Unit 3 Study Guide: Chapter 13
Define the term allergen, discuss the mechanism by which they trigger an allergic response, and state what factors can impact the signs, symptoms, and severity of an allergic response.
An allergen is any antigen that triggers IgE production; antigens that do not noticeably affect nonallergic individuals. The allergen exposure called sensitizing exposure triggers the immune system to produce IgE. Plasma cells (activated B cells) release IgE which binds to the surface of mast cells or basophils (granulated leukocytes). In post-sensitization exposure, previously made IgE anchors to mast cells, the allergen binds to IgE antibodies, and induces degranulation causing the release of proinflammatory factors, triggering an allergic response. The signs, symptoms, and severity are affected by the route of exposure and level of IgE produced. Inhaled allergens will cause respiratory issue like coughing or swollen airways; ingested allergens can cause digestive distress, skin manifestation like hives, and respiratory distress. Portals of entry include inhalants, injectants, ingestants, and contactants. Injected allergens like bee stings can allow the allergen to enter the circulatory system which may provoke more severe reactions. The level of IgE produced also affects severity. The spectrum of inflammatory cytokines released by mast cells is directly related to signs and symptoms. -Prostaglandins can dilate blood vessel, constrict bronchioles, and cause headaches. -leukotrienes can constrict bronchioles, which can be deadly especially when combined with airway obstruction by mucus buildup. Leukotrienes are released in allergic asthmatic reactions. -histamine, serotonin, and bradykinin can cause dilated blood vessels and skin manifestations, increased peristalsis of intestine causing diarrhea or vomiting, and/or promoting secretory glands on epithelial tissues, causing runny or stuffed noses.
Define the term "autoimmune disorder" and provide examples of such disorders.
Autoimmune disorders are the chronic conditions that result from damaging self-tissue attacks from a lack of self-tolerance; more than 100 different autoimmune diseases have been described; autoantibodies, T cells, and in some cases both mount an abnormal attack against self-antigens; affect 5-8% of the population and 80% afflicted are women; can be systemic, involving several major organs, or organ-specific, involving only on organ or tissue. Examples: Respiratory: Wegener's granulomatosis, sarcoidosis, some forms of pulmonary fibrosis Neuromuscular: Multiple sclerosis, Guillain-Barre syndrome, Myasthenia gravis, Moersch-Woltmann syndrome, some forms of optic neuritis Connective tissue (bone, joints, and skin): some juvenile idiopathic arthritis, rheumatoid arthritis, ankylosing spondylitis, scleroderma, autoimmune psoriasis Kidneys: IgA nephropathy/Berger's disease, Goodpasture syndrome, glomerulonephritis, membranoproliferative glomerulonephritis (MPGN) Gastrointestinal and Pancreatic: Crohn's disease, ulcerative colitis, autoimmune hepatitis, celiac disease, primary biliary cirrhosis Systemic/Blood: systemic lupus erythematosus, autoimmune hemolytic anemia, Behcet's disease, antiphospholipid antibody syndrome (APS) Endocrine system: Graves' disease, Hashimoto's disease, Ord's thyroiditis, Type I diabetes mellitus, autoimmune pancreatitis
Explain how the ABO and Rh antigens impact blood type and determine if a transfusion is compatible or not.
Blood type refers to the presence of antigens on the surface of red blood cells. These antigens include -carbohydrates: A, B, O -protein: Rh (Rhesus) factor—indicated by a "+" Type O blood lacks A and B antigens and will not be agglutinated by other blood types, making it a universal donor. Type O blood lacks A and B antigens and has A and B antibodies; Type A blood as A antigens and B antibodies; type B blood has B antigens and type A antibodies. Type AB blood lacks agglutinating antibodies, making it a universal recipient. Incompatible transfused red blood cells cause a hemolytic transfusion reaction, which lyses red blood cells, could kill the patient, and for which there is no therapy, only supportive care to reduce kidney failure. Signs and symptoms include fever, chills, lower back pain, chest pain, tachycardia, and reduced blood pressure.
Discuss the different classes of transplants and define the term "immune-privileged site."
Classes of grafts: -autografts: transplants from self: no rejection will occur -isografts: transplanted tissue from identical twin; typically safe from immune rejection -allografts: similar to the host, but not genetically identical; closer MHC match, higher the chance the tissue will be tolerated -xenografts: interspecies transplants; reject Immune-privileged site: some tissues are immunologically privileged during embryonic growth; these tissues are least likely to be rejected (eye, brain, uterus, testicles).
