Regulation Tolerance

Question 1

control of the immune response

Answer 1

• response must be turned down when the antigen has been destroyed
• failure may result in an AI

Question 2

CTLA-4 competes with

Answer 2

CD28 for B7

-CTLA-4 causses an inhibitory response

Question 3

PD-1

Answer 3

inhibitory receptor found on cytotoxic T cells
-it interacts with PD-L1 found on tumor cells and PD-L2 found on dendritic cells and macrophages thereby inhibiting the immune response

Question 4

pembrolizumab and nivolumab

Answer 4

-anti-PD-1 checkpoint inhibitors

Question 5

activation induced cell death

Answer 5

-activated T cells develop Fas Ligand that interacts with Fas normally presents on t cells results in apoptosis

Question 6

T regulatory cells

Answer 6

-produce IL-10 and TGFbeta which supress T cells

Question 7

IFN gama inhibits

Answer 7

TH2 cells

-produced by TH1

Question 8

IL-4 inhibits

Answer 8

• TH1

- produced by TH2

Question 9

immunological tolerance

Answer 9

• lack of response to a specific antigen

- failure to induce specific immunity to that antigen

Question 10

self tolernce

Answer 10

• unresponsiveness to self
• occurs in the thymus (negative selection)
• this is called a Central tolerance

Question 11

peripheral tolerance

Answer 11

-cells that escape central olerance are dealt with by mechanisms of peripheral tolerance. This involves clonal deletion and clonal anergy

Question 12

clonal deletion

-how is this mediated

Answer 12

• continuous exposure to self antigens causes continuous stimulation of T cells causing apoptosis of autoreactive lymphocytes
• this occurs by the process of activation-induced cell death (Fas-L)

Question 13

clonal anergy

Answer 13

-absence of co-stimulatory signals especially B7-CD28

Question 14

adult tolerance

Answer 14

• difficult to induce
• lack of co-stimulatory signals B7 and CD28 would fix but also would suppress the system overall
• high dose of an antigen could cause tolerance under special circumstances but this is not useful in human situations
• oral tolerance possible under special circumstances but this does not work in human trials
• antigens without adjuvants may cause tolerance

Question 15

autoimmune diseases

Answer 15

• immunological response against self antigens due to loss of self tolerance
• failure of negative selection in the thymus
• failure of immunological control mechanisms
• fundamental problem is an imbalance between immune activation and immune control

Question 16

autoimmune hemolytic anemia

Answer 16

• body creates antibodies against RBC’s

- blood film shows broken and fragmented red cells typical of hemolytic anemia

Question 17

immunological factors that could give rise to autoimmunity

Answer 17

• exposure of hidden antigens (sympathetic opthalmia). damage to cell releases hidden antigen and immune response ensues
• polyclonal lymphocyte activation: viruses (EBV) stimulate B cells nonspecifically or superantigens stimulate T cells
• defective T cell regulation (TREGS and CTLA-4)

Question 18

super antigens

Answer 18

• attaches to the outside of the T cell receptor and to the MHC class 2 molecule causing T cell activation
• this happens nonspecifically
• staphylococcal food poisoning and toxic shock syndrome
• massive IL2 and IFN gama

Question 19

defective T cell regulation

Answer 19

• T cell regulators (TREGS)

- CTLA-4: competes with CD28 for B7, if CTLA-4 is defective then there will be uncontrolled activation of the T cell

Question 20

genetic factors of autoimmunity

Answer 20

• more common in family members.
• increased incidence in twins
• associated with many different MHC types

Question 21

microbial factors in AI

Answer 21

• molecular mimicry
• abnormal activation of lymphoid cells (EBV)
• microbes may damage tissue leading to release of hidden antigens
• microbes may function as adjuvants and stimulate immune responses

Question 22

Rheumatic fever

Answer 22

-caused by a strep infection that turns someones own immune system against them (molecular mimicry)

Question 23

hormonal factors of AI

Answer 23

• most AI diseases are much more common in females
• NZB/NZW mice
• females die at 9 months
• males die at 13 months

Question 24

damage to the tissues in AI may be mediated by

Answer 24

• antibodies: autoimmune hemolytic anemia
• T cells: crohns disease, IDDM, psoriasis, MS
• both humoral and CMI: hasimotos thyroiditis or rheumatoid arthritis

Question 25

delayed sensitivity may cause | -these are t celll mediated AI diseases

Answer 25

- insulin dependent diabetes mellitus - rheumatoid arthritis - multiple sclerosis - crohns disease - psoriasis - celiacs disease - these are primarily through t cell attack and may be followed by a secondary antibody production

Question 26

fetal tolerance

Answer 26

-fetuses are very easy to induce immunological tolerace in

Question 27

sympathetic opthalmia

Answer 27

-damage to one eye releases hidden antigens which will mount an immune response that could cause damage to the other eye

Question 28

polyclonal lymphocyte activation

Answer 28

- this is an immunological factor contributing to AI - causes non-specific activation of lymphocytes - EBV (mono) stimulates B cells - superantigens stimulate T cells

Question 29

how could we treat t cell mediated AI diseases?

Answer 29

- blocking the mhc-tcr interaction in the specific area which is being attacked - may be able to use antibodies to do so

Question 30

what is the most common AI disease in this country

Answer 30

-grave disease in women (hyperthyroidism)