Soluble mediators of the immune system Flashcards
(44 cards)
4 main sources of BRMs by (mononuclear leukocytes)
Biological response mediators (BRMs)
-B lymphocytes: secrete specific Abs
-T lymphocytes: secrete soluble mediators (IL-2, other-ILs, GM-CSF, TNF-β, IFY-γ)
-Monocytes and macrophages: secrete (IL-1, other ILs, GM-CSF, TNF-α, M-CSF, IFN-α)
–NK lymphocytes: secrete IFN-α
^modulate individual’s own immune response
Classes of BRM immunotherapy
-Active— use of microbial or chemical immunomodulators (adjuvants) in a specific or non-specific form
-Adoptive— use of soluble mediators, such as ILs, to regulate components of the immune systems
-Passive— Transfer of preformed antibodies to tumorous recipients, such as monoclonal antibodies
-Restorative— application of soluble substances, such as interferons, for a wide range of diseases
What are Cytokines, what do they do?
-A polypeptide product of activated cells (lymphocytes or macrophages) that control a variety of cellular responses & thereby regulates the immune system
-Most cytokines have multiple activities & act on numerous cell types
-synthesized and secreted by cells of the innate/adoptive immunity in response to microbial & other Ag exposures (variety of host defense)
-Very potent; act on neighboring cells by binding to their surface cytokine receptors
-effect limited to local area; BUT CAN HAVE systemic effects
What are Lymphokines vs Interleukins
(separate?)
-Lymphokines— cytokines produced by activated lymphocytes
-Interleukins— cytokines produced by leukocytes that act on other leukocytes
Describe the role of cytokines in innate immunity
-mediate early inflammatory reactions to microbial products
-stimulate adaptive immune response
Cytokines in adaptive immunity
-stimulate proliferation/ differentiation of Ag-stimulated lymphocytes
-activate specialized effector cells (e.g macrophages)
What actions do the different cytokines share?
They differ in molecular structure but share the following
-secrete cytokines in rapid bursts (keep? in response to cellular activation)
-bind to specific receptors on target cells
-regulate receptor expression in T/B cells, for positive amplification or negative feedback
-excite the same functional effects w/ multiple cytokine (redundancy)
-act close to site of synthesis/ same cell or (different) neighboring cell
-influence the synthesis & actions of other cytokines
What’s a Cytokine storm
-Severe immune reaction characterized by
the rapid release of a high concentration
of cytokines into peripheral blood
circulation
-biological concepts not completely understood
-associated w/ covid-19
-termed in 2005 w/ h1n1 bird flu
-important factor— the kinetics of cytokines & chemokine gene expression
What chemokines make the cytokine storm? Think broad categories. Not asking for specifics like IL-1 or TNF-alpha
-ILs, CSFs, TNFs, IFNs, chemokines
-severe damage can occur b/c body attacks own cells/tissues rather than fighting virus (acute lung injury is common)
-SARS chemokines => strong pro-inflammatory response => pulmonary fibrosis
Interleukins (ILs)
-cytokines produced by leukocytes that affect the inflammatory process thru increase in soluble factors (or cells)
-modulate inflammation (IL-1)
-Modulate immunity by regulating growth, mobility, & differentiation of lymphoid cells
-many different individual families/superfamilies of ILs have been identified w/ overlapping functions
Interferons (IFNs)
-cytokines produced by T lymphocytes & other cells that inhibit viral synthesis or act as immunes suppressors
-natural defensive responses to foreign components (microbes, tumors, Ags)
Type I IFNs
-mediate in early innate immune response to viral infections
-consist of IFN-α and IFN-β
^structurally different; bind to same cell surface receptor; similar biological functions
IFN-γ
-Principal macrophage-activating cytokine
-critical for innate immunity & specific cell-mediated immunity
-Stimulates expression of MHC class I and MHC II
-costimulates APCs
-Promotes the differentiation of naïve CD4+ T cells to the TH1 subset
-Inhibits the proliferation of TH2 cells
Tumor necrosis factor (TNF)
- Principal physiologic functions is to stimulate the recruitment of neutrophils & monocytes to sites of infection (to eradicate microbes)
- principal mediator of acute inflammatory response to gram negative bacteria (other microbes)
- responsible for many systemic complications of severe infections
- TNF receptor family stimulate gene transcription or induces apoptosis in a variety of cells
Stem cell factor (c-kit ligand)
-Cytokine interacts w/ tyrosine kinase membrane receptor (the protein product of the cellular oncogene c-kit)
-Acts on immature stem cells
-Needed to make bone marrow stem cells responsive to other CSFs (Does not cause colony formation itself)
-May play role in sustaining, viability & proliferative capacity of immature T cells in the thymus & mast cells in mucosal tissues
Colony stimulating factors (CSF)
-Variety of CSFs (like G-CSF and GM-CSF) are made by T cells -Provide a link between lymphoid and hematopoietic systems
-G-CSF and GM-CSF regulate the production of granulocytes and monocytes—allows T cell system to promote inflammatory response
-necessary for survival, proliferation, & differentiation in precursor cells of the immune system
-Increases circulating leukocytes in patients w/ AIDS, chemo patients, bone marrow transplants (important in treatment of disease)
Transforming growth factors (TGFs)
-products of virally transformed cells
-induce phenotypic transformation in nonneoplastic cells
TGF-β
-group of 5 cytokines released by cells (Macrophages & platelets)
-potent inhibitor of IL-1-induced T cell proliferation/ differentiation
-inhibits proliferation/activation of lymphocytes (T-cell p/d) & leukocytes (activation of macrophages)
Chemokines
Large family of structurally homologous
cytokines that:
-Move leukocyte from the blood to site of infection
-Regulate/maintain migration of PMNs & mononuclear (immune cells) to lymphoid organs/ specialized cells
3 families Largest, second, third families
other functions:
-increase the affinity of leukocyte integrins to their endothelial ligands
-regulate traffic of lymphocytes (& other leukocytes) thru peripheral lymphoid tissues
CC chemokine
Part of large family - attract mononuclear cells to sites of chronic inflammation
CXC chemokine
Part of second family - attracts PMNs to acute inflammation; activates monocytes; direct WBC to vascular lesions
CXC3 chemokine
Part of third family - forms a cell adhesion receptor capable of arresting cells under physiologic flow conditions (WBC slowing down & crossing blood vessel)
what are Acute phase proteins / reactants?
(APPs)
what triggers them?
-a group of glycoproteins associated w/ acute phase response
-various protein rise to various rate/ lvls in response to injury
-increased synthesis starts shortly after trauma (initiated/sustained by pro-inflamm-cytokines)
- >20 APPs have role in inflammation
clinically useful acute phase proteins (APPs)
-CRP binds to membranes of microbes & activates complement
-Inflammatory mediators C3/C4 of complement
-fibrinogen
-transport protein => haptoglobin
-inhibitors => α1- antitrypsin
-α1-acid glycoprotein
