Mast cells has lots of different granules filled with primary mediators, has phylopodia to help it move.

Originally thought to be of myeloid origin, but of hemapoetic, Leave bone marrow as immature mast cell (no granules in blood) Go into tissueto mature phenotypically mast cell in skin might look different from mast cell in lung for e.g.

Activation of Mast Cells Each granule contains only one mediator and they are differentially released
Direct interaction

Toll receptors e.g. 4pathogens bind to it and they synthesize de novo mediators and releasing themnot releasing granules.
Fc Receptor-mediated activation

Interaction between b-cell superantigen and Fc receptor on surface of mast cells. Mast cell activated.makes some mediators de novoreleases some granules.
Complement receptor mediated activation

Complement receptor activated by complement. Some de novorelease of some granules.

Mast cells respond to a variety of pathogens and release a variety of mediators.

Primary mediators-already made and ready to be releasede.g. histamine, heparin, serotonin Secondary mediators-PGD2chemotactic can be both

Most of the roles, e.g. asthma, allergies, itchiness, that we associate with mast cells are detrimental

Have IgE antibodies pollen specific antibodies.causes release of things like histamine etc from mast cells Look up IgE mediated hypersensitivity.-called hypersensitive because pollen isnt necessarily something you want to be moutnign an immune response against

Mast cells act as sentinels.activated at surface of skin etc. Histamine acting in brain makes you sleepy, but they have a new class that doesnt cross the blood-brain barrier.

Finding beneficial roles of mast cells Used three different models -occurrence of mast cell deficient sash mouse-mutation in c-kit receptorsneed Stem cell factor to bind to c kit for progenitors become mast cell precursos.. Mast cells dont have c-kit on receptors in sash mice. Mutation also affects melanocytes. FACS shows all other immune cells normal. Pharmalogical-giving cromolyn-blocks mast cellsseems to block Ca channels to block degranulation of mast cells. So mast cells are there but they are not releasing granules or becoming activated. Isolation/culturs of mast cells

Functions Sepsis-Mast cells enhance resistance if you happen to be bitten by a snake or honeybee. Lack of mast cells in these mast cell deficient mice.contributes to death in case of being bitten by Antigen presentation to T cells-Mast cells can present antigen.they are not constitutive presenters like dendritic cells but can at times. Cancer-Use model of pancreatic cancer. Could inducepancreatic cancer in wild type mice and then do this but also give cromolyn, then give tumor to genetically mast cell deficient mice. In mice that lacked mast cells or ability to activate them had smaller tumors. Comes down to formation of blood vessels. Mast cells contribute pro angiogenic factors that help form blood vessels. In their absence tumor has issues vascularizing. If injected right in could cause shrinking. Obesity- Obese humans and mice have more mast cells in their white adipose tissue.Not sure if it is cause or effect. Are mast cells contributing to making someone fat? Tryptases are proteases found specifically in mast cellsused as marker for mast cells. Put mice on western diet-those without mast cells eat same amount, but gain less weight. If you dont have mast cells, you gain less weight. Lose weight if you inject cromolyn Took mast cell deficient mice and replaced with mast cells from cytokine deficient mice. Mast cells deficient in IL 6 and INF-g have issues regaining weight. Specifically mast cell derived IL 6not same result if you just knock out IL6Back to blood cell formationneed vessels to grow fat.

Mast Cells in The Brain Immune cells do reside in the brain. E.g. microglia, dendritic cells, T cells. Mast cells are present in the brain across species. In brains of doves, two hours after mating, mast cells are seen. Mast cell levels can increase after stimuli such as stress or mating. Tests to determine link between mast cell levels and anxiety. -Elevated plus maze.more anxious mouse stays in covered part..less anxious mouse goes to cliff like part. Mast cell deficient Sash mice were more anxious, also for open field arena. Control mice find platform much fasterhave issues with spatial learning and memory

Slice Brain-Posterior Hippocampus-predominant region mast cells found in. Hippocampus associated with learning and memory and anxity and depression.

Effect probably most prominent in development. Mast cells release serotonin in brain . Mast cells The brain can also affect the immune system It seems that acute stress helps you ramp up immune system and fight off pathogens etc. Chronic stress seems to be detrimentalhave basal level of inflammation and less ability to fight off infection. Some parts due to cortisol can help fight off things

PANDAS Associated with onset