Immune Function and Stress PDF

Monday, March 4, 2024 IMMUNE FUNCTION AND STRESS What is the immune system? Immunity: The ability of the body to ght infection and/or foreign invaders by producing antibodies (lymphocytes) or killing infected cells (natural killer cells) Immune System: The system in the body responsible for maintain...

Monday, March 4, 2024 IMMUNE FUNCTION AND STRESS What is the immune system? Immunity: The ability of the body to ght infection and/or foreign invaders by producing antibodies (lymphocytes) or killing infected cells (natural killer cells) Immune System: The system in the body responsible for maintaining homeostasis by recognizing harmful from non-harmful organisms and produces an appropriate response Foreign Invaders Pathogens: Viruses, bacteria or other living thing that causes disease/immune response. Antigens: Toxins that pathogens produce that cause harm to an organism - When B- T- cells encounter them, they’ll destroy antigens - B cells create antibodies Memory cell: storage of antibodies created to fight off already exposed antigens - T cells have to recognize the antigens for B cells to recognize them Natural killer cells: lymphocytes with no specific memory (i.e.killing machines) - Non-specific IMMUNE SYSTEM 1. 2. 3. 4. Blood: White Blood Cells (Lymphocytes) in particular Lymph nodes Thymus Gland: Produces T Lymphocytes Bone Marrow: Produces B Lymphocytes FIRST LINE OF DEFENCE: THE SKIN - Purpose: provides Physical and Chemical barriers - Physical: hard to penetrate, made of indigestible keratin - Chemical: tears, sweat SECOND LINE OF DEFENCE: NON-SPECIFIC IMMUNE RESPONSE - These are defences the body uses no matter what the invader may be, including: Phagocytosis: done by Macrophages - Macrophage: A phagocytic cell found in the liver, spleen, brain and lungs. Travels to all areas of the body to find and eat pathogens, also releases cytokines fi 1 Monday, March 4, 2024 Travels to lymph nodes where meets T cells and activates B cells - Cytokines: cells that bind to other cells receptors to alert of pathogens around Natural Cell Killers Inflammation: caused by release of Histamine from leukocytes Fever: caused by histamines. The fever (high temp) kills invaders by denaturing their proteins THIRD LINE OF DEFENCE: SPECIFIC IMMUNE RESPONSE - This is a speci c response to a speci c pathogen/antigen. - The response involves the creation of Antibodies ANTIBODIES - Y-shaped protein molecule - Produced by B-Lymphocytes - Function: Recognize antigens, bind to and deactivate them. THE PATHWAY OF SPECIFIC IMMUNE RESPONSE Helper T cells helps B cell make antibodies fi fi 2 Monday, March 4, 2024 IMMUNE RESPONSE RE-EXPLAINED 1. 2. 3. 4. 5. 6. 7. 8. 9. Antigen infects cells Macrophage ingests antigen and displays portion of it on its surface. Helper T- Cell recognizes antigen on the surface of the macrophage and becomes active. Active Helper T-Cell activates Cytotoxic (killer) T-Cells and B-Cells. Cytotoxic T-Cells divide into Active Cytotoxic T-cells and Memory T-Cells. Active Cytotoxic T-Cells kill infected cells. At the same time, B-Cells divide into Plasma Cells and Memory B-Cells. Plasma cells produce antibodies that deactivate pathogen. Memory T and Memory B cells remain in the body to speed up the response if the same antigen reappears. 10. Suppressor T-Cells stop the immune response when all antigens have been destroyed. PRIMARY.VS. SECONDARY IMMUNE RESPONSE Primary Immune Response - This is a response to an invader the First time the invader infects the body. - No measurable immune response for first few days. - Next 10 – 15 days antibody production grows steadily Secondary Immune Response - A more rapid response to an invader the 2nd time it invades the body - Antibody production increases dramatically and in a much shorter time period 3 Monday, March 4, 2024 PASSIVE.VS. ACTIVE IMMUNITY Active Immunity - This is immunity where the body is “actively” producing antibodies to fight infection. Ex: You have a throat infection and you are actively creating antibodies to fight it. - Vaccination: An injection of a weakened strain of an infectious microbe (pathogen) that causes the body to undergo active immunity (produce antibodies). Passive Immunity - This is immunity where antibodies are given to a person from the blood of another person or animal - This immunity only lasts for a short period of time. ex: Breastfeeding mothers