Immunology Concepts

Question 1

three phases of autoimmune disease pathogenesis

Answer 1

induction, inflammatory, destructive phases

Question 2

elimination of auto reactive t cells

Answer 2

when immature t cells encounter a high affinity Ag-MHC complex for their TCR, they are deleted in the thymus or periphery

Question 3

signal 1

Answer 3

specific recognition of Ag/MCH complex by TCR

Question 4

Signal 2

Answer 4

co-stimulation via CD28 on T cell with APC CD80/86

Question 5

T cell inactivation/anergy

Answer 5

occurs when T cells encounter signal 1 without signal 2

Question 6

inhibitory co-receptor on T cells that binds to CD80/86

Answer 6

CTLA4

Question 7

how can tolerance be broken?

Answer 7

defective thymic deletion, aberrant help and lack of normal regulation

Question 8

mechanisms for loss of tolerance

Answer 8

defective apoptosis in thymus, immunization with auto antigen, exposure to cross reactive antigens, lack of normal regulation/supression

Question 9

Fas mutation

Answer 9

no apoptosis in the thymus=no selection or tolerance induction. clinically: lymphoproliferation, autoantibodies, nephritis, arthritis

Question 10

how many hyper variable regions do antibodies have?

Answer 10

6

Question 11

function of hyper variable regions on antibodies?

Answer 11

antigen binding (specificity)

Question 12

heavy chain antibody rearrangement

Answer 12

VDJ

Question 13

light chain antibody rearrangement

Answer 13

VJ

Question 14

how many antibody hyper variable loops does it take to bind an antigen?

Answer 14

just 1

Question 15

cross reactivity

Answer 15

other antigens may fit the same antibody, either with similar shapes or by binding in a different way (6 hyper variable loops but only 1 needed)

Question 16

molecular mimicry

Answer 16

when a external antigen looks like an auto antigen. can bypass tolerance.

Question 17

how do autoantibodies cause cellular damage?

Answer 17

they bind to cell receptors and can either initiate abnormal cell activation or prevent normal ligand binding. or they can form immune complexes when bound to soluble antigens (deposit in vessels, complement activation).

Question 18

serum sickness

Answer 18

immune complex mediated disease caused by immunization with a foreign protein can elicit

Question 19

HLA alleles

Answer 19

associated with certain rheumatic diseases

Question 20

how do MHC molecules bind to peptides?

Answer 20

either by binding the peptide backbone (class 2, plasticity) or through the use of specificity pockets (class 1, semi-specificity). both classes do both.

Question 21

MHC1 pathway

Answer 21

endogenous. antigen is synthesized within a cell, degraded by ER, and associated with MHC1 on cells surface to be recognized by CD8 T cell

Question 22

MHC2 pathway

Answer 22

exogenous. endocytosed antigen is degraded by endosome and peptides are associated with HC2 on surface of APC to be recognized by CD4 t cell.

Question 23

TH2 cell

Answer 23

induced via IL4. secretes IL4. defense against parasitic worms, allergy, asthma

Question 24

TH1 cell

Answer 24

induced via IL12. secretes IFNgamma. defense against intracellular pathogens

Question 25

TH17 cell

Answer 25

induced by TGFb & IL6, secretes IL17, defense against extracellular bacteria, AUTOIMMUNITY, cancer

Question 26

Treg

Answer 26

induced by TGFb, secretes TGFb, immunosuppression

Question 27

epitope spreading

Answer 27

stems from the ability of a single activated APC to present multiple antigens. normal. additional t cells may become activated when antigens are complexed together.

Question 28

Autoantigens in RA

Answer 28

T cell immunity to cartilage auto antigens (Type 2 collagen, aggrecan, HC gp39), ubiquitous BiP from the ER, Rheumatoid factor, citrullinated peptide and protein antibodies

Question 29

rheumatoid factor

Answer 29

IgM anti-IgG. enhances the antigen presentation of immune complexes, may have regulatory role

Question 30

citrullinated protein/peptide antibodies

Answer 30

bind to synovial lining cells, fibrinogen, collagen type 1. more likely than rheumatoid factor to be pathogenic.

Question 31

non HLA genes linked to rheumatoid disease

Answer 31

all regulate NO production. their mutations are thought to be a consequence of natural selection against TB. so when we treat patients with anti-TNF therapy, need to be mindful of TB reemergence

Question 32

environmental triggers of RA (combined with HLA DR allele)

Answer 32

smoking, coffee drinking, oral contraception (oxidative stresses)

Question 33

how does oxidative stress possibly lead to RA?

Answer 33

results in protein mutation –> increased protein citrullination –> anti-citrullinated protein antibody generation

Question 34

which antibodies are indicative of lupus?

Answer 34

anti-nuclear antibodies (ANA)