Abstract

Brain coordinates physiological, immunological, and behavioral responses to stress. A typical stress response is “freeze, fight or flight”. It involves the release of catecholamines by the sympathoadrenal system and activation of the hypothalamopituitary- adrenal (HPA) axis to produce various hormones that prepare the organism for a particular response. Stress generally leads to a strong suppression of the adaptive immune system and a partial suppression of the innate immune system. The brain controls the immune organs through hormones produced by the HPA axis and through direct control by neurotransmitters. In turn, immune mechanisms affect behavior and brain development. Brain microglia support developing neurons, phagocyte dead and inactive cells, and participate in the formation of connections between neurons through synaptic pruning. Peripheral immune cells regulate neurons through neurotransmitters and inflammatory mediators such as IL6, TNF, PGE2, histamine, and others. These mediators induce sickness behavior during illness. They also alter the developing brain during maternal stress, maternal immune activation, and early life stress predisposing the brain to a mental illness. Immune mechanisms contribute to psychiatric and neurodegenerative disorders.