Type II Antibody-mediated cytotoxic hypersensitivity

Type II

Antibody-mediatedcytotoxic hypersensitivity

The four types of hypersensitive responses

Kuby J et al., Immunology 2003

Type II hypersensitivity reactions (1)

- Caused by antibody to cell surface antigensand components of the extracellular matrix.

- These antibodies can sensitize the cells for antibody-dependent cytotoxic attack by K cellsor for complement-mediated lysis.

- Type II hypersensitivity is seen in the destructionof red cells in transfusion reactions and inhaemolytic disease of the newborn.

Type II hypersensitivity reactions (2)

- Innocuous antigens can cause Type IIhypersensitivity reactions insusceptible individuals by binding to the surfaces of circulating blood cells.

- IgG antibodies against cell-surface receptorsthat disrupt the normal functions of thereceptor, either by causing uncontrollableactivation or by blocking receptor function.

Antibody-Dependent Cell-mediated Cytotoxicity (ADCC)

Kuby J et al., Immunology 2003

ABO blood group

Kuby J et al., Immunology 2003

Development of erythroblastosis fetalis (hemolytic disease of the newborn) caused when an RH- mother carries an RH+ fetus, and effect of treatment with anti-Rh antibody, or Rhogam

Kuby J et al., Immunology 2003

Graves’ disease: Hyperthyroidism Myasthenia gravis: Muscle weakness

(hormones) (neurotransmitter)

Effector mechanisms of antibody-mediated disease

C

Type III

Immune complex-mediated hypersensitivity

The four types of hypersensitive responses

Kuby J et al., Immunology 2003

Type III hypersensitivity reactions (1)

- Directed against soluble antigens

- Caused by the deposition of antigen/antibodycomplexes in tissue and blood vessels.

- The complexes activate complement and attractploymorphs and macrophages to the site.

- These cells may exocytose their granule contentsand release reactive oxygen and nitrogen intermediates to cause local tissue damage.

Type III hypersensitivity reactions (2)

- The deposition of immune complexes intissues causes a local inflammatoryresponse known as an Arthus reaction.

- Serum sickness is a classic example of atransient immune complex-mediated syndrome.

- In situations in which antigen persistssubacute bacterial endocarditischronic viral hepatitissystemic lupus erythematosus (SLE)

Development of a localized Arthus reaction

Immunology (Fig. 16-15), 5th edn 2003 Kuby J

The multiple activities of the complement system.

Immune complex disease

- The immune complexes produced may bind to vascularendothelium and kidney glomeruli and activate complement(MAC generation).

- It initiates the acute inflammatory responses that destroy thevessel walls or glomeruli and lead to thrombosis, ischemicdamage to tissues, and scarring.

- Some of the late complement proteins may activateprothrombinases in the circulation that initiate thrombosis.

Figure 12-23Serum sickness is a classic example of a transient

immune complex-mediated syndrome

Type IV

Delayed-type hypersensitivity (DTH)

(Cell-mediated hypersensitivity)

The four types of hypersensitive responses

Kuby J et al., Immunology 2003

Type IV hypersensitivity reactions

- T-cell mediated

- 1st group: Tissue damage is caused by the activationof macrophages by TH1 cells, which resultsin an inflammatory response.

- 2nd group: Damage is caused by the activation by TH2cells of inflammatory responses in whicheosinophils predominate.

- 3rd group: Damage is caused directly by cytotoxic T cells (CTL).

Figure 12-24Type IV hypersensitivity responses

Overview of the DTH response

Kuby J et al., Immunology 2003

Figure 12-26 part 1 of 2The delayed-type (type IV) hypersensitivity response is directed by chemokines and cytokines released by TH1 cells stimulated by antigen (1)

Figure 12-26 part 2 of 2The delayed-type (type IV) hypersensitivity response is directed by chemokines and cytokines released by TH1 cells stimulated by antigen (2)

A prolonged DTH response can lead to formation of a granuloma

Lytic enzymes released fromactivated macrophages in agranuloma can cause extensivetissue damage.

Kuby J et al., Immunology 2003

A Second Exposure to Poison Oak May Result in Delayed-Type Hypersensitivity

Kuby J et al., Immunology 2003

Immunology (Fig. 16-20), 5th edn 2003 Kuby J

Development of delayed-type hypersensitvity reaction after a second exposure to poison oak

Secrete INF-γ and other cytokines

Activated macrophages

Secrete mediators of inflammation

Figure 12-28Blistering skin lesions on hand of patient with

poison ivy contact dermatitis

There are four types of hypersensitivity reaction mediated by immunological mechanisms that cause tissue damage

Kuby J et al., Immunology 2003