Ch 7
Commono autoimmune disorders: • Endocrine system: - Type ___ diabetes (pancreatic beta cells) - Hashimoto hypothyroidism (thyroid gland cells) • Neuromuscular system: - Myasthenia gravis (neuromuscular junction) - ______ (nerve tissue / myelin) • Heart: - _____ - Cardiomyopathy
1 multiple sclerosis rheumatic fever
Alloimmunity • Histocompatibility antigens are not present in RBC • Instead, several blood group antigens determine compatibility of blood transfusion - These antigens are expressed only on erythrocytes • The most important antigens on RBC: 1.The ABO system (4 groups): • Type ___ • Type ___ • Type ____ • Type ___ 2. The Rh system (2 groups): • Rh ____ (___) • Rh ____ (___)
A B AB O Positive(+) negative(-)
Type I: IgE-mediated Reactions • The most common allergic reactions • The IgE antibody is produced by ____after exposure to an allergen (environmental antigen) • Repeated exposures to the allergen elicits enough IgE to "sensitize" the person • In a sensitized person, re- exposure causes IgE to initiate ____ degranulation
B-cells mast cell
The ABO + Rh Blood Groups • Type ____ is the universal donor because the donor's RBCs do not have either the A & B antigens or the Rh antigens - The antibodies in the recipient's blood (serum) do not have any antigens to attack • The reason that the antibodies in the donor's serum do not attack the RBCs of the recipient: - These antibodies are destroyed rapidly - The donated blood had already been removed from the donor, so these antibodies are no longer made by the donor's B-lymphocytes • Type _____ is the universal recipient
O negative AB positive
Type II: Tissue-specific Reactions • Examples: 1. Allergy: • Reaction to certain drugs such as penicillin: when the drug binds to ____, they are recognized as different (non-self) 2. Autoimmunity: • Autoimmune hemolytic anemia: destruction of self RBC 3. Alloimmunity: • _____ reactions (ABO and Rh systems): destruction of donor's RBC • Hemolytic disease (jaundice) of the newborn (Rh): destruction of the baby's red blood cells
RBC blood transfusion
Rh Blood Groups • The Rh antigen is named after ____, where it was discovered • Blood transfusion Rh incompatibility: - Blood transfusion reaction occurs when the donor is Rh positive (+) and the recipient is Rh negative (-) - The donor's RBCs have the Rh antigen, which are foreign to the recipient, thus - The the recipient develops____ antibodies (IgG type) • Maternal-fetal Rh incompatibility: - When the mother is Rh (___) and the fetus is Rh (___) - The mother develops anti-Rh antibodies - The antibodies break down the RBC in the fetus' blood - Result: jaundice of the newborn (yellow skin due to break down of RBC)
Rhesus monkey anti-Rh -,+
Jaundice of the Newborn • Treatment: - Treatment is usually not necessary • Frequent feedings to keep the baby well- hydrated is encourage - When bilirubin blood levels are very high, phototherapy treatment is prescribed - ____ (____) light helps break down bilirubin • Prevention for subsequent babies: - Injecting the mother within 72 hours after delivery of the 1st baby with Rh immune globulin can prevents her from forming the antibodies again
Ultraviolet(blue)
Type I: IgE-mediated Reactions • The tissues that respond to histamine: 1. ____: vasodilation and increased vascular permeability resulting in ____ • Widespread vasodilation/edema can cause ____ 2. respiratory tract: ____ of airways (bronchial smooth muscles) resulting in breathing difficulties (e.g., asthma) 3. ____: cramping, vomiting, diarrhea 4. skin: itching, erythema (reddish skin-rash), & swelling 1. ____ (welts): swelling on surface of skin 2. _____: local swelling beneath the skin - Usually occurs around the eyes and lips but may also be found on the hands, feet, and throat 5. Other tissue: edema/inflammation such as edema of larynx, conjunctivitis, rhinitis (e.g., hay fever)
Vascular system edema anaphylactic shock constriction GI tract Hives angioedma
Hypersensitivity • Sometimes normally functioning immune responses are not _____ • Theses inappropriate immune responses are referred to as hypersensitivity, which is characterized by the immune system destroying ____ tissues\cells 1. Allergic reaction occurs when the immune system _____ (is hypersensitive) to noninfectious environmental antigens 2. Autoimmune disease occurs when the immune system attacks the person's own ___ and ____ 3. Alloimmune response occurs when transplanted organs or blood cells (blood transfusion) from a donor are ____ because they are recognized as non-host cells
advantageous healthy overreacts cells, tissues rejected
