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MIMM 214 > T Cells 4 > Flashcards

T Cells 4 Flashcards

1
Q

what is the response by TH1 cells called?

A

Type 1 Response

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2
Q

what is the main TH1 function? what are the 5 other functions of TH1?

A

MAIN: activate M1 macrophages

OTHER:
1. Killing infected macrophages
2. Help CD8+ T cells
3. stimulate monocyte differentiation in bone marrow
4. recruit macrophages by changing adhesion molecule expression
5. recruit macrophages by chemotaxis

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3
Q

why do TH1 cells need to activate macrophages?

A

some pathogens PERSIST in macrophages and resist macrophage killing

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4
Q

how can pathogens persist in macrophages? (2)

A
  1. inhibit fusion of phagosome and lysosome
  2. prevent acidification so lysosomal proteases do not activate
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5
Q

how do TH1 cells activate macrophages? (5 steps)

A
  1. recognizes pMHC II on macrophage
  2. CD40L on TH1 binds CD40 on macrophage
  3. secretes IFN-gamma
  4. macrophage activity increases
  5. production of TNF-alpha from macrophage increases
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6
Q

what are the 2 names of macrophages activated by TH1?

A
  1. M1 Macrophage
  2. Classically-Activated Macrophage
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7
Q

what is the survival signal that is sent to macrophage?

A

TNF-alpha is secreted from macrophage and binds receptors on macrophage, sending survival signal to macrophage

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8
Q

what type of signaling does TNF-alpha use?

A

autocrine –> TNF-alpha secreted by macrophage and binds receptors on macrophage

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9
Q

what do M1 macrophages do to TH1 cells?

A

activates them as a feed-forward loop

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10
Q

how do M1 macrophages activate TH1 cells?

A

TNF-alpha and IFN-gamma work together to increase expression of:
1. MHC I and II
2. CD40
3. B7 molecules
4. IL-12

therefore, allowing CD4+ T cells to bind macrophages and become effector TH1 cells

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11
Q

what other type of T cell can activate M1 macrophages? with what cytokine?

A

IFN-gamma from effector CTLs

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12
Q

when do TH1 cells kill infected macrophages?

A

if macrophages are chronically infected

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13
Q

how do TH1 cells kill infected macrophages? (4)

A
  1. TH1 cells recognize pMHC II on infected macrophage
  2. FasL on TH1 cell binds Fas on infected cells
  3. apoptosis of macrophage
  4. bacteria is released and can be phagocytosed by other macrophages
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14
Q

can TH1 directly kill infected cells? why or why not?

A

yes

they use FasL to kill infected macrophage

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15
Q

what 2 types of cells express FasL?

A
  1. CTL
  2. TH1
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16
Q

how do TH1 cells help CD8+ T cells?

A

TH1 cell secretes IL-2 to stimulate CD8+ T cell proliferation via CROSS-PRESENTATION

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17
Q

what type of signaling is used by TH1 to activate CD8+ T cells? what does this mean?

A

paracrine –> TH1 must be close to naive CD8+ T cell

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18
Q

where does TH1 activate naive CD8+ T cell?

A

in lymph node (secondary lymphoid organ)

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19
Q

where does TH1 stimulate increased differentiation of monocytes?

A

in bone marrow

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20
Q

how do TH1 cells stimulate increased differentiation of monocytes? (4)

A
  1. TH1 cell secrete IL-3 and GM-CSF
  2. IL-3 and GM-CSF circulate in blood and act on precursors in bone marrow
  3. increased monocyte production
  4. ultimately allows for macrophage production
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21
Q

what type of signaling is used by TH1 and IL-3/GM-CSF to cause monocyte differentiation?

A

endocrine

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22
Q

why does TH1 change expression of adhesion molecules?

A

so macrophages can more easily migrate to site of infection for diapedesis

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23
Q

where does TH1 increase expression of adhesion molecules?

A

on neighbouring endothelium

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24
Q

how does TH1 change expression of adhesion molcules?

A

TNF-alpha

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25
Q

how does TH1 recruit macrophages?

A

TH1 secretes CCL2 chemokine for chemotaxis –> attracts macrophage to site of infection

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26
Q

ultimately, what are the 2 ways that TH1 recruits macrophages to site of infection?

A
  1. changes expression of adhesion molecules on endothelium
  2. secretion of CCL2 chemokine for chemotaxis
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27
Q

where does TB infect?

A

lung macrophages

28
Q

why does TB lead to chronic infection?

A

often resistant to anti-microbial effect of macrophages

29
Q

what do TH-1 cells form during TB infection?

