Hypersensitivity Types II and III Flashcards
Erythroblastosis fetalis also known as
Hemolytic disease of the newborn (HDNB)
Speed of Hypersensitivities from fastest to slowest
Type 1- Type II-Type III-Type IV
•Type II hypersensitivity represents damage resulting when the ____________immune system becomes directed against self.
Humoral
IgM antibodies in plasma that cross-react with blood group antigens not present on an individual’s own RBCs are called ____________
isohemagglutinins
Arthus reactions
Hypersensitivity Type III
Can be induced by insect bites, inhalation of fungal or animal protein
Characterized by local and sometimes severe inflammation of blood vessels
A local reaction
- Intradermal injection of Ag induces Abs, which form Ag-Ab complexes in the skin
- Initiates an inlammatory reaction that peaks approximately 4 to 10 hrs post injection
- Inflammation is characterized by swelling and localized bleeding, followed by fibrin deposition
- Edema, necrosis, and activation of complement
Hypersensitivity Type III
Immune Relationship
Mechanism of tissue injury
Presentation
Immune Relationship
- Immune Complex mediated
- Antigen-antibody complexes form
- Antigens can be self or foreign
Mechanism of tissue injury
- Complexes are filtered out of circulation and deposited in healthy tissue and capillary beds
- Neutrophils attracted and complement activated by Ab-Ag complex
- Neutrophils release lysosomal enzymes
- Healthy tissue damaged
Presentation
- Widespread molbility of Ab-Ag complexes allows for vasculitis and system manifestations
- Compared to type II with generally localized reactions
Diabetes Type II
Hypersensitivity Type II NonCytotoxic
Anti-Insulin receptor antibody
- Inhibits binding of insulin
- Hyperglycemia
•Rh- individual may have Abs against Rh antigen, but usually only after 1st exposure to Rh Ag called ____________
Sensitization
Pernicious anemia
Hypersensitivity Type II Noncytotoxic
Low Intrinsic factor
- Secreted from parietal cells of the stomach
- Necessary for the absorption of vitamin B12
Anti-intrinsic factor Ab
- Inhibits binding of IF of gastric parietal cells to receptor
- Leads to neautralization of IF
- Decreased vitamin B12 absorption; macrocytic anemia and hypersegmented neutrophils
Resection of terminal ileum
Intestinal infections
- Diphyllobothrium latum
Hypersensitivity Type II
- Type II hypersensitivity represents damage resulting when the humoral immune system becomes directed against self.
- The mechanisms of type II hypersensitivity are those of antibody effector function.
- Antibodies may bind specifically to tissue antigens
- In both cases, the deposited antibodies induce inflammation, leading to tissue injury.
- Type II is cy-2-toxic
- Ab and complement lead to MAC
Idiopathic thrombocytopenic purpura
Anti-platelet Abs (IgG) bind to platelets triggering complement cascade resulting in the formation of MAC and cell lysis.
When platelets are depleted, clotting abnormalities occur, resulting in petechia and ecchymoses seen in the patient.
Type II Cytotoxic hypersensitivity
Serum sickness
Hypersensitivity Type III
Most is caused by drugs (like beta-lactams, sulfa drugs, anti-venin) acting as haptens
Abs to the foreign proteins are produced, complex formed and deposited in membranes, fix complement and lead to tissue damage
- Activate/consume C3 and result in decreased serum levels of C3
Fever, urticaria, arthralgias, proteinuria, lymphadenopathy
Usually self-limited, and will resolve with withdrawal of the offending agent
Hypersensitivity Type III reactions
Involve Abs against soluble Ags circulating in the serum
- Type III, immune complex of 3 things stuck together
- Ag-Ab-complement
Un-cleared immune complexes
Acute rheumatic fever
Hypersensitivity Cytotoxic Type II
An autoimmune disease that follows untreated pharyngeal streptoccocal infection
Ab against streptococcal cell wall binds healthy tissue
- Heart and joint inflammation
Risks include right-sided heart disease
- Secondary to valvular dysfunction
- Most often mitral stenosis
Systemic Lupus Erythematosis
Hypersensitivity Type III
Anti-dsDNA, anti-Sm, anti Rho Abs in complex with Ag
- Butterfly facial rash
- Nephritis
- Arthritis
- Vasculitis
Type of effector mechanisms. Types I, II, and III are ________ mediated. Type IV is _______ mediated.
Antibody; cell
Bullous pemphigoid
Hypersensitivity Cytotoxic Type II
Patients with bullous pemphigold are generally elderly
Auto Abs against the basement membrane of the epidermis
- Speration of epidermis from basement membrane
- Results in formation of tense and intact blisters
- Subepidermal
- Less fragile, intact, don’t rupture
Prevention/ Treatment of Hemolytic Disease of the Newborn (Erthroblastosis fetalis)
- RhoGAM (anti-RhD IgG) given to mother at 28 weeks withinin 72 hours of delivery, which prevents mother from developing B cell memory of RhD
- For severe reactions, fetus can be given an intrauterine blood-exchange transfusion to replace fetal Rh+ red blood cells with Rh- cells.
- In less severe cases, a blood-exhange transfusion is not given until after birth, primarily to remove bilirubin
- Infant is also exposed to low amounts of UV light to break down the bilirubin and prevent cerebral damage
- The mother can also be treated during the pregnancy by plasmapheresis
- A cell separation machine is used to separate the mother’s blood into two fractions: cell and plasma
- The plasma containing the anti-Rh Ab is discarded, and the cells are reinfused into the mother in an albumin or fresh plasma solution
Rheumatoid arthritis
Hypersensitivity Type III
Anti-IgM Fc region antibody complex with antigen
- joint pain, decrease in range of motion
- Destruction of cartilage and bone
*
Rh is present in around ______ % of the population.
85
Hypersensitivity pneumonitis
Hypersensitivity Type III
Inhaled dust forms an Ab-Ag complex
“Farmer’s lung”
Tests
- Bronchoalveolar lavage
- Pulmonary function test
- High resolution computed tomography
Hypersensitivity Type II
- Immune Relationship
- Mechanism of Tissue Injury
- Presentation
•Immune relationship
- Ab mediated
- IgM, IgG bind to antigen
- complement activation
- results in lysis via MAC or phagocytosis
- Effector cells
- cytotoxic
- PMN (Neutrophils), macrophages, NK cells
Mechanism of tissue injury
•Abs lead to disease via 3 different processes
- activation of complement or opsonization
- recruitment of neutrophils and macrophages that incite tissue damage
- interfere with normal receptor function
Presentation
- Disease localized to specific tissues where Abs are present
Graves’ disease
Type II Hypersensitivity NonCytotoxic
Anti-TSH receptor Ab
- Stimulation of cell-surface receptors (stimulates T3 and T4 release)
- Hyperthyroid followed by hypothyroid
Most common cause of hyperthyroidism
Female Dominant
- HLA-B8- DR3 association
Often incited during stress
Complications stress-induced catecholamine surge
- May be fatal by arrhythmia
Pregnancy complications
- anti-TSH receptor antibodies may cross placenta and produce hyperthyroidism in the fetus
___________ can induce all 4 types of hypersensitivity with various clinical manifestations. What manifestations are seen in each type?
Penicillin
Type I: Urticaria, systemic anaphylaxis
Type II: Hemolytic anemia
Type III: Serum sickness, glometulonephritis
Type IV: Contact dermitis
