Lecture 8 Diseases of the Immune System PDF

1/2567 MTH64-203E Asst. Prof. Rachasak Boonhok, [email protected] School of Allied Health Sciences, Walailak University 3  Outline Overview of immune Disease of the immune system system Terminolog...

1/2567 MTH64-203E Asst. Prof. Rachasak Boonhok, [email protected] School of Allied Health Sciences, Walailak University 3  Outline Overview of immune Disease of the immune system system Terminology Hypersensitivity (Type I, How the immune II, III, IV) system works Autoimmune diseases Transplantation Immunodeficiency (Primary and Secondary) 4 01 02 03 Define terminology Understand structure Give an example of and type of of immune system immunological immunity and concept of how disorders and briefly immune system explain their works mechanism Learning objectives Part 1: Terminology Overview How the immune system of immune works system 6 Terminology Immunology A study of the immune system which is an important branch of the medical and biological sciences. The immune system protects us from infection through various lines of defense. If the immune system is not functioning as it should, it can result in diseases, such as infection, autoimmunity, allergy, and cancer. It is also now becoming clear that immune responses contribute to the development of many common disorders not traditionally viewed as immunologic, including metabolic, cardiovascular, and neurodegenerative conditions such as Alzheimer’s. 7  Terminology Immune system A complex system of cellular and molecular components whose primary function is distinguishing self from non-self and defense against foreign organisms or substances Immune response Collective and coordinated response against foreign organisms or substances 88  Immune system: Type of immune system Divided into 2 parts determined by the speed and specificity of the reaction; Action is taken by the body to defend itself from pathogens or abnormalities called “immune response” Nature Reviews Cancer, 4, 11-22, 2004 https://www.paediatricfoam.com/2020/09/immunodeficiency/ 9  Overview of human immune defenses 10 https://www.enzolifesciences.com/science-center/technotes/2021/may/tools-to-study-adaptive-and-innate-immune-response/  Barrier defenses of human body Physical/anatomical barriers Skin, hair Mucous membranes Chemical barriers Sweat/secretions (low pH) Mucus, tears, saliva, breastmilk (immunoglobulin, lysozyme-antimicrobial activity) Semen (zinc and defensins) Biological barriers Normal flora (non-pathogen) https://letstalkscience.ca/educational-resources/stem-in-context/immune-response 1111 Immune system Components of immune system 1. Organs and tissues 2. Immune cells 3. Humoral substances: including secreted antibodies, complement proteins, and certain antimicrobial peptides Immune functions Defense Homeostasis www.healthyandnaturalworld.com Surveillance 1212  Immune system 1. Organs and tissues Bone marrow Thymus Spleen Lymph node Liver Mucosal associated lymphoid tissue Cutaneous associated lymphoid tissue https://courses.lumenlearning.com/ap2/chapter/anatomy-of-the-lymphatic-and-immune-systems/ 1313  Immune system 2. Immune cells Myeloid lineage Granulocytes Monocyte/macrophage Dendritic cells Lymphoid lineage T lymphocytes B lymphocytes Torang et al. BMC Bioinformatics 2019 Natural killer (NK) cells 14  Immune system 3. Humoral substances Antibody Complement system Cytokines Acute phase proteins etc. *https://www.news-medical.net/life-sciences/Types-of-Antibodies.aspx https://en.wikipedia.org/wiki/Cytokine https://theconversation.com/antibody www.bio-rad-antibodies.com 15  Key concept of immune system 1. The chief function of the immune system is to distinguish between “self” and “non-self”. https://ib.bioninja.com.au/ 1616  Key concept of immune system 2. The immune system consists of 2 overlapping compartments i.e. innate immunity and adaptive immunity. 1717 https://sphweb.bumc.bu.edu/  Key concept of immune system 3. Immune cells recognize antigens by immune cell receptors (antigen-specific receptor). : Innate immune cells : Adaptive immune cells T cell receptor (TCR) B cell receptor (BCR) Antibody 1818 David M. Arana, et al. Microbial Biotechnology (2009) 2(3), 308–320 Nicholas Manolios, et al. Cell Adhesion & Migration 4:2, 273-283 2010  Key concept of immune system 4. The immune system is tightly regulated. Eliminate of self-reactive cells during their development process by apoptosis. Permanent inactivation of self-reactive cells through a process called “clonal anergy”. Inhibition of self-reactive cells by regulatory or suppressor T cells and inhibitory cytokines. 