Lecture 6 - Autoimmune Disorders

Question 1

what are the targets for autoimmune disorders?

Answer 1

protein antigens or nucleic acids

Question 2

how do self-reactive T or B cells form?

Answer 2

gene rearrangement created lymphocytes that are specific for self-antigens

Question 3

how are self-reactive lymphocytes removed?

Answer 3

destroyed or down regulated

Question 4

where does central self tolerance occur?

Answer 4

thymus or bone marrow

Question 5

what is the mechanism of central self tolerance?

Answer 5

clonal deletion

Question 6

what are the mechanisms of peripheral central tolerance?

Answer 6

anergy, cell death and immune deviation

Question 7

where do T cells form and develop?

Answer 7

originate in bone marrow but develop in thymus

Question 8

what cells undergo positive selection?

Answer 8

only cells that bind to self MHC with low affinity

Question 9

what cells undergo negative selection?

Answer 9

cells that bind with high affinity to self MHC and peptides

Question 10

what cells undergo apoptosis in central tolerance?

Answer 10

cells that fail to interact with any MHC or peptides

Question 11

how are T reg cells made?

Answer 11

some self-reactive T cells that encounter self antigens in the thymus develop into T reg cells

Question 12

what happens to B cells that recognise self antigens?

Answer 12

they are deleted or become self tolerant

Question 13

what us clonal deletion?

Answer 13

physical elimination of a cell

Question 14

what is Clonal anergy?

Answer 14

lack of co-stimulation or low affinity antigen binding leads to cells not being activated through signalling blocks or inhibitory receptors

Question 15

what is regulation in peripheral tolerance?

Answer 15

regulation or suppression caused by inhibition of cellular activites by interaction with other cells such as T reg cells

Question 16

what is immune privilege?

Answer 16

limited lymphatic drainage with low levels of MHC expression and expression of FasL to kill infiltrating T cells

Question 17

what happens to B cells that are exposed to lots of soluble antigen?

Answer 17

down regulate surface IgM and become anergic, up regulate fasmolecules to cause apoptosis

Question 18

how do B cells change their antigen specificity?

Answer 18

when binding to an antigen with low affinity they re-express their RAG-1 and RAG-2 genes which cause DNA recombination

Question 19

what is susceptibility phase?

Answer 19

before onset of disease, influences by genetic factors that effect tolerance induction, regulation and HLA associations

Question 20

what is the initiation phase?

Answer 20

hidden epitopes revealed or new ones created

Question 21

how are new epitopes created?

Answer 21

post translational modification, proteolytic cleavage of intracellular antigens

Question 22

what is the propagation phase?

Answer 22

corresponds with the onset of clinical disease, tissue damage provides antigen to further drive immune responses

Question 23

what is the regulation/resolution phase?

Answer 23

immunoregulatory pathways that result in natural inhibition or resolution of the disease, quite rare

Question 24

what are the factors associated with organ specific autoimmunity?

Answer 24

affects one organ yet can be directed against multiple antigens on that organ

Question 25

how is non-organ specific autoimmunity caused?

Answer 25

as associated with self-molecules that are widely distributed, often associated with connective tissue

Question 26

what are the methods used to detect antibodies?

Answer 26

IF, RIA, ELISA, Immunoprecipitation, multiplex, immunoblot

Question 27

what are the different antigens used in the lab?

Answer 27

cells, tissues or purified or recombinant antigens

Question 28

how are cells prepped for lab use?

Answer 28

extracted via chemical extraction such as lysis buffer or mechanical extraction such as freeze thaw

Question 29

how are tissues prepped for lab use?

Answer 29

frozen or embedded into parafin

Question 30

why is purification of antigens important?

Answer 30

maintains conformational epitopes, structure and postranslational modifications

Question 31

what are the types of antisera?

Answer 31

hybridoma, polyclonal or monoclonal

Question 32

what is a hybridoma?

Answer 32

single clone of B cells that are fused with myeloma cell to immortalises them

Question 33

what are the qualitative tests?

Answer 33

immunofluorescence, immunodiffusion, immunoprecipitation

Question 34

what are the quantitative tests?

Answer 34

ELISA, microarray

Question 35

how is rheumatoid factor determined?

Answer 35

nephelometry or turbidometry

Question 36

how does counter-immunoelectrophoresis work?

Answer 36

electrical current applied across a gel, antigen moves towards the anode and antibody moves towards cathode, forming line or precipitation

Question 37

what can direct immunofluorescence be used to investigate?

Answer 37

complement and Ig deposition in tissue

Question 38

what is ELISA most commonly used to detect?

Answer 38

autoAB

Question 39

what are the types of multiplex technologies?

Answer 39

planar arrays and suspension arrays

Question 40

what are antinuclear antibodies?

Answer 40

antibodies directed against nuclear components of cells

Question 41

what are antinuclear antibodies used to investigate?

Answer 41

connective tissue diseases

Question 42

what are the membrane anionic phospholipids?

Answer 42

cardiolipin and phosphatidylserine

Question 43

what are the targets for antiphospholipid antibodies?

Answer 43

phospholipid binding proteins or phospholipid protein complexes

Question 44

what are the clinical presentations of antiphospholipid antibodies?

Answer 44

autoimmune disease characterised by vascular thrombosis and pregnancy morbidity