pass antibodies to their children through the milk. AUTOIMMUNE DISEASE Autoimmune disease: diseases where the immune system begins to attack itself - Rheumatoid Arthritis – crippling disease of the joints. - Lupus – disease of blood and organs. - Multiple Sclerosis – disease of nervous system ALLERGIES Allergy: An exaggerated response by the immune system to an allergen Allergen: a normally harmless substance that causes an allergic reaction - ex: dust, pollen, mould, food, insect stings Types of Allergic reactions There are two types of allergic reactions 1. Immediate – occurs within seconds and normally lasts for about 30 mins. 2. Delayed – takes longer to react and can last for a much longer time. What happens during an allergic reaction? During an allergic reaction antibodies cause histamines to be released from certain cells. Histamines cause: - Swelling of tissues - Release of fluids (runny noses and eyes) - muscle spasms (some cases) Anaphylaxis or anaphylactic shock: the sudden and severe allergic reaction to a substance that can cause death. 4 Monday, March 4, 2024 Treatments for Allergies - Avoidance of material – especially food. - Epinephrine – “epi – pen” - Antihistamines -- benadryl Interaction of all the systems Psychoneuroimmunolgy: Investigations of the bidirectional linkages between the CNS, the endocrine system and the immune system, and the clinical implications of these linkages 5 Monday, March 4, 2024 NORADRENALINE Noradrenergic fibers innervate immune organs (lymph node, thymus, spleen, bone marrow) Release NE in close proximity to immune cells (greater density in T cell areas) Leukocytes express a and b adrenergic receptors NE and E can influence leukocyte activity e.g., macrophage production of TNFa NE and E can Alter Lymphocytes - Immediate exposure (30 min) ! increase in # of lymphocytes, natural killer cells - Longer exposure (days) ! decrease in # of natural killer cells NE can alter innate and adaptive immune function in organs and in circulation - “Fine tunes” immune responses, allowing for quick adjustments (within minutes) - Shift from Th1 to Th2 CORTISOL Cortisol has the effect of - inhibiting lymphocyte proliferation - inhibiting production of proinflammatory cytokines - Shift from Th1 to Th2 cell 6 Monday, March 4, 2024 Immune response to stress Exposure to Acute Stressor Immune System Response min to hrs post stressor onset - Redistribution of immune cells (increase in leukocytes in blood) - Increase in innate, non-specific immunity (increased NK cell activity) - (Decrease in specific immunity) Exposure to Short-term Stressors Alterations in Speci c Immunity days or weeks post stressor onset - Decrease in Th1 cellular immune response (e.g., proliferative response of lymphocytes) - Increase in Th2 humoral immunity (e.g., Th2 cytokine production) Exposure to Chronic Stressors Alterations in Non-speci c and Speci c Immunity months to years post stressor onset - Decrease in both Th1 cellular and Th2 humoral immune response - Decrease in innate, non-specific immune responses (except inflammatory activity) - Persistent inflammatory activity (e.g., increased pro-inflammatory cytokine production) INDIVIDUAL DIFFERENCES AND THE IMMUNE SYSTEM WHEN UNDER STRESS - Age Disease Status Gender Personality Emotions Coping strategies PRENATAL EXPOSURE TO STRESS AND IMMUNE FUNCTION - Diminished cytokine response of leukocytes in rhesus monkeys Altered lymphocyte count in male mice and adrenal hypertrophy was observed in female mice. As compared to females, NK cytotoxicity was lower in male mice Female rats had suppressed proliferation of B-cells where male rats had decrease NK cytotoxicity Stress and effects on the aging immune system Study — Stress and effects on the aging immune system Results: Stress = ✓ Mimics ✓ Intensifies fi fi fi 7 Monday, March 4, 2024 ✓ Accelerates ✓ Changes in functionality of cells ✓ Decrease telomere function and length Study — Intensi ed Effects of Aging on Immune System Age and Chronic Stress Interacting to Predict Responses to Influenza Vaccine Results: ✓ Caregivers and well matched controls ✓ Found main effect of stress ✓ Heightened deficits in older participants Study — Accelerated Effects of Aging on Immune System ✓ Stress may accelerate the effects of aging on inflammation ✓ Average caregiver experienced a 4 time increase in IL-6 ✓ Among those caregivers, participants who were older than 75 had