19 How the immune system works 20 Summary of immune system Antigens Host Innate immunity Adaptive immunity Failure Success Failure Decrease activity Prevention and Overreacting to self control infection Hypersensitivity Autoimmunity 2121  1. Hypersensitivity (Type I, II, III, IV) 2. Autoimmune diseases 3. Transplantation Part 2: 4. Immunodeficiency (Primary and Disease of Secondary) the immune Defect of immune components in terms of system Function Amount Etiology is different depending on the disease and some are unknown. 22  Hypersensitivity Hypersensitivity as an immunological dysfunction is defined as exaggerated or inappropriate response of the immune system, which is mostly targeted at innocuous antigens with consequent tissue damage. 23  Hypersensitivity: Type I (IgE) A pathologic immune reaction to non- infectious antigens mediated by IgE. It is the basis for allergy and atopy. The allergens that result in a type I hypersensitivity may be harmless (i.e., pollen, mites, or foods, drugs, etc.) or more hazardous such as insect venoms. 24  Hypersensitivity: Type I (IgE) Clinical manifestations Nasal allergic rhinitis or hay fever Ocular allergic conjunctivitis, potentially due to seasonal allergens such as pollen or mold spores Dermatological hives, atopic eczema, or erythema Soft tissue angioedema Pulmonary reactions, such as allergic asthma or hypoxia Systemic reaction, which is a life-threatening medical emergency, and also known as anaphylaxis. https://www.dreamstime.com/stock-illustration-allergy-infographic-allergies-also-known-as-allergic-diseases-medical-set-elements-symbols-your-design-image66739088 25 Example of type I hypersensitivity :Anaphylaxis 26  Hypersensitivity: Type II (IgG, IgM) A pathologic immune reaction to non-infectious antigens mediated by IgG and IgM, which recruit complement or cytotoxic cells. It underlies blood transfusion reactions, Rh factor responses, and some hemolytic anemias. 27  Mechanism of type II hypersensitivity :Antibody-mediated complement activation *https://www.creative-diagnostics.com/complement-system.htm 28  Mechanism of type II hypersensitivity :Antibody-dependent cell-mediated cytotoxicity (ADCC) Mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell. NK cells is typically interacted with IgG. Macrophages, neutrophils and eosinophils can also mediate ADCC. 29 https://step1.medbullets.com/immunology/105048/antibody-dependent-cell-mediated-cytotoxicity-adcc  Example of type II hypersensitivity 1) Blood transfusion reaction Blood transfusion is the most common therapeutic procedure performed in hospitalized patients. However, ~1% of transfused products result in serious adverse reactions. Mechanism: host antibodies react with foreign antigens on the incompatible transfused blood cells and mediate destruction of these cells. Antibody can mediate cell destruction by activating the complement system to create pores in the membrane of the foreign cell and mediate cell destruction by ADCC. 3030 https://www.nih.gov/news-events/nih-research-matters/storing-blood-transfusion Example of type II hypersensitivity 1) Blood transfusion reaction 31  Example of type II hypersensitivity 2) Hemolytic disease of fetus and newborn (HDFN) HDFN occurs when the immune system of the mother sees a baby's RBCs as foreign. 32 https://askhematologist.com/hemolytic-disease-newborn/  Example of type II hypersensitivity 3) Drug-induced immune hemolytic anemia Blood disorder that occurs when a medicine triggers the body's defense (immune) system to attack its own red blood cells. This causes red blood cells to break down earlier than normal, a process called hemolysis. 33 *https://ykhoa.org/d/image.htm?imageKey=HEME/105902 Example of type II hypersensitivity 3) Drug-induced immune hemolytic anemia 34 *https://nurseslabs.com/anemia/  Example of type II hypersensitivity 4) Autoimmune Thyroiditis Immune system attacks your thyroid The thyroid gland is part of your endocrine system (produces hormones that coordinate many of your body's function, ex. the body's metabolic rate controlling heart, muscle and digestive function, brain development and bone maintenance. a. Hashimoto’s thyroiditis: involves the formation of anti-thyroid antibodies that attack the thyroid tissue, causing cell death and progressive fibrosis. b. Grave’s disease: circulating autoantibodies (Thyroid-stimulating immunoglobulins or TSIs) bind to and activate thyrotropin receptors, causing the thyroid gland to grow and the thyroid follicles to increase synthesis of thyroid hormone. 