Immune tolerance/ Regulation

Question 1

what is the most imp factor to controlling immune response

Answer 1

ANTIGEN
It induces activation, proliferation + differentiation of lymphocytes

Question 2

what happens to the lymphocytes once antigen is ridden of

Answer 2

The immune response subsides.
Most lymphocytes specific for it die by apoptosis.
Only a few of the best are kept as memory
cells.

Question 3

B lymphocytes hv inhibitory Fc receptors for IgG. What does this do

Answer 3

Prevents the B-cell activation.
Its a signal that there are already enough IgG antibodies, + no further production is needed.

Question 4

where does this feedback regulation (Fc inhibitor stuff) evident

Answer 4

Myeloma: susceptibility to bacterial infection is increased + normal immunoglobin production is impaired.

T cells: T cell lymphoma leads to deficiency for normal T cells + susceptibility to intracellular pathogens

Question 5

CD4 T helpers up regulate immune response. what down regulates immune response. what do they do

Answer 5

Regulatory T cells/ T suppressors (TREG)

Treg cells form in the thymus. They distinguished by expression of transcription factor FoxP3.
It switches on a set of genes responsible for regulatory activity.

They interact with other T cells on surface of antigen presenting cells and down-regulate T effector activity by contact-dependent signaling / cytokines.

Question 6

Antibodies can have different antigenic determinants on them. what are the determinants located on the V region called?

Answer 6

Idiotypic

Antibodies against them = Anti idiotypic antibodies

Question 7

What role does the idiotype - anti idiotype network hv on immune system

Answer 7

regulates immune response but more a secondary role

Question 8

whats an exception with this idiotype network

Answer 8

B cells reacting against T-independent antigens.
They may stimulate each other by anti-idiotype
antibodies instead of using T-helpers.

Question 9

How does the idiotype – anti-idiotype network works

Answer 9

• presence of an antigenic determinant (epitope) stimulates production of Ab, which
  introduces production of other types Ab2 (Ab2α, Ab2β, Ab2γ).

Question 10

what does each Ab2α, Ab2β, Ab2γ do

Answer 10

. Ab2α is directed to the idiotope of Ab1

• Ab2β is directed to the paratope of Ab1
• Ab2γ is directed to the near antigen epitope-binding site idiotope of Ab1.

Question 11

what are Anti-idiotypic antibodies used for

Answer 11

stop autoantibodies from attacking self cells with
minimal side effects and long- lasting immunity.

Question 12

What are Ir (Immune response) gene

Answer 12

genetic mapping shows they identical to mHC genes

Question 13

What causes a poor response (MHC and antigen)

Answer 13

when particular MHC variant doesn’t bind to antigen well / in complex where antigen resembles a self antigen + induces tolerance

Question 14

what shows the diversity of MHC

Answer 14

that no MHC is good for all antigens

Question 15

Nueroendocrine reg- what substances supress/ upregulate immune response

Answer 15

Supress: Glucocorticoids, testosterone and
progesterone

upregulate: estrogens, thyroid hormones, growth hormone + insulin

Question 16

whatt are Glucocorticoids also used for

Answer 16

immunosuppressive drugs (after
transplantation).

Secreted during stress response; therefore,
stress makes us susceptible to
infections.

Question 17

Def immune tolerance

Answer 17

lack of immune response against a substance
that has access to normalfunctioning
immune system + characteristics of
antigen.

**Tolerance to self antigens

Question 18

where does self vs non self discrimination occur. when does it become inefficient

Answer 18

INNATE IMUNITY: Phagocytes have pattern recognition receptors detecting the characteristic surfaces of bacterial cells.

inefficient: When foreign substances cannot be recognized as foreign by their general appearance.
(pathogen toxin “looks” like any other protein.)

Question 19

** True immune tolerance, , is acc adaptive by definition. what is it then

Answer 19

Immune tolerance is a function of the entire immune system. It recognizes self antigens based on the
context in which they appear.

