autoimmunity

Question 1

what is autoimmunity

Answer 1

Defined as the presence of immune responses against self-antigens

Question 2

what does autoimmunity cause a huge potential for

Answer 2

Huge potential for generation of autoreactive B cells (and T cells) in primary lymphoid tissues during normal lymphocyte development

Question 3

how are antibodies generated

Answer 3

Antibodies are generated by the production of heavy chain (HC) and light chain (LC) polypeptides that are synthesized from two separate immunoglobulin (Ig) genes

Question 4

gene segments

Answer 4

both heavy chains and light chains are composed of them, it creates lots of variation as they’re randomly selected

Question 5

heavy chain rearrangement

Answer 5

loose the intervening segments. creates a unique VDJ region

Question 6

how is the 3D shape of an antibody formed

Answer 6

the VDJ and VJ region creates the 3D form that recognises a specific antigen. completely random

Question 7

how are self reactive cells made

Answer 7

Antigen receptor gene rearrangement in developing T cells and B cells is RANDOM. therefor some self reactive cells are made by accident these are usually killed during development but in some situations they arent

Question 8

How does the immune system deal with the presence of autoreactive T cells and B cells?

Answer 8

Specific ‘tolerance’ mechanisms are used to kill or inactive auto-reactive lymphocytes

Question 9

what are the tolerance mechanisms

Answer 9

Deletion of self-reactive lymphocytes in primary lymphoid tissues (central tolerance)

Regulatory T cells (TREG cells) can help inactivate auto-reactive lymphocytes in peripheral tissues that escape central tolerance (peripheral tolerance)

Question 10

What are regulatory T cells ?

Answer 10

they inactivate lymphocytes to stop excessive reactions. they are crucial for the suppressing hyper-reactive or auto-reactive T cells

Question 11

how to Treg cells stop hyper reaction

Answer 11

via the production of anti inflam cytokines

Question 12

how does autoimmune disease occur

Answer 12

genetic susceptibility > initiating event (could be infection) > breakdown of immune tolerance to self-antigens > can lead to autoimmune phenomena or disease

Question 13

genetic influences in autoimmune disease

Answer 13

Monogenic disorders - single gene defects causing autoimmune diseases are rare (IPEX syndrome). or a complex genetic interplay (HLA genes)

Question 14

IPEX syndrome

Answer 14

A rare genetic disorder of immune dysregulation, Severe infections, Intractable diarrhoea, Very early onset insulin dependent diabetes.

Question 15

what are the treatments for IPEX syndrome

Answer 15

Cure: hematopoietic stem cell transplantation (HSCT)
Supportive care: immunosuppressive drugs plus total parental nutrition

Question 16

science behind IPEX syndrome

Answer 16

condition is X linked, causes of peripheral tolerance mechanisms due to absence if Treg cells

Question 17

what are normal HLA molecules

Answer 17

MHC molecules in humans are also referred to as HLA molecules. T cells only see peptides exhibited on a defined framework. HLA molecules are able to present many peptides

Question 18

HLA alleles

Answer 18

certain HLA alleles have been linked to increased (or decreased) risk of developing autoimmunity. some are better at binding self peptides than others so have a higher chance of autoimmunity

Question 19

sex differences in autoimmunity

Answer 19

there’s a clear sex bias in certain autoimmune diseases. eg sex hormones are known to influence lymphocyte function on males versus females

Question 20

pregnancy and autoimmunity

Answer 20

alterations in disease severity for some autoimmune diseases are known to occur during pregnancy. as fetal developed effects immune system autoimmunity

Question 21

environmental influences

Answer 21

Several environmental factors can trigger autoimmunity in genetically predisposed individuals
eg infections, smoking, hormone level, tissue damage

Question 22

mechanisms to do with environmental autoimmunity

Answer 22

molecular mimicry, alterations to self antigens

Question 23

example of molecular mimicry

Answer 23

acute rheumatic fever after strep infection. some antibiotics cross react with heart tissue causing rheumatic fever

Question 24

tissue injury and antigen sequestration

Answer 24

Self-antigens normally sequestered from the immune system can become exposed and cause an autoimmune reaction during infections/trauma

Question 25

classification of autoimmune diseases: clinical classification

Answer 25

organ specific diseases. non-organ specific or multisystem autoimmune diseases

Question 26

Classification of Autoimmune Diseases. pathological classification

Answer 26

hypersensitivity reaction. immune response that results in bystander damage to self. usually exaggeration of normal immune mechanisms. basis for autoimmune disease

Question 27

autoimmune disease driven by type II hypersensitivity reactions

Answer 27

autoimmune haemolytic anaemia, graves disease, pemphigus vulgaris

Question 28

autoimmune diseases driven by type III hypersensitivity reactions

Answer 28

rheumatoid arthritis, systemic lupus