Cykines In Health And Disease Flashcards
what do cytokines do?
serve as chemical messengers of the immune system
are cytokines antigen specific?
no
true/false: cytokines are glycoproteins that act over only short ranges
false: act over short and long ranges and can therefore result in systemic effects
they are glycoproteins
how do cytokines exert their functional effects?
bind to specific receptors on the target cell
cytokines have ______________________, meaning that one cytokine can affect the activity of many different target cell types
pleiotropic properties
what is functional redundancy?
more than one cytokine (or other signal) can act on a single cellular target
what does autocrine mean with cytokines?
a cytokine can act on the same cell that secreted it
what are the two results of the fact that cytokines rarely act alone in vivo?
synergistic effects: work together to create a bigger effect than the sum of the two
antagonistic effects: one cytokine inhibits the activity of another
what do interleukins (IL) do?
regulate interactions between leukocytes
can act on other cell types
what do interferons (IFNs) do?
interfere with viral replication within host cells
also other functions
what interferons (IFNs) are in each class?
type I: IFN-alpha and IFN-beta
type II: IFN-gamma
what do tumor necrosis factors (TNFs) do?
cause necrosis by inducing local inflammation and thrombosis of tumor blood vessels
potent mediators of acute inflammatory response to infectious agents
what cells stimulate the expansion and differentiation of bone-marrow progenitor cells?
colony-stimulating factors (CSF)
what are two types of chemokines and what do they do?
affect leukocyte movement
monocyte chemotactic protein-1 (MCP-1) attracts monocytes
interleukin-8 (IL-8) attracts neutrophils
what are the primary mechanisms utilized by the innate immune system to combat extracellular bacteria?
complement activation
phagocytosis
inflammatory response
what do macrophages produce in response to bacterial products?
TNF-alpha
IL-1
chemokines
what acts on vascular endothelium to induce the expression of adhesion molecules at the site of infection?
TNF-alpha and IL-1
what induces the secretion of IL-8 by endothelial cells?
action of TNF-alpha and IL-1 on vascular endothelium
what does TNF-alpha stimulate in neutrophils?
microbial activities
what induces fever?
TNF-alpha and IL-1 lead to increase synthesis prostaglandin E2 (PGE2) which acts in the hypothalamus
what is prolonged production of TNF-alpha associated with?
cachexia
how do macrophages and dendritic cells respond to intracellular bacteria?
secrete IL-12 which induces local production of IFN-gamma (produced by natural killer cells)
what do macrophages do after being exposed to IFN-gamma?
destroy phagocytized bacteria present in phagosomes or phagolysosomes
what does cytokine-mediated innate immunity against viruses consist of?
inhibition of infection by type I IFNs
NK cell-mediated killing of virus-infected cells
what do IFN-alpha and IFN-beta do to infected and neighboring uninfected cells?
cause them to synthesize a number of enzymes, which interfere with viral transcription and replication
uninflected host cell that has responses to these and is resistant to viral infection is in “antiviral state”
what stimulates the proliferation and cytotoxic function of NK cells?
IL-15
IL-12
what determines the differentiation of a naive CD4+ T cell into a particular Th cell subset or induced Treg?
cytokines secreted by the innate immune response
not random process
what does IL-12 induce naive Th cells to do?
differentiate towards Th1 subset which produce IFN-gamma and TNF-alpha
what does IFN-gamma do?
promotes Th cells to differentiate into Th1
activates macrophages to kill
promotes class switching in B cells
what are the most important cytokines that lead to cytotoxic T lymphocyte responses against intracellular microbes?
IL-12 and/or type I IFNs
when an intracellular pathogen can induce strong innate cytokine responses ie strong IL-12 and/or type I IFN responses, help from _____________________ to generate ____________________ is not required
Th1 cytokines
CTL responses
true/false: the Th1 pathway is known to facilitate cell-mediated or cellular immunity
true
what does Th2 differentiation occur in response to and what do they produce?
antigens
IL-4, IL-5, IL-13
what are the functions of IL-4?
differentiation Th to Th2
stimulates B cell Ig heavy chain class switching to IgE
class switching to IgG subclasses
what type of immunity is the Th2 pathway known to facilitate?
humoral immunity
what type of immunity is the Th1 pathway known to facilitate?
cell-mediated or cellular immunity
what is the key cytokine that Th17 cells produce?
IL-17
what does IL-17 do?
stimulates TNF-alpha, G-CSF, neutrophil chemotactic chemokine IL-8
production antimicrobial peptides
what do induced or adaptive regulatory T cells (Tregs) produce?
TGF-beta and IL-10 which suppress inflammatory response
what is sepsis?
bacterial infection in bloodstream or body tissues
what is septic shock or endotoxin shock?
from sepsis
cardiovascular collapse, disseminated intravascular coagulation, and hypoglycemia
what happens in septic shock to IL-1 and TNF-alpha?
too much
cause systemic clinical and pathological abnormalities
what does TNF-alpha do that leads to shock?
increased expression pro-coagulation protein and decreased expression anti-coagulation proteins on endothelial cells
what does nitric oxide do to the heart?
produced by cardiac myocytes
inhibition myocardial contractility and leads to heart failure
true/false: systemic inflammatory response syndrome (SIRS) is related to organ failure due to the escape of fluid from blood into extra vascular space which leads to organ dysfunction and failure
true
what is acute respiratory distress syndrome caused by?
leakage fluid into lungs
what cytokines are produced in superantigen-mediated toxic shock?
IL-1 and TNF-alpha by macrophages
also others
true/false: a cytokine generally binds with a few different types of receptors on the surface of a cell to exert its function(s)
false: only one type of receptor
true/false: some cytokines can have endocrine action. for example, they can get into the blood stream and act on the bone marrow progenitor cells
true
true/false: both Th1 and Th2 responses can lead to class switching to IgG type of antibodies
true
true/false:IL-8 cytokine can help neutrophils with locating pathogens in an inflammatory site
true: IL-8 attracts neutrophils and MCP-1 attracts monocytes
true/false: effects of IFN alpha and IFN beta lead to an antiviral state in uninfected cells
true
what is the function of IL-5?
activates and stimulates differentiation and growth of eosinophils
what is the function of IL-13?
stimulated mucus production of goblet cells of airways and gut
what is the function of IL-4 and IL-13 together?
stimulates peristalsis of gut to promote elimination of helminths
what is the Th2 pathway known to facilitate?
humoral immunity
with extracellular bacteria in tissues, macrophages respond to bacterial products by producing ________________________________________
TNF-alpha, IL-1, and chemokines
what do TNF-alpha and IL-1 stimulate?
extravasation
microbicidal activities neutrophils (only TNF-alpha)
IL-8 (attracts neutrophils)
fever (prostaglandin E2)
in viral infections, ______________ are secreted by the virus-infected cells, and APCs
type 1 interferons (IFN-alpha and IFN-beta)
IL-15 stimulates the ________________ of NK cells
IL-12 enhances the ________________ of NK cells
proliferation
cytotoxic function
IL-12 induces naive Th cells towards the ______ subset, which produces ____________
Th1
IFN-gamma and TNF-alpha
what induces recruitment of leukocytes and inflammation?
TNF-alpha
______ differentiation occurs in response to antigens
Th2
Th2 cells produce _________________________
IL-4, IL-5, IL-13
what does IL-5 do?
activates eosinophils and stimulates growth/differentiation
____ differentiation occurs in response to extracellular bacteria and fungi
Th-17
