The Immune System PDF

The Immune System Max Riveros Annemay Lelis  ▪ Three Broad Groups ▪ Innate – Monocytes, neutrophils, eosinophils, basophils, mast cells and natural killer cells ▪ Adaptive – B and T cells (Helper T cells and...

The Immune System Max Riveros Annemay Lelis  ▪ Three Broad Groups ▪ Innate – Monocytes, neutrophils, eosinophils, basophils, mast cells and natural killer cells ▪ Adaptive – B and T cells (Helper T cells and cytotoxic T cells) or lymphocytes ▪ Combination Cells of the ▪ Macrophages and dentritic cells Immune System  ▪ Innate ▪ First line of defense ▪ Molecular and cellular defense mechanisms that are present prior to exposure ▪ Limit the spread of infection and, in some cases, eliminate the invading pathogen, mediate the initiation and Innate vs. development of adaptive immunity that is pathogen- specific and work in concert with adaptive immune Adaptive responses Immunity ▪ Does not remember the interaction with a specific invader for help during potential future encounters  ▪ Adaptive Immunity ▪ Specificity and memory ▪ Goal is to specifically recognize the threat, promote an effective immune response, destroy/remove the invading pathogen, and establish long-term memory ▪ Requires preactivation (days to weeks for a full effect) ▪ Results when a pathogen gains entry into the body and a Specific specific response is elicited against the invader Immune System ▪ Is activated if a threat is present at a high enough level for a prolonged period of time (activation threshold) ▪ If the threat is encountered again, the body responds more rapidly  Protection acquired by introduction (either naturally from environmental exposure or artificially by vaccination) of an antigen (any molecule that binds specifically to an antibody or T-cell receptor) into a responsive host Active Immunity Deliberate exposure to a harmless version or component of a pathogen generates immunologic memory but not disease induced by the infectious agent itself  ▪ Antigens ▪ Bacteria, viruses, parasites, foreign tissues, and large proteins possess constituents that are defined as antigenic because they can interact specifically with antigen receptors in our body ▪ Antibodies ▪ Produced by B cells and consist of two identical heavy (H) Antigens and chains and two identical light (L) chains Antibodies ▪ The heavy chain possesses four or five immunoglobulin domains Immunoglobulins (Ig)  Cell-Mediated Immunity Protects the host against infection by intracellular pathogens T cells destroy microbes that are able to survive in the cytoplasm or phagocytic vesicles of infected cells Sometimes be harmful to the host, as they are responsible for the rejection of transplanted tissue and certain autoimmune diseases  ▪ Positive Selection - to ensure that the T cell can identify peptides restricted by the MHC of the host ▪ Negative Selection - delete cells that recognize “self” peptides of the host ▪ Immunologic Tolerance - the immune system is Selection and rendered nonreactive to self Immunologic ▪ Autoimmune Disorders - Failure of negative selection will lead to autoimmune disease in which T cells Tolerance recognize and react against “self” antigens presented by “self” major histocompatibility complex (MHC)  The principal function of the immune system is to eliminate infectious agents and abnormal “self” components (e.g., cancer cells) without attacking the body’s own tissues The immune system must maintain a state of balance such that when an external or internal Key Points threat is encountered, an appropriate response is generated to control the invader, and the system returns to equilibrium Most pathogens are encountered after they are inhaled or ingested  Phases of the Immune Response Recognition phase – innate immune receptors Amplification phase – Effector Phase – bind to the invader. Production of soluble Removal of antigens Adaptive immune factors and recruitment (phagocytosis, lysis, recognition involves of cells neutralization) highly specific antigens Termination phase – Memory – T and B dampens the immune lymphocytes have lower system after clearance of threshold for activation antigen: Major key and react more quickly  Factors Affecting Immunity ▪ Nutrition ▪ Reduction of gut bacteria after antibiotics ▪ Deficits in calories/protein intake and vitamins can depress T and B cell function ▪ Zinc deficiencies are associated with malabsorption syndrome ▪ Burns ▪ Decreased intact skin – decreased external defense  ▪ Exercise can regulate the ability of the immune system to initiate a response against pathogens ▪ Depending on the intensity, activity or exercise can enhance or suppress immune function ▪ Enhanced during moderate exercise, and impaired during strenuous/intense/long duration exercise Exercise and the (marathons) ▪ Intense exercise can suppress the