Type IV Hypersensitivity •Specific allergy examples: 1. _____: Poison ivy or poison oak cause a delayed hypersensitivity reaction - The allergen is a plant resin, a hapten Skin reactions to chemicals, cosmetics, detergents, clothing, topical medicines and metals are elicit by the same mechanism (allergen is a hapten) 2._______ to drugs such as penicillin • Penicillin is a hapten which binds to proteins in skin cells and causes a rash • Anemia reaction to penicillin is caused by a Type II reaction (antibodies are involved in RBC destruction)
allergic contact dermatitis skin reaction
Type II: Tissue-specific Reactions • Also called ____-mediated cytotoxic hypersensitivity • Tissue-specific antigens are expressed on the ____ of cells in specific tissues or organs - Limited to the cells or tissues that express that particular antigen (RBC, bone marrow) • Type II reactions: - Begin with antibodies binding to tissue- specific antigens - End in the destruction of the target (host) cell by macrophages or by NK Cells
antibody plasma membrane
Type III: Immune-compledx Mediated Reactions Caused by antigen-antibody (immune) complexes The mechanism involves: 1. Large quantities of ____ complexes (IgG and IgM) form in the blood 2. They are deposited in the ____walls (between the endothelial cells and the basement membrane) 3. The antigen-antibody complexes activate the plasma complement system 4. Proteins of the complement system and the antigen- antibody complexes attract neutrophils (and other leukocytes) to the area
antigen-antibody capillaries'
Type I: IgE-mediated Reactions • Desensitization to prevent future allergies: - Injections of minute amounts of allergen in increasing doses over a prolonged period of time - May reduce the severity of the allergic reaction in treated individuals • Treatment for existing allergies: - _____ - _____ - Epinephrine injections prevent anaphylactic shock by counteracting the effects of histamine, i.e., by increasing vasoconstriction and bronchiodilation (opening the airways)
antihistamines anti-leukotriens
Type I: IgE-mediated Reactions • Genetic predisposition: some individuals appear to be prone to allergies and are called ___ • Atopic individuals: - Produce ___ concentration of IgE - Their airways and skin are more responsive to IgE • Genetic predisposition: - If one parent has an allergy, ___% of the offspring develop allergies - If two parents have an allergy, ____% of the offspring develop allergies - Risk is higher in children of atopic ___ than ___
atopic higher 40 80 mothers, fathers
Type IV: Cell-mediated Tissue Destruction Example 1. allergy: • Contact with poison ivy and metals (contact dermatitis) • Interaction with certain drugs, e.g., skin reaction to penicillin 2. ____: • Type I diabetes mellitus (insulin-dependent): the self-antigen is a protein on the beta cells of the pancreas • Rheumatoid arthritis: the self-antigen is a specific collagen (protein) in joints 3. _____: • Graft and transplant rejection (after 2 weeks or more) 4. _____: • NK cells and Tc cells attack and destroy tumor cells
autoimmunity alloimunity tumor rejection
Common autoimmune disorders • GI system: - ____ disease (intestines) - Ulcerative colitis (large intestines) - Chronic active hepatitis (liver) • Connective tissue: - Ankylosing spondylitis (joints) - Rheumatoid arthritis (joints) - Systemic lupus erythematosus (multiple systems\organs) - Scleroderma (skin)
celiac
The ABO Blood Groups • These antibodies are of the IgM type • When large volumes of whole blood are transfused the ABO system must be matched • Otherwise the antibodies in the recipient's blood (serum) bind to (attack) the antigens (A and/or B) on the donor's erythrocytes • This destroys (causes ____ and ____ of) the donor's erythrocytes in the transfused blood • A harmful transfusion reaction can be life threatening
clumping, lysis
Type IV: Cell-mediated Tissue Destruction • Always a ____ hypersensitivity reaction • Mediated by specifically sensitized T cells, does not involve antibodies • The T cells are either / or: 1. _____ (Tc): • Attack and destroy target cells directly (by lysosomal enzymes that are toxic to cells) 2. _____(Th): • Specific T-helper cells (Td cells) produce lymphokines that recruit macrophages to phagocytose target cells
delayed Cytotoxic T cells Lymphokine-producing cells
Type IV: Cell-mediated Tissue Destruction • Mechanism for allergy: - The allergen is a ___: a molecule that is too ____ to induce an immune response (poison ivy, penicillin) - Haptens bind to a protein on the host cells - When binding with host cell proteins, the hapten plus the host protein become a neo-antigen (a new antigenic determinant) - The _____ is recognized as a foreign antigen and only then the immune response is initiated • Always a delayed reaction (occurs 1-2 days after re-exposure) - The immune system attacks the neo-antigen on the host cell's membrane and destroys the cell
hapten,small neo-antigen
