Autoimmunity

Question 1

what is autoimmunity

Answer 1

the presence of immune responses against self tissues/cells

Question 2

when does auto immunity become dangerous

Answer 2

when there is HIGH titres of auto-antibodies or auto-reactive T cells

Question 3

what can high titres of auto-antibodies or auto-reactive T cells cause

Answer 3

significant tissue/organ damage, chronic inflammation

Question 4

what is the initiating event of autoimmune diseases

Answer 4

exposure to noxious substance or environmental factor

Question 5

what determines whether a autoimmune reaction will be driven

Answer 5

genetic susceptibility- build up of many susceptible genes

Question 6

what occurs after the initiating event

Answer 6

breakdown of self tolerance- loss of immune regulation- generation of auto-reactive B and T cells

Question 7

what does the breakdown of self tolerance lead to

Answer 7

autoimmune phenomena/disease

Question 8

what is a monogenic disorder

Answer 8

single gene defect causing autoimmune diseases that are rare

Question 9

what is IPEX syndrome

Answer 9

a rare monogenic disorder of immune disregulation

Question 10

what genes are commonly involved in the complex genetic interplay that results in most autoimmune diseases

Answer 10

HLA genes, sex genes, immune response genes

Question 11

how does ipex syndrome present

Answer 11

overwhelming systemic autoimmunity in early childhood causing a wide range of symptoms

Question 12

a mutation in what gene leads to IPEX syndrome and why

Answer 12

FOXP3, as essential for the development of regulatory T-cells

Question 13

why are only males affected by IPEX syndrome

Answer 13

as it is X linked

Question 14

what are T follicular helper cells

Answer 14

antigen experienced CD4+ T cells that produce interleukins that lead to B cell co stimulation

Question 15

what is the role of T regulator cells

Answer 15

secrete anti inflammatory cytokines that can act on all of the other T and B cells supressing their activity (ymphocytes)

Question 16

what does loss of balance of T Reg cells lead to

Answer 16

loss of control of T cell activation- uninhibited; loss of control of adaptive immune response = autoimmune disease

Question 17

why do healthy T reg cells prevent autoimmune disease

Answer 17

as suppress hyperactive T cells

Question 18

how do defective T Reg cells affect peripheral tolerance

Answer 18

leads to failure of peripheral tolerance= IPEX

Question 19

what are tolerance mechanisms

Answer 19

control populations of T and B cells

Question 20

describe central tolerance

Answer 20

deletion of self-reactive lymphocytes in primary lymphoid tissues

Question 21

describe peripheral tolerance

Answer 21

inactivation of self-reactive lymphocytes in peripheral tissues that escape central tolerance

Question 22

why must self reactive lymphocytes be deleted

Answer 22

as healthy T and B cells don’t recognise self antigen

Question 23

what is HLA

Answer 23

human leukocyte antigen- gene complex coding for MHC proteins in humans

Question 24

how can each individual express 12 MHC genes

Answer 24

2 variants of each HLA molecule type= 2 copies of chromosome 6 from parents

Question 25

why is different types of MHC molecules a good thing

Answer 25

as each better at presenting different peptides- able to present T cells with a wider range of peptides- polymorphisms makes all these genes differnt

Question 26

where do all nucleated cells express HLA class 1

Answer 26

cell surface

Question 27

how can sex differences affect autoimmune disease

Answer 27

sex bias in predisposing genetic factors, hormonal influences in lymphocyte function, pregnancy

Question 28

what is molecular mimicry

Answer 28

when pathogenic peptides mimic self antigens triggering a immune response targeting self antigens

Question 29

what environmental factors can contribute to autoimmune disease

Answer 29

infection- molecular mimicry

Question 30

give an example of molecular mimicry

Answer 30

acute rheumatic fever after streptococcal infection; strep. M5 protein v similar to cardiac tissue proteins, drives hypersensitivity reaction which targets self antigens

Question 31

what type of hypersensitivity reaction is acute rheumatic fever after streptococcal infection

Answer 31

type 2 as dealing with immune system vs self antigens bound to surface of cell

Question 32

what is reactive arthritis and what can it follow

Answer 32

sterile inflammation secondary to bacterial infection

Question 33

what is antigen sequestration

Answer 33

sequestered antigens are ones that cannot interact with the immune system during development so exposure to them due to damage (e.g to blood brain barrier, testes or eye) could drive autoimmune response

Question 34

what do super antigens cause

Answer 34

toxic shock syndrome

Question 35

what are two examples of super antigens

Answer 35

staphylococcal proteins, clostridium endotoxin

Question 36

why is immune regulation important in autoimmunity

Answer 36

as maintain self tolerance

Question 37

what is the clinical classification of autoimmune disease

Answer 37

organ-specific or non-organ specific/multi system diseases

Question 38

what is the pathological classification of autoimmune disease

Answer 38

gel and coombs classification (hypersensitivity reactions)

Question 39

what type of hypersensitivity reaction is not applicable to autoimmune conditions

Answer 39

type 1- immediate hypersensitivity (allergy)

Question 40

describe the mechanism of graves disease

Answer 40

mediated by type 2 mechanisms- | antibodies bind to TSH receptor (thyroid stimulating hormone)

Question 41

what is graves disease the leading cause of

Answer 41

hyperthyroidism

Question 42

describe goodpasture's syndrome

Answer 42

mediated by type 2 mechanisms- antibodies bind to glomerular basement membrane in lungs and kidneys leading to bleeding from the lungs and kidney failure

Question 43

how are type 2 hypersensitivity reactions managed

Answer 43

plasmapheresis (removal of pathogenic antibody) immunosupression (switch off B cell production of antibody)

Question 44

give two example of type 2 mediated autoimmune diseases (bound anitgen)

Answer 44

graves disease and good pastures syndrome

Question 45

what is an example of an autoimmune disease mediated type 3 mechanisms

Answer 45

systemic lupus erythematosus (SLE)- auto-antibodies against nuclear antigens

Question 46

how are type 3 hypersensitivity reactions managed

Answer 46

control symptoms- limit sun exposure, analgesia, hydroxychloroquinine, decrease inflammation and production of auto-antibodies

Question 47

give three examples of type 4 hypersensitivity mediated autoimmune diseases (delayed hypersensitivity)

Answer 47

type 1 diabetes, coeliac disease, Rh arthritis

Question 48

what does an overwhelming og clearing mechanism mean

Answer 48

oxygen will not be cleared