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Cellular Week 2 > Lymphocyte Trafficking > Flashcards

Lymphocyte Trafficking Flashcards

1
Q

Fungi respond to what type of Th response?

A

Th1

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2
Q

Activation via PRR leads to signal transduction..

A
  • cytokine expression
  • co-stimulator expression (B7)
  • Type 1 interferons!! (innate antiviral response)

leads to acute inflamm, adaptive immunity, and antiviral state

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3
Q

How do adjuvants work?

A

Increase induction of costimulator molecules (b7)

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4
Q

pattern of cytokines being released depends on which set of receptors is being activated (for ex. TOLL or cytoplasmic, etc)

A

…

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5
Q

TNFalpha, IL-1, IL-6 have overlapping functions as pro-inflammatory cytokines, and at high levels act in an endocrine manner. Can function as “endogenous pyogenes” = fever inducing agents. Cytokines produced by monocytes are sometimes called…

A

monokines

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6
Q

Anti-TNF antibodies used in treating what?

A

autoimmune/autoinflammatory disorders

rheumatoid arthritis, psoriasis, and IBD

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7
Q

TNF activates?

A

neutrophils

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8
Q

TNF, IL-1, IL-6 are important in activating acute phase proteins. Also important for cachexia (TNF) - act on muscle cells and cause their atrophy and death/fat cells to metabolize (cytokines on non immune cells). TNF binding to cells causes death (why called necrosis).

A

…

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9
Q

IL-1 is important for what?

A

Th17 differentiation!

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10
Q

IL-6 is important for?

A

B cell proliferation/ab production

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11
Q

Which cytokine is involved in septic shock?

A

TNF-alpha
LPS stimulates TNF alpha production from macrophages
Shock is very complex bc inhibitors for TNF alpha have failed to reduce it.

Toxic shock syndrome comes from super antigens! - causes cytokine storm and shock.

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12
Q

Which cytokine is chemotatctic for neutrophils?

A

IL-8 (CXCL8)

chemokine

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13
Q

Which cytokine promotes a Th1 response?

A

IL-12

activates NK cells (increased cytotoxic activity)

leads to increased IFN-gamma

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14
Q

Macrophages release IL-6, TNFalpha, IL1B, CXCL8, and IL-12

A

…

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15
Q

Which two cytokines antagonize each other?

A

IL-10/IL-12

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16
Q

IL-10?

A

Antagonizes IL-12
pushes toward a TH2 noninflmmatory response
Produced by innate and then t cells in a positive loop

reduced expression of costimulators and class II MHC molecules

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17
Q

High levels of TGF-beta in certain anatomical sites (such as the eye) lead to the term…

A

immunologically privileged sites due to its anti-inflammatory activity.

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18
Q

TGF-beta pushes toward what response?

A

Th17 anti-inflammatory response!
shuts down regular T cells and pushes them towards regulatory type!

increased in places where inflammation is detrimental (eye,brain,testes,etc)

(inhibition of inflamm T cells, Th17 promoted, regulatory T cell promoted)

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19
Q

Type 1 Interferons

A

NOT IFN-gamma (that is type II)

Exs: IFN-alpha/beta

antiviral state, increased MHC Class I expression
NK Cells are activated!

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20
Q

Type I inerferons have a higher antiviral activity and less immunoregulatory activity than type II!

Type I are important components of the INNATE immunity against viruses.

Infected cells produce type I interferons. They don’t help the infected cell but inform the neighboring cells that they are infected and protect them.

Interferons are NOT ANTIGEN SPEICIFIC! but they do inhibit viral production in some way.

A

…

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21
Q

Interferons Type I have been used as therapies but not well tolerated by patients. .

They inhibit protein synthesis by phosphorylating EF-2. OR degrade viral RNA or they inhibit viral gene expression/virion assembly…lots of diff functions.

A

…

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22
Q

Type of interferons that influence macrophages?

A

type II! IFN-gamma.

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23
Q

M1 macrophages

A

phagocytic and inflammatory.
induced by th1 cytokines

IFN-gamma promotes this type.

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24
Q

m2 macropahges

A

wound repair, fibrosis
induced by the type cytokines.

produces IL-10 and TGF-beta

25
Q

Chemokines are small peptides that attract cells via GRADIENTS to appropriate tissues and bind to GPCRS. They are important mediators of inflammation and T and B cell trafficking.

A

….

26
Q

People who are HIV resistant in the chemokine co-receptor are resistant to HIV infection. (HIV binds to both the CD4 receptor and chemokine receptor in order to enter cells).

A

…

27
Q

Cytokines who what type of immunity?

A

innate.

28
Q

Innate immunity characteristics

A

use PRRs
multiple receptor types per cell
essentially all cells of a single cell type are active against all antigens

29
Q

adaptive immune system characteristics

A

use ag-specific receptors
ONE RECEPTOR TYPE PER CELL
ag specific clonal selection, low frequency for any given Ag.