35  Facial swelling, hair loss, goiter, weight gain, Increased hunger, weight loss, excessive depression, etc. sweating, disturbed sleep, etc. 36 *Giorgio Stassi and Ruggero De Maria. Autoimmune thyroid disease: New models of cell death in autoimmunity. Nature Review Immunology 2002.  Example of type II hypersensitivity 5) Myasthenia Gravis Autoimmune disease of the neuromuscular junction (NMJ) caused by antibodies that attack components of the postsynaptic membrane. This impairs neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. *William D. Phillips and Angela Vincent. Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms. F1000Res. 2016 37 *www.thaihealth.or.th/blog/myblog/topic/1114  Example of type II hypersensitivity 6) Rheumatic fever (RF) Caused by the gram-positive bacteria Streptococcus pyogenes that follows a nontreated throat infection in susceptible children. The disease manifests as polyarthritis, carditis (most serious complication), chorea, erythema marginatum, and/or subcutaneous nodules. (RHD), progressive and permanent valvular lesions. *Historical aspects of rheumatic fever. https://doi.org/10.1111/jpc.12808 *Luiza Guilherme and Jorge Kalil. Rheumatic fever and rheumatic heart disease: cellular mechanisms leading autoimmune 38 reactivity and disease. J Clin Immunol. 2010  Hypersensitivity: Type III (Ag-Ab immune complex) A pathologic immune reaction to non- infectious antigens mediated by antibody- antigen immune complexes. It underlies damage associated with several disorders, including rheumatoid arthritis and systemic lupus erythematosus. 39  Example of type III hypersensitivity 1) Hypersensitivity vasculitis An extreme reaction to a drug, infection, or foreign substance. It leads to inflammation and damage to blood vessels, mainly in the skin. *https://www.slideshare.net/ariyantoharsono/serum-sickness-22519087 40  Example of type III hypersensitivity 2) Serum sickness An immune-mediated hypersensitivity reaction due to the injection of serum (nonhuman sources — usually animals) or drug that is characterized by rash, arthritis, and fever and commonly associated with other systemic features. One of the most common types of A diffuse rash on the back of a medication that causes serum sickness is Caucasian male. (License: Public Domain) antivenom. This is given to people who’ve been bitten by a venomous snake. 41 *https://www.lecturio.com/magazine/pediatric-serum-sickness-symptoms-and-treatment/  Example of type III hypersensitivity 3) Rheumatoid Arthritis (RA) An autoimmune and inflammatory disease that immune system attacks healthy cells in body by mistake, causing inflammation (painful swelling) in the affected parts of the body. RA mainly attacks the joints, usually many joints at once (hands, wrists, and knees). The lining of the joint becomes inflamed, causing *https://medlineplus.gov/ency/article/000431.htm damage to joint tissue, causing long-lasting or chronic pain, unsteadiness (lack of balance), and deformity (misshapenness). *https://www.cdc.gov/arthritis/basics/rheumatoid-arthritis.html 42 *https://medlineplus.gov/ency/article/000431.htm  Example of type III hypersensitivity 4) Systemic Lupus Erythematosus (SLE) SLE is an autoimmune disease in which the immune system attacks its own tissues, causing widespread inflammation and tissue damage in the affected organs. Autoantibodies against tissue antigens ex. DNA, histones, RBC, leukocytes, platelets, clotting factors It can affect the joints, skin, brain, lungs, kidneys, and blood vessels. Antinuclear antibodies (ANA) Homogenous pattern Peripheral pattern 43 *http://www.cai.md.chula.ac.th/lesson/lesson4502/contents/systemic_sle.html  Hypersensitivity: Type IV (T cells) Often called delayed type hypersensitivity as the reaction takes several days to develop. It involves Activated T cells, which release cytokines and chemokines Macrophages and cytotoxic CD8+ T cells that are attracted by these moieties. No antibodies involves Cell-mediated reaction that can occur in response to contact with certain allergens resulting in what is called contact dermatitis ex. Tuberculin test, allograft rejection. Play a major role in tissue damage observed during infections with slow- growing intracellular organisms, such as M. tuberculosis (tuberculosis). 