M8 Flashcards
are involved in the regulation of
the immune response
Cytokines
Small soluble proteins that regulate the immune
system, orchestrating both innate immunity and the
adaptive response to infection
CYTOKINES
Chemical messengers, produced by several different
types of cells, have activity-modulating effects on the
hematopoietic and immune systems through
activation of cell-bound receptor proteins
CYTOKINES
induced in response to stimuli (e.g.
LPS, flagellin) through ligation of cell adhesion
molecules or through recognition of foreign antigens
by host lymphocytes
CYTOKINES
Cytokines are produced in the presence of
antigens such as the ones containing
___ AND __, which are
bacteria
lipopolysaccharides and flagellin
Direct the growth, differentiation, and gene expression
by many different cell types, including leukocytes.
CYTOKINES
Expression of cytokines and their receptors is ___
regulated
highly
Whenever there would be an inducing
stimulus (e.g. LPS or flagellin) or any
presence of antigen molecules, certain
_______would cause the
cytokine gene to become activated, thus,
producing cytokines
cytokine-producing cells
Once they are in the ______, they will
attach and send signal, causing the target
cell for its gene to be activated, which then
leads to different biological effects
receptor
Same cell
secretes and
receives cytokine
signal
AUTOCRINE
Cytokine signal
secreted to a
nearby cell
PARACRINE
Cytokine signal
secreted to
circulatory
system; travels to
distant cells
ENDOCRINE
■ Cytokine-producing cell and target
cell are the ____
same
Involvement of the circulatory
system where there is travel
ENDOCRINE
Cytokine-producing cell (CPC) will
secrete cytokines and go to ___ and ____
blood
vessel and distant responding cell
Cytokines are ____,one cytokine can have
different effects on different cells
pleiotropic
Cytokine-producing cell is the activated
____
T-helper cell
T helper will secrete the ____
cytokine IL-4
Cytokine-producing cell that is the activated
T-helper cell will secrete three types of
cytokines ____
(IL-2, IL-4, IL-5)
_____ will act together on the B-cell, it
will cause B-cell to induce class switch to ____
IL-4 and IL-5, IgE
REDUNDANCY ACTIVATED TH CELLS
IL2,4,5
SYNERGY ACTIVATED TH CELLS
IL4,5
ANTAGONISM REDUNDANCY ACTIVATED TH CELLS
IL4 AND IFNY
_____ would counter interleukin
4, causing the blockage or cessation from
inducing class switch to IgE
Interferon gamma
In a___, cytokines can stimulate the
production of other cytokines.
cascade effect
one cytokine-producing cell causes
the activation of another cell to produce
cytokines
DOMINO AFFECT
In cascade induction, when interferon gamma cytokine targets
macrophage, it causes macrophage to
become cytokine-producing cell, releasing
the _____
cytokine IL-12
IL-12 will have the target cell, activated
T-helper, also causing the activated T-helper
to secrete___
interferon gamma, tumor necrosis
factor, IL-2, and other cytokines
STRUCTURAL GROUPING
- Interferons
- Tumor Necrosis Factor
- Interleukins (IL-1 to IL-32)
- Transforming Growth Factors (TGF)
- Colony stimulating factors (CSF
Mediators and regulators of innate immunity
● Act on ___ and ___ to
stimulate early innate response
endothelial cells and leukocytes
Mediators and regulators of adaptive immunity
● Act on ____to stimulate and regulate
adaptive responses to specific things
lymphocytes
Stimulators of hematopoiesis
● Act on the ___to stimulate growth
and differentiation of ___ and ___
bone marrow , leukocytes and
lymphocytes
CYTOKINES OF INNATE IMMUNE SYSTEM
● Type 1 IFN (IFN-ɑ, IFN-β)
● IL-1
● IL-6
● IL-12
● IL-15
● IL-18
● TNF-ɑ
● TGF-β
● Chemokines
TYPE 1
(IFN-ɑ AND IFN-β)
Interferes with viral replication and cell division.
TYPE 1 (IFN-ɑ AND IFN-β)
Activates natural killer cells and enhances Class-1
MHC expression, thus increasing the recognition and
killing of virus=infected cells
TYPE 1 (IFN-ɑ AND IFN-β)
IFN-ɑ:
leukocytes
IFN-β:
fibroblasts, epithelial cells
IL-1 family consists of
IL-1β, IL-1a, and IL-1RA
Origin of IL1
monocytes and macrophages
______acts as an antagonist to IL-1 by blocking the
IL-1 receptor and limiting the availability of the
receptor for IL-1.
IL-1RA
Acts as an endogenous pyrogen and induces fever
in acute phase response through its actions in the
hypothalamus
IL1
IL1:Acts as an ____ and induces fever
in acute phase response through its actions in the
hypothalamus
endogenous pyrogen
Induces the production of vascular cell-adhesion
molecules as well as chemokines and IL-6.