levels of IL-6 that made him/her at risk for disease ✓ Average non-caregiver participant would not reach this until the age of 90 POSSIBLE PROBLEMS RELATED TO IMMUNE DYSFUNCTION - HIV/Aids Cancer Cold flu Herpes Recovery injury (wound healing) Infection Cancer and Stress Studies in humans inconsistent - Cancer not homogenous disease Many other risk factors e.g. family history, aging. - Recent animal models postulate that chronic stress can disregulate DNA repair and regulation of cell growth, processes that have been shown to be major factors in tumor formation - Suppression of immune system may lead to increase of virus associated cancers e.g Karposi's sarcoma GROWTH, SPREAD AND RECOVERY - Recent animal models have also found that chronic stress seems to promote tumor growth and angiogenesis - Suppressing effect of chronic stress on the immune system also impacts the recovery period after surgery fi 8 Monday, March 4, 2024 - More support of strong interaction between chronic stress and cancer growth than between chronic stress and cancer development in humans. Study — Reoccurring Upper Respiratory Tract Infection (URTI) and Stress in Children Participants: Children with 10+ recurring URTI in the past (experimental) Measures: psychological assessment and sIgA measurements Results: Children with rURTI reported more stressful life events in the past year ✓ 82% of the ill children ✓ 29% of the healthy children Association between incidence of URTI and low local levels of slgA Children who experience recurring colds reported greater life event stress Greater depression, anxiety, and stress-prone personality (neurotic, less assertive, and introverted) ✓ Do not establish direction of association (which causes which) Healthier children have higher response (higher concentration of sIgA and albumin) vs sicker children ✓ Higher E, less N, less A, less D Common Cold and Stress Study — Common cold and stress Participants: 40% of participants were infected with a cold Results: Participants who were exposed to chronic stressors had a greater chance of developing a cold Age positive association with incidence of cold Study — Duration of Chronic Stressors and Risk of Developing a Cold Results: Positive correlation between the duration of stressors and the susceptibility of becoming infected with a cold As duration of stressors increased, the risk for developing a cold increased as well Study — Type of Chronic Stressors and Risk of Developing a Cold Stressors related to either work or interpersonal problems associated with a greater risk of developing a cold compared to those participants who did not have any chronic stressors Chronic stress interacts with other factors that diminish the immune system (smoking, exercise, etc.) Study — Personality, Social Network and the Risk of Developing a Cold Results: Personality didn’t have an effect Social group didn’t have an effect 9 Monday, March 4, 2024 Only chronicity had an effect Wound healing and Stress Study — Pain and Wound Healing in Surgical Patients Participants: Women aged 21-48 with gastric bypass Hypothesis: patients with more pain post surgery would heal more slowly ¨Why might pain influence wound healing? ✓ Neuroendocrine and immune function are relevant to wound repair ✓ The immune system plays a key role in the early wound repair process ✓ If immune system less efficient = slower healing Results: the hypothesis was correct: ✓ patients who reported higher pain during 28 days postsurgery experienced slower healing ✓ on day 25, the patients who ranked less pain, were 25% away from being fully healed ✓ patients who ranked greater than an 8 were still about 75% away from being fully healed Study — Enhanced Wound Healing After Emotional Disclosure Intervention Participants: Men (longitudinal) that write about a traumatic event (vs time management) Measures: self report questionnaires Results: Participants who wrote about traumatic events had significantly smaller wounds 14 and 21 days after the biopsy compared with those who wrote about time management ✓ People with therapeutic way to deal with stress give immune system a boost = healing faster Study — Stress, Cortisol Levels, and Wound Healing Low levels of cytokines at site of wound were found in participants with high levels of cortisol (= stress) Slower healing group showed higher stress levels, lower optimism and higher cortisol compared to faster healing 10