concentration of Immune System lymphocytes, suppress NK cell activity ▪ Lead to deleterious oxidation of cellular macromolecules  NK Cells – enhancement with exercise until person is accustomed to the exercise level (response to physiologic stress, not exercise) After intense and long duration exericse, the concentration of NK Effects on cells and NK cytolytic activity declines below preexercise values May be a cumulative adverse effect in athletes who induce these changes several times per week Components of Inflammatory Response - moderate exercise as well as resistance training and long-lasting endurance Immunity exercise is known to induce proinflammatory cytokines Due to increased cardiac output and increased serum epinephrine Strenuous or high-intensity exercise, defined as exercising at a minimum of 80% of maximal oxygen consumption (VO 2max), can suppress immune function and damage enough tissue to evoke the acute-phase response in human beings  ▪ Aging - associated with a decline in the normal functioning of the immune system that is described by the term immunosenescence ▪ Exercise - Habitual exercise is capable of regulating the immune system and delaying the onset of immunosenescence Exercise, Aging, ▪ Apoptosis - Some exercise conditions have been shown to delay apoptosis and Apoptosis ▪ Failure to activate this genetically regulated cell death may result in cancer and certain viral infections ▪ Exercise may delay apoptosis, but exercise-induced apoptosis is a normal regulatory process that removes certain damaged cells without a pronounced inflammatory response, thereby ensuring optimal body function  ▪ Intense exercise has no detrimental effect on immune function or rate of infections in older adults ▪ Could maximize cardiopulmonary and musculoskeletal function without impairing immune function in frail, elderly people ▪ Intense exercise during an infectious episode should Older be avoided Population ▪ If the symptoms are located above the neck, such as a stuffy or runny nose, sneezing, or a scratchy throat, exercise should be performed cautiously through the scheduled workout at half speed  ▪ Immunodeficiency diseases- HIV/AIDS Disorders of ▪ Chronic fatigue syndrome the immune ▪ Hypersensitivity disorders- Type I to Type IV system Hypersensitivity ▪ Autoimmune disorders- SLE, Fibromyalgia Primary CAUSED BY: genetic defect, either innate host or adaptive immunity Complement proteins or Phagocytes Susceptible to recurrent infections Starts in childhood Immunodeficiency Secondary Disorders Most common CAUSED BY: Infection, aging, malnutrition, chemotherapy, immunosuppression AIDS HIV Prevalence in 2019 1.18 Million Did NOT know they were infected  New HIV diagnosis by Race/Ethnicity, 2019 New HIV diagnosis by subpopulation, 2019 Why is this the case?  Pathogenesis & Clinical manifestations CD4 count 200-500 cells/mm3 1-6 wks post exposure, flu- Generalized adenopathy, nausea, like symptoms diarrhea, fever, or neurological symptoms Asymptomatic Acute HIV Virus HIV retrovirus disease: Symptomatic syndrome: No continues to A variety of Advanced HIV Development infects T4 Infection HIV disease & HIV infect clinical signs disease or of (helper) settles in immune antibodies lymphocytes & symptoms AIDS, elevated opportunistic lymphocytes lymphoid system is detected (1-3 as CD4 cells develops viral load infections or CD4+ cells tissue (ie. compromised wks) are depleted Lymph node) CD4 count < 200 cells/mm3 CD4 count > 500 cells/mm3 Wasting, dementia, opportunistic 1-20 yrs infection (CMV, pneumonia, kaposi Clinically healthy, some fatigue sarcoma) Myalgia/arthralgia Dyspnea Flu-like CMV RA manifestation Hypoxia symptoms Fever, sore throat Bacterial pneumonia Avascular necrosis (infections) Generalized adenopathy TB Pelvic pain Cardiomyopathy Weight loss Viral or fungal infections Delayed healing Endocarditis Lethargy, Fatigue Vaginal infections Pain syndrome Nonproductive cough Fevers, night sweats MSK Cardiopulm Constitutional Opportunistic Neuro Integ Malignancy Other Encephalitis: gait, Alopecia AIDS related lymphoma Lipodystrophy syndrome tremors, delayed reflexes Rash Kaposi sarcoma Lymphedema Dementia: memory, Delayed wound healing Cervical cancer Renal/Liver failure behavioral Visual disturbances Radiculopathy HIV-related psychiatric Peripheral neuropathy disorder Oral thrush  Prevention is KEY! Routine screening ages 13-64 yrs. Diagnosis Presence of antibodies Test to differentiate between HIV-1 and HIV-2 Medical Treatment Management Not a cure, goal to prolong life Prevent advancing to AIDS Reduce risk of transmissibility Meds Antiretroviral therapy (HAART) HIV vaccines (not FDA approved) Postexposure prophylaxis (PEP) Pre-exposure prophylaxis (PrEP)  ▪ Guidelines for healthcare workers (HCWs) ▪ Occupational exposure must be reported ▪ Take 