Topic 4 Unwanted Immune Respones

Front 1

Define hypersensitivity

Back 1

These are exaggerated immune responses that may cause damage to the individual
-Quite often these respones are made to innocuous (harmless) antigens

Front 2

What are the two types of hypersensitivity?

Back 2

Delayed hypersensitivity (mediated by antibody) or delayed-type hypersensitvity (mediated by Th1 cells)

Front 3

What is immediate hypersensitivity?

Back 3

Refers to allergic responses that are due to histamine released by mast cells or basophils

Front 4

How does mast cells and basophils cause immediate hypersensitvity?

Back 4

Mast cells and basophils have receptors that bind IgE molecules.
-When these bound IgE molecules bind an antigen, the cell degranulates and releases large amounts of histamine

Front 5

What are allergens?

Back 5

Antigens that bind to IgE on mast cells are allergens

Front 6

How does immediate hypersensitivty manifests itself in the respiratory system?

Back 6

This is seen as excess mucus secretion accompanied by sneezing and coughing

Front 7

How does immediate hypersensitivty manifests itself in the skin?

Back 7

This is seen as a rapid inflammatory-like response (hives or welts)

Front 8

How does immediate hypersensitivty manifests itself in the gut?

Back 8

This manifests as diarrhera or vomitting

Front 9

What drugs block the release of histamine?

Back 9

Anti-histamines block the receptor for histamine on endothelial cells and can prevent allergic response (but not the release of histamine)

Front 10

What is the theory behind allergy shots?

Back 10

Recall that new B cells are made everyday. The theory behind allergy shots is that immunizing a person repeatedly with small doses of antigens will result in the naive B cells becoming activated and producing lots of IgG antobides in the blood or IgA antibodies in the secretions. The idea is that the IgG and IgA antibodies will bind the allergen before it can bind to the IgE attached to the mast cell or basophil

Front 11

How do we have allergies?

Back 11

It requires at least two exposures to a substance
-Initial exposure will result in a parimary response in which IgM antibodies are made
-Subsequent exposure to the same antigen will result in the class switching of the memory B cells so that they produce IgE antibodies

Front 12

Where is delayed-type hypersensitivity (DTH) observed in?

Back 12

Only in secondary responses.

Front 13

What is DTH mediated by?

Back 13

Activated Th1 cells
This is also known as TH1 mediated inflammation

Front 14

How does DTH work?

Back 14

Th1 cells serete substances that cause an inflammatory response
-This inflammatory response takes 1 to 2 days to develop
-Cytokines made by the Th1 cells increase blood flow to the area
-They also attract neutrophils and macrophages that release bacterical substances
-

Front 15

What is an example of a DTH rxn?

Back 15

A positive reaction to a tuberculin test

Front 16

What is a tuberculin test?

Back 16

It is a test used to see if a patient has been previous exposed to the organism that causes tuberculosis, Mycobacterium tuberculosis (MTB0
-MTB is an intracellular pathogen

Front 17

What happens during the tuberculin test that causes a DTH rxn?

Back 17

A non-infectious extract from M. tuberculosis is injected under the skin
-If you have been previously exposed to M. tuberculosis, a DTH rxn (redness and swelling) will develop at the site of injection after 1-2 days

Front 18

What does attenuated mean?

Back 18

Reduced in strength
-Applies to vaccines when you give a harmless related organism to an infectious one

Front 19

What is the theory behind graft rejection?

Back 19

-Different people have different versions (alleles) of MHC proteins on their cells
-In an organ transplantation, the transplanted cells from the donor may have different MHC proteins than those of the recipient
-Since these other alleles of MHC proteins are not normally present in your body, T cells that bind strongly to these foreign MHC proteins on the transplanted cells will not have been deleted in the thymus
-Recall during the negative selection process the T cells that bind your own MHC proteins too storngly are eliminated
-Thus it is possible that both T helper cells and CTL-Ps have TCRs that by chance bind to these foreign MHC proteins very strongly
-Helper T cells that recognize foreign MHC class II proteins can become activated and differentiate into either a Th1 type or Th2 type T helper cell
-Activated Th1 cells that are formed infiltrate into the graft and then recruit and activate macrophages
-Activated macrophages secrete proteases and other inflammatory mediators that damage the graft

Front 20

What is graft?

Back 20

tissue or organ transplanted from a donor to a recipient;

Front 21

What is the graft rejection response similar to?

Back 21

Delayed type hypersensitivty

Front 22

What specific cells attack the graft?

Back 22

-Activated Th1 cells also provide IL-2 to allow the CTL-Ps to become activated CTls
-Activated Th2cells that are formed help activated Bcells that recognize the foreign MHC proteins
-These B cells differentiate into plasma cells that secrete antibodies that bind to the foreign cells
-Complement casade is activated and the membrane attack complex kills the foreign cells
-CTLpPs that recognizes the foreign MHC class I proteins can become activated CTLs and then kill the transplanted cells
-This is one of the main causes of graft rejection

Front 23

How do we improve the chances of a successful transplant?

Back 23

-Attempts are made to choose a donor whose HLA alleles (versions of MHC proteins) match as closely as possible to those of the reciepent (ie a donor who has the fewest number of different alleles from the receipent)
This process off determining which HLA alleles are expressed on a persons cells is called tissue tying

Front 24

What is the best donor?

Back 24

Identical twins because all their genes will be identical
-Grafts from identical twins are almost always accepted
-A close relative is next choice since they would share many but not all HLA alleles

Front 25

If there are HLA differences between the donated tissue and the recipient, what do we do?

Back 25

It is often necessary to prevent T cells (CTL-P cells particulary) from getting activated
-Drugs such as cyclosporin-A are used to suppress T cell function
-However this increases the risk of viral infections since the ability to kill virus-infected cells is also supprssed