Type I: IgE-mediated Reactions • Mast cell degranulation releases ____ • Histamine receptors on the plasma membrane of cells in various tissues mediate the allergic response • Treatment: - Anti-histamines may decrease the acute allergic reaction
histamine
Alloimmunity • Graft rejection - Following organ transplantation there is often an immune response of the recipient against histocompatibility antigens on the donated tissue • _____ antigens are found on the plasma membrane of most cells in the body: - ____ = Human Leukocyte Antigens - ___ = Major Histocompatibility Complex - This is a type IV, cell-mediated reaction • Without immunosuppressive drugs, most donated organs will be rejected within 2 weeks - Methods to decrease the rejections of the graft: • HLA matching of donor and recipient • The use of immunosuppressive drugs
histocompatibility HLA MHC
Type I: IgE-mediated Reactions •Manifestations of systemic anaphylaxis - Generalized itching - ____ (urticaria) and erythema - Local ____ (angioedema) or edema - GI ___, vomiting, diarrhea - Numbness & tingling mostly around the face and mouth - Irregular heart beat (dysrhythmias) - Breathing difficulties (bronchial constriction and laryngeal edema) - Weakness/dizziness • Anaphylacticshock - Widespread vasodilation and edema - Hypotension and a ____pulse - Loss of consciousness
hives swelling cramps rapid, weak
Jaundice of the Newborn • Also called neonatal _____ - Bilirubin is a yellow breakdown product of _____ - Destruction of the infant's RBCs by the mother's antibodies creates a sudden buildup of bilirubin in the baby's blood (hyper-bilirubinemia) • Usually begins during the first day of life - Before birth, the placenta removes the bilirubin from the infant's blood to be processed by the mother's ____ - Immediately after birth, the baby's own liver takes over, but is not fully mature, so this can take time - Thus, bilirubin levels are higher after birth • Usually newborn jaundice is not harmful and resolves without treatment within 1-2 weeks - But, it could lead to extreme tiredness and poor feeding
hyper-bilirubinemia hemoglobin liver
Allergies • The most common and the least life threatening of all hypersensitivity reactions • Introduced in 4 possible ways: a. son contact b. _____ c. ingestion d. ____
injection inhalation
Type III Hypersensitivity 5. The _____ attempt to ingest the immune complexes, but cannot because the complexes are bound to the capillary wall 6. The neutrophils discharge their _____ (killing agents) into the vessel wall 7. This promotes massive ____ which causes further damage to the vessel wall 8. This leads to ____ & _____in vessel wall These reactions are not organ-specific but occur in _____, especially blood vessels in the skin, joints, and kidneys - Unlike type-II reactions which are organ-specific
neutrophils lysosomal enzymes inflammation hemmorrage and tissue death blood vessels
Hypersensitivity •Hypersensitivity reactions are classifies in two different ways: 1. According to the stimulus (3 types): a. Allergy: exaggerated immune response against allergens (____, _____ antigens) b. Autoimmunity: misdirected immune response against the host's own cells c. Alloimmunity: immune response against beneficial foreign tissue (transplanted tissue/organ or blood transfusion) 2. According to the type of reaction (4 types): a. Type I: ____-mediated b. Type II: ____-specific reactions c. Type III: _____mediated d. Type IV: ____reactions
non-infectious, environmental IgE tissue immune-complex cell-mediated
Alloimmunity Occurs when an individual's immune system reacts against antigens on tissue of another individual There are three types of alloimmunity: 1. ____ transplantation and ____ tissue • The immune system of a recipient of an organ transplant reacts ____ antigens on the donor's cells 2. ___ during pregnancy • Transient neonatal disease: the maternal immune system becomes sensitized against the antigens of the fetus (Rh) 3. ____ transfusion • The immune system of a recipient of a blood transfusion reacts against antigens on the donor's red blood cells
organ, grafted against fetus blood
Rh Blood Groups • Maternal-fetal Rh incompatibility is an example of transient neonatal disease: - Maternal antibodies against erythrocyte antigens induce anemia in the child because: - The fetus is a hybrid between the mother and father and expresses ____ antigens that are foreign to the mother - Occasionally fetal antigens cross the placenta and elicit an immune response in the mother (B-cells make Ig) - Maternal antibodies (Ig) may be transported to the fetal circulation and produce alloimmne disease in the fetus - Although the symptoms may be manifested immediately after birth (and may be fatal), the source of these antibodies (mother) is removed at birth, so if the symptoms are treated the disease will disappear
paternal
