CYTOKINES Flashcards
• Chemical messengers that regulate the immune system, orchestrating both innate and adaptive response to infection
Cytokines
Small proteins produced by several different types of cells that influence hematopoietic and immune systems through activation of cell-bound receptors
Cytokines
Cytokines are released through
activation of cell-bound receptors
• In response to binding of stimuli to specific cell receptors
•Through recognition of foreign antigens by host lymphocytes
ACTION OF CYTOKINES
APE
Autocrime
Paraceine
Endocrine
• Autocrine:
• Paracrine:
• Endocrine:
affects the same cell that secreted it
affects a target cell in close proximity
systemic activities
Action of cytokines as a whole
• Different cytokines work together (network of cytokine expression) to regulate leukocytes activity, and leads to elimination of the infection
Initially grouped based on their activities and first site of isolation:
Lymphokines
Monokines
Interleukins
Initially grouped based on their activities and first site of isolation:
• Lymphokines -
• Monokines -
• Interleukins -
released from lymphocytes.
released from monocytes and macrophages.
cytokines released from leukocytes that mainly act on other leukocyte.
Cytokines are
Currently grouped as families of:
TICTIC
Tumor Necrosis Factor (TNF)
interferon (IFN)
chemokine
transforming growth factor (TGF)
interleukins (IL)
colony stimulating factor (CSF)
ATTRIBUTE OF CYTOKINES
PRSAC
Pleiotropy
Redundancy
Synergy
Anatagonism
Cascade induction
• Pleiotropy: single cytokine may have different actions
• Redundancy: different cytokine activate same pathway and genes
• Synergy: cytokines complement and enhance each other
• Antagonisim: one cytokine counteract the action of another cytokine
• Cascade induction: cytokine secreted by a certain cell can activate target cells to produce additional cytokines
cytokine secreted by a certain cell can activate target cells to produce additional cytokines
• Cascade induction:
: one cytokine counteract the action of another cytokine
• Antagonisim
: cytokines complement and enhance each other
• Synergy
: different cytokine activate same pathway and genes
• Redundancy
: single cytokine may have different actions
• Pleiotropy
Massive overproduction and dysregulation of cytokines produce…
hyperstimulation of the immune response
• Hypercytokinemia or Cytokine Storm
• Example:
Influenza A and Francisella tularensis
• Leads to shock, multi-organ failure, or even death
• Hypercytokinemia or Cytokine Storm
• Main cause of death in the 1918 Spanish flu pandemic
Hypercytokinemia or Cytokine Storm
Nomenclature PAST
(based on which they originated from)
• Lymphokines
• Monokines
• Interleukins (act on other leukocytes)
Nomenclature
Present
(grouped into families)
• Tumor Necrosis Factor (TNF)
• Interferon (INF)
• Chemokine
• Transforming Growth Factor (TGF)
• Interleukins
• Colony Stimulating Factor (CSF)
• Produced by many different cell types
• Function: to increase APRs and to recruit WBCs to the area of infection
• IL-1, TNF-alpha, IL-6, Chemokines, TGF-beta, INF-alpha, INF-beta
INNATE
ADAPTIVE
• Mainly secreted by…
• Function: Directly affect…
T cells
(Th cells)
T-and B-cell function
INNATE IMMUNE RESPONSE
nterleukin-1
•- rarely found outside the cells
• - more important in
systemic response; endogenous pyrogen (induces fever by acting on the hypothalamus)
• - blocks II-1 receptor
IL-1alpha
IL-1beta
IL-1RA (IL-1 receptor antagonist)
• Can induce lysis in tumor cells
Tumor Necrosis Factor
- most prominent
• mainly triggered by bacterial
lipopolysaccharide
• Can induce expression of Class II MHC
→ T-cell activation
• Excess soluble forms are bound by
TNFR1 (TNF receptor 1), while excess membrane-bound form are bound by
TNRF2
• Central mediator of pathological processes in RA and other inflammatory illnesses
• TNF-alpha
• Pleiotropic
• Stimulate B-cell proliferation and maturation