IL1
Origin of IL1
macrophages, T cells, osteoblasts
It is part of the cytokine cascade released in response
to lipopolysaccharide and plays an important role in
acute phase reactions and the adaptive immune
response
IL6
IL-1 causes the secretion of ____which is
a part of a cascade effect, wherein one
cytokine would cause the creation of another
cytokine
IL-6
expressed by a variety of normal and
transformed cells, including T cells, B cells monocytes
and macrophages, fibroblasts, hepatocytes,
keratinocytes, astrocytes, vascular endothelial cells
and various tumor cells
IL6
● 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
IL6
IL-12
(NK STIMULATORY FACTOR)
ORIGIN OF IL12:
B cells and macrophages
IL12 Stimulates the production of IFN-γ by __
NK and T cells
stimulating the differentiation of naive T cells into Th1
cells and enhancing cytolytic functions of activated
NK cells and CD8+ T cells
IL12
Growth factor for activated NK-LAK cells
IL12
ORIGIN OF IL15
T cells
It is produced in response to viral infection and other
signals that trigger innate immunity
IL15
Promotes proliferation of NK cells
IL15
Produces survival signals for memory lymphocytes
IL15
Acts as synergist in LAK cell induction process
IL15
Increases anti-tumoral activities of T-killer and NK
cells and can be chemoattractant for T lymphocytes
IL15
__is key condition for IFN-γ synthesis
Endogenous IL-15
ORIGIN OF IL 18
MACROPHAGE
Acts as synergist with IL-12 which stimulates the
production of IFN-γ by NK and T cells
IL18
High IFN-γ production under integrated effect of ____ AND ___ suppresses tumor growth
IL-18
and IL-12
TNf-A
CACHECTIN
Activates T cells through its ability to induce
expression of _____molecules, vascular
adhesion molecules, and chemokines
MHC class II
Activates T cells through its ability to induce
expression of MHC class II molecules, vascular
adhesion molecules, and chemokines
TNF-a
When secreted at higher levels, TNF can have
deleterious systemic effects, leading to septic shock,
causing a decrease in blood pressure, reduced tissue
perfusion, and disseminated intravascular
coagulation. The latter may lead to uncontrolled
bleeding
TNF-a
ORIGIN OF TNF B
T CELLS
Active transforming growth factor (TGF-) is primarily a
regulator of cell growth, differentiation, apoptosis,
migration, and the inflammatory response.
TNF B
acts as a control to help down-regulate the
inflammatory response when no longer needed
TNF B
INHIBITORY CYTOKINE
TNF B
_____regulates the expression of CD8 in CD4–
CD8– thymocytes and acts as an autocrine inhibitory
factor for ____thymocytes
TGF-β , immature
_____blocks the production of IL-12 and strongly
inhibits the induction of IFN-γ
TGF-β
Family of cytokines that enhance motility and promote
migration of many types of white blood cells toward
the source of the chemokine (chemotaxis)
CHEMOKINES
Chemokines Structural grouping:
C Chemokines, CC Chemokines,
CXC Chemokines and CX3C Chemokines
control the
migration of cells during the normal
development and maintenance of tissues
and lymphoid organs
homeostatic chemokines
produced in
response to infection or injury and direct the
migration of leukocytes into the infected or
damaged site
inflammatory chemokines
some
chemokines promote the development of
blood vessels (pro-angiogenic) others
prevent the development of blood vessels
(anti-angiogenic).
Angiogenic chemokines:
CYTOKINES OF ADAPTIVE IMMUNE SYSTEM
● Th1 cytokines
○ IFN-γ
○ IL-2
● Th2 cytokines
○ IL-4
○ IL-10
● IL-5
● IL-13
ORIGIN OF IFN Y
Th1 cells
Regulation and activation of CD4 Th1 cells, CD8
cytotoxic lymphocytes, NK cells, bactericidal activities,
___ and ___
IL-12R and IL-18R
stimulates antigen presentation by MHC I and
MHC II molecules
IFNY
Stimulator of macrophages and boosts their tumoricidal activity
IFN y
ORIGIN OF IL2
TH cells
It drives the growth and differentiation of both T and B
cells and induces lytic activity in NK cells.
IL2
_____alone can activate proliferation of Th2 cells and
helps to generate IgG1 and IgE producing cells
IL-2
ORIGIN OF IL4
: T cells & mast cells
Induces differentiation of naive helper T cells (Th0
cells) to Th2 cells.
IL4
Promotes the production of IgG2a and IgE and, along
with IL-5, drives the differentiation and activation of
eosinophils in both allergic immune responses and
the response to parasitic infections.
IL4
ORIGIN OF IL10
monocytes, macrophages, CD8+ T cells and
Th2 CD4+ T cells
Inhibits activated macrophages; displays potent
abilities to suppress antigen presenting of APCs.
IL10
Released by Tc cells to inhibit the action of NK cells
during immune response to viral infection.
