Tolerance and Autoimmunity

Question 1

cross reactive epitopes

Answer 1

a foreign antigen may stimulate autoimmunity if a response is generated against a microbial epitope also found in the host

Question 2

foreign antigens as adjuvants

Answer 2

3 mechanisms:

1. certain infections, such as Epstein Barr or Coxsackie virus, act as adjuvants that enhance the immune response by upregulating Tol receptors and amplifying cytokine response.
2. response induced by a microbe cause more harm than the microbe itself
3. foreign antigens become absorbed into the surfaces of cells and act as a hapten-carrier complex

Question 3

foreign antigens in circulation

Answer 3

circulating immune complexes are taken up via Fc receptors and processed by DCs and macrophages, causing mediator release damage to surrounding cells. immune complexes may also cause complement activation

Question 4

explain 2 theories that detail how autoimmunity rxns start

Answer 4

1. sequestered antigen- tolerance induction occurs during the embryonic development. antigens not present or anatomically hidden at this time are not recognized as “self”. later in life, trauma or infection can expose them to the immune system causing a rxn
2. immunologic deficiency- a deficient immune system response allows the persistence of inflammation, which leads to the discovery of autoantigens or the uncovering of sequestered ones

Question 5

describe autoimmunity in autoimmune hemolytic anemia and immune thromoctopenic purpura

Answer 5

IgG binds to red blood cells, causing complement activation and Fc-mediated cellular destruction.

of the 2, Fc-mediated destruction seems more important b/c

1. adding IVIG to compete with the auto-IVIG helps and
2. successful therapies down regulated Fc-receptors on monocytes and macrophages

Question 6

describe myasthenia gravis

Answer 6

characterized by weakened and easily tired muscles

Abs against various muscle cell molecules exist, in particular to the Ach receptor. these receptors activate complement, block the binding sites, damage the muscle cells, or cross-link the receptor so they become non-functional

Question 7

describe graves disease

Answer 7

most commonly presents with hyperthyroidism

Abs bind to the thyroid stimulating hormone receptor, constitutively activating it and causing the release of thyroid hormone

Question 8

describe systemic lupus erythematosus

Answer 8

autoantibodies damage target tissue by direct interaction and via the formation of immune complexes that activate complement. life threatening instances occur w/ vasculitis or kidney damage

Question 9

describe 4 general mechanisms by which autoimmune diseases either initiate or progress

Answer 9

1. autoAB mediated cell destruction
2. autoAB interference w/ receptor function
3. autoAB form immune complexes resulting in tissue damage
4. endocrine dysfunction

Question 10

hashimotos thydoiditis

Answer 10

autoAbs bind thyroid stimulating receptors and inhibit them

Question 11

name 5 factors that may contribute to autoimmunity

Answer 11

1. genetics- autoimmune diseases seem to cluster in families. in humans, the strongest associated gene is the HLA type. additionally, the microbiome is an important factor
2. sex- more common in females, probably d/t interactions between neuroendocrine and immune systems
3. age- more common in older pts probably d/t less stringent immune monitoring
4. infections- certain diseases are linked to infections
5. drugs

Question 12

describe treatment options in cases of autoimmunity

Answer 12

1. non-specific inflammation reducers- NSAIDS, glucocorticoids, TNF-blocking agents
2. Cytotoxic drugs/ lymphoid irradiation- used to destroy bone marrow precursors
3. Rituximab (anti-CD20)- refractoy rheumatoid arthritis
4. plasmapheresis (removal of plasma and replacement w/ plasma from normal donors)- helpful for Ab mediated diseases
5. IVIG- out-compete autoreactive IgG
6. idiotype-targeting therapies for the autoreactive Ab