Immuno tolerance

Question 1

What two things are required to INDUCE Th0 cells into iTREGS? Where does this happen?

Answer 1

1. CD4+ naive binding Ag and TGF B

2. occures in PERIPHERY

Question 2

What 3 fates could T/ B cells have in Central tolerance?

Answer 2

1. BCR editing
2. formation into TREGS
3. APOPTOSIS

Question 3

Would we positively select for T cells with HIGH or LOW avidity ? Where does this selection occur ?

Answer 3

LOW avidity , binds self antigens at a certain threshold

THYMUS

Question 4

What receptors are important for TREG survival and function?

Answer 4

IL-2 Receptor (CD25) and CTLA -4

Question 5

Which two things are needed to convert naive cells to Th 17 cells?

Answer 5

TGF b and IL-6

Question 6

Which two things are needed to convert naive cells to iTREGS cells?

Answer 6

TGF b and IL-2

Question 7

Where are iTREGS induced?

Answer 7

Lymph node or GI tract

Question 8

What may cause a T cell in the periphery to become anergic?

Answer 8

1. ab binding without costimulation (B7/CD28)

2. ab binding & engaging inhibitory receptor CTLA4 or PD-1

Question 9

Would you want to block or open the CTLA 4 / pD-1 receptors in a cancers?

Answer 9

BLOCK , to prevent them form blocking the T cell response. MORE TUMOR supression

Question 10

Defect in Lyn , SHP-1 or CD22 leads to autoimmune disease due to which tolerance?

Answer 10

1. Peripheral B cell tolerance

due to inability to inhibit B cell signaling via those factors

Question 11

What are the two reasons for T cell apoptosis in Peripheral tolerance ?

Answer 11

1. Tcell- self Ag causes increase in pro apoptotic factors

2. T cell - self Ag cause increased expression of death receptors FAS / FASL

Question 12

What major roles does TREG play in peripheral intolerance? (3)

Answer 12

1. inhibit CD4+ activation by APCs
2. Inhibit T cell differentiation into CD8+ and CTL
3. prevent T cells from signaling B cells to make Abs

Question 13

What is the result of deficiency of AIRE? What tolerance mechanism is effected?

Answer 13

1. deficiency in AIRE mean T cells that bind self Ags Will NOT be removed
   (can cause damage)
2. central tolerance affected

Question 14

Two mechanisms of Automimmunity ?

Answer 14

1. susceptability genes

2. environmental triggers

Question 15

What are the intrinsic and extrinsic functions of CTLA-4?

Answer 15

1. intrinsic, acts on T cells and sends inhibitory signals

2. extrinisic, acts from TREGs and inhibitis T cell activation by binding CD80

Question 16

What is the best treatment option for person with autoimmune disease?

Answer 16

NO CURE / treat sxs

Question 17

What type of mechanism of automimmune disorder is seen in Rheumatoid Arthritis and multiple sclerosis?

Answer 17

1. molecular mimicry

Question 18

What is the molecule mimicking in Rheumatoid Arthritis and Multiple Sclerosis?

Answer 18

RA–> cardiac myosin & Strep Ags

MS–> myelin based protein & virus Ags

Question 19

What is required for polyclonal BYSTANDER activation in to elicit autoimmune response?

Answer 19

a microbe causing ROBUST inflammation and activating the self reactive lymphocytes

Question 20

What is involved in “release of previously sequestered Ags”?

Answer 20

microbes kill cells and cause release of DAMPS that leads to autoimmunity

Question 21

What are the 3 methods microbe Ags can initiate autoimmune disorder?

Answer 21

1. molecular mimicry
2. polyclonal bystander activation
3. release of sequestered Ag

Question 22

Type of hypersensitivity for INflammatory Bowel Disease?

Answer 22

Type 4

Question 23

Type of hypersensitivity for rheumatoid arthritis?

Answer 23

Type 4

Question 24

Type of hypersensitivity for systemic lupus erythematous?

Answer 24

Type 3

Question 25

In a study of cell-mediated immune responses, it is observed that repeated stimulation of CD4 cells receptive to self-antigens results in loss of those CD4 cells. Within these CD4 cells there is activation of genes leading to apoptosis. Which of the following genes is most likely to be upregulated within these stimulated CD4 cells?

a. bax
b. bcl2
c. fas
d. kRAS
e. n-myc

Answer 25

C.

Fas gene activation leads to apoptosis in this circumstance when there is restimulation of a T cell (more likely when abundant self antigen is present). BCL2 inhibits apoptosis while Bax promotes apoptosis.

Question 26

A 10-year-old boy develops a fever with sore throat. A week later his symptoms resove, but 2 weeks later he begins to develop malaise with fever. Auscultation of his chest reveals a friction rub and a cardiac murmur. Laboratory studies shown positive serologic tests for anti-DNAase and anti-hyaluronidase. By which of the following mechanisms has his cardiac disease most likely developed?

a. stimulation of selft reactive CD8 cells
b. cross reactivity with M proteins
c. increased B7 costimulator production
d. reduced IL 10 by T cells

Answer 26

B

he streptococci have M proteins that are antigenically similar to those found in the heart. Antibodies made to these M proteins can cross react with self antigens.

Question 27

Antinuclear Abs can be used to detect…?

Answer 27

SLE

Question 28

A 26-year-old woman has developed a photosensitive facial skin rash along with joint and muscle pains over the past year. On physical examination there is no joint deformity, warmth, or tenderness. Laboratory testing reveals positive serologic tests for antinuclear antibody and anti-double stranded DNA. A mutation in which of the following genes is she most likely to have?

a. adenosine deaminase
b. bruton tyrosine kinase
c. complement C2
d. Fas
e. immunoglobulin

Answer 28

C.

She has findings with systemic lupus erythematosus, an autoimmune disease. A deficiency of complement components such as C2 can predispose to development of lupus-like disease.