deck_21090472

Question 1

What is immunological tolerance?

Answer 1

Specific immunological non-reactivity (unresponsiveness) to an antigen, due to a previous exposure to the same antigen

Question 2

What is a tolerogen?

Answer 2

Its an antigen that induces tolerance

Question 3

Immunological tolerance is the ability to recognize an antigen and choosing to “ignore” it, rather than just not recognizing it. True or false?

Answer 3

True

Question 4

Immunological tolerance is a property of an organism. True or false?

Answer 4

True

Question 5

Why is it more important to make T cells tolerant than B cells?

Answer 5

B cells cannot make antibodies for most antigens without the help of T cells

Question 6

If an immature lymphocyte recognizes a self antigen, it is immediately apoptosis’d. True or false?

Answer 6

False. B cells can change their specificity and T cells can become regulatory CD4 T Lymphocytes.

Question 7

In the peripheral tissues (aka after maturation), if a lymphocyte recognizes a self-antigen, it is signaled for apoptosis. True or false?

Answer 7

False. It can also be inactivated (anergy), suppressed by Tregs, or even just ignore the self-antigen

Question 8

Where does lymphocyte ignorance occur?

Answer 8

When an antigen is a self antigen in an immune privileged site

Question 9

What is the importance of the AIRE in the thymus?

Answer 9

Its a gene (?) present in medullary thymic epithelial cells which expresses antigens present in peripheral tissues for immature lymphocytes to try and bind. If they do, they get sent for apoptosis (or receptor editing or tregs)
Basically its the gene that produces the antigens that will be presented to the lymphocytes which they CANNOT bind to

Question 10

What happens if there is no AIRE?

Answer 10

There is no negative selection, and the lymphocytes that should have failed the “test” go on to fuck up with the antigens in the human body (autoimmunity)

Question 11

There are three mechanisms in peripheral T cell tolerance, but only one of them requires the input of a Treg. Which is it?

Answer 11

It’s Block in activation (not to be confused with anergy)

Question 12

(This question might be wrong)
How does a T cell know if its interacting with a self antigen or a microbe?

Answer 12

If the dendritic cell presenting the antigen also has B7 interacting with the T cell’s CD28

Question 13

Sometimes autoreactive T lymphocytes ignore its cognate Ag. Why?

Answer 13

They are either in too low concentration, or the antigen is located in areas which the immune system doesn’t reach.

Question 14

The eyes, for example, are immunologically privileged sites. As such, they can never experience autoimmunity. True or false?

Answer 14

False. If they experience trauma, it can lead to the release of the intraocular proteins, which are carried to the lymph nodes, and the activated T cells return through the bloodstream and fuck up the same protein on BOTH eyes.

Question 15

For a T cell to respond, all it needs is for an antigen to be presented by a professional antigen-presenting cell (APC). True or false?

Answer 15

False. It also needs to activate receptors on the T cells, such as CD28.

Question 16

How can a T cell become unresponsive?

Answer 16

It detects an antigen without co-stimulation. (The T cell remains viable but is unable to respond to the self antigen).

OR

It can detect an antigen with co-stimulation, but the co-stimulation leads to a block in signalling from the APC.

Question 17

Why are CD28 and CTLA-4 similar and yet opposites?

Answer 17

Because they are both co-stimulators of T cells, but CD28 induces proliferation while CTLA-4 leads to functional inactivation (anergy)

Question 18

Despite doing opposite things, CD28 and CTLA-4 are not competitors for the same receptor. True or false?

Answer 18

False. They are competitors.

Question 19

APCs don’t need to bind CD28 directly to the cell they want to suppress to suppress them. They can, for example, bind to a Treg, which induces suppression of response in another cell. True or false?

Answer 19

False. Everything is correct, except its not CD28 they bind, its CTLA-4

Question 20

The mediator of apoptosis of activated T and B cells is FAS. True or false?

Answer 20

True

Question 21

A deficiency in FAS allows for relatively normal life but a deficiency in FASL leads to systemic autoimmunity. True or false?

Answer 21

False. A deficit in either leads to systemic autoimmunity

Question 22

What are eTACS?

Answer 22

They are extra-thymic Aire-expressing cells which can delete self-reactive T cells outside of the thymus.

Question 23

How are Tregs developed?

Answer 23

Induced by self-antigen recognition during T cell development

Question 24

How are pTregs formed?

Answer 24

In response to antigen exposure in the periphery

Question 25

Tregs are dependent on IL-2 because they don't produce it. True or false?

Answer 25

True

Question 26

IL-2 released while a T cell responds to a self or a foreign antigen presented by a DC causes more Tregs to show up and to control the response of the T cell. True or false?

Answer 26

True

Question 27

How can Tregs control effector cells?

Answer 27

- Modulation of dendritic cell - Metabolic disruption - Generation and secretion of anti-inflammatory cytokines - Direct cytotoxicity

Question 28

How can Tregs prevent T effector cells from activating?

Answer 28

They interact with the DC's receptors (CD80-86 and MHC-II), which prevents the DC from maturing and leads to the inhibition of the T effector cells

Question 29

How do Tregs destabilize the metabolism of T effector cells?

Answer 29

By being fat fucks and consuming all the IL2 signals, leaving none to active the T effector cells.

Question 30

______ can control T effector cells by generating and secreting anti-inflammatory cytokines, such as _____, ______, and _______, which restrains ___ and ____ immune responses and the production of IFN-_ and IL-17, respectively.

