Hypersensitivities 4

Question 1

Type IV hypersensitivity

Answer 1

• delayed type hypersensitivity
• cell mediated (which is different than other reactions)
• mechanism of tissue damage involving activated macrophages and cytotoxic T cells

**they are technically the “normal” mechanism for recovery from intracellular infections

Question 2

What is activated to result in Type IV Hyper sensitivity?

Answer 2

• Antigen presented by antigen presenting cells activates Th1 cells leading to cytokine released, macrophage activation and CD8+ T cell destruction of cells

Question 3

Delayed Type Hypersensitivity skin test (DTH)

Answer 3

• reaction to the intra-dermal injection of antigen and can be used for testing for involvement of cell mediated immunity
• 5 days after injection. Measure swelling site

**If unexposed animal= no response
** if previously exposed animal (has memory) then DTH reaction occurs

Question 4

Two possible outcomes of Type IV hypersensitivity

Answer 4

1. antigen is cleared
2. antigen persists

Question 5

Antigen being cleared:

Answer 5

• lesions indurate and resolve (due to T cells and macrophages)
• limits the replication and spread of viruses
• means of killing and clearing intracellular bacteria and protozoa
• use of this reaction in the dermis is the classical test for cell-mediated immunity

Question 6

Antigen persists:

Answer 6

• granuloma forms, accumulations of macrophages, some fuse to form multi-nucleate “giant cells”, fibrosis and pathological consequences

Question 7

Feline leprosy

Answer 7

• chronic cutaneous Mycobacteria infection resulting in granuloma infection
• hyper sensitivity IV example

Question 8

Mycobacteria paratuberculosis (Johne’s)

Answer 8

granulomatous gastroenteritis resulting in malabsorption syndroms
- leading to severe weight loss

**positive staining within macrophages= brown

Question 9

Leishmaniasis

Answer 9

• protozoa in dermal macrophages resulting in granulomatous dermatitis

Question 10

Plant material in lungs

Answer 10

• plant material inside lungs, will result in granuloma (macrophages under effects of TNF fuse to form multi-nucleate cells)

Question 11

Contact hypersensitivity

Answer 11

-dermatitis on contact with a wide range of chemical or biological substances

*Contact irritant: substance causes direct tissue inflammation

• Type IV hypersensitivity: usually occurs in response to prolonged exposure to small “reactive” molecules (ex. latex, shampoos, leathers,metal-nickel)

Question 12

Contact hypersensitivity steps

Answer 12

1. chemical contact epidermis of skin
2. Enter and combine with carrier protein to form hapten
3. macrophages phagocytose hapten-carriers and present the antigen to T cells
4. activated T cells attack the sensitized epidermal cells creating vesicles

Question 13

Sensitization

Answer 13

Hapten-carrier complex is phagocytosed by Langerhans cells in the skin and provokes an immune response

Question 14

Hapten

Answer 14

A molecule that is too small to be an antigen on its own but when absorbed into the epidermis of skin, it can become associated with a larger self protein (carrier) in the skin

Question 15

Re-exposure to hapten

Answer 15

-delayed type hypersensitivity reaction occurs in the skin
*intensely pruritic

Question 16

Diagnosis/therapy of contact hypersensitivity

Answer 16

Patch Test

• trans-dermal introduction of suspect agents/haptens applied by gauze taped to skin for 48-72 hours

Question 17

Graft Rejection

Answer 17

• a type of Type IV hypersensitivity

Question 18

Types of grafts

Answer 18

1. autograft
2. isograft
3. allograft
4. Xenografts

Question 19

Autograft

Answer 19

• grafting within an individual

Question 20

Isograft

Answer 20

• grafting between genetically identical individuals (homozygous twins or inbred mice)

Question 21

allograft

Answer 21

• grafting between genetically different individuals of the same species

Question 22

xenografts

Answer 22

grafting between individuals of different species

Question 23

Allograft Rejection

Answer 23

• involves antibodies, T cells, and type IV hypersensitivity
• Targets: histocompatibility antigens (MHC I, MHC II, blood group antigens)

Question 24

where do blood group antigens occur?

Answer 24

• on all nucleated cells as well as RBCs

Question 25

Graft vs. Host Disease

Answer 25

Graft: donated tissue
Host: receiver of transplant

**Lymphocytes in the graft develop an immune response to the host/recipient tissues

** Recipient immuno-suppressed prior to transplant to try and prevent graft rejection (recipient attacking graft)