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What is a hypersensitivity?
- -Any immune response against a foreign antigen exaggerated beyond the norm
- -Immune system is hyperactive
What are the four types of hypersensitivity?
- 1. Immediate
- 2. Cytotoxic
- 3. Immune complex-mediated
- 4. delayed or cell-0mediated
What is Type 1 Immediate?
- -Local/systemic reaction that results from the release of inflammatory molecules in response to an antigen
- -Develops within seconds or minutes
- -Commonly called allergy
- -Antigens that stimulate are called allergens
What happens during a type 1 reaction?
An APC shows the antigen by MCH II and T-helper cell activates B- cells which release immunoglobins and IgE! If allergic
What happens during the second exposure in a type I reaction?
- The mast ccell, basophil, or eosinophil is sensitizied and IgE receptors are ready to go. Capillaries are leaky and degranulation realeases: histamines, kinins, proteases, leukotrienes, prostaglandins, and other inflmammatory molecules are released.
What are clinical signs of a localized type 1 reaction?
- -Usually mild and localized
- -site depends on portal of entry
- -Small inhaled allergens may reach lungs and cause asthma
- -Some food allergens (diarrhea and other GI signs)
- -Local dermatitis may produce hives or urticaria
What are clinical signs of a systemic type 1 reaction?
- -Many mast cells may degranulate at once, releasing large amounts of histamine and inflammatory mediators
- -Acute anaphylaxis or anaphylactic shock can result
- -Must be treated with epinephrine
- -Uticaria can be systemic
How do you diagnosis type 1 hypersensitivity?
- -based on detection of high levels of IgE aginst a specific allergen
- -ImmunoCAP specific IgG blood test, CAP RAST, pharmacia CAP
- -Alternatively, diagnose using skin tests
How do you prevent type 1 hpersensitivity?
- -Identifiy and avoid allergens
- -Food allergens identified using an elimination diet
- -Immunotherpy (allergy shots) can help prevent allergic reactions
- -IT is the administration of a series of injections of dilute aggergen, must be repeated every two-three years
How do you treat type 1 hypersensitivity?
- -Administer drugs that counteract inflammatory mediators (Antihisamines)
- -Treat asthma with a corticosteroid and a bronchodilator
- -Epinephrine neutralizes many mechanisms of anaphylaxis
- -Relaxes smooth muscle, reduces vascular permeability, used in emergency treatment of shock and asthma
What is Type II (Cytotoxic) Hypersensitivity?
- -Results when cells are destroyed by an immune response
- -Often combined activities of complement and antibodies
- -Many autoimmune diseases
What are examples of Type II reaction?
- -Destruction of blood cells following an incompatible blood transfusion
- -Destruction of fetal RBC cells in hemolytic disease of the newborn
What happens in transfusion reaction?
-The individual receives the wrong blood type and their antibody reacts with donor's antigen
What are the different blood antigens?
-A, B, AB, or O
What happens in hemolysis?
- The transfusion of the donor blood, agglutination and complement binding by receivers antibodies, and hemolysis of donor blood
What is the Rh system?
- -Rh antigen, common to RBC and rhesus monkeys
- -85% of people are Rh+
- -If an Rh- woman is carring an Rh+ fetus, the fetus may be at risk for hemolytic disease
How do you prevent hemolytic disease of the newborn?
- -Mother is given Rhogam (Destorys any Rh+ in the body, so the immune system does not see it and attack it)
- Rhogam is an anti-Rh immunoglobulin.
- -Given within 48 hrs of birth
Does hemolytic disease happen with the first birth?
-No, it is because blood from the baby comes through the placenta and the mother's immune system can recognize it and create antibodies, it is the second baby that has to be watched for hemolytic disease
What test do you use to see if the mother is Rh-?
The coombs test
What are drug-induced cytotoxic reactions?
- -Some drug molecules can form haptens.
- -Haptens spontaneously bind to blood cells or platelets and stimulate the production of antibodies. Antigen binding site
- -Can produce: Immune thromboctopenic purpura, hemolytic anemia, agranulocytosis, greatly decreased # of neutophils
What is the deveopment of immune thrombocytopenic purpura?
- The drug molecule bind to platelets forming drug-platlet complex
- Complexes are antigenic, triggering a immune response
- Antibodies bind to drug molecules, complement binds to antibodies. MAC attack and platelet # goes down
What is type III (immune-complex mediated) hypersensitivity?
- -Caused by formation of immune complexes
- -Can cause local reactions: hypersensitiivty pneumonitis, glomerulonephritis.
- -Can cause systemic reactions: Systemic lupus erythematosus (anti DNA antibodies), rhematoid arthritis
What occurs during a type III reaction?
-Antigen combines with antibody. Phagocytes remove some of the complexes, but some lodge themselves in the vessel wall. Thus leaving inactive and active complexes. These attract neutrophils which release inflammatory chemicals. These chemcials are released on the blood vessal and cause damage to that vessel
What is hypersensitivity pneumonitis?
- -Type III reaction
- -Disease in which your lungs become inflamed when you breathe in a certain dust.
- -The inhalation stimulates the production of antibodies.
- -Subsequent inhalation of teh same antigen stimulates the formation of immune complexes and activates complement
- -IgG not IgE
What is glomerulonephritis?
