Regulation of the Immune Response- Diebel

Question 1

What happens at the end of an immune response when there is reduced antigen exposure or increased CTLA-4/B7 interactions?

Answer 1

Results in reduced expression of IL-2 and it’s receptor—>

Apoptosis of antigen specific T cells……some survive to become memory cells

Question 2

Intracellular organisms elicit what type of immune response?

Answer 2

Cell Mediated Immune Response

NK Cells, CD8+ cells, etc

Question 3

Extracellular organisms elicit what type of immune response?

Answer 3

Humoral Immune Response

Complement, antibodies

Question 4

What neat interleukin is produced with the CD28/B7 interaction?

Answer 4

Inc. in IL-2

Question 5

Important molecules necessary for tolerogenic DC:T Cell interactions?

Answer 5

CD152 (CTLA-4)
IL-10
TGF-beta

Question 6

What is a tolerogenic DC? What makes it tolerogenic?

Answer 6

Tolerogenic DC lead to clonal deletion or anergy of antigen-specific T-cells

They express low levels of CD86, MHCII, CD40, and CCR7……they’re sittin around being bums

Question 7

What percent of CD4+ T cells are Tregs?

Answer 7

10%

Question 8

What do Tregs do? What is the inborn lack of Treg cells called?

Answer 8

Limit autoimmune responses, dampen responses against microbial and viral antigens, allergens, and allografts, and protect fetuses during pregnancy.

IPEX (Immunodysregulation, polyendocrinopathy, enteropathy, X-linked) Syndrome….whew!

Question 9

What are the different Treg effector mechanisms?

Answer 9

• Immunosuppressive cytokines (IL-10, TGF-beta, IL-35)
• IL-2 consumption
• Cytolysis (granzyme mediated)
• Modulation of DC maturation and function

Question 10

IL-10 and TGF-beta induce what in B cells?

Answer 10

Proliferation and class switch recombination

Question 11

What are the 3 different ways you can have issues with Tregs?

Answer 11

• Complete absence of Tregs (IPEX)
• Insufficient Treg effector functions
• Resistance of effector T cells to Treg effector functions

Question 12

What happens when you have a B cell that recognizes self antigen?

Answer 12

• VDJ recombination to avoid self reactivity
• Clonal deletion—–>apoptosis
• Anergy, downregulate BCR, upregulate CD5
• Lack of T cell help or survival factors—–>apoptosis

Question 13

What happens with antigens administered subcutaneously or intradermally?

Answer 13

Evokes an active immune response (TH1 response)

Question 14

What happens with antigens administered IV, orally, or aerosol?

Answer 14

May cause tolerance or an immune deviation from one type of CD4+ T cell response to another (TH2 response)

Question 15

Th1 cytokines (IFNγ, TNFβ, IL-2) promote?

Answer 15

Cell Mediated stuff……
Macrophage activation
Antibody-dependent cell-mediated cytotoxicity
Delayed-type hypersensitivity

Question 16

Th2 cytokine (IL-4, IL-5, IL-9, IL-10, and IL-13) promote?

Answer 16

Humoral Immunity Stuff....... 
IgG1 and IgE isotype switching
Mucosal immunity
Stimulation of mast cells, eosinophil growth and differentiation
IgA synthesis

Question 17

How can antibodies cause B Cell Suppression?

Answer 17

The antibodies bind up all the antigen so the plasma cells aren’t being stimulated….can also get receptor cross-linking that results in a (-) growth signal

***Can also get a pro-proliferative signals with big immune complexes (B cell, IgM, complement, follicular DC)

Question 18

TH1, TH2, and TH17 chemotactic signals?

Answer 18

TH1- CXCR3 and CCR5
TH2- CCR3, CCR4, and CCR8
TH17- CCR6

Question 19

What is special about the anterior chamber of the eyes and the testes?

Answer 19

They are immune privileged….normally immune responses don’t take place here

Question 20

Individuals with defects in C1q, C1r, and C1s are predisposed to what?

Answer 20

SLE and lupus nephritis

Question 21

Individuals with dificiency in C3 have increased susceptibility to what?

Answer 21

Bacterial infections ——> immune complex disease

Question 22

TLR4 is an important sensor for what?

Answer 22

Gram (-) bacterial infections

Question 23

what happens to individuals with a mutation in the IL-7R alpha?

Answer 23

Reduced number of T cells

Question 24

what happens to individuals with mutations in the common cytokine receptor γ chain (γc)?

Answer 24

reduced numbers of T and NK cells and impaired B cell function, in part attributable to the lack of T cell help

Question 25

What happens to individuals with mutations in the IFNγ receptor (IFNγR) or IL-12 receptor (IL-12R)?

Answer 25

They have an increased susceptibility to mycobacterial infection

Question 26

What is CCR5 and why do we care about it?

Answer 26

CCR5 is a co-receptor used in the entry of macrophage-tropic strains of HIV-1 into cells. A mutation that inactivates this receptor is found in some individuals of European origin, but is rare in populations of Asian or sub-Saharan African descent. Individuals homozygous for this CCR5 mutation are very resistant to HIV-1 infection. In this case resistance is related to the reduced primary spread of the virus rather than an enhanced immune response against it.

Question 27

What is the connection between increased levels of IgE and eosinophils?

Answer 27

IL-5 increases both IgE production and eosinophils

Question 28

What is the classic presentation of IPEX?

Answer 28

Intractable watery diarrhea, leading to failure to thrive, dermatitis, and autoimmune diabetes developing in infancy

Question 29

What causes IPEX?

Answer 29

Missense or frameshift mutations in FOXP3 result in loss of function of Treg cells and uninhibited T-cell activation

Question 30

Why is IVIg therapy a decent treatment option for IPEX?

Answer 30

It provides humoral immunity protection so you don't elicit a cell mediated T cell response.......because if you have a T cell response in IPEX it goes crazy because there are no Tregs to check it

Question 31

So you better vaccinate those IPEX babies so they don't get sick right?

Answer 31

Wrong! If you vaccinate them they'll elicit a T cell response that goes nuts because they don't have Tregs....if you do a BM transplant first then they can be vaccinated.

Question 32

Is a total BM transplant necessary in IPEX?

Answer 32

No, you just need a little bit to get some Tregs going. It's not like you need to wipe out all the old BM and replace it.....you just need some Tregs to settle things down.

Question 33

What is AIRE? Why is it important?

Answer 33

I don't know.....I spaced out during this.....whoops.....