activated B cells, TGF-β typically inhibits proliferation and may function as an autocrine regulator to limit the expansion of activated cells.
TGF-β induces expression of Foxp3, a transcription factor that causes Treg cells to suppress the activity of other T cells.
