Diebel-T Cell receptors and MHC Complex Flashcards

1
Q

What are Th1 cells induced by?

A

DC1
IL-12
IFN alpha

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2
Q

What cytokines to Th1 cells make?

A

IL-2
IFNy
(TNFB)

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3
Q

What are the main functions of a Th1 cell?

A

IFNy polarizes macrophages into M1, activates and attracts them.

IL-2 helps CTLs get activated by antigen.

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4
Q

What cytokines do M1 macrophages release to intensify inflammation?

A

TNF alpha

IL-1

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5
Q

What causes contact sensitivity?

A

Normally T cell recognizes antigens and a macrophage removes them but this system can also damage local tissues. Over stimulation of Th1 cells (poison ivy)–> contact sensitivity.

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6
Q

What induces Th2 cells?

A

DC2

IL-4

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7
Q

What cytokines do Th2 cells make?

A
IL-4
IL-5
IL-6
IL-10
IL-13
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8
Q

What are the main functions IL-4?

A

IL-4 polarize macrophages into M2, activates and attracts them.

IL-4 also attracts eosinophils specialized for killing parasites like protozoans and worms.

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9
Q

What are the main functions of Th2 cells?

A

Th2 cells often act AFTER Th1. They are involved in healing (debris removal, scar formation, and walling off pathogens that M1 macrophages couldn’t kill).

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10
Q

Explain the ying and yang of T cell immunity.

A

Th1- active urgent destruction of invaders

Th2- later stages of inflammation, repair and healing

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11
Q

What are the 2 ways that Th2 mediates parasitic immunity?

A

Th2 secretes IL-4 which attracts eosinophils which are specialized for killing parasties.

Th2 gives rise to Th2fh cells that migrate to lymphoid follicles and secrete IL-4. High amts of IL-4 switch IgM/IgD to IgE–> parasite resistance.

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12
Q

What induces Th17 cells?

A

TGFB + IL-6
IL-21
IL-23

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13
Q

What are the main functions of IL-17 and 22?

A

Attract and activate inflammatory cells.

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14
Q

What helper cell is often implicated in autoimmune disorders?

A

Th17

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15
Q

What Th are Th17 most similar to?

A

Th1
Both lead to the accumulation of angry M1 macrophages.
Also plays a role in maintaining integrity of mucosal surfaces.

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16
Q

What cytokines does Tfh make?

A

Many of the ones that Th1 and Th2 make

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17
Q

What are the functions of IL-2, IL-4 and IFNy secreted by Tfh cells?

A

Help B cells switch isotypes

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18
Q

What induces Treg cells?

A

Natural TGFB

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19
Q

What cytokines are made by Treg cells?

A

TGFB

IL-10

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20
Q

What are the main functions of TGFB and IL-10?

A

Supress Th1,2,17,Tfh by contact and soluble factors

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21
Q

Most Treg cells ahve what phenotype?

A

CD4/CD25

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22
Q

What happens if Treg doesn’t work?

A

You can get overactive immune responses and self reactivity.

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23
Q

All Th cells have what surface marker?

A

CD4

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24
Q

What are the two ways that a CTL can initiate apoptosis?

A
  1. Fas (CD95) receptor cross linked to the Fas ligand (CD95L) activates apoptotic pathway
  2. secretion of lytic granules that lead to apoptosis:
    granzymes
    perforins
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25
Q

How and where are CTLs activated?

A

Lymph node after contact with an antigen bearing DC

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26
Q

What IL is required for activation of CTLs?

A

IL-2 from Th1

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27
Q

What IL is required for conversion of CTL into memory cells?

A

IL-21

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28
Q

What percent of T cells are left after a couple weeks of infection and what cells are these?

A

5%
Memory cells–they can replace themselves and quickly differentiate into effector cells when re-exposed to low antigen concs.

29
Q

Could my T cells work in your body?

A

NO!

T cells are antigen specific and MHC restricted to cells of your own body

30
Q

What cell is the BEST APC?

A

Dendritic cells

31
Q

T cells ONLY see antigen when….

A

it’s complexed w/ cell surface MHC molecules

**B cells focus on free antigen by making antibodies

32
Q

Class I products are found on…

A
nucleated cells 
(essentially found on all your cells except RBCs)
33
Q

Class II products are found on…

A

the surfaces of dendritic and macrophage type cells and B cells

34
Q

What is an important quality of DCs?

A

They CONSTITUTIVELY express high levels of MHC and B7

35
Q

What is the difference between DCs and macrophages?

A

Macrophages aren’t always on–they have to be activated!

They’re activated by phagocytosis of Class II molecules.

36
Q

What do B cells constitutively express and how are they activated?

