The main functions of the immune system are protection against infectious disease (1), promotion of tissue repair (2) and destruction of malignant transformations (3). Unwanted side effects of the immune system are tissue damage (1) and discomfort and sickness (2).

The lymphocytes are the B-cells (1), T-cells and NK-cells (3). The goal of B-cells is antibody production. Cytokines are hormones produced by immune cells that initiate the inflammatory response. They are the signal molecules of the immune system. Immune cells are the same as leukocytes. Antibodies are soluble antigen receptors

The immune response to infection consists of several steps:

1. There is an infection
2. The microbes are intercepted by sentinel cell underneath the mucosa surfaces.
3. There is a local alarm response (e.g. swelling).
4. The microbes are presented to lymphocytes (i.e. lymph nodes).
5. The lymphocytes become armed effector cells.
6. The lymphocytes move into the blood cells and move to the place of the infection (i.e. people get ill; this takes a few days).

The infection meets the inside of the body on mucosa surfaces. The skin has a mechanical barrier (1), has endogenous flora (2) and is a bit acidic (i.e. low pH) (3). The mucosa has a mechanical barrier (1), has endogenous flora (2) and has antimicrobial proteins (3).

There are other protective factors when the mechanical barrier of the skin are breached:

1. Physical barrier (i.e. body temperature).
2. Chemical barrier (i.e. antimicrobial proteins, including antibodies).
3. Phagocytic cell responses (i.e. sentinel cells that destroy infectious agents, initiate inflammatory response and transport antigen to lymphoid organs).

Phagocytic cells use pattern recognition receptors to detect pathogens.

Activation refers to cellular or molecular changes that initiate or facilitate an immune response. Antigen refers to any molecule that activates the immune system (i.e. antibody generator).

Antigen-presenting cells migrate to second lymphoid tissues via draining lymphatics. This is done to maximize the probability that a unique antigen will encounter its unique receptor. In the lymphoid organs, antigen is presented to local naïve lymphocytes. Distinct MHC molecules are associated with distinct groups of antigens and distinct immune responses. Upon activation, naïve lymphocytes start to divide and become antigen-eliminating effector cells. This makes the lymphocyte ready to tackle the infection.

The T-lymphocytes have the function of destruction of cancerous and virally infected cells. The T-helper cells take care of immune regulation via the release of cytokines. It does this by orchestrating the activity of the phagocytic cells and the activity of other leukocytes.

The functions of immunoglobins (i.e. antibody) are:

1. Neutralization
   The antibody prevents bacterial adherence.
2. Opsonization
   The antibody promotes phagocytosis.
3. Complement activation
   The antibody activates complement which enhances opsonization and lyses some bacteria.

Adaptive immunity is mediated by lymphocytes. The B-cells and T-cells have adaptive immunity. All other cells have innate immunity. Innate immunity always responds in the same way to infection. B-cells and T-cells (i.e. adaptive immunity) learn and respond more effectively after the first infection.

When the antigen is eliminated, the effector cells die. A small population of long-lived memory cells survive. If there is infection with the same pathogen, the immune response is faster because of the memory cells.

The nervous system and the immune system speak a common biochemical language and communicate via a complete bidirectional circuit involving shared ligands (e.g. neurotransmitter; hormones; cytokines). The immune cells release cytokines which influence the brain and the brain releases hormones which influences the immune system. However, the brain also produces cytokines and the immune system also produces hormones.

Prolonged stress dysregulates the immune system and makes one more vulnerable to infection. Acute stress provides an adaptive response which helps the immune system. During a period of stress, the number of lymphocytes and NK cells go up.

Stressors can increase the susceptibility to infectious agents (1), influence the severity of infectious disease (2), diminish the strength of immune responses to vaccines (3), reactivate latent herpesviruses (4), lead to slow wound healing (5) and can increase the production of pro-inflammatory cytokines that are associated with age-related diseases (6).

Individuals that are stressed are more likely to have negative health habits (e.g. smoking). There is a poorer antibody response in individuals who are stressed both in regular infection and in viral or antibacterial vaccine. Being stressed leads to a delayed, shorter and weaker immune response. Stress dysregulates the humoral and cellular immune responses to pathogens. It also suppresses the response of memory cells to herpesvirus infection.

Experiencing a stressful situation leads to the activation of the HPA and SAM axis. The production of adrenocorticotropic hormone by the pituitary gland results in the production of glucocorticoid hormones. The SAM axis can be activated by stimulation of the adrenal medulla to produce catecholamines adrenaline and noradrenaline.

The stages of wound healing are the inflammatory stage (1), the proliferative stage (2) and wound remodelling (3). The immune system has a key role in the early stages of wound healing but the production of inflammatory cytokines is disrupted by stress.

People with chronic diseases have an increased risk of psychological disorders. For people with chronic diseases, there generally is no role impairment unless that person has a comorbid mental disorder. Inflammation causes sickness behaviour.

Neural and glial-cells detect and respond to cytokines. The amygdala and orbitofrontal activation predict the inflammatory severity. There are elevated markers of inflammation in clinical and non-clinical depression. In addition to this, anti-inflammatory drugs have an anti-depressant effect and some anti-depressants have an anti-inflammatory effect.

Depression boosts cortisol levels and increases in cortisol can provoke immunologic changes. Immune modulation through the stress hormones might occur through binding of the hormone to its cognate receptor at the surface of the cell (i.e. directly) or through inducing dysregulation of the production of cytokines.

Individuals with low-grade inflammation show negativity bias (1), impaired emotion recognition (2), hyperresponsivity to negative social cues (3), impairments in maintaining effort (4), less flexible adaptation to reinforcement change (5) and reduced motor speed (6). It appears as if inflammation impairs dopamine-related functions.

The inflammatory cytokine Il-6 is produced by T-cells (1), B-cells (2), monocytes (3) and non-lymphoid cell types (4). Il-6 induces C-reactive protein (CRP). The combination of IL-6 and CRP is imperative in the process that leads to the development of cardiovascular disease. The production of IL-6 is augmented by negative emotions.