- -Type III reaction
- -Immune complexes circulating in the bloodstream are deposited on the walls of glomeruli
- -Damage to the glomerular cells impedes blood filtration
- -Kidney failure and ultimately death result
What is rheumatoid arthritis?
- -Type III reaction
- -Chronic, inflammation of synoium of joint
- -Immune complexes depositied in the joint
- -Results in release of inflammatory chemicals
- -Joints break down and become distored
- -Trigger not well understood
- -Treated with anti-inflammatory drugs
What is Systemic Lupus Erythematosus?
- -Type III reaction
- -Autoantibodies against DNA result in immune complex formation
- -May other autoantibodies occur: against RBC, platelets, lymphocytes, muscle cells
- -Trigger unknown
- -Treatmeat with immunosuppressive druges reduces autoantibody formation, treatment with corticosteroids reduces inflammation
What is Type IV (delayed or cell-mediated) Hypersensitivity?
- -Inflammation 12 to 24 hours after contact with certain antigens
- -Results from actions fo antigen, antigen-presenting cells, and T cells
- -Delay reflects the time it takes for macrohpages and T cells to mirgrate and proliferate at the site of the antigen
What is the TB response?
- -Type IV
- -Skin exposed to TB or vaccine reacts to an injection of tuberculin beneath the skin
- -Used to diagnose contact with antigens of M.tuberculosis
- -No response if no vaccine or individual has not been infected with
- -Red hard swelling with infected or immunized
What is allergic contact dermatitis?
- -Type IV
- -Poison Ivy
- -cell-mediated immune response resulting in an intensely irritating skin rash
- -Triggered b chemically modified skin proteins that the body regards as foregin
- -In many cases, acellualr, fulid filled blisters develop
- -Haptens include the oil of poison ivy, formaldehyde, latex, cosmetics
- -Can be treated with corticosteroids
What is a graft rejection?
- -Type IV
- -Rejection of tissues of organs that have been transplanted
- -Graft perceived as foreign by recipient
- -Normal immune response against foreign MCH proteins present on graft
- -Likelihood of rejection depends on the degree to which the graft is foreign to recipient
What are the types of grafts?
- -Autograft- same person
- -Isograft- genetically identical sibling or clone
- -Allograft: gentically different member of same species (rejected)
- -Xenograft- Differ species (rejected)
What is graft v. host disease?
- -Type IV
- -Donated bone marrow cells regard the patient's cells as foreign
- -Donated takes over body and tries to kill it
- -Donor and recipient differ in MCH class I so the grafted T cells attack recipient's tissue
- -Donor and recipient differ in MCH II so grafted T cells attack the host's APC
- -Immunosuppressive drugs can stop this disease
What is donor-recipient matching?
- -MCH compatibility between the donor and recipient difficult due to a high degree of variability. The more closely the donor and recipient are related, the smaller the difference in their MCH
- -preferable grafts are donated by parent or sibling
- -Tissue typing used to match donor and recipient
What do immunosuppressive drugs do?
- -Immunosuppressive drugs important to success of modern transplation.
- Important classes are:
- -Glucocorticoids: steriod hormones
- -Cytotoxic drugs-Chemo
- -Cyclosporine-Organ transplant, so no rejection
- -Lymphocyte-depleting therapies-prevent autoimmune disease
What is an autoimmune disease?
- -Against cell
- -Occurs more often in the elderly
- -more common in women
- -May result when an individual beings to make autoantibodies or cytotoxic T cells against normal body components.
What are some hypothetical caues of autoimmune disease?
- -Estrogen may stimulate T cells
- -Some maternal cells may cross the placenta, colonize the fetus, and trigger disease later in life
- -Environmental factors like viral infections
- -Genetic factors- MCH genes
- -T Cells may encounter self-antigens that are normally hidden
- -Microorganisms may trigger autoimmunity due to molecular micicry
- -failure of normal control mechanisms of the immune system
What are the two categories of autoimmune disease?
-systemic and single-organ
What is a single-organ autoimmune disease?
- -one organ affected
- -Affecting blood cells (autoimmune hemlytic anemia)
- -Affecting endocrine organs
- 1. Type 1 diabetes (no B cells of pancreas produce insulin)
- 2.Graves disease-Thyroid is overactive
- 3. nervous tissue- multiple sclerosis
- 4. CT- rheumatoid arthritis
What is a immunodeficiency disease?
- -When the immune system is not working well
- -Conditions resulting from defective immune mechanisms
- Two types: primary and Acquired
What is primary immunodeficiency disease?
- -Result from some genetic or developmental defect, develop in infants and young children
- -Many inherited defects in all the body's line of defenses
- -Examples: Chronic granulomatous disease, severe combined immunodeficiency disease (SCID-Bubble boy), Digeorge syndrome, bruton-type agammaglobulinemia
What is acquired immunodeficiency disease?
- -Develop as a direct consequence of some other recognized cause
- -Develops later in life
- -Opportunistic infection low Cd4 cells in presence of HIV
- -severe stress-suppression of cell-mediated immunity results from an excess production of corticosteroids
- -Malnutrition and enviromental factors-inhibit T and B cell production