A

MHC II

Antigen binding to Ab before they express costimulatory molecules

37
Q

Describe a characteristic T cell receptor.

A

2 chains that are alpha and beta or gamma and delta. Both alpha and beta domains have transmembrane domains.

Constant and variable portion

38
Q

What molecule is associated w/ the TCR complex and is involved in downstream signaling?

A

CD3

39
Q

What molecule has:
4 Ig like domains
binds to a conserved region on Class II

A

CD4

40
Q

What signal transduction molecule does CD4 bind to?

A

p56 which then forms a bridge and also binds a chain of CD3

41
Q

What molecule has:
aB heterodimer or aa homodimer
ONE Ig domain held together by a disulfide bond
Binds Class I

A

CD8

42
Q

What co-receptors add to CD4/8 binding affinity?

A

CD2- LFA-3
LAF-1- ICAM-1
CD28- B7
CD45R- CD22

43
Q

Rearrangement of the alpha chain (V, J and C segments) leads to…

A

selection of a VJ combination attached to a single C segment

*alpha chain has a cytoplasmic tail making the TCR alpha receptor membrane bound

44
Q

The alpha chain is most similar to the….

A

Light chain

45
Q

The beta chain is most similar to the….

A

Heavy chain

46
Q

Rearrangement of the beta chain leads to…

A

A selection of a VDJ combination attached to one of two C gene segmenents

47
Q

Does somatic hypermutation play a role in generating TCR diversity?

A

NOOOO

Can’t happen because there’s no way to change it once the T cell leaves the thymus.

48
Q

Describe the process of TCR gene rearrangement…

A
  1. Pre-T cells express Rag1/2
  2. Enzymes recognize conserved recombination signal sequences flanking the regions of the VDJ coding sequences in the DNA
  3. RAG1/2 complex joins the various DNA segments and throws away DNA info in between
  4. Each rearranged DNA sequence encodes a single type of TCR
49
Q

How do you increase diversity in TCR gene rearrangement?

A
  1. Alternating joining of the D seq to VJ, VDJ, or VDDJ

2. Somatic mutation can be added btwn v and D and D and J domains

50
Q

What is TCR allelic exclusion?

A

Each T cell will produce ONE beta chain from just ONE chromosomal loci.

51
Q

Where does T cell selection occur and what are the three things T cells must do?

A

Thymus

  1. Not recognize SELF
  2. Not recognize free antigen (Ab’s job)
  3. Recognize antigenic peptide plus self MHC
52
Q

What are MHC molecules also known as?

A

HLA

53
Q

How many class I gene loci are there and what are they?

A

3

HLA-a
HLA-b
HLA-c

54
Q

What is B2 microglubluin?

A

A gene product that associates w/ the other MHI peptides.

55
Q

How many peptides does the MHC II gene locus encode?

A

2!

Alpha subunit and a beta subunit are expressed together on the cell surface

56
Q

What are the three major class II gene loci?

A

DP
DQ
DR

57
Q

How does polymorphism relate to the gene loci of MHC I and II?

A

Polymorphism give you:
a unique identity
allows you to distinguish btwn self and non self

58
Q

What are medically significant MHC polymorphisms?

A
HLA:
B27
DR2
A3/B14
DQ2/GQ8
DR3
DR4
59
Q

HLA-B27

A

Ankylosing spondylitiis

Individuals are 90% more likely to develop disease (destruction of vertebral cartilage)
Also linked to psoriasis, inflammatory bowel disease, reiter’s syndrome.

60
Q

HLA-DR2

A

Narcolepsy

Linked to: MS, hay fever, SLE

61
Q

HLA-A3-B14

A

hemochromatosis

too much Fe absorption which can lead to internal organ damage

62
Q

HLA-DQ2/GQ8

A

Celiac disease

63
Q

HLA-DR3

A

Type I diabetes

Graves Disease

64
Q

HLA-DR4

A

rheumatoid arthritis

type I diabetes

65
Q

How many different class I and class II molecules can a cell potentially express?

A

MHC I- 6

MHC II- 12

66
Q

Why are there 6 different class I subtypes?

A

There are three genes one the loci (A,B,C) that you can inherit from either your M/D generating 6 options. One of these alleles will always be combined with the B2 chain leading to 6 different types.

67
Q

Why are there 12 different class II subtypes?

A

There are three loci w/ two alleles for each loci.
DQ, DR, DP. Each allele can be inherited from mom or dad. This means that for each locus there are 4 different possibilities leading to 4x3=12.

68
Q

What are lectins?

A

Lectins are proteins that function as immune molecules that can gum up the surfaces of foreign invaders, they can also bind to and stimulate T and B cells.

69
Q

What is pokeweed mitogen (PWM)?

A

PWM is a lectin that stimulates both T and B cells to divide.