A

allows production of GRANULOMA

30
Q

describe the structure of granuloma

A
  1. core of infected macrophages
  2. surrounded by layer of activated macrophages
  3. surrounded by layer of TH1 cells
31
Q

how does the granuloma help fight infection?

A

core becomes necrotic –> infected macrophages die

32
Q

how do infected macrophages in granuloma die? (2)

A

combination of:
1. lack of oxygen
2. cytotoxic molecules secreted from activated macrophages

33
Q

what is signal 3 of TH2?

A

IL-4

34
Q

what are the 3 effector cytokines of TH2?

A
  1. IL-4
  2. IL-5
  3. IL-13
35
Q

what pathogen does TH2 respond to?

A

helminths

36
Q

what is the role of TH2 effector cytokines?

A

recruit + activate granulocytes (eosinophils, mast cells, and basophils)

37
Q

what are dysregulated TH2 responses involved in?

A

allergies

38
Q

what is the sequence of events of TH2? (4)

A
  1. signal 3: IL-4
  2. TF: STAT 6 activated and goes to nucleus
  3. master transcriptional regulator (TF): GATA-3 activated
  4. secretes IL-4, IL-5, IL-13
39
Q

what are parasitic helminths?

A

multicellular worms

40
Q

where do parasitic helminths colonize?

A

gut of animals and humans (1 billion ppl)

41
Q

what type of infection do parasitic helminths cause?

A

usually asymptomatic infection, causing chronic infection

42
Q

what are the 4 TH2 responses to helminths?

A
  1. can clear pathogen
  2. reduce worm burden
  3. “weep and sweep”
  4. facilitate tissue repair
43
Q

does TH2 always clear infection? what happens when it doesnt?

A

not always –> can cause chronic infection if not cleared

44
Q

what is an additional response to helminths besides TH2 cells?

A

IgE antibodies

45
Q

what is the “weep” part of the “weep and sweep” response?

A

promotes cell turnover and mucous production to wash away the parasite

46
Q

how does TH2 cause the “weep”? (2)

A
  1. IL-13 increases mucous production by goblet cells
  2. increases turnover of epithelial tissue
47
Q

why does TH2 cause epithelial tissue turnover?

A

helminths often adhere to GIT lining and kill cells

so getting rid of dead cells is helpful, and also can help get rid of parasite

48
Q

what is the “sweep” part of the “weep and sweep” response? how does it work?

A

enhance worm expulsion

IL-13 stimulates SMC to contract and physically remove the helminth

49
Q

what type of macrophages do TH2 cells recruit and activate?

A

M2 macrophage

50
Q

what 2 cytokines activate M2 macrophages?

A
  1. IL-4
  2. IL-13
51
Q

what is another name for M2 macrophages?

A

alternatively activated macrophages

52
Q

what are 3 roles of M2 macrophages?

A
  1. tissue repair
  2. form granulomas to trap worms in tissue
  3. release toxic mediators by ADCC
53
Q

how do M2 macrophages help with tissue repair?

A

via cleaning debris

54
Q

what is ADCC?

A

Antibody-Dependent Cell-Mediated Cytotoxicity

55
Q

what does ADCC do?

A

kill affected macrophages or parasite itself

56
Q

how do macrophages use ADCC to kill target cells?

A

antibodies coat target cells

M2 macrophages recognize constant region of antibodies via Fc receptors and KILL

57
Q

what cytokine is involved in eosinophil activation?

A

IL-5

58
Q

how do eosinophils kill parasites with granules?

A

eosinophils have granules that contain Major Basic Protein (MBP) that can kill parasites

59
Q

how do eosinophils kill parasites by ADCC? (3 steps)

A
  1. IgE antibodies coat parasite
  2. eosinophils recognize constant region of antibodies via Fc receptors
  3. eosinophils specifically target pathogen and degranulate it to kill it
60
Q

how does TH2 activate mast cells?

A

with cytokines

61
Q

how do mast cells exert their effect?

A

mast cell granules have histamine and other molecules

62
Q

what are the 3 effects of histamine and molecules in granules?

A
  1. increase vascular permeability
  2. increase intestinal motility so parasite leaves gut
  3. increase recruitment of inflammatory cells like macrophages
63
Q

do mast cells also use ADCC? if so, how?

A

yes

IgE antibodies coat parasite, mast cell expresses Fc receptors

64
Q

what cytokines do basophils secrete?

A
  1. IL-4
  2. IL-13
65
Q

what are the 3 effects of basophils?

A
  1. activate goblet cells for mucous production
  2. allow vasodilation
  3. histamines (ADCC)

MIMM 214 (33 decks)

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