hypersensitivities, autoimmune diseases, and immune deficiencies

PGH Gell and RRA Coombs classification

classification scheme in which hypersensitivity reactions are divided into 4 types

type 1 hypersensitivity

type; allergies

immediate hypersensitivity, IgE-mediated hypersensitivity

other names for type 1 hypersensitivity

type 1 hypersensitivity

type; localized or systemic reactions

type 1 hypersensitivity

type; result from the release of inflammatory molecules such as histamine in response to an antigen

sensitization upon initial exposure, degranulation of sensitized cells

2 part mechanisms considered in immediate hypersensitivity

allergic rhinitis or hay fever, asthma, food allergies, atopic dermatitis

4 examples of type 1 hypersensitivity reactions

hay fever

other name for allergic rhinitis

mold spores, pollens, feces, dead bodies of house dust mites

allergenic rhinitis is caused by (4):

water exudations of the conjunctiva, nasal mucosa, URT, sneezing, coughing

5 symptoms of allergic rhinitis

mast cells

asthma is triggered by the degranulation of ___________

lower

asthma reaction develops in the ____________ respiratory tract

asthma

is triggered by the degranulation of mast cells and develops in the lower RT

airway edema, mucus secretion, bronchoconstriction, airway obstruction, inflammation

5 symptoms of asthma

primary response

primary/late response of asthma; occurs within minutes from allergen exposure

primary response

primary/late response of asthma; bronchoconstriction

primary response

primary/late response of asthma; vasodilation

primary response

primary/late response of asthma; mucus buildup

late response

primary/late response of asthma; occurs hours later after allergen exposure

late response

primary/late response of asthma; occlusion of the bronchial lumen with mucus, proteins

late response

primary/late response of asthma; cellular debris

late response

primary/late response of asthma; sloughing of the epithelium

late response

primary/late response of asthma; thickening of the basement membrane

late response

primary/late response of asthma; fluid buildup (edema)

late response

primary/late response of asthma; hypertrophy of the bronchial smooth muscle

late response

primary/late response of asthma; mucus plug

late response

primary/late response of asthma; spirals of bronchial tissue

Curschmann's spirals

Bronchial asthma (whorled mucous plugs)

hives or urticaria

food allergies develop as these

eggs, soy, dairy products, shellfish, peanuts

5 examples of food allergies

atopic urticaria

also known as hives when food allergen is carried to sensitized mast cells in the skin, causing swollen and red eruptions

wheal and flare response

development of hives in the skin when food allergen is present

p-k reaction

other name for wheal and flare reaction

allergic eczema

other name for atopic dermatitis

atopic dermatitis

an inflammatory disease of the skin

atopic dermatitis

frequently associated with a family history of atopy

young children

atopic dermatitis is observed most frequently in _______________

infancy

atopic dermatitis often develops during _____________

IgE

in atopic dermatitis, these levels in the serum are often elevated

TH2 cells, eosinophils

in atopic dermatitis, ______ are involved and an increased number of ___________ is observed

TH1 cells

delayed type hypersensitivity reactions involve this

antigen dose, mode of antigen presentation, genetic constitution

3 factors that regulate type 1 responses

low doses

repeated ___________ of antigen induces a persistent IgE response

higher doses

______________ of antigen result in transient IgE production

IgG

higher doses of antigens result in transient IgE production and a shift toward ____________

adjuvant

this induces a strong IgE response

50%

if both parents are allergic, there is a _________ chance that a child will also be allergic

30%

if only one parent is allergic, there is a ________ chance that a child will also be allergic

avoid contact with known allergens, hyposensitization, use of homonized monoclonal anti-IgE

3 ways type 1 hypersensitivities can be controlled medically

hyposensitization

immunotherapy with repeated injections of increasing doses of allergens

hyposensitization

repeated introduction of allergen by subcutaneous injections

IgG production; T-Cell mediated suppression

hyposensitization causes a shift toward _____________________ or to induce _________________ that turns off the IgE response

T-Cell mediated suppression

hyposensitization induces this possibly by a shift to the TH1 subset and IFN gamma production

TH1 subset, IFN-gamma production

T-cell mediated suppression is done by a shift to the __________ and ______________

FCepsilonRI

antibodies bind to IgE, but only if IgE is not already bound to __________

histamine

IgE bound to FCepsilonRI would lead to ____________ release

type 2 hypersensitivity

when cells are destroyed by an immune response, typically by the combined activities of complement and antibodies

cytotoxic hypersensitivity, IgG mediated cytotoxic hypersensitivity

other names for type 2 hypersensitivity

ABO system and transfusion reactions, Rh system and hemolytic disease of the newborn, drug-induced cytotoxic reactions

