Lecture 16: Hypersensitivity Rxns

Question 1

immediate type

Answer 1

Type I HS

Question 2

immune complex

Answer 2

Type III HS

Question 3

modified self

Answer 3

Type II HS

Question 4

delayed type

Answer 4

Type IV HS

Question 5

What Ab isotype mediates type I HS?

Answer 5

IgE

Question 6

What Ab isotype mediates type II HS?

Answer 6

IgG

Question 7

What Ab isotype mediates type III HS?

Answer 7

IgG

Question 8

What Ab isotype mediates type IV HS?

Answer 8

not Ab mediated; it is T cell mediated

Question 9

Describe the “priming” of a type I HS reaction.

Answer 9

1. first exposure to Ag
2. extraction of Ag across epithelium and taken up by APC
3. Ag presented to CD4 T cell (NOT naive)
4. Th2 activated
5. Th2 secretes IL-4 (and activates B cell?)
6. B cells diff into plasma cell
7. plasma cell produces IgE
8. IgE bound up by FcR on mast cell

Question 10

What are some properties of antigens that promote the priming of Type I HS reaction?

Answer 10

Antigens that prime Th2:

• proteins that bind MHC class II
• allergens are often proteases
• low dose
• low molecular weight (to cross mucous membrane)
• high solubility

Question 11

T or F: you usually have a type I HS reaction the first time you are exposed to an Ag.

Answer 11

false: the system has to be primed –> you see rxn after the 2nd exposure

Question 12

T or F: A TI-1 Ag can initiate a type I HS.

Answer 12

false: must be a T dependent Ag (Th2 mediates B cell production of IgE)

Question 13

Once the immune system is primed, what initiates a type I HS reaction?

Answer 13

Ag has to crosslink 2 or more IgE on the surface of mast cells –> degranulation

Question 14

How many IgE need to be crosslinked to cause a cause mast cell degranulation

Answer 14

2 or more

Question 15

Where are mast cells found? How is this significant?

Answer 15

beneath epithelial layer –> Ag get to them quickly –> rapid degranulation after sys has been primed

Question 16

T or F: The IgE that coat a single mast cell share the same exact specificity.

Answer 16

false: there are varient different specificities

Question 17

What enzymes are found in mast cells and that are their fucntion?

Answer 17

trypase
chymase
cathespin G
carboxypeptidase

remodeling of connective tissue matric

Question 18

What are the toxic mediators in mast cells? What are their biological effects?

Answer 18

histamine and heparin

toxic to parasites
inc vascular permeability
causes smooth muscle contraction

Question 19

What is the major cytokine released by mast cells? What effect does it have?

Answer 19

TNF-a

• promotes inflammation
• stimulate cytokine production by many cell types
• activates endothelium

Question 20

What is a wheal and flare reaction?

Answer 20

local degranulation of mast cells causing a hive (due to injection of Ag to test for specific hypersensitivity)

Question 21

What is urticaria?

Answer 21

a rash due to type I HS (all over body = systemic exposure)

Question 22

What does mast cell degranulation in the GI tract cause?

Answer 22

inc fluid secretion and peristalsis –> expulsion of GI tract contents (diarrhea, vomiting)

Question 23

What does mast cell degranulation in the airways cause?

Answer 23

decreased diameter and inc mucosal secretion –> expulsion of airway contents (phlegm, coughing)

Question 24

What does mast cell degranulation in the blood vessels cause?

Answer 24

inc blood flow and permeability –> edema, inflamm, inc lymph flor and carries Ag to lymph nodes (to prime T/B cell response –> anaphylactic shock)

Question 25

Ag in blood stream enters tissues and activates connective tissue mast cells throughout the body (is...)

Answer 25

anaphalaxis

Question 26

What affect does anaphylaxis have on the heart and vascular system?

Answer 26

1. inc capillary permeabiluty - fluid enters tissues --> swelling/edema (including tongue) 2. Loss of BP (from fluid loss) 3. dec O2 to tissues 4. irregular heartbeat 5. anaphylactic shock 6. loss of consciousness

Question 27

What is the effective treatment of anaphylaxis? Why?

Answer 27

epinephrine --> causes rebound of BP

Question 28

What are common allergens that elicit systemic anaphylaxis?

Answer 28

drugs serum venoms peanuts

Question 29

What syndromes are IgE mediated?

Answer 29

``` systemic anaphylaxis wheal and flare Hay fever Bronchial Asthma Food Allergy ```

Question 30

Describe the type II HS reaction.

Answer 30

(Penicillin-induced) 1. Penicillin binds RBCs and leukocytes 2. Self determinant on RBC changes 3. (for some people) self determinant is recognized as invader and complement is deposited 4. these complement laden RBCs are phagocytosed by macrophages 5. macrophages process these RBCs and load altered self peptides onto MHC class II 6. recognized by Th2 cells 7. Th2 activate B cells --> plasma cells 8. plasma cells secreted IgG which binds to penicillin-altered RBCs 9. activation of C1-C9 --> LYSIS OR Activation of C1-C3 --> phagocytosis of RBC-Ab immune complex by macrophage

Question 31

What gross change is associated with penicillin hypersensitivity reaction?

Answer 31

rash

Question 32

Describe type III HS.

Answer 32

1. Ag injected into into a person with IgG Ab specific to it 2. Immune complexes form with that Ag in tissue 3. Complement activated 4. C5a that results binds C5a-R on mast cell 5. immune complex binds FcgRIII on mast cell 6. Degranulation 7. local inflammation, inc fluid and protein release, phagocytosis, and blood vessel occlusion (vasculitis, nephritis, arthritis)

Question 33

What organ is most susceptible to type II HS?

Answer 33

kidney

Question 34

How long does a type III HS reaction to present?

Answer 34

1-2 hrs after Ag exposure

Question 35

In a subcutaneous type III HS reaction, what is the name of the resulting disease and where are the immunocomplexes deposited?

Answer 35

Arthus Reaction on perivascular area

Question 36

What is "farmer's lung"?

Answer 36

a type III HS reaction in which immune complexes are deposited in lung due to constant exposure to a mold in hay

Question 37

What are 2 type III HS immune complex diseases?

Answer 37

farmer's lung and bird-Fancier disease

Question 38

Describe type IV HS.

Answer 38

(delayed hypersensitivity) 1. Ag is processed by tissue Ag and stimulates Th1 cells 2. Th1 secrete: -chemokines -> macrophage recruitment -IFN-g -> activ macrophages, inc release of inflamm mediators -TNF-a and LT -> local tissue destruction; inc expression of adhesion molecules on blood vessels -IL-3 and GM-CSF -> monocyte production by BM

Question 39

Describe the tuberculin reaction.

Answer 39

1. small amt of MTB protein injected sub-Q 2. picked up and processed by macrophages 3. Th1??? cell recognizes Ag and releases cytokines 4. T cells, phagocytes, fluid, and protein move into sub-Q tissue 2. look for inflamm response 24-72 hrs later

Question 40

How does poison ivy elicit a hypersensitivity response?

Answer 40

Pentadecatechol penetrates skin and covalently binds host proteins forming new, non-self Ag--> T cell spc tp Ag are produced