Mic 205 Immune Disorders Ch 18 PDF
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Arizona State University
Patrick Daydif
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Summary
These lecture notes cover immunologic disorders, including hypersensitivity reactions, such as Type I (immediate), Type II (cytotoxic), and Type III (immune complex). It also introduces immunodeficiency diseases and discusses various testing methods for hypersensitivity.
Full Transcript
MIC 205 - Microbiology Lecture 16: “ Don’t look at me!! I am disgusting!” Ch. 18: Immunologic Disorders Lecturer: Patrick Daydif Office: UCENT 356 Phone: (602) 496-0599 Email: [email protected] Office Hours: Please refer to Canvas (or by appointment)...
MIC 205 - Microbiology Lecture 16: “ Don’t look at me!! I am disgusting!” Ch. 18: Immunologic Disorders Lecturer: Patrick Daydif Office: UCENT 356 Phone: (602) 496-0599 Email: [email protected] Office Hours: Please refer to Canvas (or by appointment) The best way to contact me and answer your questions is Face to Face. 1 Immunologic Disorders Results in an overreaction or under reaction of the immune response Over-reaction – Allergy & Autoimmune – Allergy: immune system reacts to an antigen it usually ignores and typically results in a hypersensitivity condition. – Any immune response against a foreign antigen exaggerated beyond the norm – Type I, Type II, Type III, Type IV Autoimmune: the immune system is reacting to “self” therefore, has lost the ability to distinguish self/non-self – Affecting: Blood cells, Endocrine organs, nervous & connective tissue, and other major organ systems. – Under reaction Immunodeficiency Diseases – No or little directed Immune response – Primary (at birth) or acquired immunodeficiency diseases 2 2 Type I (Immediate Hypersensitivity) Allergens: Pollen-hay fever, cats, bee stings, foods, drugs, ragweed, dust mites. Exposure to allergens will cause the release of inflammatory molecules. – histamine, kinins, proteases, leukotrienes, and prostaglandins Two step process (sensitization & degranulation) that is IgE-mediated. Immediate! Occurs in seconds to minutes. 3 3 1 Type I (Immediate Hypersensitivity) Sensitization Primary exposure to the allergen B cell activation will start the specific immune response. Plasma cells will produce an IgE response against the allergen (antigen). IgE bind to mast cells, basophil, or eosinophil. 4 4 Type I (Immediate Hypersensitivity) Degranulation – Subsequent exposure – Allergen binds IgE on mast cells, basophil or eosinophil – Release of histamines and other cytokines (degranulation) – Starts the inflammation response. Usually mild reaction (Localized) - Dependent on the portal of entry. - Reddening of skin, swelling, watery eyes, hives… - Small inhaled allergens may reachthe lungs and cause asthma 5 5 Type I (Immediate Hypersensitivity) Systemic Anaphylaxis (Anaphylactic Shock) – Starts localized then spreads systemic – Many mast cells may degranulate at once, releasing large amounts of histamine and inflammatory mediators. Drops blood pressure, violent contractions of the bronchial muscle. Airway constricted & fills with mucous Death within minutes Treatment – Prevention of Desensitization, so stay away from the allergen! – Mild reaction: Antihistamines, Corticosteroid, bronchodilator for asthma – Systemic Anaphylaxis: Immediate use ot Epinephrine 6 6 2 Testing for Type I (Hypersensitivity) ImmunoCAP specific IgE blood test. Diagnosis based on detection of high levels of IgE against specific allergen within the patient’s blood. Similar to an ELISA Diagnose using skin tests Immunotherapy can help prevent allergic reactions – Administer a series of injections of diluted allergen – Must be repeated every two to three years 7 7 Type II (Cytotoxic Hypersensitivity) Results when cells are destroyed (cytotoxic) by an immune response. – Combined activities of complement and antibodies (IgM and IgG). – Examples Destruction of blood cells following an incompatible blood transfusion. Destruction of fetal red blood cells in hemolytic disease of the newborn. Drug-induced – Penicillin Reaction This occurs as a component in many other autoimmune diseases. 8 8 Type II (Cytotoxic Hypersensitivity) Donor's blood group antigens may stimulate the production of antibodies in the recipient that binds to the transfused cells. Activates the complement system. Destruction of donated blood cells can occur in hours to days. Triggers blood clotting within vessels and circulatory failure 9 Hemolytic anemia 9 3 Type II (Cytotoxic Hypersensitivity) Hemolytic disease of the newborn – Rh antigen Common to red blood cells of humans & rhesus monkeys – About 85% of humans are Rh- positive (Rh+) – Rh– woman carrying an Rh+ fetus may be at risk for hemolytic disease. – RhoGAM is administered to prevent hemolytic disease of the newborn. 