Lecture 9: Health And Immunity PDF

Lecture 9: Health and Immunity  Before We Start: A Disclaimer The immune system is super complex Consists of 65+ cells & a plethora of signaling molecules each with their own specialized function(s) Immune cells/factors have numerous amounts of...

Lecture 9: Health and Immunity  Before We Start: A Disclaimer The immune system is super complex Consists of 65+ cells & a plethora of signaling molecules each with their own specialized function(s) Immune cells/factors have numerous amounts of interactions further adding to complexity I can’t teach everything there is to know about the immune system What is sickness? The behavior and physiology of sick people (and animals) changes dramatically. They tend to: – Ignore food and beverages. – Lose interest in social interaction. – Have excess or fragmented sleep. – Feel depressed and irritable. – Have impaired attention and memory. The behavioral and cognitive changes that accompany physical illness have been termed sickness behavior. Sickness behavior may represent a motivational state responsible for helping individuals cope with infection. What is psychoneuroimmunology? The study of the interaction between the mind, brain, and immune system. As we will see, one’s psychological state can interact with the immune system and the immune system can interact with the brain. – These interactions are important for everything from the common cold to cancer. The brain and immune system therefore have bidirectional communication. – Psychoneuroimmunology is a two-way street. This field of study constitutes a major advance from earlier viewpoints that saw infectious diseases as strictly physical phenomena. What is the immune system? The human body is a warm, moist and nutritive environment – a climate perfectly suited for microorganisms of all kinds. The immune system is responsible for protecting your body from microbial overgrowth. The immune system monitors the internal environment for signs of invasion by bacteria or viruses, as well as evidence of tissue damage. The immune system is extremely Macrophages are immune cells that are able to seek powerful, and is highly regulated in out and engulf bacterial order to maintain optimal levels of invaders. function. How does the immune system work? Unlike the nervous system, the immune system is decentralized. – Immune cells circulate throughout the blood stream and act directly where they are needed. Thymus Lymph nodes Organs such as the spleen, lymph Spleen nodes, thymus, and bone marrow act as factories and repositories for immune cells. Like the nervous and endocrine Bone marrow systems, the immune system relies on chemical communication to organize its functions. Prenatal Immunity Fetal brain considered “immune- privileged; limited immune surveillance – TH1 cytokines can still affect brain cells For example: When the maternal immune system is activated (e.g., infection), cytokines, including those produced by TH1 cells (like interferon-gamma, IL-2, and TNF- alpha), can cross the placenta and influence fetal brain development – Environmental factors can also epigenetically program the fetal immune system However: Maternal antibodies (primarily IgG) can cross the placenta. – Provides passive immunity to the fetus, giving it temporary protection against pathogens the mother has been exposed to or vaccinated against The immune system, in brief The immune system has two basic divisions: Innate – Innate immune system. immune – Adaptive immune system. system Cell-mediated immunity (T cells) Antibody-mediated immunity (B cells) The immune response is a coordinated effort between all three systems that typically follows the same progression (see figure). – Innate immune system activates the different divisions of the adaptive immune system Antibody- Cell-mediated mediated immunity immunity The various branches of the immune system communicate with each other using chemical messengers called cytokines – Adaptive immune system “cell” + “movement” (G.). – Cytokines are like hormones for immune signaling. The innate immune system The innate immune system is used for “general purpose” immunity, and is sensitive to molecules that are universally present on bacteria. Cells such as macrophages have receptors on their membranes that bind to pathogens and trigger A macrophage attacking bacteria phagocytosis (phago – ‘eating’, cyto – ‘cell’ (G). – In phagocytosis, the macrophage destroys the pathogen by “eating” it. When activated, cells of the innate immune system (such as macrophages) release cytokines A macrophage reaching out into circulation. to engulf two particles. The adaptive immune system The adaptive immune system is activated by cytokines, and involves two systems of leukocytes (white blood cells). Cell-mediated immunity involves T cells named because they develop in the thymus). – T cells are activated by cytokine signals and interaction with macrophages. A cytotoxic T cell attacking Once activated, T cells proliferate and an infected body cell. develop into a form that attacks body cells that have been infected. Plasm Antibody-mediated immunity a (B) cell involves B cells named because they develop in bone marrow). – B cells (plasma cells) produce antibodies Antibodies that bind to antigens on pathogens to kill or deactivate them. Cytokines and the immune response After ingesting pathogens, macrophages release cytokines such as interleukin-1 (IL- 1) (inter – “between”, leukos – “white”). Macrophage IL-1 stimulates T helper cells to release IL-2. IL- 1 IL-2 induces the proliferation and development of antibody producing B cells (plasma cells) T helper and cytotoxic T cells. cell Cytokines also: – Trigger an inflammatory response (redness, fever, aches, etc.) IL- – Attract more innate immune cells. 