44  Autoimmune diseases Occurs when the immune system attacks self-molecules as a result of a breakdown of immunologic tolerance to autoreactive immune cells. Many autoimmune disorders have been strongly associated with genetic, infectious, and/or environmental predisposing factors. Classification of autoimmune diseases A. Localised (organ specific) autoimmune diseases: mainly affect a single organ or tissue. Grave’s disease/Autoimmune Thyroiditis/Hashimoto's thyroiditis (thyroid) Myasthenia gravis (nerves, muscles) Diabetes Mellitis Type 1a (pancreas) B. Systemic autoimmune diseases: affect many body organs and tissues at the same time. Rheumatic fever (heart, joints, brain, skin) Rheumatoid arthritis (joints, less commonly lungs, skin, eyes) Systemic Lupus Erythematosus (skin, joints, kidneys, heart, brain, red blood cells, other) 45 *https://www.allergy.org.au/patients/autoimmunity/autoimmune-diseases  Transplantation Transplantation is the process of moving cells, tissues or organs from one site to another for the purpose of replacing or repairing damaged or diseased organs and tissues. Rejection is caused by the immune system identifying the transplant as foreign, triggering a response that will ultimately destroy the transplanted organ or tissue. To minimize the risk of rejection, donor and recipient are carefully matched prior to transplantation (based on their blood group and tissue typing). Immunosuppressive drugs are used to prevent and to treat transplant rejection by dampening the overall immune response. Non-specific Leave patients more susceptible to disease As well as being associated with numerous unwanted side effects. 46 *https://www.immunology.org/policy-and-public-affairs/briefings-and-position-statements/transplant-immunology  Transplantation *https://www.slideshare.net/EvithPereira/transplant-pathology 47  Example of transplantation reaction :Graft-versus-host disease (GVHD) GvHD happens when particular types of white blood cell (T cells) in the donated stem cells or bone marrow attack your own body cells. This is because the donated cells (the graft) see your body cells (the host) as foreign and attack them. There are two forms of GvHD: Acute graft versus host disease (aGvHD). Chronic graft versus host disease (cGvHD). https://www.aboutkidshealth.ca/article?contentid=1569&language=english “Autologous graft versus host disease (GvHD) involving the skin of a patient's arm appeared shortly after signs of engraftment appeared.” The patient had undergone autologous peripheral blood stem-cell transplantation to treat ovarian cancer. (Courtesy of Romeo A. Mandanas, MD, FACP) 48  Immunodeficiency Results from a failure or absence of elements of the immune system (lymphocytes, phagocytes, complement system, antibody, etc.) to defend itself against bacteria, viruses, and parasites: 2 types. 1. Primary immunodeficiency (PID) (genetic) Poor or absent function in one or more components of the immune system. Most PIDs result from inherited defects in immune system development and/or function 2. Secondary immunodeficiency (SID) (acquired) SID are the result of disease or other environmental factors weakening the immune system. SIDs are more common than PIDs and are the result of a primary illness, such as HIV, or other external factor such as malnutrition or some drug regimens. Most SIDs can be resolved by treating the primary condition. 49  Primary Immunodeficiency 5 4 1 3 2 50 https://www.paediatricfoam.com/2020/09/immunodeficiency/  Example of primary immunodeficiency 1) X-linked agammaglobulinemia (XLA) or Bruton agammaglobulinemia An inherited immunodeficiency disease caused by mutations in the gene coding for Bruton tyrosine kinase (BTK). BTK is critical to the maturation of pre–B cells to differentiating mature B lymphocytes. Very low levels of protective immune system proteins (Ig/Ab) which make you more likely to get infections. Common infections ex. Haemophilus influenzae, Streptococcus pneumoniae, and staphylococci at different sites ex. gastrointestinal tract, joints, lungs, skin, respiratory tract. 51  Example of primary immunodeficiency 2) IgA deficiency Most common primary immunodeficiency defined as decreased serum level of IgA (normal levels of other immunoglobulin isotypes). IgA is found in mucous membranes, especially in the respiratory and digestive tracts. It is also found in saliva, tears, and breastmilk. IgA deficiency is a genetic health problem that can be passed down through families. Most people with an IgA deficiency don’t have any symptoms. There is no cure for IgA deficiency. Immunotherapy does not work to treat it. Complications for IgA deficiency include asthma, diarrhea, ear and eye infections, autoimmune diseases, and pneumonia. You can limit the spread of germs and illnesses by washing your hands often and staying away from large crowds. 