3 examples of type 2 sensitivity

ABO system and transfusion reactions

result if an individual receives different blood types

ABO blood group incompatibilites

immediate ABO system and transfusion reactions are most commonly associated with ____________________

complement-mediated lysis

ABO blood group incompatibilities lead to __________________

IgM isohemmaglutinins

triggers complement-mediated lysis

hemoglobinuria

free hemoglobin detected in the plasma, caused by incompatibilities in ABO bloodgroup

bilirubin

in ABO system and transfusion reactions, some of the hemoglobin gets converted to this, which at high levels is toxic

fever, chills, nausea, clotting within blood cells, pain in lower back, hemoglobin in urine

6 symptoms of hemoglobinuria

termination of transfusion, maintenance of urine flow with diuretic

TX of hemoglobinuria

acute tubular necrosis

the accumulation of hemoglobin in the kidney can cause ________________

delayed hemolytic transfusion

occurs in individuals who have received repeated transfusions of ABO compatible blood that is incompatible for other blood group antigens

2-6

delayed hemolytic transfusion reactions develop between _________ days after transfusion

IgG

the predominant isotype in delayed hemolytic transfusion

IgG

less effective than IgM in activating complement

fever, low hemoglobin, increased bilirubin, mild jaundice, anemia

5 symptoms of delayed hemolytic transfusion

erythroblastosis fetalis

hemolytic disease in the newborn (HDN) caused by a blood group (Rh factor) incompatibility between the mother and the fetus

Rh-specific B cells

Rh System and Hemolytic Disease of the Newborn; fetal RBCs activate _____________, resulting in production of Rh specific plasma cells and memory B cells in the mother

IgM

Rh System and Hemolytic Disease of the Newborn; secreted __________ antibody clears the Rh1 fetal RBCs from the mother's circulation

memory cells

Rh System and Hemolytic Disease of the Newborn; secreted IgM antibody clears the Rh1 fetal RBCs from the mother's circulation, but ___________ remain, a threat to any subsequent frequency with an Rh+ fetus

placenta; uterine wall

Rh System and Hemolytic Disease of the Newborn; at the time of delivery, separation of the ___________ from the ____________ allows larger amounts of fetal umbilical-cord blood to enter the mother's circulation

IgG anti-Rh antibodies

Rh System and Hemolytic Disease of the Newborn; activation of memory cells remaining in the mother's circulation results in the formation of ________________ which cross the placenta and damage the fetal RBC

mild to severe anemia, accumulation of lipid-soluble bilirubin in the brain

Rh System and Hemolytic Disease of the Newborn; develops in the fetus

administering antibodies against Rh antigen to the mother within 24-48 hrs after first delivery

Rh System and Hemolytic Disease of the Newborn; TX

Rhogam

an immune serum that prevents a mother's blood from becoming sensitized to foreign antibodies from her fetus

Rhogam

binds to any fetal RBCs that enter the mother's circulation at the time of delivery

Rhogam

facilitates the clearance of fetal RBCs before B cell activation

Rhogam

ensures the memory-cell production can take place

IgG anti-Rh antibodies

in a subsequent pregnancy, it is unlikely to produce these antibodies

intrauterine blood-exchange transfusion

Rh System and Hemolytic Disease of the Newborn; TX for severe reactions to replace fetal Rh+ RBCs with Rh cells

10-21 days

Rh System and Hemolytic Disease of the Newborn; for severe reactions, intrauterine blood-exchange transfusions are given every __________ until delivery

blood exchange transfusion after birth

Rh System and Hemolytic Disease of the Newborn; in less severe cases, this is done primarily to remove bilirubin

UV light

Rh System and Hemolytic Disease of the Newborn; in less severe cases, the infant is exposed to low levels of __________ to break down bilirubin

cerebral damage

this is prevented if bilirubin buildup is stopped in infants

plasmapheresis

Rh System and Hemolytic Disease of the Newborn; TX of a mother during pregnancy

cell separation machine

Rh System and Hemolytic Disease of the Newborn; plasmapheresis uses this to separate the mother's cells and plasma of blood

anti-Rh antibody

Rh System and Hemolytic Disease of the Newborn; in plasmapheresis, the plasma containing the ____________ is discarded

albumin, fresh plasma solution

Rh System and Hemolytic Disease of the Newborn; in plasmapheresis, the plasma containing the anti-Rh antibody is discarded and cells are re-infused into the mother in an _____________ or _______________

immune thrombocytopenic purpurae, agranulocytosis, hemolytic anemia

3 examples of drug-induced cytotoxic reactions

hemolytic anemia

reduction in red cells due to excessive destruction caused by drugs

penicillin

a drug that can induce all four types of hypersensitivity with various clinical manifestations

type 3 hypersensitivity

formation of immune complexes

immune complex-mediated hypersensitivity

other name for type 3 hypersensitivity