Lecture 17: Over-Reactions of the Immune System

type I sensitivity (name, Ab type, Ag)

• name: anaphylactic HS

• Ab type: IgE

• Ag: exogenous (soluble)

type I sensitivity (effect, appearance)

• effect: 1st exposure: IgE and memory cells. Repeated exposure: release of inflammatory meditators from mast cell granules

• appearance: wheal and flare (raised, itchy red skin area)

type II sensitivity (name, Ab type, Ag)

• name: cytotoxic HS

• Ab type: IgG, IgM

• Ag: cell surface

type II sensitivity (effect, appearance)

• effect: complement activation

• appearance: lysis and necrosis

type III sensitivity (name, Ab type, Ag)

• name: immune complex HS

• Ab type: IgG

• Ag: soluble (protein, drug)

type III sensitivity (effect, appearance)

• effect: depositing of small immune complexs when Ag > Ab

• appearance: erythema, edema and necrosis

type IV sensitivity (name, effector, Ag)

• name: cell mediated / delayed type HS

• effector: T cells

• Ag: various

type IV sensitivity (effect, appearance)

• effect: T cells secrete cytokines leading to lesions

• appearance: redness, hardening, fluid pockets

first response to an allergen

gives rise to adaptive immunity and immunological memory

second response to an allergen

causes inflammation and tissue damage

process of the mast cell in type I HS

• when a person encounters Ag the adaptive immune response produces IgE and memory cells (sensitization)

• when exposure is repeated Ag binds to IgE, causing immediate release of inflammatory mediators (mast cell granules)

2 main purposes of stored and synthesized mediators in mast cells in type I HS

• early: mast cells produce lymphocytes and expel pathogen

• late: eosinophils directly kill pathogens, amplify eosinophil production and recruit leukocytes

immediate reaction in type I HS

occurs very shortly after exposure, wheal and flare reaction due to degranulation

late phase reaction in type I HS

occurs hours after exposure due to molecules synthesized upon activation

function of epinephrine in type I HS

it increases blood pressure which counteracts the lowering of blood pressure due to anaphylaxis

3 main treatments for type I HS

1. prevention

2. drugs (antihistamines, epinephrine)

3. desensitization

2 theories of the mechanism of desensitization for type I HS

1. stimulates IgG production, which competes with IgE for antigen

2. inhibits mast cell and basophil activity

what cell initiates a TH2 response by secreting IL-4?

basophils

two signals that drive isotype switching to IgE during hypersensitivity

• IL-4 and IL-3

• CD40L (basophil) binds CD40 (B cell)

how are incompatibility of blood group antigens (in blood transfusion) & hemolytic anemia are examples of Type II HS?

antigens on the surface of erythrocytes have the potential to cause a cytotoxic HS rxn due to the presence of Anti-B antibodies (if antigen A is present) or Anti-B antibodies (if antigen A is present)

how does size of an immune complex affect development of HS? (type 3 HS)

• small immune complexes are not cleared by complement and are deposited when Ag > Ab

• large and medium immune complexes are cleared by complement activation

how to decrease immune complexes in type 3 HS

complexes decrease as Ab increases

how do the immune complexes cause damage in type 3 HS?

deposition of immune complexes causes inflammation

7 theories of what could be responsible for the rise in hypersensitivities

1. viral infection

2. sensitization followed by cross-reactivity

3. diet shift

4. genetic basis

5. vaccines

6. hygiene theory (hyper sanitization)

7. antibiotics

hapten

a low MW molecule, such as an organic molecule or metal ion, that binds to a carrier, such as self, to form an antigen in type IV HS

how does poison ivy cause type IV HS

• when the organic molecule in poison ivy penetrates the skin cells a hapten is formed

• Ag introduced → phagocytosis → DC migration → Ag presentation → T cell activation → T cell secretion of cytokines → lesions

hypersensitivity

the state of heightened reactivity to an antigen

sensitized

allergen inducing a primary immune response to inducing hypersensitivity (allergy)

atopy

the state of being predisposed to allergies

anaphylactic shock

IgE mediated allergic reaction to a systemic Ag