autoimmunity and tolerance

Question 1

define autoimmunity

Answer 1

ADAPTIVE immune response against self antigens

Question 2

what occurs in autoimmune disease

Answer 2

breakdown of self tolerance (particularly) - often chronic, otherwise self tissue would be destroyed immediately

Question 3

what needs to occur for disease to be autoimmune

Answer 3

must be adapative immune response- disease must be caused by same antibodies if analysed in lab- disease must also become better if autoimmune response removed- may have history of autoimmune disease eg MHC association

Question 4

genes and environmental factors leading to autoimmune disease

Answer 4

genes (show by twin studies), sex (WOMEN more vulnerable), infections (creates inflammation), diet, stress, and microbiome

Question 5

how autoimmune reactions described

Answer 5

based on organs affected, autoantigens involved (eg RBC antigens in haemolytic anemia), and the type of immune response

Question 6

types of autoimmune reactions- hypersensitivity

Answer 6

type 2 hypersensitivty- antibodies against CSM antigen: type immune complex against soluble antigen: type 4- T cell mediated ie delayed: NEVER TYPE 1

Question 7

examples of type 2

Answer 7

haemolytic anemia, graves

Question 8

what occurs in goodpastures syndrome, with organ involved

Answer 8

autoantibodies binds to basement membrane in kidney glomerulus

Question 9

example of type 3+ difference to type 2

Answer 9

SLE- immune complex in glomerulus/skun/joints: more systemic than type 2

Question 10

example of type 4

Answer 10

type 1 diabetes, multiple sclerosis and rheumatoid arthritis- T cells heavily involved

Question 11

most important genetic factor for autimmune disease

Answer 11

HLA class 11 ie shows importance of T cells in pathogenesis

Question 12

what is tolerance

Answer 12

acquired inability to respond to an antigen: 3a’s- acquired, antigen specific, and active process (especially in new born)

Question 13

types of tolerance, including types of peripheral

Answer 13

central (during maturation of lymphocytes) and peripheral (once self reactive lymphocytes are mature and get to periphery)- either anergy, suppression, or ignorance

Question 14

T and B cell central tolerance with location

Answer 14

in thymus, those that bind MHC WEAKLY are selected, those that bind MHC strongly are destroyed: B cell tolerance occurs in BONE MARROW

Question 15

APECED and AIRE- what occurs if mutated

Answer 15

APECED is a disease caused by mutation in the TF AIRE- AIRE is a regulator which helps delete self reactive T cells in thymus- if mutated, CENTRAL tolerance fails= autoimmune disease

Question 16

important features that go wrong in central autoimmune tolerance

Answer 16

less tolerance, less apoptosis, and less CLEARANCE of antigen- thus autoimmune diseases involves multiple defects

Question 17

what is anergy

Answer 17

absence of COSTIMULATION- thus naive T cells can’t get activated

Question 18

when does ignorance occur

Answer 18

occurs when antigen conc too low, when MHC class 2 not present (most cells don’t have it), or in IMMUNOLOGICALLY PRIVILEGED sites (immune cells can’t get into eg eye)

Question 19

example of failure of ignorance

Answer 19

sympathetic opthalmia due to trauma of an eye

Question 20

what is supression

Answer 20

by reg T cells

Question 21

molecules present in reg T cells

Answer 21

CD4/25, as well as CTLA-4 and FOXP3 (important T.F)

Question 22

example of failure of supression

Answer 22

IPEX- due to mutation in FOXP3 gene= more autoimmune reactive T cells

Question 23

how infections can affect tolerance

Answer 23

can mimick self molecules, create a inflammatory environment, effects of reg T cells, or damage to immunologically privilege sites