What is homeostasis?
The ancient pathway or Toll pathway is a pathway of host defense against infection where microbes and their products release NFkB from its site in the cytosol.
Homeostasis is the maintenance of equilibrium (constant internal conditions) in a biological system by means of an autoimmune mechanism. Without homeostasis, an organism cannot survive. The proliferation and differentiation of cells are important for the development and maintenance of multicellular organisms. It is kept by extracellular factors that interact with receptors on lymphocytes. These extracellular factors induce signaling pathways; they are:
Ancient pathway or Toll pathway
Signals via lymphocytes
What is the ancient signaling pathway or Toll pathway?
(refer to p. 184, fig. 5.20)
is a transcription factor in lymphocytes and is activated by lipopolysaccharide and microbes.
NFk B triggers a protease cascade that makes a ligand for the Toll receptor (has a TIR domain on the cytoplasmic domain) which is homologous to the cytoplasmic domain of the IL-1 receptor (IL-1R), so this is called the Toll/IL-1R domain.
This binds to adaptor protein MyD88 initiating protein-protein interactions or the death domain.
This death domain interacts with another death domain on a serine/threorine innate immunity kinase (SILK).
SILK initiates a cascade of TRAF6 (TNF [tumor necrosis factor] -receptor-associated factor 6) and NFk B kinase (NIK), which in turns activates two kinases: Ik k-a and Ik k-b à or dimer Ik k.
Ik k phosphorylates Ik B (inhibitory protein) which is then degraded. This releases NFk B to move into the nucleus and activate genes involved in host defense mechanisms against infections.
***Overall idea: The Toll pathway is an ancient pathway used in innate defenses in host multicellular organisms.
What do cytokines do?
(refer to p. 185, fig. 5.21)
Cytokines are a collection of small proteins (~ 20,000 daltons). They act on specific receptors in a direct and rapid pathway affecting the behavior of cells.
Many cytokine receptors use receptor-associated kinases to active specific transcription factors by means of a rapid pathway.
Most cytokines are associated with Janus kinases (JAKs; they have two symmetrical kinase-like domains) which phosphorylate cytosolic proteins called signal transducers and activators of transcription (STATs).
This leads to dimerization of STATs and now STAT dimers can move into the nucleus to activate genes, which promotes the growth and differentiation of lymphocytes.
***Overall idea: Cytokines induce a rapid signaling pathway that activates gene transcription affecting cellular behavior. There are different types; such as lymphokines, interleukins, chemokines.
How is homeostasis related to lymphocyte populations?
Homeostasis allows the numbers of lymphocytes to remain constant. B and T lymphocytes have homeostatic regulations of resting and activated B and T cells. This is maintained by signals the lymphocytes receive through their antigen receptors.
Receive signal through interactions with self-MHC:self-peptide complexes.
The signals enable the T cells to survive.
The T cells are delivered to cells that are capable of T cell activation (mostly dendritic cells).
B. B cells
Receive signals through antigenic receptor in order to survive.
B cell receptors are needed to keep re-circulating B cells alive.
They have a role in perceiving and transmitting survival signals to each B cell.
***Overall idea: Homeostasis provides the defense of the organism against both infectious microorganisms and diseased cells of the body itself. This is completed by the immune system as a whole, which in turn uses lymphocytes.
What is apoptosis?
normal cell (a), nucleus of cell (b) apoptotic cell (c), nucleus of apoptotic cell (d)