Answer 30

Tregs IL-10, IL-35, and TGF-β Th1 and Th17 IFN-γ

Question 31

Tregs can indirectly kill T effector cells by signaling other cells to make them induce apoptosis on T effector cells. True or false?

Answer 31

False. Tregs can directly kill them by the release of Granzymes A and B and perforing.

Question 32

Tregs can produce adenosine which inhibits T effector cell responses. True or false?

Answer 32

True

Question 33

What happens if there is no FoxP3?

Answer 33

Without functional FOXP3, Tregs fail to develop properly, leading to severe autoimmune diseases like IPEX syndrome in humans

Question 34

Tregs have non-immune related functions. This function is tissue repair and maintenance, and is the same no matter what tissue the Treg is in. True or false?

Answer 34

False. They contribute to tissue maintenance and repair in non-lymphoid tissues, promote insulin sensitivity in adipose tissue, and produce growth factors in muscles.

Question 35

What is avidity?

Answer 35

Its the strength of all the bindings the antibodies on the surface of B cells are doing

Question 36

If a B cell weakly recognizes a self antigen in the bone marrow, it leads to either apoptosis or receptor editing. True or false?

Answer 36

False. It leads to reduced receptor expression, which leads to anergy.

Question 37

B cells need to go to the thymus to test for self antigens. True or false?

Answer 37

False. The bone marrow has stromal cells, hematopoietic cells and molecules circulating in the blood plasma that it can use for self antigens.

Question 38

What does receptor editing actually change?

Answer 38

Just the light chain of the antibody

Question 39

What happens when a B cell detects a self antigen in peripheral tissues?

Answer 39

It either kills itself, becomes anergic, or can trigger some inhibitory receptors which prevent B cell activation

Question 40

If a B cell detects a self antigen, why does it not activate and instead become inhibited?

Answer 40

Because a self antigen only binds the BCR of the B cell. A foreign antigen on the other hands binds to the BCR, co receptors, innate immune receptors and helper T cells, which provides a much stronger signal.

Question 41

A cause of an autoimmune disease is easy to find, but the disease is hard to treat. True or false?

Answer 41

False. The cause is hard to find.

Question 42

Explain in few words how autoimmunity can result from a combination of genetic and environmental factors.

Answer 42

Because of bad genes, a self reactive lymphocyte is created. A disease happens, and one of the APCs presents a self antigen Normally the lymphocytes would just ignore it, but since a whoopsie doopsie happened, this lymphocyte reacts to the antigen It multiples Bam, autoimmune disease.

Question 43

While there are autoimmune cells, there cannot be autoimmune antibodies. True or false?

Answer 43

False.

Question 44

What do you need to produce autoimmune antibodies?

Answer 44

CD4 T cells that are responsive to the self antigen

Question 45

Oh shit, I have an autoimmune antibody that has DNA as an antigen. I should be fine, right?

Answer 45

No you fucking retard. When a cell dies and releases its contents, your antibody is going to bind to it, and afterwards bind to DCs, which will cause it to intake the DNA and activate TLR-7 and TLR-9, which will begin production of IFN-alfa IFN-alfa increases BAFF production by monocytes and dendritic cells, and BAFF interacts with receptors on B cells. BAFF also increases autoreactive B cell survival, which leads to increased autoantibody production TL:DR: Autoantibody will grab DNA ---> take it to DC ---> DC starts making IFN-alfa ---> IFN-alfa increases BAFF production ---> BAFF increases autoreactive B cell survival ---> More autoantibody production

Question 46

Autoantibodies can form immune complexes. What happens to these complexes?

Answer 46

It gets deposited in tissues, triggers inflammations, and causes tissue damage.

Question 47

The brain is generally safe from autoimmune leukocytes, as the BBB is impermeable to these cells. True or false?

Answer 47

True

Question 48

If the BBB is impermeable to leukocytes, how do diseases like multiple sclerosis occur?

Answer 48

An unknown trigger causes inflammation in the brain and the BBB becomes permeable, allowing leukocytes and blood proteins to pass.

Question 49

Most human autoimmune diseases are polygenic. True or false?

Answer 49

True.

Question 50

How does an infection lead to autoimmune?

Answer 50

It can either activate a DC to express costimulators while it's "holding" a self antigen, and so, when an autoreactive T cell interacts with it, instead of going anergic, it becomes activated (because it has the cofactors) OR The antigen from the microbe is the same as the self antigen/cross reacted with self antigen (molecular mimicry), and the self-reactive T cell recognizes the microbial antigen, which causes it to destroy it and any tissue that holds that antigen.

Question 51

Autoimmune diseases are more prevalent in women because they have better immunity. True or false?

Answer 51

True

Question 52

Estrogen promotes innate cell survival. True or false?

Answer 52

False. Estrogen promotes activation, survival, hypermutation and class switch recombination in B cells, leading to higher autoantibody diseases

Question 53

Why is the level of AIRE problematic in women?

Answer 53

Because they have much less of it after puberty, which results in impairments in central tolerance.

Question 54

What does the X chromosome have to do with an increase in autoimmune disease in women?

Answer 54

The X chromosome codes for some immune proteins, which are compensated by the organism randomly silencing genes in the X chromosome to avoid producing double the amount of those proteins... except some genes aren't silenced. Some of these genes are the ones that code for immune proteins, leading to increased expression and auto immunity.

Question 55

I don't feel like making a question about this but know that the therapy for immune disorders involves

Answer 55

basically blocking everything related to a T cell activation. This includes: Anti TNF Anti-IL-1 Anti costimulation etc etc