52 https://www.hopkinsmedicine.org/health/conditions-and-diseases/immunoglobulin-a-deficiency  Example of primary immunodeficiency 3) Digeorge syndrome DiGeorge syndrome is caused by a problem with a person's genes, called “22q11 deletion”. Decreased numbers of T cells. Cause a range of problems (poor development of several body systems). Most common issues are; Heart and speech problems Behavioral, learning, and mental health problems *https://www.pinterest.co.kr/amp/pin/345440233894541433/ DiGeorge syndrome has been reported to be associated with thymic hypoplasia (thymus underdeveloped) and thymic aplasia (absence of the thymus). 53 *Lisa C. Zuckerwise, et al., in Obstetric Imaging: Fetal Diagnosis and Care (Second Edition), 2018  Example of primary immunodeficiency 4) Severe combined immunodeficiency (SCID) Rare disease, fatal The most common way SCID is inherited is called X-linked recessive, passed on by the mother. Commonly known as "bubble boy disease”, is a defect in the specialized white blood cells (B- and T-cell) that defend us from infections. SCID patients are susceptible to recurrent infections ex. pneumonia, meningitis, etc. and can die before the first year of life. https://www.newbornscreening.info/scid-severe-combined-immunodeficiency/ https://www.bbc.com/news/world-us-canada-47969367 https://primaryimmune.org/story-david-vetter David Vetter, who came to be known *Genes and Disease. National Center for Biotechnology Information (US). Bethesda (MD): National Center for 54 in the 1970s as the bubble boy Biotechnology Information (US); 1998  Example of secondary immunodeficiency : Human immunodeficiency virus (HIV) infection The most common of chronic infections which can lead to SID disorders is acquired immune deficiency syndrome (AIDS), resulting from HIV infection. The virus attacks CD4+ T cells, a type of white blood cell that plays a critical role in preventing infection, and gradually depletes their numbers. Once the T cell count is less than 200 cells per ml of blood, symptoms of AIDS begin to manifest and the patient is at high risk of recurrent infections that will eventually lead to death. *Immune Response to HIV wallchart, Nature Reviews Immunology in partnership with STEMCELL Technologies 55 https://www.immunology.org/policy-and-public-affairs/briefings-and-position-statements/immunodeficiency  Clinical indicator diseases for adult HIV Respiratory Bacterial pneumonia, Aspergillosis Aseptic meningitis/encephalitis, Cerebral abscess Space occupying lesion of unknown cause Guillain-Barrà syndrome Neurological Transverse myelitis Dementia, Peripheral neuropathy Leukoencephalopathy Severe or recalcitrant seborrhoeic dermatitis Skin Severe or recalcitrant psoriasis Multidermatomal or recurrent herpes zoster infection Oral candidiasis, Oral hairy leukoplakia Chronic diarrhoea of unknown cause Gastrointestinal Weight loss of unknown cause Salmonella, Shigella or Campylobacter, Hepatitis B, C infection Malignant Anal cancer or anal intraepithelial dysplasia, Lung cancer, Hodgkin’s lymphoma Vaginal intraepithelial neoplasia Gynaecological Cervical intraepithelial neoplasia (histology grade 2 or above) Blood Any unexplained blood dyscrasia, including thrombocytopenia, neutropenia and Infective retinal diseases including herpes viruses and toxoplasma Eye Any unexplained retinopathy Lymphadenopathy of unknown cause Ear, nose and throat Chronic parotitis, Lymphoepithelial parotid cysts Mononucleosis-like syndrome (primary HIV infection) Other Any lymphadenopathy of unknown cause Any sexually transmitted infection 56 *HIV: pathology, diagnosis and prevention. Clinical Pharmacist, CP, July/August 2014, Vol 6, No 6;6(6):DOI:10.1211/PJ.2014.20065899  Q&A 57  In-class exercise (30min) Go to WU e-learning -> MTH64-203E 1/2567 Lecture8 Diseases of the immune system -> “In-class exercise” Submit your exercise in WU e-learning Discuss & Share 58  Posttest (15min) Go to WU e-learning -> MTH64-203E 1/2567 Lecture8 Diseases of the immune system -> “Posttest” Discuss & Share 59 HOMEWORK: Individual assignment 1/2567 Topic summary 1-2 pages DO NOT copy and paste from the lecture/other internet sources Submit in WU e-learning within 1 week 60  Abbas AK, Litchman AH, Pillai S. Cellular and Molecular immunology. 7th ed., Philadelphia: Saunder. 2012 Rajni Kumrah, et al. Genetics of severe combined immunodeficiency. Genes & Diseases (2020) 7, 52-61 Warren Levinson. Review of Medical Microbiology and Immunology. 13th ed., Philadelphia: McGraw-Hill education. 2012 Murphy K, Travers P, and Walport M. Janeway’s Immuno Biology. 7th ed., Garland Science, New York, 2008 Kindt, TJ, Goldsby, RA Osborne, BA. Kuby Immunology. 6th ed., W.H. Freeman and Company, New York, 2007 https://www.immunology.org/policy-and-public-affairs/briefings-and-position- statements/transplant-immunology 61