• Induce CD4+ T-cells to produce more pro- and anti-inflammatory cytokines
• Only one IL-6 receptor has been identified that consists of:
•______ and _____ (the common signal-transducing receptor subunit used by several cytokines
Interleukin-6
IL-6Ra (the IL-6-specific receptor) and gp130
INNATE IMMUNE RESPONSE
Chemokines
• Over____ kinds
• functions
40
Enhance motility and promote migration of WBCs toward the chemokine source via chemotaxis
Four families based in position of N-terminal cysteine residues
CXC (alpha)
CC (beta)
C
CX3C
• HIV uses chemokine receptors_____ and _____ as co-receptors for infection of CD4+ T cells and macrophages
• During polymorphisms (or alterations) in the aforementioned receptors,
the virus ability to enter the cell is blocked or diminished
• Long-term non-progression of disease
• Asymptomatic with Normal CD4+ T-cell counts and immune function, as well as low or undetectable viral loads
CXCR4 and CCR5
• Activates expression of CD8 in DN thymocytes
• Inhibitory effects on immature thymocytes
• Blocks production of IL-12 and inhibits induction of IFN-gamma
Transforming Growth Factor-ß
• Has antiproliferative activity in a wide variety of cell types
• Help downregulate inflammatory response when no longer needed
Transforming Growth Factor-ß
• Transforming Growth Factor-ß
→ oral tolerance to bacteria normally found in the mouth
• TGF-ß1, TGF-B2, TGF-B3
• Th2 production of TGF-ß
• Activates NK cells
Type I Interferons (INF-a and INF-B).
• Produced by dendritic cells and induce production of proteins and pathways that directly interfere with viral replication and cell division
Type I Interferons (INF-a and INF-B).
INNATE VS ADAPTIVE IMMUNE RESPONSE
INNATE
• Produced by many different cell types
• Function: to increase APRs and to recruit WBCs to the area of infection
ADAPTIVE
• Mainly secreted by T cells (Th cells)
• Function: Directly affect T-and B-cell function
• Produced by many different cell types
• Function: to increase APRs and to recruit WBCs to the area of infection
INNATE IR
• Mainly secreted by T cells
(Th cells)
• Function: Directly affect T-and B-cell function
ADAPTIVE IR
T-Helper 1
Product
IFN-y
IL-2
Increases expression of MHC Class I and II increased likelihood of antigen capture and recruitment of T cells
IFN-y
Most potent activator of macrophages → activated or “super” macrophages → vs intracellular pathogens and tumors
Also activates CD4+ Th1 cells, CD8+ T cells, and NK cells
IFN-y
AKA T-cell growth factor (like Th2)
IL-2
Help generate IgG1 and IgE-producing cells
IL-2
T-Helper 2
IL-4
IL-10
IL-13 has similar effects, but IL-13 can inhibit secretion of cytokines by monocytes
IL-4
Production of IgG2a and IgE, and II-5 → differentiation and activation of eosinophils in both allergic responses and parasitic infections IL-10
IL-4
Also stimulates differentiation of naïve CD4+ T-cells
Turns off the genes that promote Th1 cells
IL-4
Anti-inflammatory, block cytokine production, and inhibits antigen presentation
IL-10
Antagonist to IFN-y → thus, it is a downregulator of immune response
IL-10
T-Regulatory
Products
TGF-B
IL-10
Anti-inflammatory, block cytokine production, and inhibits antigen presentation
TGF-B
Induces expression of Foxp3, a transcription factor which causes T-reg cells to suppress the activity of other T-cells
TGF-B
Downregulator of immune response
Anti-inflammatory, block cytokine production, and inhibits antigen presentation
IL-10
T-Helper 17
Product
IL-17
= most studied IL-17 cytokine
IL-17A
Necessary for secretion of antimicrobial peptides in bacterial and fungal infections at mucosal surfaces
Makes cells produce CXC ligand 8 (CXCL-8), which is crucial for continuous recruitment of neutrophils to site of inflammation
Directly induces IgE production by B cells
IL-17
MAJOR
PROINFLAMMATORY
CYTOKINES
TNF-a
IL-1
IL-6
IFN-Y
MAJOR ANTI-INFLAMMATORY
CYTOKINES
TGF-B
IL-10
IL-13
IL-35