Autoimmunity • Many autoimmune diseases begin after ____ infections that leave no trace • The original insult that caused the autoimmunity response may or may not be apparent 1. Examples of non-apparent original insults include ___ and ____ 2. Examples of more apparent original insults include drug-induced ____ and virus-induced changes (such as rubella infection) 3. The only autoimmune disease that has been conclusively associated with a preceding infection (group A streptococcal infection) is rheumatic heart disease
preexisting RA SLE anemia
Blood Groups • Rh blood groups: 1. Rh positive: the antigen is ___ on RBC (85% of North Americans, dominant trait) 2. Rh negative: no antigen on RBC but circulating anti- Rh antibodies in the blood (15%, recessive trait) • ABO blood groups: 2 antigens create 4 groups 1. Type A: the person has the A antigen on their RBC and circulating ____ antibodies in their blood 2. Type B: the person has the B antigen on their RBC and circulating ___ antibodies in their blood 3. Type AB: the person has both the A and B antigens on their RBC and _____in their blood 4. Type O: the person has ____on RBC but both ____ and ____circulating antibodies in their blood
present anti-B anti-A no circulating antibodies no antigens, anti-A, anti-B
Type I: IgE-mediated Reactions • Anaphylaxis (anaphylactic reaction): - A serious allergic reaction with a ____ onset occurring within a few minutes of re-exposure - It may be either: 1. ____ anaphylaxis: - Confined to a limited area and/or to one system - Usually involves the ___: symptoms include erythema, hives, and local edema 2. ___ (generalized) anaphylaxis: - Anaphylactic reaction involving multiple systems - May progress to anaphylactic shock
rapid local skin Systemic
Hypersensitivity • The inappropriate hypersensitivity reaction always takes place after _____ to an antigen, not _____ • Hypersensitivity reactions are either: 1. ____: minutes to hours after re-exposure, or 2. _____: hours to days after re-exposure • All hypersensitivities may be life threatening
re-exposure, immediately immediate delayed
Hypersensitivity • The four types of hypersensitivity reactions: - Type I: IgE-mediated allergic reactions, such as ___ allergic rhinitis (mast cells) - Type II: tissue-specific reactions, including ____ diseases such as hemolytic anemia (macrophages\NK) - Type III: immune-complex-mediated reactions such as systemic lupus erythematosis (neutrophils) - Type IV: cell-mediated reactions, such as ____(poison ivy) (lymphocytes and macrophages) • Types I, II, and III are mediated by _____, while type IV is mediated by ___ • Upon re-exposure, Types ____are immediate while type ____ is delayed (1-2 days) • May be allergies, autoimmunity or alloimmunity
seasonal autoimmune contact dermatitis antibodies t lymphocytes 1,2,3 4
Autoimmunity • Autoimmunity is a breakdown of ____, in which the body's immune system begins to recognize self-antigens as foreign - Immunologic tolerance to self antigens develops during the embryonic period • A disturbance in the immunologic tolerance of self-antigens causes the immune system to react against some self-antigens and destroys the host's own tissues • _____ (antibodies against self- antigens) are produced or T lymphocytes are employed against self-antigens
self tolerance auto-antibodies
Allergies • Most allergens are ________ • Typical allergens: - Pollens (tree, grass, and weed) - Molds and fungi - Food (milk, egg, fish, wheat) - Animals (dander, sting/bite) - Cigarette smoke - Components of house dust (dust mites) - Medications (penicillin, sulfa)
small proteins
Type III Hypersensitivity • Examples: - ____ erythematosus (autoimmune disease) - Skin lesions of syphilis and leprosy (the immune system fights against the infected cells) - Reactive arthritis (as a reaction to an infection in another part of the body antibodies attack joints)
systemic lupus
Type I: IgE-mediated Reactions • Anaphylactic shock: - Caused by widespread ____, which leads to hypovolemia and severe hypotension (systolic BP < 60 mmHg) - The severe _____ may lead to vascular collapse and inadequate tissue perfusion, which results in shock - If not treated, the shock will result in loss of consciousness and eventually death - Treatment: • Get immediate emergency care (call 911) • _____ injection: to promote both ____ and_____
vasodilation hypotension epinephrine, vasoconstriction, bronchiodilation
Autoimmunity • Autoimmune diseases are seen more frequently in: - _____ than __ - ____ than ____ - The ___-____ year-old age-group • A genetic predisposition is implicated by: - Existence of the disease in families - The increased incidence in twins • In most autoimmune disorders there are frequent remissions and exacerbations (symptoms come and go)
women, men blacks, whites 20-40
