Immunology week 6 Flashcards
What is the specific effect that TLR have on MHC molecules
TLR are a sensing system. APCs use them to detect pathogens and initiate immune
responses by 1. Production of cytokines that activate the APCs themselves, hence the
increase in expression of MHC molecules, 2. Production of chemokines and recruitment
of other immune cells to sites of infection, 3. Increased uptake of pathogens for antigen
processing and presentation.
Are superantigens T dependent AG?
Superantigens are not T-dependent. They interact directly with T cells. Their direct
interaction with B cells (a different mechanism) does not lead to antibody production,
instead leads to B cell apoptosis. I do not teach superantigen effect on B cells, as it is not
very clear what the mechanism is, and moreover it is limited to certain Staphylococcal
antigens, and does not elicit a protective mechanism but rather an immune evasion of
Staphylococcal pathogens such as S. aureus.
The first part is a duplicate of wk 5
specifically
AG processing &
Presentation see wk 5 cards 2-44
Cytokines,
Chemokines,
receptors
Immune response is only possible when ?
Interxn is coordinated by?
Immune response is only possible when interxn between hematopoietic,
lymphoid, & inflammatory cells is possible
○ Interxn is coordinated by cytokines
Definitions:
cytokines=
cytokines= low molecular weight proteins or glycoproteins mainly
produced by lymphocytes and other cells in the body
Definitions:
chemokines=
chemokines= recruit and activate leukocytes
Definitions:
chemotaxis=
chemotaxis= phenomenon in which cells move from an area of low chem
signal to an area of high chem signal
Properties of cytokines
They bind to their receptors on target cells with ?
They bind to their receptors on target cells with high affinity
Properties of cytokines
what is Autocrine?
Autocrine- cytokines can bind to a receptor located on the same cell
Properties of cytokines
What is Paracrine?
Paracrine- cytokines can bind to a receptor found on a neighboring cell
Properties of cytokines
What is Endocrine?
Endocrine- cytokine can bind to a receptor found on a distant target cell
Properties of cytokines
what is: Pleiotropic action-
Pleiotropic action- one cytokine can have different biological effects on
target cells
Properties of cytokines
What is Redundant action?
Redundant action- 2+ cytokines exert the same effect on the same cell
Properties of cytokines
What is Synergistic action?
Synergistic action-effect of 2+ cytokines is greater than the additive
effect of individual cytokines
Properties of cytokines
What is Antagonistic action?
Antagonistic action-action of 1 cytokine inhibits the effects of another
cytokine
Properties of cytokines
What is Cascade action?
Cascade action- action of a cytokine leads to the induction of 1 or more
cytokines which activate others (domino effect)
Properties of cytokines
can they act in a specific or nonspecific manner?
They can act in a nonspecific manner
Cytokines, hormones, growth factors
All 3=secreted factors but they have different expression
Growth factors- ?
how expressed?
Growth factors- expressed constitutively
Cytokines, hormones, growth factors
All 3=secreted factors but they have different expression
Hormones and cytokines are expressed in response to ?
Hormones and cytokines are expressed in response to discrete stimuli
Cytokines, hormones, growth factors
All 3=secreted factors but they have different expression
are cytokines short or long lived?
Cytokines- short- lived
Cytokines, hormones, growth factors
All 3=secreted factors but they have different expression
Hormones- are they endocrine, autocrine, paracrine?
cytokines-are they endocrine, autocrine, paracrine?
Hormones- endocrine manner
cytokines-endocrine, autocrine, paracrine
Cytokines, hormones, growth factors
All 3=secreted factors but they have different expression
Hormones- produced by what?
Hormones- produced by special glands
Cytokines, hormones, growth factors
All 3=secreted factors but they have different expression
Cytokines- produced by what?
Cytokines- produced by many different cells
Cytokines, hormones, growth factors
Functions of cytokines:
(5)
Functions of cytokines
○ Cellular and humoral immunity
○ Inflammatory response
○ Hematopoiesis- what is this?
○ Reg. of intensity and duration of IR
○ Wound healing
Fun. of cytokines cont- if he gives ex I would know them :)
*This is a graph, you will need to look at the graph on p. 22
Cytokines and receptors
what are they? examples?
(4)
Immunoglobulin superfamily receptors
Class I cytokine receptors- hematopoietin
Class II cytokine receptors- interferon
TNF receptors
Cytokines and receptors
At least 1 subunit is required for
? and a second
subunit is required for
?
At least 1 subunit is required for cytokine binding and a second
subunit is required for signal transduction
Cytokines and receptors
Cytokines with a 2nd signalling subunit- usually have ?