10 10 Type II (Cytotoxic Hypersensitivity) Drug-induced cytotoxic reactions – Penicillin and most drugs are too small to trigger immune responses. Drugs can become antigenic if bind to larger molecules. Penicillin binds to platelets, thus triggering an immune response. The complex triggers the humoral response and recruit complement to form MAC and lyses the cells. Inhibits the ability of the blood to clot due to a decrease in platelets. Agranulocytosis & Hemolytic anemia 11 11 Type III (Immune Complex–Mediated) Caused by the formation of immune complexes Some of the complexes are removed by phagocytes Other complexes will bind to blood vessel walls or be trapped in organs & joints. Inflammation response will cause tissue damage Can cause localized and Systemic reactions 12 12 4 Type III (Immune Complex–Mediated) Localized reactions – Hypersensitivity pneumonitis Inhalation of antigens into lungs stimulates antibody production Subsequent inhalation of the same antigen results in the formation of immune complexes and actives complement system. – Farmer’s lung-> Hay spores – Pigeon’s lung-> Dust from pigeon feces – Glomerulonephritis (glo·mer·u·lo·ne·phri·tis) Immune complexes in the blood are deposited in glomeruli (Kidneys) Damage to the glomerular cells impedes blood filtration 13 Kidney failure and, ultimately, death result 13 Type III (Immune Complex–Mediated) Systemic Reactions Rheumatoid arthritis Systemic Lupus Immune complexes deposited in – Antibodies bind to DNA to the joints result in the release of form immune complex formation inflammatory chemicals. – DNA- antibody complexes are Loss of the cartilage of the joint and deposited in the skin bone loss – Many other auto-antibodies can Treated with anti-inflammatory also occur drugs Symptoms: rash, light sensitivity, 0.5-1 percent of the U.S. adult joint pain, bleeding disorders, kidney population damage, neurological symptoms… 16,000 diagnosed/year (US) (90% women) Treatment: Immunosuppressive drugs & glucocorticoids 14 14 Type IV (Delayed or Cell-Mediated) Inflammation 12 to 24 hr after contact with certain antigens – Actions is due to antigen, antigen-presenting cells, and T cells – Delay reflects the time it takes for macrophages and T cells to migrate to and proliferate at the site of the antigen 3 Major Classes of reactions Turberculin Response Contact dermatitis – poison ivy – latex – soaps Graft rejection – Rejection of tissues or organs that have been transplanted 15 15 5 Type IV (Delayed or Cell-Mediated) Contact dermatitis – Cell-mediated immune response (T- cells) – Results in an intensely irritating skin rash – Triggered by chemically modified skin proteins that the body regards as foreign – Acellular, fluid-filled blisters develop in severe cases – Can be treated with glucocorticoids 16 16 Type IV (Delayed or Cell-Mediated) Tuberculin Response – An injection of tuberculin beneath the skin causes a reaction in an individual exposed to tuberculosis or tuberculosis vaccine. – Used to diagnose contact with antigens of M. tuberculosis If, No response when individual not infected or vaccinated If, Red, hard swelling (10mm) develops in individuals previously infected or immunized – 24- 72hr post-exposure – IM response is generated by memory T-cells 17 17 Type IV (Delayed or Cell-Mediated) Graft rejection – Rejection of tissues or organs that have been transplanted – Grafts perceived as foreign by a recipient undergo rejection due to difference in MHC I or II molecules – Immune response against foreign MHC on graft cells difficult because of a high degree of variability – Immunosuppressive drugs can stop graft-versus-host disease 18 18 6 Development of Autoimmune Diseases Loss of recognition of self vs. non-self (clonal deletion) – Result when an individual begins to make autoantibodies or cytotoxic T cells against normal body components Occur more often in the elderly – Immune exhaustion Are more common in women than in men – Differences in hormone levels between men and women Genetic and Environmental (Examples diseases) – Autoimmunity affecting endocrine organs Type I diabetes mellitus (juvenile) – T cells destroy insulin-secreting cells of the pancreas – Autoimmunity affecting nervous tissue Multiple sclerosis – T-cells destroy the Myelin sheaths that surround neurons – Autoimmunity affecting connective tissue – Rheumatoid arthritis – Autoimmunity affecting blood cells – Autoimmune hemolytic anemia 19 19 Immunodeficiency Diseases Primary (Inborn: genetic defects) – Agammaglobulemia B-cell deficiency Treated with mass doses of immune serum & antibiotics IgA deficiency is most common – DiGeorge Syndrome Due to the lack of a thymus gland T-cell deficiency – Viruses pose a greater threat Treat with thymic steam cells – Severe Combined Immunodeficiency (SCID) Deficiency or lack of T and B-cells Bubble boy Acquired – Infectious agents – like those that cause: leprosy, tuberculosis, AIDS – Immunosuppressants – damage T and/or B cells Chemotherapy/radiation therapy 20 20 AIDS Acquired Immunodeficiency Syndrome Caused by Human Immunodeficiency Virus (HIV) Target cells – T helpers and macrophages Death: opportunistic infections/cancers 21 21 7 AIDS Signs and Symptoms Less than 200 CD4+ T cells per cubic millimeter of blood, is when a AIDS diagnosis is given 22 22 Transmission of HIV Sexual (0.5 to 1.0 % transmission) – Majority of all HIV have been passed through unprotected sexual relations Transmission can occur when an infected individual comes in contact with the genital, oral, or rectal mucous membranes of a noninfected person. Blood products (90% transmission) – Blood present with HIV comes in contact with Break in the skin Open wounds IV drug use Blood/ plasma transfusions Organ transplants Tattoos and piercing – Mosquitoes No reports of transmission Mother to child ( 30% transmission) – The virus is transmitted to the child during pregnancy, at childbirth, and during breastfeeding at a rate of about 25% – Use of ARVs and C-sections can reduce this to about 1% 23 23 Testing for HIV The time between when a person gets HIV and when a test can accurately detect it is called the window period. The window period varies from person to person and also depends upon the type of HIV test. Some tests can detect HIV sooner than others. 24 24 8 People living with HIV/AIDS Worldwide: UNAIDS estimated that 36.7 million people are living with HIV as of 2021 – Of these, 36.7 million were adults and 1.7 million were children (