Provide examples of autoimmune type III hypersensitivities.
Examples of AUTOIMMUNE type III hypersensitivities: -Systemic Lupus Erythematosus: autoantibodies against DNA, histones, ribosomes, and ribonucleoproteins; system (gastrointestinal, lung, kidney, and thyroid issues); often manifests with rash across cheeks and nose, fatigue, join pain, fever, and/or hair loss -rheumatoid arthritis: auto antibodies against rheumatoid factor (mainly in lining of joints); severe arthritis; mainly in wrists and hands; can cause bone erosion that deforms joints -Scleroderma: autoantibodies mainly against centromeres and topoisomerases (enzymes for DNA replication); attack on connective tissue; all organs may be affected; external manifestations includes hardened, thickened, and tightened skin -Sjogren's syndrome: autoantibodies against rheumatoid factor (with or without rheumatoid arthritis); antibodies to nuclear proteins; systemic; affects up to 4% of population; early signs include enlarged parotid gland, dry eyes and mouth; often develops with other autoimmune disorders, especially lupus -Poststreptococcal glomerulonephritis: antibodies against Streptococci cross-react with proteins in the kidney; may develop after untreated Streptococcus pyogenes infection; antibiotics make it rare in developed countries; usually resolves in weeks to months but may progress to renal failure.
Provide examples of autoimmune and nonautoimmune type IV hypersensitivities.
Examples of autoimmune type IV hypersensitivities: -Guillain-Barre syndrome: nervous system disorder where T cells attack nerves that regulate muscle contractions; results in loss of motor function or paralysis. -Hashimoto thyroiditis: T cell-mediated attacks on thyroid resulting in hypothyroidism -Type I diabetes: insulin-producing cells in the pancreas are destroyed resulting in loss of blood sugar regulation -Multiple sclerosis: myelin-producing cells are damaged; leads to compromised nerve signaling -Celiac disease: gluten consumption exposure causes T cells to attack the lining of the small intestine; leads to extreme inflammation and tissue damage; prevents absorption of essential vitamins and minerals from food Examples of nonautoimmune type IV hypersensitivities (most triggered by haptens): -Tuberculin skin test: detects exposure to Mycobacterium tuberculosis; tuberculin purified protein derivative (PPD) is injected into the skin of the forearm; injection site is observed within 48-72 hours; positive result recorded if induration develops and lesion meets a certain size criterion -contact dermatitis: caused by drugs, nickel, chromate, poison ivy toxin (pentadecacatechol); T cells are sensitized (requires a sensitizing and provocative dose); secondary exposure of same antigen leads to inflammation and generates and extremely itchy (pruritic) red rash -transplant rejection: when donor tissue displays surface molecules of a different MHC class, the T cells of the recipient will recognize its foreignness and react against it -graft-versus-host disease (GVHD): may occur in bone marrow transplants; where graft attacks host tissues; white blood cells made in the transplanted bone marrow attack the new body they inhibit.
Discuss the general approaches to diagnosing and managing autoimmune disorders.
General signs and symptoms of autoimmune disorders: join and muscle pain, fatigue, rash, organ dysfunction, and low-grade fever; presentation differs based on what tissues are affected. Diagnosing often involves detecting self-reactive immune system cells and/or autoantibodies. Depending on the suspected disorder, the clinician may also order hematological tests that look for specific inflammation and metabolic factors. An autoimmune disorder is rarely definitively diagnosed using a single test. Managing autoimmunity usually involves: suppressing the immune response and/or reducing inflammation that damages tissues, for example, anti-inflammatory drugs, corticosteroids, pain-killing medications, immunosuppressant drugs, and physical therapy. Treatment for autoimmunity usually leads to secondary immunodeficiency. So far there are no cures or preventions for autoimmune disorders.
Provide examples of type II hypersensitivities and state if they are mediated by cytolytic or noncytolytic mechanisms.
Goodpasture syndrome: connective tissues of kidney and lungs are attacked; cytolytic mechanisms Autoimmune hemolytic anemia: red blood cells are attacked when bound to drugs like cephalosporins and penicillin; cytolytic mechanisms Rheumatic heart disease: antibodies made against Streptococcus pyogenes cross-react with patient's heart valves; cytolytic mechanisms Myasthenia gravis: neuromuscular condition; caused by inactivation of receptor and NONcytolytic mechanisms Graves' disease: leads to hyperthyroidism; caused by receptor overactivation and noncytolytic mechanisms
Outline the development of hemolytic disease of the newborn and describe how it is prevented.
