Immuno Assignment #4 Flashcards

1
Q

What molecules/cells link innate and adaptive immunity?

A

Cytokines, in conjunction with the presentation of foreign antigen by antigen presenting cells (aka dendritic cells)

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2
Q

how does a dendritic cell develop in vitro?

A

In vitro —> GM-CSF, IL-4 and FLT3 ligand stimulate production of dendritic cells from CD34+ stem cells.

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3
Q

how does a dendritic cell develop in vivo?

A

In vivo —> bone marrow derived precursors mobilize to the circulation where they differentiate into immature dendritic cells.

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4
Q

what cytokines are involved in the in vivo process of dendritic cell development?

A

GM-CSF, flt3 ligand, and M-CSF.

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5
Q

what is the role of an antigen-presenting cell in an immune response

A

Professional antigen presenting cells deliver antigen to CD4+ T cells.

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6
Q

what is needed on the antigen presenting cell for effective presentation?

A

an antigen fragment must be displayed within the groove of antigen presenting molecules, proteins encoded by the major histocompatibility complex (MHC).

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7
Q

In addition to dendritic cells what are two other cells that are considering antigen presenting cells?

A

Macrophages and B cells

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8
Q

why are dendritic cells called the “Gate-keeper” in peripheral tissues?

A

Capture antigens and carry them to secondary lymphoid tissues.

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9
Q

Dendritic cells are present on all lymphoid and non lymphoid tissues, except???

A

Brain

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10
Q

what molecules on a dendritic cell are critical for antigen presentation leading to activation of CD4+T cells?

A

HLA-Class II (MHC Class II)

B7-1/CD80 and B7-2/CD86

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11
Q

Describe general structure of a HLA-class II molecule

A

Heterodimer (two transmembrane polypeptide chains)

Bind antigenic fragments 15-30 AA long

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12
Q

Describe the properties of the molecules

A
  1. Only expressed on dendritic cells and all other APCs
  2. Normal APC expresses all three heterodimers
  3. Polymorphic in population
  4. Co-dominant expression
  5. IFNgamma up regulates expression of HLA class II
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13
Q

what are the three different isotopes that play a role in antigen presentation

A

DP, DQ and DR (Structurally similar and expressed on APC)

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14
Q

Number of different heterodimers that will be expressed on the dendritic cell if the parents are genetically unrelated?

A
minimum of six different class II molecules will be expressed on the cell surface 
(one copy of each HLA will be inherited per parent)
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15
Q

In this course MHC and HLA are used interchangeably, what is the reason for the different nomenclature?

A

In humans the MHC are referred to as HLA in recognition of the fact that the proteins are human leukocyte antigens

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16
Q

What is the reason for referring to MHC molecules as H2 molecules?

A

Class II MHC is for any species while H2 is for mouse.

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17
Q

list the Class II MHC molecules for the mouse

A

H2-mouse —> H2-IA, H2-IE

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18
Q

what is the advantage of polymorphism in the expression of MHC molecules?

A

advantageous for population survival because antigen fragments must associate with MHC molecules to be delivered to T cells, cells that are absolutely required for adaptive immunity.

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19
Q

what is the advantage of co-dominant expression of MHC molecules?

A

allows one to form 6 different stable heterodimers

20
Q

what is the first step in the sequence of events that leads to the display of a microbial peptide with class II MHC on the cell surface?

A

When microbes penetrate the host’s physical defenses some of the microbes are endocytosed by antigen presenting cells.

21
Q

what are subsequent steps in the antigen process and presentation

A

include the fusion of the endocytotic vesicle with lysosomes that release their contents into the endosome.

22
Q

what is the second fusion process in the antigen process and presentation

A

the newly formed vesicle fuses with an endosome that contains the class II MHC, creating a chimeric endosome.

23
Q

In creating a chimeric endosome, what complex is then exposed to lysosomal enzymes?

A

Class II MHC/Ii complex is exposed to lysosomal enzymes, the Ii chain is degraded, and an antigenic peptide binds in the newly exposed groove of the class II MHC.

24
Q

What happens to the chimeric endosome?

A

migrates to, and fuses with, the cell membrane such that the antigen peptide/class II MHC complex is displayed in the surface of the antigen presenting cell.

25
Q

Finally when these complexes are recognized by T cell receptors present on CD4+T cells what happens?

A

the T cell is activated to secrete cytokines

26
Q

what are the cytokines secreted by dendritic cells?

A

IL12–> target: NK cells; role –> activates NK cells to secrete IFNgamma
IL15 and IL18 —> target: NK cells; role —> enhances IFNgamma induced by IL-12
IL23 –> target: Th17 cells; role —> stabilization of Th17 cells during differentiation of Thp cells to Th17 cells in the presence of TGFB, IL-1 and IL-6

27
Q

what is cross presentation?

A

the process by which exogenous antigens are presented on the cell surface with Class I MHC molecules instead of Class II

28
Q

what cells mediate cross presentation?

A

only dendritic cells

29
Q

Following cross presentation exogenous antigens can be presented within the context of what cells?

A

Class I MHC to CD8+ T cells

30
Q

what two other cells function as antigen presenting cells but not in a primary immune response?

A

Macrophages and B cells

31
Q

Why can HIV infect dendritic cells?

A

dendritic cells express CD4, a molecule that, on T cells, determines T cell lineage and function. CD4 is one receptor for HIV. Immature dendritic cells express both CD4 and chemokine receptors.

32
Q

HIV is initiated by interaction of viral envelope proteins with what two receptors?

A

CD4 molecules

Chemokine receptors: CCR5 and/or CXCR4

33
Q

what cells are the main producers of IFNgamma?

A

Th1 cells

NK and ThO are also producers

34
Q

explain the phenomenon of class II MHC restriction

A

CD4+T cells only recognize antigenic peptides if they are displayed with Class II MHC molecules present on the surface of antigen presenting cells.

35
Q

what molecule serves to direct the transport of class II MHC molecules through the golgi, from where they are released within endosomes

blocks the binding of superfluous peptides that the MHC heterodimer might encounter in the endoplasmic reticulum

A

Invariant chain

36
Q

Dendritic Cell —> HLA-Class II/peptide

what is the CD4+ T cell activation?

A

T cell antigen receptor (TCR)

37
Q

Dendritic cell —-> HLA-Class II

what is the CD4+ T cell activation?

A

CD4

38
Q

Dendritic cell —> B7-1/CD80

what is the CD4+ T cell activation?

A

CD28

39
Q

Dendritic cell —-> B7-2/CD86

What is the CD4+ T cell activation?

A

CD28

40
Q

Dendritic cell —> LFA-3

what is the CD4+ T cell activation?

A

CD2

41
Q

Dendritic cell —> ICAM-1

what is the CD4+ T cell activation?

A

LFA-1

42
Q

Dendritic cell —> ICAM2

what is the CD4+ T cell activation/

A

LFA-1

43
Q

Dendritic cell —> CD40

What is the CD4+ T cell activation?

A

CD40L (CD154)

enhances T cell response

44
Q

Dendritic cell –> B7-1/CD80

what is the CD4+ T cell DOWN REGULATION?

A

CTLA4/CD152

again inhibition of T cell response

45
Q

Dendritic cell –> B7-2/CD86

what is the CD4 + T cell DOWN REGULATION?

A

CTLA4/CD152

again inhibition of T cell response