Innate Immunity: Inflammation: Part One Flashcards
What are cytokines
small molecular weight, soluble proteins that function as chemical messengers and orchestrate innate and adaptive immune responses
Who produce cytokines?
- leukocytes
- T helper
- dendritic cells
- macrophages
- many other cell types (for example)
- epithelial cells
- endothelial cells
- bone marrow stromal cells
What are the 5 cytokine types?
- interleukins
- chemokines
- colony stimulate factor
- interferons
- tumor necrosis factor
What do interleukins do?
communicators between leukocytes (IL-1 – IL-35)
What do chemokines do?
control chemotaxis
What does colony stimulating factor (CSF) do?
affect hematopoiesis
what do interferons do?
What does tumor necrosis factor do?
autocrine
cytokines affect the same cell that secretes them
paracrine
cytokines affect another local cell
endocrine
cytokines affect cells in different parts of the body via blood or lymph
pleiotropy
cytokines that affect multiple cell types
redundancy
cytokines that affect the same cell BUT you only need one to function
synergy
cytokines that work on the same cell AND you require them together to function
antagonism
cytokines that have opposite affects
TNF function
- pro-inflammatory cytokine
- increase NK cytotoxicity
- increase phagocytic activation
- increase vascular permeability
IL-1 function
- pro-inflammatory cytokine
- increase endothelial adhesiveness
- increase chemokine production
IL-6 function
- pro-inflammatory cytokine
- promote monocyte recruitment
- induces fat and muscle to metabolize to raise the local temperature
chemokines
- pro-inflammatory cytokine
- attraction of neutrophils, monocytes, and effector T cells
IL-10 function
- anti-inflammatory cytokines
- decrease TNF and IL-12 production
- decrease MHC and B7 expression on macrophages
IL-1ra
anti-inflammatory cytokines
TGF-beta function
anti-inflammatory cytokines
IFN-alpha and IFN-beta function
inhibition of virus replication
IFN-gamma function
- macrophage-activating cytokine
- enhance phagocytic cells ability
IL-4 function
B cell activating cytokine
IL-5 function
B cell activating cytokine
IL-6 function
B cell activating cytokine
IL-21 function
B cell activating cytokine
IL-2 function
T cell activating cytokines
IL-4 function
T cell activating cytokines
IL-12 function
- T cell activating cytokines
- increase IFN-gamma production by NK
- increase NK cytotoxicity
How does inflammation start?
- tissue WBCs (macrophages and mast cells) detect PAMPs via PRRs and secrete pro-inflammatory cytokines
- now permeable capillaries allow antimicrobial proteins and complement proteins to enter infected tissue
- WBCs slowed by adhesion molecules expressed by vascular endothelium
- neutrophils enter infected tissue and are guided by CXCL8 gradient
- phagocytosis, repair, clotting downstream
- neutrophils die quickly but macrophages last longer
histamine
- increase vascular permeability
- increase vasodilation
C3a
- increase vascular permeability
- increase vasodilation
C5a
- increase vascular permeability
- increase vasodilation
- chemoattractant
CXCL8
recruits neutrophils from the blood and guides them to the infected tissue
How do neutrophils get to the infected tissue?
- vascular endothelium express selectins
- neutrophil’s s-Lex weakly binds to the selectin and starts rolling and slowing
- eventually the neutrophil’s LFA-1 binds to the endothelium’s ICAM-1
- this allows the neutrophil’s CXCL8 receptor to bind to the CXCL8 and be drawn between cells into the tissue
- the neutrophil follows the CXCL8 to the infection source
3 roles of inflammation
- kill
- contain
- repair