Question 20

What is an example of Blood chimeras

Answer 20

RAY OWEN CALF EXPERIMENT - dizygotic twin calves who had diff blood types apparently exchanged blood cell precursors in utero through placenta

Question 21

What was observed with early exposure to antigen to tolernace? evidence?

Answer 21

exposure to an antigen early in
life INDUCES TOLERANCE to that antigen (normally used to distinguish between self and non-self.

• Peter Medawar.
  He exchanged skin grafts between dizygotic cattle twins and found that those that carried erythrocytes
  from the twin (bone marrow chimeras) accepted also the skin graft.

Question 22

If antigen removed, tolerance lost. WHY and evidece

Answer 22

Reliable immune tolerance requires continuous
exposure to antigen, especially during development.

• Frog experiment - when organ is removed (eye lens) during devpmt phase then transplanted back, it may be rejected. (1 removed, graft accepted. both removed, tolerance lost and graft rejected

Question 23

** how to achieve chimerism based tolerance

Answer 23

mixed chimerism - organ and bone marrow from same donor are transplanted at same time

Question 24

What is clonal deletion

Answer 24

elimination of cells that strongly bind antigen in
the peripheral tissues and then undergo
apoptosis.

Question 25

lymphocytes differentiating in the central lymphoid
organs are checked for autoreactivity. what happens to those that bind strongly to self antigens

Answer 25

They dont leave organ and die

Question 26

What is CENTRAL TOLERANCE

Answer 26

Immature B cells reacting to self antigens are forced
to edit their receptors. If editing fails to remove self-
reactivity, the cell is induced to die by apoptosis
(negative selection).

(Autoreactive B cells not that bad cos most of not
activated without T-helpers.)

Question 27

Autoreactive T cells dangerous. What does central tolerance do to these

Answer 27

thymocytes do negative
selection in thymic medulla.

Stromal cells present self-antigens to them and
induce apoptosis in those that react too strongly.

Question 28

Limitation to central tolerance

Answer 28

If an antigen is introduced after the foetal / neonatal period, there will already be mature T cells specific for it.
cant eliminate by central tolerance then

Question 29

PERIPHERAL TOLERANCE ( when central doesnt work)

Answer 29

Elimination of foreign antigens sometimes
requires antibodies cross-reacting with self-antigens.

autoantibodies formed after tissue injury can help to clear the released self-antigens.

Question 30

what is anergy

Answer 30

if antigen is presented to a naïve T cell without co-stimulatory signal B7, the T cell
becomes inactive

Question 31

AIRE is tanscriptio factor what does it do

Answer 31

activates genes for many proteins specific for other organs, e.g. insulin. So these
proteins are produced in small quantities and presented to thymocytes in order to establish
central tolerance to them.

Question 32

what does mutations in AIRE cause

Answer 32

rare autoimmune disorder APS-1 (due to central tolerance failure)

Question 33

**Medullary thymic epithelial cells with active gene
for AIRE, located in corticomedullary junction of
thymus. what does it do

Answer 33

These cells produce tissue-specific antigens (TSAs) and can give these antigens to thymic dendritic cells.

Dentritic cells present TSAs to immature T cells.
Post-Aire cells also express TSAs but at a lower level and are found near Hassall’s corpuscles.

Expression of TSAs in the medulla affect Treg cells
+ negative selection of T cells, which are critical
for maintaining central tolerance.

Question 34

what is the role of TREGS for immune tolerance

Answer 34

controlls if immune responses to self-antigens+ foreign antigens if the response is too strong or prolonged

Question 35

how do TREGS control

Answer 35

works by forcing the too-active lymphocyte into inactive state (suppression).
( will work if antigen-presenting cell supplies В7)

Question 36

What is proof that TREGS needed to down regulate immune response

Answer 36

evident in boys having no functional Treg cells cos of mutations in marker FoxP3.

Straight after birth,
they develop IPEX syndrome

They get watery diarrhea, eczematous dermatitis, and endocrinopathy
Unless treated by bone marrow transplantation, patients die within 1-2 years.