Immunologic Tolerance and Autoimmunity

Question 1

T cells showing now affinity at all or very strong affinity to self Ag

Answer 1

Undergo apoptosis

Question 2

Treg cells express high levels of

Answer 2

CTLA-4

Question 3

Induced Treg cells

Answer 3

CD4 T cells in the periphery can be induced to express FoxP3 upon Ag recognition in the presence of TGF-b
Ag recognition in presence of TGF-b induces FoxP3 expression if IL-6 is NOT present (in the presence of IL-6, RORyt expression will be induced = Th17 cell)

Question 4

Treg cells release what cytokines and cause what in APCs

Answer 4

Release IL-4, IL-10, TGF-b

Reduce expression of CD40, CD80/86, IL-12 and increase IL-10 expression in APCs

Question 5

Ag recognition without CD28/CD80 costimulation

Answer 5

Leads to Anergy or apoptosis

Question 6

Weak recognition of self Ags by B cells in bone marrow may lead to

Answer 6

Anergy

Question 7

What does it mean if a B cell is expressing the Lambda light chain instead of Kappa light chain

Answer 7

Any B cells with a Lambda light chain has undergone BCR editing

Question 8

What happens to B cells that recognize self Ag in periphery in the absence of specific Th cells

Answer 8

Anergic or apoptosis
CD22* inhibitory receptor is phosphorylated by Lyn* and then recruits SHP-1 tyrosine phosphatase, attenuating BCR signaling
Defects in any of those proteins can lead to autoimmunity

Question 9

Microflora essential functions

Answer 9

Suppresses pathobionts through induction of Treg cells and IL-10
Anti inflammatory activities
Development of GALT

Question 10

Medullary thymic epithelial cells

Answer 10

Play key function as APCs in thymus

Express large number of peripheral tissues-restricted SELF-Ags for presentation to developing T cells

Question 11

AIRE mutation

Answer 11

Causes breakdown of CENTRAL TOLERANCE

AIRE acts as a TF, and mutations in AIRE are associated with decreased expression of peripheral SELF-Ags in thymus

Question 12

CTLA-4 KO mice present with what symptoms

Answer 12

Massively enlarged LNs and spleen and fatal multi-organ lymphocytic infiltrates

Question 13

Two important properties of CTLA-4

Answer 13

Expression low on resting T cells until they are Ag activated
Once CTLA-4 expression increases, it terminates continuing activation of the responding T cells

Question 14

Cell intrinsic/extrinsic action of CTLA-4

Answer 14

Intrinsic- Engagement of CTLA-4 on T cell delivers inhibitory signals
Extrinsic- Treg cell CTLA-4 binds B7(CD80) on APC and makes it unavailable for the T cells CD28 receptor to bind- blocks T cell activation

Question 15

4 ways autoimmunity is prevented

Answer 15

Immunological ignorance- anatomical barrier b/w T cell and Ag
Deletion- FasL
Inhibition- CTLA-4
Suppression- Treg release IL-10, TGF-b

Question 16

Immune privileged sites

Answer 16

Mechanical barriers prevent autoimmune reactions in these sites
Eye
Brain
Pregnant uterus
Ovary
Testis
Adrenal cortex
Hair follicles

Question 17

Which genes are mainly associated with autoimmune disorders

Answer 17

MHC genes- mostly class II

Question 18

Microbial Ags can initiate autoimmune disorders through

Answer 18

Molecular mimicry (Rheumatic fever-Cardiac myosin/streptococcal Ags, MultipleSclerosis-Myelin basic protein/Epsteinn barr, influenza A, papillomavirus)
Polyclonal/bystander activation
Release of previously sequestered Ags (microbes kill cells and cause release of DAMPs)

Question 19

SLE

Answer 19

Prototypical Immune complex mediated disease (Type III hypersensitive)
Anti-DNA Abs frequently found, they form complexes and cause glomerulonephritis, arthritis, vasculitis
Anti-nuclear Ab test is diagnostic

Question 20

Rheumatoid arthritis

Answer 20

Type IV hypersensitivity, Th17 cells play key role
Th1, B cells, plasma cells and macrophages also involved
Patients have circulating IgG or IgM called rheumatoid factor that react with Fc portion of circulating IgG