2 – Activate the adaptive immune system. Plasm Cytotoxi a (B) c T cell cell So in general, cytokines are molecules that coordinate the immune response, and tell the body that it is under attack. The immune system can affect the Cytokines in the brain Cytokines are like ‘sickness hormones’, so it makes sense that they can communicate with the brain. Cytokines like IL-1 signal sickness to the brain through a variety of mechanisms: – The vagus nerve connecting the brain to the abdominal organs. – Receptors on blood vessels in the brain detect circulating IL-1 or pathogens and stimulate cytokine production in the brain. – Circulating IL-1 can be actively transported into the brain. IL-1 Cytokines in the brain are linked to sickness behavior. – By informing the brain of infection, cytokines allow the animal to make appropriate adjustments to its behavior. Cytokines and depression Sickness behavior is quite similar to depressed behavior. Could cytokines play a role in depression? There are three pieces of evidence in favor of this view: 1. Giving people cytokine treatment can produce depressive symptoms. – Example: AIDS and cancer patients treated with cytokines often develop depression & suicidality. 2. Depression is more common among people suffering from inflammatory diseases. – Example: Cardiovascular disease, type 2 diabetes, rheumatoid arthritis. 3. Anti-depressant treatment improves certain components of sickness behavior in mice. – Example: Sick mice show reduced preference for sugar water and social exploration, but these symptoms are improved by anti-depressants. The brain can affect the immune system… Stress and the immune system It has been known for some time that the HPA axis can affect the immune system. – You can think of HPA axis hormones as a negative feedback signal for the immune system. – Cortisol is anti-inflammatory (remember, the immune system increases inflammation via cytokines) This fits into our view that the stress response is designed to help the body deal with short-term challenges. – For a short-term challenge, the body can save a lot of energy by shutting down the immune system. This energy can be used to cope with enemy attacks, survive starvation, etc. Problems arise when the HPA axis is over- or under-activated. – Chronic stress can lead to disease, and the interaction between the stress response and the immune system can explain why this happens. – On the other hand, having a weak HPA axis can lead to the immune system getting out of control. Still, this relationship is paradoxical. Stress suppresses immunity, yet seems to exacerbate (increases) inflammatory and autoimmune diseases. – More later Acute stress & immune function Despite the simple relationship suggested in the previous slide, not all stress suppresses the immune system. In fact, the short-term effect of a mild stressor is to augment immunity. Leukocytes are redistributed following an acute mild stressor. They move from the spleen and blood to the skin, lymph nodes, and other ‘battle stations’. – This may be in order to prepare the animal for physical damage – a wound for example. These rapid effects appear to be mediated by the SAM axis, as treatment with epinephrine and norepinephrine can mimic the immune-enhancing effect of acute mild stress. Chronic stress makes you sick Laboratory experiments that have exposed human volunteers to the common cold find that stress plays a role in getting sick. – Specifically, they found that the odds of getting sick were directly related to how much stress the person had experienced during the past year. – A positive and optimistic cognitive style seems Rhinovirus – the common cold. to protect against developing a cold. Exam periods at university are stressors that seem to produce increased rates of upper respiratory tract infection (common cold, influenza, etc.,) The same relationship is seen with other viruses such as influenza, and bacteria like Toxoplasma. Stress and disease Other diseases show evidence of being affected by stress. The frequency and duration of genital herpes flare-ups can be reduced by stress control procedures such as Herpes illustration removed for your protection. relaxation. There is no evidence that stressful life experiences cause cancer, however there is a fair bit of evidence that stress increases the rate of cancer progression and mortality. – This is difficult to study in humans, as research is typically retrospective, and simply having cancer may color your perception of past stressful experiences. Medical procedures themselves (surgery, etc.,) may be stressful. This danger must be balanced with possible benefits. – Then again, treatments with no known physiological mechanism may work simply by reducing stress (we call this the placebo effect.) Social factors Chronic social stress increases susceptibility to the common cold. – Social stress is one of the most potent stressors known. On the other hand, having more and better friends seems to reduce the Bullying is a form of social odds of getting sick. stress Positive social support seems to support the immune system. This may explain the success of “holistic” medical treatments that incorporate social support. Can Brain Disorders be Caused by Inflammation? PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) Anti-NMDA- receptor autoimmune encephalitis