Innate soluble molecules – Jan. 16
- Soluble molecules include: 1. Cytokines. 2. Acute-phase proteins. 3. Complement proteins. Most
soluble molecules have a role in both innate and adaptive immunity.
- Cytokines are proteins secreted by activated cells (such as activated immune cells). Cytokines are
messengers, and they are how cells communicate with other cells and also to itself. Cytokines dictate
what cells do. They activate or suppress most cell behaviours such as proliferation, growth,
maturation, and survival. Mode of action – A cytokine binds to its receptor on the cell surface, which
then signals/tells the cell how to behave. There are many cytokines that are used clinically to help
treat diseases such as autoimmune diseases, viral diseases (HIV), and cancers.
- Cytokine families: There are six cytokine families, of which we will only talk about three.
Chemokines, Interferon (IFN) Type I, and Tumor Necrosis Factor (TNF) are cytokine families that all
play a key role in innate immunity. Other cytokine families are interleukins (IL), growth factors (GF),
and colony stimulating factors (CSF).
- Hematopoiesis is regulated by cytokines.
- Activated cells secrete many types of cytokines simultaneously. Cells first become activated by
binding either PRRs to PAMPs or cytokine receptors to cytokines. PRR-PAMP binding results in
activation of the cell and cytokine secretion.
- Type I Interferons: There are two types – IFN-α and IFN-β. They are important antivirals. They are
secreted by virus-infected cells. When a cell gets infected with a virus, it secretes chemokines and
type I IFNs. IFN tells NK cells to kill the infected cell. The NK cell has a receptor for IFN. IFN binds to
this receptor and this activates the NK cell. Activated NK cells release toxic enzymes onto the infected
cell, causing apoptosis. There is also a binding interaction between the virus-infected cell and the NK
cell. The infected cell expresses a stress-induced ligand that the NK cell binds to. NK cells provide an
early response to viral pathogens. Type I IFNs are secreted very early after a viral infection, before
NK cells are activated. Type I IFNs secreted by infected cells also induce uninfected cells to produce
antiviral enzymes to protect themselves from viral infections. These enzymes inhibit viral replication.
The virus can still enter the cell, but it won’t be able to replicate (transcription is blocked).
- Type I IFNs are used clinically to treat viral infections like viral hepatitis B and C and herpes virus.
- While Type I IFN is traditionally associated with antiviral responses, recent studies have
demonstrated that some intracellular bacteria also induce Type I IFN responses. The mechanisms of
Type I IFN induction and its role in host defense against intracellular bacteria, however, are largely
unclear. Intracellular bacteria are difficult to destroy by innate immunity; adaptive immunity is
- Chemokines: They are chemoattractant cytokines. Their function is to attract immune cells. Cells
leave the blood and are recruited to sites of infection because of chemokine attraction. Circulating
immune cells exit the blood and enter infected tissue by crossing endothelial cells. Endothelial cells
are specialized epithelial cells that line blood vessels.
- Tumor necrosis factor (TNF): It is a cytokine that is secreted by activated phagocytes. TNF activates
endothelial cells to vasodilate and increase blood vessel permeability. Endothelial cells have
receptors for TNF. Increased permeability of blood vessels allows immune cells to leave the blood.
Macrophages and immature dendritic cells phagocytose the pathogen and then they release TNF.
They also release chemokines. TNF binds to TNF receptors on endothelial cells, and this results in
more immune cells being released from the blood into the tissue. Cytokines can also enter into the
- Inflammation: Activated phagocytes secrete chemokines, TNF, and other cytokines. TNF binds to
endothelial cells. Vasodilation and increased vascular permeability cause redness, heat, and swelling.
Inflammatory cells migrate into the tissue, releasing inflammatory mediators that cause pain. When they enter the tissue, they know where to go because of chemokines. Infect tissue has a lot more cell