IL10
Predominantly an inhibitory cytokine
IL10
ORIGIN OF IL5
Th cells and mast cells
Activates eosinophils and serve as link between T cell
activation and eosinophilic inflammation
IL5
Stimulates growth and differentiation of eosinophils
and activates mature eosinophils
IL5
Growth and differentiation-inducing factor for activated
T and B cells; induces class-specific B cell
differentiation (IgA production)
IL5
Aids in specifying to become an IgA
antibody
IL5
ORIGIN OF IL13
T CELLS
Similar to IL-4 but appears to have less effect on T or
B cells than IL-4
IL13
Inhibit activation of macrophage and antagonize
IFN-Y
IL13
Important mediator of allergic inflammation and
disease
IL13
Activation of lymphocytes requires 2 signals:
- Being antigen
- Being molecules that are produced during
innate immune response to microbes or
injured cells.
Activation of the small lymphocytes whether
it is a T cell or a B cell and even an NK cell
ADAPTIVE IMMUNITY
____ stimulates the differentiation of naïve CD4+ T
cells to the Th1 subset of effector cells.
IL-12
______stimulate the differentiation of
naïve CD4+T cells to the Th17 subset of effector
cells.
IL-1, IL-6, and IL-23
stimulate the differentiation of
naïve CD4+ T cells to the Th2 subset of effector cells
IL-25, IL-33, and TSLP
TSLP
thymic stromal lymphopoietin
promotes the survival of memory CD8+ T cells.
● IL-15
promotes the production of antibodies by
activated cells.
IL16
○ is a cytokine that is produced by and inhibits
activation of macrophages and DCs.
IL10
excellent example of negative feedback
regulator
IL10
○ functions as competitive inhibitor of IL-1
IL-1 receptor antagonist (IL-IRA)
act as “decoy” that
competitively inhibits IL-1 binding to the Type
1 signaling receptor.
● IL-1 receptor antagonist (IL-IRA)
self consume/self killing;
“starvation”; a type of apoptosis
AUTOPHAGY
inhibitors of JAK-STAT
signaling pathways linked to cytokine
receptors
Suppressors of cytokine signaling
(SOCS) proteins
- limit responses of these
cells to exogenous cytokines such as type 1
interferons
○ SOCS proteins
negatively regulates
proinflammatory responses of cells to TLR
signaling
SHP-1
If it encounters a healthy cell, NK
cells are ____
not activated
When there will be too much NK
cells like an inhibitory receptor,
there would be a
___
normal cell
MHC ____stops or
prevents the activation of
NK cells
class I
Naive (inactivated) B cells bind antigens to
bind to the _____
membrane-bound antibodies
Occurs when IgG antibodies bind to the FcγR
present on the B cells and antigen cross links that IgG
antibody with the membrane bound immunoglobulin
TURNING OFF THE B CELL RESPONSE
Naive CD4+ T cells
T helper
precursor cells (Thp)
___is a coreceptor
that is required for optimal activation of T
cells because it participates in intracellular
signaling events.
CD4
Th1 cells secretes
type 1 cytokines
Naive C8+ T cells that leave the thymus are cells that
are referred to as____
pre-cytotoxic T lymphocyte (pCTL)
can be activated at the site of
infection and not solely in secondary lymphoid tissues
Memory CD4+ T cells
can be activated at the site of the
infection, irrespective of whether this is an initial
response or a subsequent encounter
CD8+ T cells
Ingestion and elimination of ____by phagocytes
is also a major reaction of_____ immunity, but T cells
greatly enhance its function of phagocytes
microbes , innate
SUBSETS OF CD4+ EFFECTOR CELLS
● Th1
● Th2
● Th17
th1
IFN y
Th2
Th2 cells: IL-4, IL-5, IL-13
. Th17 cells
IL-17 and IL-32
Autoimmunity;
chronic
inflammation
th1
Allergy
🔊 also involved in
parasitic, but more
specifically in allergic
Th2
Extracellular
bacteria and
fungi
Th17
Extracellular
pathogens
Tfh
Eosinophil and
mast cells
activation;
alternative
macrophages
activation
Th2
Neutrophil
recruitment and
activation
Th17
Macrophage
activation
Th1
A normal homeostatic mechanism that is necessary
for maintaining normal cell numbers
apoptosis
● Occurs through a series of biochemical reactions
within cell that lead to chromatin condensation, DNA
fragmentation, cell shrinkage, and membrane
blebbing
apoptosis
2 major pathways:
○ Mitochondrial (or intrinsic) pathway
○ Death receptor (or extrinsic) pathway
Regulated by BCL-2 proteins
○ Mitochondrial (or intrinsic) pathway
maintain or
control the apoptosis through this pathway
○ Mitochondrial (or intrinsic) pathway
responsible in preventing
apoptosis by staying inside the mitochondria
Cytochrome c
must NEVER come into
contact with the cytochrome C
APAF 1
This pathway is initiated when cytoplasmic
proteins belonging to the BH3 family binds to
the proteins Bax and Bak
Mitochondrial/Intrinsic pathway
____will lead to DNA fragmentation,
damage… until the entirety of the cell is
damaged
Caspase 9
Cytochrome C will only come out when BH3
proteins bind to the___ and __
Bax and Bak
When this interaction occurs, changes in
FAS receptor leads to FADD trigger
activation of ______
procaspase 8
which initiate caspase that
activate BH3 protein bind to Bax and Bak,
leading apoptosis via mitochondrial pathway
caspase 8
