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Soluble immune mediators
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Lecture detailing soluble immune mediators
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Lecture 3 - Soluble Immune MediatorsInflammation
- Signs:
o Heat/pain/redness/swelling.
- Good:
o Clears infection/prevent the spread of infection/activate long term immunity wound healing.
- Bad:
o Scarring/permanent tissue damage/autoimmunity/cancer.
Inflammation= response to injury and damage.
Acute= comes on quickly with a short duration.
Chronic= long-term.
Pathogen= organism capable of inflicting disease.
Key Cell Types in Acute Inflammation
Innate Adaptive
Neutrophil/eosinophil/basophil. Macrophage/dendritic cell. B cell/T cell.
GRANULOCYTES. MONOCYTES. LYMPHOCYTES.
Acute Inflammation Overview
1) Tissue injury, chemical signals. Histamines [DAMP’s and PAMP’s] are released.
2) Dilation and increased leakiness of blood vessels. Phagocytes move to the area [chemokines and
cytokines recruit and activate other cells].
3) Phagocytes [macrophage and neutrophils] consume bacteria and cell debris. The tissue heals.
Pattern Recognition Receptor
Respond to pathogen-associated molecular patterns (PAMP’s) like lipopolysaccharides.
Phagocytosis.
Recruit other cells.
Promote inflammation.
Protect neighbours.
Respond to danger-associated molecular patterns (DAMP’s) like elements of DNA.
PRR’s= receptors of the innate immune system.
Lipopolysaccharides= endotoxin in the outer membrane of gram-negative bacteria- structure and protect.
Mediators of Inflammation-Cytokines
Low molecular weight protein (<30kDa).
Have a broad role cell to cell communication.
Function like hormones.
They are usually Interleukins like IL-1, IL-2. It also includes non-interleukins such as Interferon (IFN)
and tumour necrosis factor (TNF).
Act through specific receptors and have diverse effects.
They can be adaptive and innate.
, Autocrine= cell signalling where cells release hormones and chemicals that bind to autocrine receptors on the
same cell which causes change.
Paracrine= cell signalling where cells produce signals to induce change in nearby cells.
Endocrine= signalling where the signal molecules are released into the bloodstream by a cell. Signals travel to
receptors they can bind to on target cells in the body.
JAK-STAT Signalling
Signals downstream of G-protein coupled receptors and cytokines receptors.
Cytokine receptors rely on this pathway to transfer signals inside the cell.
IL-2 Receptors
Lymphokine receptor cells.
Intermediate affinity= gamma and beta.
High affinity= gamma, beta, and alpha.
Low affinity= alpha.
Treg cells express IL-2Ra chain (CDC25).
1. Cell recruitment Chemokines, IL-1, IL-8.
2. Protect neighbours IFN alpha and IFN beta (type 1 interferon).
3. Promote inflammation IL-1, TNF-alpha, IL-6.
Pro-Inflammatory Cytokines
IL-1, IL-6, TNF-alpha, and many others.
CYTOKINE SOURCES MAIN FUNCTIONS
TNF-alpha Macrophages, mast cells Fever/weight
loss/inflammation/some tumour
necrosis/expressed adhesion
molecules/activate neutrophil
IL-1 Macrophages, endothelial cells Fever/induce acute phase
proteins/express adhesion
molecules/activate
macrophage/haematopoiesis
(new cells)
IL-6 Macrophages, some tumour cells Fever/induce acute phase
proteins/haematopoiesis/matures
B cells.
Pyrexia
Systematic increase in body temperature.
IL-1, TNF-alpha, IL-6 = pyrogens [act on hypothalamus].
Acute Phase Response
IL-1, TNF-alpha and IL-6 are drivers of the acute phase response.
Acute Phase Proteins
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