Hemolytic disease of the newborn (HDN) occurs when antibodies are formed when an Rh- mother is sensitized to the Rh factor in a prior pregnancy. Maternal IgG antibodies against the Rh factor cross the placenta; it leads to fetal red blood cell lysing and induces a severe, possibly fatal anemia in the baby. If a mother is already sensitized against the Rh factor, she has antibodies to the Rh antigen and there is no effective way to prevent HDN. Pregnancies should be closely monitored and fetal blood transfusions may be required. To prevent HDN, women can never be sensitized to the Rh factor; Rh(D) immunoglobulin (RhoGAM) is given.
Define the term hypersensitivity.
Hypersensitivities are inappropriate immune responses (e.g., allergy and autoimmunity), they can be localized and therefore restricted to a given tissue or system and spread through the body and affect multiple tissues and organ systems.
Discuss why cancer can be considered a failure of the immune system.
Immune system protects us against infection as well as cancer; developing cancer is a failure of the immune system. Patients with secondary immunodeficiencies, for example, HIV patients and transplant recipients on immunosuppressants, are more likely to contract certain cancers (because their immune systems failed them).
Compare and contrast primary and secondary immunodeficiencies.
Immunodeficiency is the lack of a properly functioning immune system. Primary immunodeficiency is congenital; the result of a genetic defect; an inborn error that affects one or more immune factors and leads to deficient immunity. There are over 150 lifelong disorders, they are relatively rare and have a broad spectrum of effects (some are manageable and survivable, others have limited treatment options and result in a decreased life span). Patients tend to experience recurring, persistent, and sever infections, often caused by opportunistic pathogens. 50% are due to B cell issues, 30% are linked to T cell defects, 18% are errors in phagocytes, and 2% relate to complement deficiencies. Therapies for primary immunodeficiencies include bone marrow transplants, intravenous or subcutaneous antibody administration, cytokine therapies, and experimental treatments (e.g., stem cell transplants, thymus transplantation, gene therapy). Secondary immunodeficiencies are acquired (not inborn) and more common than primary immunodeficiencies. In secondary immunodeficiencies, the patient starts out with a normal immune system and then experiences a decline in immune system rigor, often due to age, certain infectious agents (pathogens with virulence factors that directly inhibit host immune defenses by breaking down antibodies, interfering with cellular signaling, or directly infecting immune system cells like HIV which progresses into AIDs when enough helper T cells are lost; examples include Human T cell lymphotropic viruses, Epstein-Barr virus, and Measles virus), medical interventions (chemotherapy, radiation, steroid anti-inflammatory drugs like corticosteroids, anti-seizure medications, and immunosuppressants), and systemic disorders (e.g., diabetes, malnutrition, alcoholism, hepatitis). Secondary immunodeficiencies caused by medical intervention is usually reduced when the patient stops taking the drug, but some patients are not able to stop (organ transplant recipients).
Describe what type I hypersensitivities are and provide examples.
Type I hypersensitivities are allergic reactions driven by IgE interacting with soluble antigens. An allergy is a scenario where the immune system fights off a perceived threat that would otherwise be harmless. Type I hypersensitivities include all allergies, including atopy (chronic local allergy such as hay fever or asthma), atopic asthma (allergy-based asthma), and atopic dermatitis (inflamed and itchy skin condition also known as atopic eczema). Allergic reactions occur IMMEDIATELY upon post-sensitization exposure. Examples of allergens: bees, penicillin, detergent, latex gloves, lotion, shrimp, peanuts, red dye, strawberries, dust mites, and pollen.
Name some features and examples of each type of hypersensitivity reaction.
