Type IV hypersensitivity

Question 1

“big picture”

Answer 1

T-cell mediated diseases

mostly chronic

Question 2

kinds of “big pic” T(IV)HS

Answer 2

CD4+ Th1 (Mac activator) mediated
Th17 (generalized inflammatory inciter) mediator
CD8+ CTL mediated

Question 3

T(IV)HS diseases: Demyelination in the central nervous system, sensory and motor dysfunction

Answer 3

Multiple sclerosis

myelin proteins targeted

Question 4

T(IV)HS diseases: inflammation of synovium and erosion of cartilage and bone in joints

Answer 4

Rheumatoid arthritis

unknown antigens in joint targeted

Question 5

T(IV)HS diseases : impaired glucose metabolism, vascular disease

Answer 5

type 1 diabetes mellitus

pancreatic islet antigens

Question 6

T(IV)HS diseases: inflammation of the bowel wall; abdominal pain; diarrhea; hemorrhage

Answer 6

Crohn’s disease

unknown role of intestinal microbes

Question 7

T(IV)HS diseases: DTH reaction in skin rash

Answer 7

Contact sensitivity

poison ivy reaction

modified skin protein

Question 8

T(IV)HS diseases : chronic inflammation

Answer 8

chronic infections

microbial proteins

Question 9

DTH

Answer 9

classical t cell mediated inflammatory reaction

delayed type hypersensitivity

damages host tissues

results from activation of CD4+ cells

reaction delayed 24-48 hours after Ag challenge

Question 10

PPD

Answer 10

purified protein derivative: protein antigen of mycobacterium tuberculosis elicts a DTH reaction called the tuberculin reaction

Question 11

DTH reactions that explain how it works

Answer 11

poison ivy (24-48 hours later)

Question 12

How does DTH work at the molecular level

Answer 12

The protein antigens are too small to elicit a reaction, but they bind to host proteins and these can be endocytozed and presented to host cell T cells

Question 13

How does DTH work time wise

Answer 13

primary contact is 7-10 days: T cell sensitization develop, producing T memory cells (NO DERMATITIS)

secondary contact 1-2 days (DERMATITIS)

Question 14

Granulomatous inflammation: structural features

Answer 14

lymph node will exhibit a granuloma: activated MOs and giant/multinucleated cells, and lymphocytes (primarily T cells): the center may be necrotic

Question 15

Secondary DTH exposure

Answer 15

1. seconds-minuntes: resident cells initiated cellular recruitment
2. MAST cells —> TNF —> neutrophil recruitment —> activation (tissue + circulating monocytes)
3. NK + (gamma/delta) T cells —> activation (tissue DCs)
4. DCs—> chemokines and TNF facilitating cellular trafficking into tissues

Question 16

First step in secondary DTH

Answer 16

antigenic activation of Mast cells, NK cells, gamma/delta cells happens in seconds

MAST cells —> TNF —> neutrophil recruitment —> activation (tissue + circulating monocytes)

NK + (gamma/delta) T cells —> activation (tissue DCs)

DCs—> chemokines and TNF facilitating cellular trafficking into tissues

Min/hrs—> Ag-DCs migrate to lymph nodes via lymphatic channels

Question 17

Second step in secondary DTH

Answer 17

Ag-DCs travel to lymph nodes, initiate adaptive T cell response

DCs—> IL-12 + T Cells—> Th1 cells
DCs present Ag to naive CD4+ T cells
Activation of Th1 T cells—> IL-12 secretion promoting T cell survival and proliferation
expansion of Th1 cells specific for antigen

Question 18

Formation of mature granuloma: time frame and final events

Answer 18

Within hours to days AFTER Ag exposure Th1 home to tissues

If Ag not eradicated, inflammation persists

Th1 —> IFN –> Mac activation
Activated Mac –> TNF + IFN —> further Mac activation
constant upregulating of Macs causes granulosome over days to weeks

Question 19

Big pic stuff

Answer 19

an infection that isn’t contained leads to constant inflammation, and thus constant Mac activation

constant TNF and IFN secretion via Th1 and Macs themselves leads to further upregulation of Mac activation, leading to eventual granulosome formation