20b - Type IV Hypersensitivity

Question 1

Type IV mechanism of tissue damage that involves activated:

Answer 1

-macrophages
-cytotoxic T lymphocytes
*antigen (via APCs) activates Th1
>leads to cytokine release, macrophage activation and (sometimes) CD8+ T cell destruction of cells

Question 2

Type IV differs from types I, II, III:

Answer 2

-‘cell-mediated’ (memory)
*not mediated through Ab
*’normal’ mechanism for recovery from INTRACELLULAR infections

Question 3

Type IV reaction can be transferred:

Answer 3

-from on syngeneic animal to another
-by Th1

Question 4

Delayed type hypersensitivity skin test (DTH skin test):

Answer 4

-type IV reaction to intra-dermal injection of antigen
-can be used for testing for involvement of cell-mediated immunity

Question 5

If antigen is injected into (DTH skin test):

Answer 5

-unexposed animal: no response
-previously exposed animal with a memory population of Th1 cells=”DTH Reaction” occurs

Question 6

Steps of DTH skin test:

Answer 6

1. Antigen injected and processed by local APCs
2. Th1 effector cell recognizes antigen and releases cytokines that act on vascular endothelium
3. Recruitment of phagocytes and plasma cells to site causes a VISIBLE LESION

Question 7

Outcomes of Type IV hypersensitivity:

Answer 7

1. Antigen is cleared
2. Antigen persists

Question 8

Antigen is cleared (Type IV):

Answer 8

-lesions indurate and resolve
>limits replication and spread of viruses
>kill and clear intracellular bacteria and protozoa
*use it for testing cell-mediated immunity

Question 9

Antigen persists (Type IV):

Answer 9

-granuloma formation
>accumulations of macrophages (some ‘giant cells’)
>fibrosis
>pathological consequences

Question 10

What kind of organisms lead to persistent infections/granulomas?

Answer 10

-obligate intracellular organisms which are resistant to macrophage-mediated killing

Question 11

‘feline leprosy’:

Answer 11

-chronic cutaneous Mycobacteria infection resulting in granuloma formation
*T cells ‘wall off the area’

Question 12

Mycobacteria paratuberculosis:

Answer 12

-granulomatous gastroenteritis results in malabsorption syndrome
>leads to severe weight loss

Question 13

Leishmaniasis:

Answer 13

-intracellular protozoa in dermal macrophages resulting in granulomatous dermatitis

Question 14

Granuloma with ‘giant cells’:

Answer 14

-macrophages under effects of TNF fuse to form multi-nucleated cells

Question 15

DTH for tuberculosis exposure:

Answer 15

-PPD-purified protein derivative of mycobacterium
*determine exposure to Mycobacteria

Question 16

Contact hypersensitivity:

Answer 16

-dermatitis on ‘contact’ with a wide range of chemical or biological substances
Ex. DTH reaction following application of neomycin ointment

Question 17

Types of contact hypersensitivity:

Answer 17

1. Contact irritant
2. Type IV hypersensitivity

Question 18

Contact irritant:

Answer 18

-substance causes direct tissue inflammation

Question 19

Type IV hypersensitivity:

Answer 19

-usually occurs in response to prolonged exposure to small ‘reactive’ molecules
Ex. drugs, dyes in carpets, shampoos, rubber, metal-nickel, flea collars

Question 20

Mechanism of contract hypersensitivity:

Answer 20

1. Sensitization
2. Re-exposure

Question 21

Sensitization:

Answer 21

-molecule too small to be an antigen is absorbed into epidermis of skin (HAPTEN)
>becomes associated with a larger self-molecule in the skin (CARRIER, ex. protein)
*get a hapten-carrier complex

Question 22

Hapten-carrier complex is:

Answer 22

-phagocytosed by Langerhans cells in the skin and provoke an immune response

Question 23

Re-exposure:

Answer 23

-DTH reaction in skin
>intensely pruritic (intense scratching)

Question 24

Diagnosis/therapy of contact hypersensitivity:

Answer 24

1. Patch test: trans-dermal introduction of suspect agents/haptens
2. ‘Antigen’ applied to skin on a gauze swab-taped in place for 48-72 hours

Question 25

What is graft rejection?

Answer 25

*Type IV hypersensitivity

Question 26

Types of graft rejection:

Answer 26

-autograft
-isograft
-allografts
-xenografts

Question 27

Autograft:

Answer 27

-grafting within an individual

Question 28

Isograft:

Answer 28

-grafting between genetically identical individuals (homozygotic twins or inbred mice)

Question 29

Allograft:

Answer 29

-grafting between genetically different individuals of the same species
*targets are histocompatibility antigens

Question 30

Histocompatibility antigens:

Answer 30

-MHC I: all nucleated cells
-MHC II: APCs
-blood group antigens: occur on all nucleated cells (as well as RBCs)

Question 31

Xenograft:

Answer 31

-grafting between individuals of different species

Question 32

Graft vs. host disease:

Answer 32

-lymphocytes in graft develop an immune response to host tissues
>recipient is usually immune-suppressed prior to transplant
*donor ‘passenger’ lymphocytes within graft mount a type IV response toward recipient cells