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Host Defense > Lecture 13 > Flashcards

Lecture 13 Flashcards

1
Q

What happnes in MS?

A
  • Myelin proteins are targeted and destroyed leading to destruction of immune system
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2
Q

What does tolerogenic mean?

A

Environment often found in tumors that induces immunological tolerance against them

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3
Q

What are Tregs required for?

A

Tolerance against self antigen

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4
Q

Types of CD4 T cells?

A

Th1
Th2
Th17

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5
Q

What is FoxP3?

A

Gene involved in Treg cells that if mutated will generate autoimmune response
Key factor for maintaining immunological tolerance

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6
Q

What happens in postive selection?

A

Select only T cells that can work with self MHC

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7
Q

What happens in negative selection?

A

Eliminates T cells reactive against self

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8
Q

What limits effect of Pos/neg selection?

A

Powerful but limited because only can involve cells that can be presented in thymus
Would not work in case of mother being pregnant

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9
Q

What are MDSCs?

A
  • Group of myeloid cells that become potent immunoregulatory cells when exposed to inflammatory cytokines and block T cell responses
  • Act like fireman in a more responsive role
  • Often associated with tumors
  • “Myelin derived suppressor cells”
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10
Q

What is clonal annergy?

A

Clonal anergy - when T cells are stimulated in manner that is not complete, cells become non responsive to further stimulation

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11
Q

What is central tollerance?

A

Intrathymic clonal deletion during maturation process of thymocytes eliminating cells that have high affinity to antigens present in thymus
Cell is eliminated if recognizes antigen

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12
Q

What is AIRE?

A

TF expressed mainly in medulla and thymus inducing expression of wide range of genes expressed in other organs allowing for negative selection
Mutation in this gene can cause many autoimmune disorders

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13
Q

What is dominant suppressive?

A

Action of Tregs that actively suppresses other effector immune cells

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14
Q

What are nTregs?

A

Thymus derived foxp3 positive cells that mainly work against self antigens
Control reaction against self antigen

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15
Q

What are iTregs?

A

Peripheral derived foxp3 positive cells mainly against foreign antigens
Control reaction against foreign antigens such as food

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16
Q

What are iTregs?

A

Peripheral derived foxp3 positive cells mainly against foreign antigens
Control reaction against foreign antigens such as food

17
Q

What are Tr1s?

A

Peripheral derived foxp3 cells that express high levels of IL10

18
Q

What is IL10?

A

Important immunosuppressive cytokine

Important in irritable bowel disease

19
Q

What is IPEX?

A

Disease caused by foxp3 mutation in which immune system attacks self tissue
Treated with bone marrow transplant

20
Q

What is Hassall’s corpuscles ?

A

Group of cells in thymic medulla that help in differentiation of foxp3+ treg cells via activation of subset of dendritic cells

21
Q

Where are iTregs generated?

A

Mostly generated in periphery after T cell maturation and respond to environmental antigens

22
Q

What does IL6 do to iTregs?

A

Under presence of high volume of inflammatory cytokines, induction of iTreg is inhibited
IL6 causes this to happen and will generate TH17 cells instead of iTreg

23
Q

Cofactor for iTregs?

A

Vitamin A/D - cofactor for induction of iTregs

24
Q

What cytokine important for iTreg?

A

TGF beta - presence of this cytokine plays crucial role in iTreg induction
IL2 - also plays role in this

25
Q

What is TGF beta important for?

A

iTreg

26
Q

Do Tr1 cells have Foxp3?

A

No

27
Q

Do Tr1 cells have Foxp3?

A

No

28
Q

What cytokine to Tr1s use?

A

IL10 - potent immunosuppressive cytokine expressed by TR1 cells

29
Q

When is Tr1 upregulated?

A

TR1 cells develop in response to antigenic stimulation when TGF beta and IL27 are present in environment
Vitamin D - upregulates IL10 production and is linked to generation of TR1
IL10/27 - both highly important in driving these cells

30
Q

What happens if antigen preseented without costimulatory signal?

A

Anergy develops when antigen is presented in absence of costimulatory CD28 signal

31
Q

What happens in CD28 is missing?

A

CD28 makes chemistry of antigen presenting reaction go much more smoothly like having your friend on a blind date with you
If CD28 not present, reaction between APC and T cell does not go too well
Anergy develops in this scenario with no CD28 activity

32
Q

What is CTLA4?

A
  • Found on T cells and competes with CD28 for B7 binding and ultimately wins as it has higher affinity for B7
  • T cells express much CTLA4 on surface which blocks CD28 activation causing anergy
  • Genetic deficiency in CTLA4 can cause lethal autoimmune disorder
  • CTLA4 is a membrane protein but can be solubilized and used to block autoimmune disorder

Host Defense (12 decks)

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