(05) Chemokines Flashcards
What are small soluble proteins and glycoproteins that regulate and mediate host immune responses via direct action on cells?
How many cytokines are there? How much variety?
Have significant _____ role in host defense
Do they locally or at a distance?
Rapidly _____ or ____ immune activites
- cytokines
- large number, lots of variety
- homeostatic
- either
- activate, suppress
Cytokines vs. Hormones/Neurotransmitters
Cell Source
Target Cell
Activities
Effect
Concentration
numerous – usually single source
many – single cell or tissue
pleiotropic and overlapping – single, defined activity
autocrine (acts on self), paracrine (acts on another cell of same type), endocrine (acts on different type of cell) – endocrine
picomolar – nanomaolar
Can cytokines cross the blood brain barrier?
What are the two ways they get into things (and explain)?
What makes cytokines in the brain?
- yes
- Diffusion (circumventricular organs - lack a blood brain barrier), transportation (transported by transporters)
- microglial cells (like the brains macrophages)
(Cytokines - general properties)
Are they antigen specific in action?
Are they pleiotropic? What does this mean?
Can an individual cytokine be made by more than one cell type?
Can they act on many cell types?
- What type of expression do they show?
- Have ____, ____ actions
- Influence the ____ and _____ (____ and _____) of other cytokines
- Signal through what?
- Do they serve strictly immune functions?
- no (they act on other host cells)
- yes, may have different activities in different situations
- yes
- yes
- brief, highly regulated
- redundant, overlapping
- synthesis, action (synergy, antagonism)
- specific receptors
- no - they have non-immune functions
(Cytokines - Families/Nomenclature)
4 groups
_____ - stimulators of hematopoiesis that regulate immature _____ growth and differentiation. These factors drive the ______ of hematopoietic _____. Examples?
______ - Mediators and regulators of lymphocytes and leukocytes. These factors are regulators of both ____ and ____ functions of other immune cells. This group is very ____ in structure and function. WIDE RANGE OF FUNCTIONS Examples?
______ - Mediators and regulators of antiviral and innate immunity. These factors can activate intracellular processes that inhibit _____ replication. In addition, several members are key regulators of ____ activity and tolerance of the developing _____. Examples?
_____ - Chemoattractants. These factors regulate the directed movement of immune cells from the blood into tissues. Examples?
- growth factors, leukocyte, terminal differentiation, progenitors
- granulocyte-colony stimulating factor (G-CSF); marcophage-CSF; oncostatin M; Interleukin-3 (IL-3)
- Interleukins (IL), innate, adaptive, diverse.
IL-2, IL-6, IL-8, IL-10, IL-12, Tumor necrosis factor -a (TNF-a)
- Interferons (IFN), viral, macrophage, fetus.
- IFN-gamma, IFN-alpha, IFN-beta
- Chemokines
- MIP-1a, IL-8, RANTES, MCP-2
(CYTOKINE RECEPTORS)
- expressed on ____ cell types and show ________.
- How specific for their ligands?
In regards to structure?
- Do receptors share some subunits?
- How are they grouped into families?
- How many types of cytokine receptors can a cell express?
- many, considerable regulation of expression
- very specific
- can be single subunit, or multimeric (homomultimeric and heteromultimeric)
- yes
- based on signal transduction mechanisms or molecular structure
- many kinds
(Interferons (IFN)
- ______ interferons with related ____ (and _____)?
- Expressed in response to _______
Why are they called interferons?
How many types?
Type IFNs are any ____ or _____
- 3-5, structure, function
- immune response
- interfere with viral replication
- two
- IFN-alpha or IFN-beta
(IFN-a/b type 1)
- Actually consists of a family of _____; involved in _____. Released from ______ cells of all types - but ____, _____, and _____ are primary sources. These cells can accelerate the differentiation of _____, thereby influencing the ____ response to specific antigens.
What are the three things this type does to fight viruses?
HE JUST SAID - JUST REMEMBER - IFN-a/b are antiviral
- glycoproteins, anti-viral activity, virus-infected, T cells, macrophages, fibroblasts, B cells, antibody
1. activate host genes to inhibit viral RNAs and replication
2. induce MHC class I expression on the host cells (presenting more antigens - increase chances of encountering cytotoxic C-cells)
3. activate NK cells to kill virally-infected cells
(IFN-gamma)
Produced mainly by?
Most Potent what?
(Are viruses always endogenous?)
(HE DIDN:T TALK ABOUT THE REMAINDER OF THIS SO DON’t STUDY - just read - he just wants us to remember macrophage activation)
(It stops macrophage migration, activates pro-inflammatory cytokine gene expression, augments phagocytosis, increases anti-tumor and antibacterial processes, and upregulates MHC expression. It also influences the production of immunoglobulin isotypes and stimulates the nerutophil respiratory burst. Finally, IFN-gamma activates vascular endothelial cell adhesion molecules expression)
- T helper cells and NK cells
- activator of macrophage immune function
- yes
What animal is interferon gamma deficient at birth? What does this mean they will have trouble with?
- foals, bacteria?
(Colony-Stimulating Factors)
- Promote the terminal differentation of ______ or _____ progenitor cells.
- Many are constitutively expressed in certain tissues, but all show altered _____ during _____
What are the four he wants us to know and what do they do?
- omnipotent, polypotent
- expression, inflammation
1. Granulocyte colony-stimulating factor (G-CSF): neutrophils, eosinophils
2. Macrophage CSF (M-CSF or CSF-1): monocyte/macrophages
3. GM-CSF: macrophages or granulocyes
4. IL-7: produced by stromal cells in the bone marrow or spleen; proliferation of lymphoid progenitors
- Many cytokines affect differentiation of _____, and how many cells of a given cell type are produced in the bone marrow can change during ____ events because the cytoknes produced change over time. THAT IS _ HEMATOPOEISIS IN NOT STATIC!
- leukocytes, inflammatory
(IL-1)
- A principal regulator of ______
- produced by wide variety of cell types, esp. activated _____ and _____
What two forms does it exist in?
What are the three funtions he wants us to remember that IL-1 (+ where they occur)?
- host inflammatory response
- macrophages, epithelial cells
- IL-1alpha and IL-1beta (have overlapping activities)
1. Hepatocytes - acute phase protein expression
2. CNS - fever induction, sleepiness
3. vascular endothelia - adhesion molecule expression (important for getting cells out of blood and into the site of inflammation) and IFN-gamma synthesis
(IL-2)
What is it produced by?
What does it do (main thing)?
- regulates proliferation of _____ (in cooperation with IL-1) as well as augments ___ synthesis
- Stimulates _____ and ____ activity against tumors
- Enhances ____ function
- IL-2 is the primary growth factor for ______ proliferation. A ____ T cell recognizes an antigen on the surface of an APC respsonds to IL-2 by undergoing a burtst of _____ primor to terminal differentiation to effector cells.
- T cell use IL-2 to make copies of itself
- activated TH1
- autocrine proliferation of T-cells
- B cells, Ig
- T cytotoxic cell, NK cell
- macrophage
- T-cell
- naive, replication
(IL-6)
- produced by activated ______, and _____
- What are the functions?
- macrophages, T cells
- acts on the liver hepatocytes to induce synthesis of acute-phase proteins (important for clearing bacteria) - these stick to bacteria and give macrophages and nuetro;hils a better chance of phagocytosing bacteria
- Also an endogenous pyrogen which acts on the hypthalamus to cuase fever