28-day course HAART ▪ Law & policy for HIV-positive HCWs Implications for ▪ Can we treat patients with HIV or AIDS? Yes. But we don’t do it as much, especially outpatient therapists ▪ What can we treat? ▪ Any exercise precautions? Depending on where they are in stage. Asymptomatic: can do whatever. Advance stage: be mindful of fatigue and opportunistic infections  ▪ Inaccurate immune response attributed to overexpression to a substance (hypersensitivity reactions) ▪ Leads to reacting to the host's own cells, transfusion/transplant reactions, or immunodeficiency ▪ Implications for therapists: Hypersensitivity ▪ Emergency action for Type I reaction or anaphylaxis ▪ US gels or creams can cause delayed reaction, use a test Disorders patch (Box 7.5 & 7.6) ▪ Type I-IV ▪ I: IgE mediated: Allergy to peanuts, Emergency! ▪ II: Tissue-specific: Organ specific ▪ III: Immune complex: SLE ▪ IV: cell-mediated: T-cell involvement, allergic reaction to jewelry, creams.  Unexplained fatigue > 6 mos. Multisystem disease commonly characterized by severe fatigue, cognitive Overview dysfunction, sleep problems, autonomic dysfunction as well as post-exertional malaise Affects 2.3 Americans, but 90% are not diagnosed Epidemiology Females, between 29 to 35 y/o Alterations in immune system response on encountered antigens leading to Pathogenesis abnormalities of the neuroendocrine system. Most report infections as a trigger. Starts with flu-like symptoms, then post-exertional fatigue associated with Clinical manifestations multisystem disease (forgetfulness, sleep disorders, hypotension, nausea) Medical management No cure. Lifestyle changes Patients have reduced exercise capacity. Implications for Any precautions? What will be your focus? Start them out slow. Overdoing it will therapists cause more fatigue Chronic Fatigue Syndrome (Myalgic encephalitis)  Autoimmune Diseases ▪ Body unable to distinguish self from non-self, causing immune system to attack normal (self) tissue. ▪ This is a spectrum of disorders ▪ Etiology: combination of factors including genetic, hormonal, environment stressors/triggers  Multisystem autoimmune disorder with a broad spectrum of clinical presentations Overview encompassing almost all organs and tissues 90% are women of childbearing years Epidemiology More common in African American and Latin women compared to Caucasians Evidence of interrelated immunologic environmental, hormonal, genetic factors Pathogenesis Strong familial link, 1st degree relatives. Clinical manifestations No two people will have identical symptoms Control the disease activity, prevent damage from disease, prevent flare-ups. Medical management Pharmacology: Corticosteroids, NSAIDs Activity modification, incorporation of rest periods. Progress gradually. Energy Implications for therapists conservation. Improve strength & endurance while avoiding undue stress on inflamed joints. Systemic Lupus Erythematosus (SLE) Mechanisms: 1. Autoantibody production (against RBCs, neutrophils, or any organ tissue) 2. Vascular abnormalities (accelerated atherosclerosis) 3. Inflammatory mediators  ▪ Arthritis: No pattern. Joints of wrists, hands, knees. Usually not destructive to bones ▪ Cardiopulmonary: Myocarditis, endocarditis, tachycardia, thrombosis ▪ Neuropsychiatric manifestations: Irritability, depression, emotional instability, Stroke ▪ Anemia ▪ Amenorrhea Fanouriakis A, Tziolos N, Bertsias G, et al. Update οn the diagnosis and management of systemic lupus erythematosus. Annals of the Rheumatic Diseases 2021;80:14-25.  Chronic widespread pain with allodynia or hyperalgesia to pressure pain Disorder of pain processing. Overview Systemic disorder, involves biochemical, neuroendocrine, and physiologic abnormalities Pain elicits an autonomic response (nausea, vomiting, increased BP/HR. 6 million Americans Epidemiology 90% are women between ages 20 – 55 years old. Prolonged anxiety and emotional stress, trauma, rapid steroid withdrawal, infections. Risk Factors More prevalent in minimally to moderately physically fit persons Fibromyalgia  Pathogenesis ANS dysfunction: NS ability to return to normally takes more time. Disruption of digestive system, sleep disturbance Immune system dysfunction: Activation of glial cells, causes prolonged release of proinflammatory cytokines, creating an exaggerated pain state.  Clinical Manifestation ▪ Muscle pain ▪ Sleep disturbance causes fatigue and exhaustion ▪ Aerobically fit people report fewer symptoms ▪ Impaired breathing mechanics ▪ Muscular activity is high with basic activities or even at rest  Implications for therapists Based on pathogenesis and clinical manifestation...... Who should be involved in their care? everybody How will you approach the person? Do not ruminate on pain. Ask them what they can do today How will you approach exercise? gradually