Type I: -features: allergies; triggered by allergens; driven by IgE interacting with soluble antigens; can be triggered by drugs; not associated with autoimmunity; immediate -examples include localized or systemic allergies Type II: -features: can by cytotoxic or noncytotoxic; driven by IgG or IgM interacting with nonsoluble antigens on cell surfaces or extracellular antigens (i.e., connective tissue proteins); response can be triggered by drugs; associated with autoimmunity but can be nonautoimmune (receptor inactivation or overactivation) -examples include hemolytic disease of the newborn, blood transfusion reactions, autoimmune disorders such as Goodpasteur syndrome, Graves' disease, and rheumatic heart disease Type III: -features: insoluble immune complex deposits in tissues; driven by IgG or IgM interacting with soluble antigens; response can be triggered by drugs; associated with autoimmunity -examples include serum sickness; autoimmune disorders like lupus, rheumatoid arthritis, and poststreptococcal glomerulonephritis Type IV -features: delayed hypersensitivity; driven by T cells interacting with soluble or cell- or matrix-bound antigens; response can be triggered by drugs; associated with autoimmunity -examples include nickel, latex, or poison ivy reactions; tuberculin skin test reactions, chronic graft rejection, and certain autoimmune disorders such as multiple sclerosis and Hashimoto thyroiditis
Name the four types of hypersensitivity reactions.
Type I: Allergies Type II: Cytotoxic Type III: Immune Complex Type IV: Delayed hypersensitivity
Describe how type II cytolytic and noncytolytic hypersensitivity reactions work.
Type II hypersensitivities involve IgG or IgM binding to nonsoluble antigens on the surface of a cell or within the extracellular environment; can lead to complement activation or subsequent cell lysis; can cause recruitment of leukocytes that lyse tagged extracellular substances and/or cells. Complement-dependent cytolysis: compliment proteins activated when host antibodies tag a target cell, leading to either the formation of a membrane attack complex (MAC) where water lyses the cell OR complement proteins opsonize target, tagging it for phagocytosis Complement-independent cytolysis: host antibodies tag target cell a leukocyte (such as a natural killer cell) is recruited directly by antibodies and triggers tagged cell to undergo lysis. Noncytolytic hypersensitivities are cause when antibodies reacting with a cell-surface receptor on self-cells cause either a receptor inactivation or overactivation.
Explain the processes that occur in type III hypersensitivities.
Type III hypersensitivities develop when IgG or IgM antibodies bind to soluble targets, leading to excessive antibody-antigen complexes which are insoluble and deposited in tissues, triggering massive inflammation as the antibody aggregates activate complement cascades; they are characterized by immune complexes depositing in tissues. Process overview: -insoluble antigen-antibody complexes form -deposition of insoluble antigen-antibody complexes in tissue attracts complement proteins -complement activates inflammation cascades and recruits leukocytes to the tissues; leukocytes release cytokines and promote inflammation.
Explain how type IV sensitivities are mediated, how they progress, and why they are called delayed hypersensitivities.
Type IV hypersensitivities are not antibody-mediated; they are T-CELL MEDIATED responses against self-antigens or otherwise harmless antigens. They progress as T cells sensitized against a self-antigen (or antigen that resembles self) promote inflammation and cytolysis. They are called delayed hypersensitivity reactions because they manifest slowly over 12-72 hours after antigen exposure.
Describe the hygiene hypothesis and its relevance to type I hypersensitivities.
When our normal microbiota community changes, our immune system may become confused. Some scientists suggest that these shifts could be linked to the rising incidence of allergy and autoimmunity. Hygiene hypothesis proposes a decrease in diversity and levels of microbes in our normal microbiota (due to cleaner and more sanitary conditions, less exposure to environment) may negatively affect immune responses. Understanding how our normal microbiota impacts our immune responses is in its infancy. Studies of germ-free animals has shown microbe-free environments lead to underdeveloped immune systems. The hygiene hypothesis proposes that clean conditions of developed countries and decreased microbiota due to antibiotic use increases the affect for developing allergies, or type I hypersensitivities. Between 1997-2011, incidence of food allergies in the U.S. increased by 50%, with just eight foods accounting for the majority of allergies.
Describe what graft-versus-host disease is and when it may develop.
graft-versus-host disease (GVHD): may occur in bone marrow transplants; where graft attacks host tissues; white blood cells made in the transplanted bone marrow attack the new body they inhibit.
Describe how serum sickness develops and how it is treated.
serum sickness: a systemic injury initiated by antigen-antibody complexes that circulate in the blood; named for condition that appeared in soldier after repeated injections of horse antiserum to treat tetanus; can also be caused by injection of animal hormones; can be caused by injection of antivenoms and anti-toxins Develops as immune complexes are deposited in blood vessels of the kidney, heart, skin, and joints; can become chronic, causing enlarged lymph nodes, rashes, painful joints, swelling, fever, and renal dysfunction Treatment of serum sickness includes anti-inflammatory drugs (steroidal or nonsteroidal) and antihistamines. Most patients fully recover within a week and have no further symptoms.
