Innate immunity and cytokines Flashcards
Name some physical and chemical barriers to microbial invasion
1) Skin and mucous membranes - block entry of pathogens and secrete antimicrobial peptides and enzymes
2) defensins - cationic peptides secreted into phagocytic vacuoles that damage bacterial membranes
3) cathelicidins - make bacterial membranes more permeable
4) lysozymes - lachrymal and saliva secretions - also break down bacterial membranes
3 cells involved in early detection
macrophages, neutrophils, dendritic cells
How do NK cells detect pathogen?
They detect host cells with depressed levels of MHC I
What is inflammation?
Controlled passage of cells and plasma from the blood into a traumatized area
What are three chemical initiators of inflammation?
IL-1, TNF-a, and complement activated by the alternate pathway
Name some adhesion molecules induced by inflammation initiating cytokines.
1) integrins - on leukocytes
2) selectins - on endothelial cells
3) others on epithelial cells
Binding of neutrophils
neutrophil integrins bind endothelial selectins and enter through diapedesis
Two chemokines that recruit phagocytes
IL-8, MCP
Order of phagocyte recruitment
1) neutrophils
2) monocytes
3) macrophages
4) lymphocytes
Actors involved in phagocytic elimination
IL-8 induced phagocytes, MIP, IFN-gamma
chemicals that destroy pathogens in phagocytic elimination
lysosomal enzymes, hydrogen peroxide, nitric oxide, O2 anion
2 phases of damage repair after excessive inflammation
1) IL-4, IL-10, and TGF-b down regulate initial cytokines
2) Platelet derived growth factor (PDGF) and TGF-b induce increased proliferation and activation of fibroblasts and production of extracellular matrix
2 subcategories of chemokines and examples
1) C-X-C (alpha) chemokines - have one amino acid between first two cysteines - include IL-8, platelet factor 4, IFN-gamma
2) C-C (beta) chemokines - have two adjacent cysteine residues
How do chemokines function?
Transmit signals via seven transmembrane, rhodopsin-like, receptors which activate and attract leukocytes to tissue damage
How do cytokines function?
Locally, in a paracrine or autocrine manner, by binding to high affinity receptors
IL-1 (a, b) - cell source and action
Cell source: macrophages, endothelial cells, dendritic cells, Langerans’ cells
Action:
- Stimulates IL-2 receptor emergence in T cells
- Enhances B cell activation
- Induces fever, acute phase reactants and IL-6
- Increases non-specific resistance
- Inhibited by IL-1 receptor antagonist
IL-2 - cell source and action
Cell source: TH1 cells Action: - T-cell growth factor - Activates NK and B cells - discovered by Kendal Smith at Dartmouth
IL-3 - cell source and action
cell source: T cells
action:
- stimulates hematopoiesis
IL-4 - cell source and action
cell source: T cells action: - MOST IMPORTANT: induction of Th1 cells - stimulates IgE production - down regulates IFN-gamma
IL-5 - cell source and action
cell source: T cells action: - growth and diff. of eosinophils - B-cell growth factor - enhances IgA production
IL-6 - cell source and action
cell source: monocytes, T cells, endothelial cells
action:
- induces acute phase reactants, fever, and late B-cell diff.
IL-7 - cell source and action
cell source: bone marrow
action:
- stimulates pre-B and pre-T cells
IL-8 - cell source and action
cell source: monocytes, endothelial cells, lymphocytes, fibroblasts
action:
- chemotaxis of neutrophils and T cells
IL-9 - cell source and action
cell source: TH cells
action:
- T cell mitogen
IL-10 - cell source and action
cell source: TH2 cells
action:
- inhibits IFN-gamma synthesis
- suppresses cytokine synthesis in general
IL-11 - cell source and action
cell source: bone marrow
action:
- stimulates hematopoiesis
- enhances acute phase protein synth
IL-12 - cell source and action
cell source: macrophages, B cells action: - MOST IMPORTANT: TH1 differentiation - IFN-gamma synth - NK and CD8 T cell cytolysis - synergizes with IL-2
IL-13 - cell source and action
cell source: TH2
action:
- inhibits inflammatory cytokines IL-1, 6, 8, and 10
- inhibits MCP
IL-15 - cell source and action
cell source: T cells
action:
- T cell mitogen
- growth of intestinal epithelium
IL-16 - cell source and action
cell source: CD8 T cells, eosinophils action: - increases MHC II - increases chemotaxis - increases CD4 T cell cytokines - decreases antigen induced proliferation
IL-17 - cell source and action
cell source: T cells
action:
- increases inflammatory response
IL-18 - cell source and action
cell source: activated macrophages
action:
- increases IFN-gamma action
- increases NK cell action
(tumor necrosis factor-alpha) TNF-a - cell source and action
cell source: macrophages, Tc and B cells, large granular lymphocytes
action:
- IMPORTANT: used by Tc cells to apoptose target cells
- cytotoxic to tumors
- causes cachexia
- mediates bacterial shock
(tumor necrosis factor-beta) TNF-b - cell source and action
cell source: T cells
action:
- cytotoxic for tumors
(transforming growth factor-beta) TGF-b - cell source and action
cell source: almost all normal cell types
action:
- inhibits proliferation of T and B cells
- reduces cytokine receptors
- chemotactic agent for leukocytes
- mediates inflammation and tissue repair
- switching B cells to IgA synth.
- wound healing, inhibits IL-2 effects
What is the main function of Th17 cells?
recruitment of neutrophils
IFN-gamma
secreted by Tc cells to apoptose target cells