30
Q

Tissue resident innate cells initiate the immune response, recruit blood-borne neutrophils, monocytes (macrophages), and then lymphocytes.

This order is important!

A

..

31
Q

lymphocytes preferentially go to the lymph node when they are naive! once stimulated, they move into circulation

A

..

32
Q

B cells don’t migrate to site of infection! only effector T cells do. B cells stay or go back to the bone marrow.

A

..

33
Q

All of the secondary lymphoid organs (except the spleen are connected by lymphatics.

A

..

34
Q

The wall of the lymph vessel has what?

A

epithelial cells that overlap each other!

When fluid outside the capillary pushes against the overlapping cells, they swing open like a door (only in one direction). Fluid inside cannot flow out!

no pumping in these vessels.

35
Q

Naive lymphocytes arrive at lymph nodes in arterial blood!!

A

…

36
Q

GALT, MALT, NALT, and BALT - lymphoid tissue outside lymph node.

GALT - lamina propria/peyer’s patch
MALT - site of high IgA production/ no afferent lymphatic structure (ag arrives via lumen of nose, trachea, etc)
BALT - rabbits/NALT more in humans - bronchial
NALT - nasal - adenoids/tonsils

A

…

37
Q

Dendritic cell are involved in dendritic trafficking!I Take Ag to lymph node although the Ag can also travel to the nodes free in the lymph fluid.

Ags in blood are captured in the spleen.

A

….

38
Q

lymph nodes collect antigen from epithelium and connective tissue.

blood borne ag are captured by APC in the spleen!

A

…

39
Q

Dendritic cells go to what place in the lymph node first?

A

T cell areas!!!

40
Q

Dendritic cells are professional APCs (with b cells and macrophages) and they initiate the adaptive IR. Trasport Ag to LN for T cell recognition. They also secrete cytokines!

Dendritic cells = tissue resident cells. Largely Epithelial cells!

Have huge processes. Hard to isolate from tissues.

A

….

41
Q

Function of dendritic cells is phagocytosis (initially) (have Fc, mannose receptors, etc). On way to traveling toward lymph node, begins to express co-stimulatory molecules and MHC Class II (B7, ICAM-1, IL-12). Basically transitions from a phagocytic cell to an APC. Maturation process. NOT IN TISSUES TO CLEAR AG! that is the neutrophils job.

A

….

42
Q

Immature dendritic cells in epidermis are called…

A

Langerhans cell

43
Q

DCs need to be activated during innate response via TLRs and cytokines.

A

…

44
Q

What is Homing? How do they get there?

A

Homing = naive T cells home to specific peripheral lymphoid tissues

Get there through HEVs (high endothelial venules).

Homing is based upon specific homing receptors on the T cells interacting with receptors on HEVs or other endothelial cells (selectin-addressin interactions).

45
Q

What two receptor interactions is important for homing?

A

selectin-addressin

ex. L-selecting with GlyCAM1

HEVs have the addressins
T cells have the selectins!

46
Q

Entry into the HEV of a lymph node by naive T cells requires what?

A

L selectin (CD62L) on the T cell

47
Q

HEV on the LN have what on their surface?

A

peripheral node addressin
ICAM-1
ICAM-2

48
Q

Signal for lymphocytes to move is provided what?

A

chemokines!

49
Q

L selection on T cell and GlyCAM-1 allow for rolling interaction. LFA-1 is activated by chemokines. Activated LFA-1 binds tighter. . Diapedesis follows.

A

…

50
Q

Naive T cells can enter lymph nodes through afferent lymph and rom the blood!! If lymphocytes are to activated by Ag in lymph node, eventually go back into blood circulation!

A

….

51
Q

Follicles in lymph node = b cell
parafollicular = t cell
storms of lymph nodes have diff chemokines in diff areas!!

DC express same chemokine receptors as T cells so go to T cell region (parafollicular)

A

…

52
Q

When a B cell is activated, it and helper T cells switch chemokine expression and migrate to opposite areas and meet in the middle!

A

…

53
Q
  • interaction with b and t cells - cognate activation and IgM released by plasma cells
  • migrate activated b cell along with follicular T helpers to the germinal center for further B cell activation (SHM and H chain class switching!)
A

..

54
Q

Where in LN does SHM and H chain class switching occur?

A

Germinal center!

55
Q

Lymphocytes that are activated will eventually change their receptor patterns for selections, chemokine receptors, and adhesion molecules. This allows what?

A

Them to leave the secondary lymphoid tissues and home back to the site of inflammation (activated endothelium) where it can implement effector function!

goes from LFA=1 (binds to ICAM on APC) to VLA-4 (will bind to VCAM on endothelium)

56
Q

Naive lymphocytes can be activated in peer’s patches… reminder… and then they will home back to site of initial inflammation.

A

….

57
Q

antigens enter LN with or without DC through afferent lymphatics!

A

…

58
Q

Only effector T cells can preferentially home back to tissue sites where Ag was first encountered!

A

..

Cellular Week 2 (9 decks)

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