Autoimmunity

Question 1

What is central tolerance?

Answer 1

Controls immune cell development, with non-self-reactive T cells being developed in the thymus and non-self-reactive B cell being developed in the bone marrow

Question 2

What is peripheral tolerance?

Answer 2

Controls immune responses in peripheral organs such as the spleen and lymph nodes.

Question 3

What organs are considered apart of the lymphoid system?

Answer 3

Bone marrow, thymus, lymph nodes, spleen and lymphatic vessels

Question 4

Describe the effect of lymphocyte precursor cells

Answer 4

They divide to become immature lymphocytes, then allow for recognition of self-antigens which can result in death (apoptosis), a change in receptors or the development of Treg lymphocytes within CD4+ T cells

Question 5

What occurs to lymphocytes within the peripheral tissues?

Answer 5

Immature lymphocytes develop into mature lymphocytes

Question 6

What is the effect of Tregs in the peripheral tissues?

Answer 6

Suppression

Question 7

What is antigen segregation?

Answer 7

When an antigen is kept in the organ through a physical barrier

Question 8

What is cytokine deviation?

Answer 8

Promotion of pro-inflammatory cytokines induces tolerance

Question 9

What is required of a functional immune system?

Answer 9

Selection of T lymphocytes expressing receptors that are major histocompatibility complex restricted but tolerant to self-antigens

Question 10

What is positive selection in regard to T-cell development?

Answer 10

T cell receptors recognise peptide bound to self-MHC molecules

Question 11

What is negative selection in regard to T-cell development?

Answer 11

T cells that react strongly to self-antigens and are removed

Question 12

What is thymic stroma MHC responsible for?

Answer 12

The repertoire of mature T cells that are able to recognise foreign antigens presented by the same MHC type

Question 13

What can thymic cortical epithelial cells do?

Answer 13

Mediate positive selection of developing thymocytes

Question 14

What is AIRE?

Answer 14

Autoimmune regulator responsible for the control of the expression of the self-proteins in thymus medulla

Question 15

How does the elimination of self-reactive thymocytes occur?

Answer 15

When immature T cells die via antigen

Question 16

What is the purpose of AIRE?

Answer 16

Promotion of expression of self-antigens in the thymus, thus deletion of autoreactive T cells. Thymic medullary cells express tissue-specific proteins, deleting tissue-reactive T cells

Question 17

What happens when AIRE is not present?

Answer 17

T cells are reactive towards tissue-specific antigens, where they mature and then leave the thymus

Question 18

Describe central tolerance within immature B cells

Answer 18

If the B cell strongly recognises self-antigens then central occurs when the antigen receptor is changed via receptor editing or death and results in negative selection

Question 19

What occurs during immune tolerance?

Answer 19

Central and peripheral tolerance occurs and involves positive and negative selection.

Question 20

What occurs during peripheral tolerance?

Answer 20

Lymphocytes that encounter sufficient quantities of self-antigens for the first time in the periphery are eliminated or inactivated

Question 21

What mechanisms can help prevent autoimmunity?

Answer 21

Activation-induced cell death, clonal anergy, clonal ignorance and suppression through regulatory cells

Question 22

What is immunological ignorance?

Answer 22

There is a barrier at the tissues that prevents APC T cell interaction

Question 23

What is clonal ignorance?

Answer 23

Antigens are sequestered in immune-privileged sites such as the brain, eye, testis, uterus (foetus) and hamster cheek pouch

Question 24

What is AICD?

Answer 24

Programmed cell death caused by the interaction of Fas receptors (Fas, CD95) and Fas ligands (FasL, CD95 ligand). It is a negative regulator of activated T lymphocytes that results from repeated stimulation of TCR

Question 25

How does T cell anergy occur?

Answer 25

No strong costimulatory or inhibitory receptors such as CTLA-4 (cytotoxic T lymphocytes-associated protein-4) blocks activation

Question 26

How do Treg cells contribute to preventing autoimmunity?

Answer 26

In autoimmune disease patients, Treg cells are defective in their suppressive abilities. Autoreactive T cells are treated with Treg cells in order to kill them off

Question 27

What is IPEX?

Answer 27

Immune dysregulation, Polyendocrinopathy, Enteropathy X-linked. Patients lack both CD4CD25 cells and CD4Foxp3 as well as contain a mutation of the FOXP3 gene. The mutation of FOXP3 is responsible for the lack of Treg cells present within the syndrome. Both autoreactive T and B cells are inhibited

Question 28

What is autoimmunity?

Answer 28

A breakdown of mechanisms responsible for self-tolerance and induction of any immune response against components of the self and does not necessarily associate with autoimmune diseases

Question 29

What do autoimmune diseases refer to?

Answer 29

A specific and sustained adaptive immune response directed against self causes tissue damage to the host. It is a failure of tolerance

Question 30

What are contributing factors to developing autoimmune diseases?

Answer 30

Genetics, infection and other environmental factors as well as age, life habits and diet

Question 31

Describe MHC role in developing autoimmune diseases

Answer 31

MHC genes control susceptibility to autoimmune disease. A defect in a single gene can be associated with autoimmune disease. Defects in genes regulating immune responses such as cytokine production or signalling can lead to autoimmunity

Question 32

What is the importance of HLA genotypes in developing autoimmune diseases?

Answer 32

Strong linkage of susceptibility to type 1 diabetes with HLA genotype. Two siblings affected with the same autoimmune disease are far more likely to share the same MHC haplotypes than they would be expected if the HLA genotype did not influence disease susceptibility

Question 33

What is the association of the MHC genotype to autoimmune disease?

Answer 33

The ability of T cells respond to a particular antigen depends on MHC genotype. Diabetes associate with MHC class I and II, this is consistent with the involvement of CD8 and CD4 T cells response to antigens presented by MHC class I and II molecules

Question 34

What is APS-1?

Answer 34

Autoimmune Polyendocrine Syndrome type 1, or Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED), in which multiple endocrine glands dysfunction. It is a genetic disorder inherited in autosomal recessive fashion due to a defect in the AIRE gene. A lack of expression allows cells to escape to the periphery, with a defective negative selection of T cells

Question 35

What is ALPS?

Answer 35

Autoimmune lymphoproliferative syndrome is a result of a mutation in Fas. It results in uncontrolled lymphocyte proliferation in the absence of infection or malignancy. Failure of apoptotic cell death of self-reactive T and B cells, results in splenomegaly, lymphadenopathy (enlargement of lymph nodes), increased lymphocytes and immunoglobulins in blood

Question 36

What happens when there are defects in cytokine production or signalling?

Answer 36

Cytokines regulate immunity and so defects will lead to autoimmunity e.g. TNF-α causes enhanced inflammation, TGF-β causes inflammatory bowel disease

Question 37

What is molecular mimicry?

Answer 37

Provides an environment that promotes lymphocyte activation or through cross-reactivity between foreign molecules on pathogens and self-molecules

Question 38

How can viral infections contribute to developing autoimmune diseases?

Answer 38

In the example of diabetes, the specific virus protein NP expressed in the pancreas, and infected NP specific CD8 T cells are activated. These circulate through the bloodstream and β cells expressing NP

Question 39

What are 4 types of autoimmune disease?

Answer 39

Type I (IgE mediated), Type II (IgG or IgM mediated), Type III (immune-complex mediated) and Type IV (T-cell mediated)