Cytokines with a 2nd signalling subunit- usually have low affinity
Cytokines and receptors
what happens after binding the signaling subunits?
But after binding the signaling subunits form a high affinity receptor
There is a graph on slide 23
Class 1 receptors-Hematopoietin
Some form subfamilies- what about the signaling subunit and the cytokine subunit?
Some form subfamilies- ID signaling subunit but different cytokine
subunit
Class 1 receptors-Hematopoietin
IL2 common y subunit-
what is the defect associated with?
hint 2 doggies?
IL2 common y subunit- defect is associated with X- linked severe
combined immunodeficiency (SCID) on basset and corgis
graphic p. 23
IL2- a,b,y subunits
have 3 chains what is the most common?
Y
IL2- a,b,y subunits
found in 3 forms
what are they and what is their affinity for IL-2?
Monomeric IL-2Ra
low affinity
Dimeric IL-2RBy
intermediate affinity
Trimeric IL-2RaBy
High affinity
*There are a bunch of handwritten notes on this slide p. 25. I don’t understand them. so look at them.
Common signalling subunit & redundancy/ anatogism
IL3,Il5, GM-CSF=act ? of each other?
IL3,Il5, GM-CSF= act redundantly of each other
Common signalling subunit & redundancy/ anatogism
IL3,Il5, GM-CSF= act redundantly of each other
what is the relevence of:
Hematopoietic cells
monocytes
megakaryocytes
neutrophils
basophils
IL3,Il5, GM-CSF= act redundantly of each other
○ Hematopoietic cells
○ Activate monocytes
○ Induce differentiation of megakaryocytes
○ Induce prolif of neutrophils
○ Degranulation of basophils to release histamine
Common signalling subunit & redundancy/ anatogism
what does possession of a common signalling subunit allow?
what can it lead to ?
**Possession of a common signalling subunit allows elicitation of an ID
signal by all involved cytokines
Can lead to antagonism b/c creates competition for the subunit
chemokines
what are they?
what do they regulate?
where are they produced?
what makes them inflammatory?
NB in ?
● Small polypeptides
● Regulate the adhesion process,
chemotaxis, activation of leukocytes
○ NB for reg. Of leukocyte migration
during homeostasis and inflammation
● Produced in peripheral lymphoid
tissues, bone marrow, etc
● Inflammatory chemokines- induced by
TNF-a
● NB in wound healing, dev. Of BV, brain,
& heart tissue
chemokines
Regulation of leukocyte migration
fill in the blank:
Increase of chemokine receptors on ? and ? —>
adhere to the ? —>
after migration they follow ? to the site of ?
● Increase of chemokine receptors on
leukocytes and endothelium
● They then adhere to the endo
● After migration they follow the
chemokine gradient to the site of
inflammation
Structural organization of chemokines & their receptors
4 conserved cysteines and they are
divided into subgroups based on the
location of the first 2
what are they? explain?
-
C chemokines- first 2 are bound by side
disulphide bonds - **CC chemokines- **first 2 are positioned
one after another and they both have a
side chain - **CXC chemokines- **between the C there is
another aa -
CX3C chemokines- between the C there
is a mucin domain
Structural organization of chemokines & their receptors
Receptor structure:
What kind of domain?
how many membrane domains?
explainthe intracellular domains?
Receptor structure
○ Extracellular domain
○ 7 transmembrane domains
○ Intracellular domains a,b,y w/ G-couple
proteins
Structural organization of chemokines & their receptors
You’re never going to believe this:
CR- binds to?
CCR- binds to?
CXCR- binds to CXC?
CX3CR- binds to?
● You’re never going to believe this:
○ CR- binds to C chemokines
○ CCR- binds to CC chemokines
○ CXCR- binds to CXC chemokines
○ CX3CR- binds to CX3C chemokines
Structural organization of chemokines & their receptors
Side note:
MIP-1a (CCL3) and MIP-1B
(CCL4) are ?
Side note:
MIP-1a (CCL3) and MIP-1B
(CCL4) are NB proinflamm.
cytokines
Lymphocytes &
Their receptors
Lymphocytes
4 kinds what are they?
what do they do?
● T cells- reg adaptive immunity very NB
for cell-mediated immune response
● B cells- responsible for AB production
● NK cells- play a role in innate immunity
● Large N:C ratio
Lymphocytes
T cells
Pre-T cells where?
where to they go?
○ Pre-t cells bone marrow-> thymus
(thymocytes)