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Fundamentals Of Immunology > T-Cell Mediated Immunity > Flashcards

T-Cell Mediated Immunity Flashcards

1
Q

Cell-mediated immunity=?

What does it respond to?

A

T cell immunity

Responds to intracellular microbes

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2
Q

What must we do to clear infection?

A

Must clear all microbial reservoirs (natural source of a microbe: which cells infected? Must get rid of), including our own infected cells

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3
Q

Which microbes require CMI control?

A

Intracellular microbes

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4
Q

How do we get from initial exposure to effector cells?

A

Dendritic cell comes in and activates CD8 (does NOT result in death of dendritic cell). FIRST interaction is about ACTIVATION, then rest of recognition is death to the cell w/ the antigen: can only replicate inside of cells

Cells activate, leave lymph, travel to site of infection, helpers tell others what to do, CD8s target and destroy infected cells

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5
Q

What do CD8s Vs CD4s talk to?

A

CD8s work am non phagocytic cells and kill infected ones

CD4s talk with phagocytic

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6
Q

Define clonal deletion

A

Recognizing self-reactive cells (negative selection) and telling them to die (clone refers to single cell

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7
Q

Explain T cell activation and what T cell activation results in

A

TCR complex engages MHC and peptide (key1)

Full activation requires co-stimulation (key2) (think double keys for nuclear launch)

Activation results in:

  • stimulation of innate and adaptive responses
  • cytokine production and release
  • inflammation
  • CTL activity
  • b cell regulation
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8
Q

What are the characteristics of a naive T cell?

A

Mature, but never been activated, has survived maturation process

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9
Q

Overview of T cell activation

A

1) antigen and co stimulation –> IL-2R (cytokine) activation and differentiation
2) cell secretes IL-2 and creates more (+ feedback loop)
3) IL-2: made for T cells for T cells= forces them to divide
4) after divided: leaves and is now called effector cell (in peripheral tissues)
5) small proportion differentiate into memory cells (long lived, keep populations up)

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10
Q

IL-2R versus IL-2

A

IL-2R is a cytokine, for activation and differentiation

IL-2 is positive feedback loop that forces T cells to divide

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11
Q

Effector cells, memory cells

A

Effector: activated and now doing work

Memory: previously activated cells (both b and T cells make them)

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12
Q

What are the 3 signals that a T cell receives during activation

A

1: TCR complex with MHC and antigen interaction (key1) must recognize both MHC and antigen
2: co-stimulation signal between CD28 (t cell surface) and B7 (surface of APC) (key2)
3: cytokines released by APC, signal tells helper T cells what form of helper t to become (1,2,17)

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13
Q

List T cell activation ligand-receptor pairs

A

T cell: APC

CD4/8 : MHC class 2/1 (signal transduction)

TCR (a/B chains) : peptide/antigen&MHC
(Antigen recognition)

CD3 : no ligand
(Signal transduction)

Zeta chains : no ligand
(Signal transduction)

CD28 : B7
(Costimulation)

Adhesion : ICAM-1

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14
Q

What is costimulation and why is it important for T cell activation? What happens if costimulation doesn’t occur?

A

B7 (APC) with CD28 (t cell)
AND MHC with TCR

Both needed to activate T cell

If costimulation doesn’t happen–> no response or tolerance, cell is turned off
(APCs only make B7 when they have engaged right receptors: been activated by binding TLR, so no costim= prob no microbial antigen, presenting with costim only happens when APC recognizes foreign)

If it does: activates and secreted cytokines

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15
Q

Central tolerance?

A

Positive and negative selection during maturation

Another later of tolerance, presenting with costim only happens when dendritic cell recognizes something foreign

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16
Q

How are CTLs activated?

A

Cell is infected with microbe
Phagocytosis by host APC (dendritic present MHC 1&2, can activate both)
TCR recognized MHC and antigen AND costimulation
Activation

*note: CD4 activation can lead to secretion of cytokines that help activate CD8

For activation of T cells: always need TCR:MHC&antigen recognition AND costim

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17
Q

What happens after T cell activation?

A

T cells talk to macrophages and B cells via cytokines

B cells --> class switch and antibody secretion
Macrophage activation: destruction of phagocytosed antigen

CD8s: seek out infected cells w/ same antigen as they were activated with once activated

Killing of infected cells

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18
Q

What is the function of IL-2?

A

IL-2 is secreted after T cell activation by antigen and costim
IL-2 receptors are also made

Sole purpose of IL-2 is for the CELL to DIVIDE

Positive feedback loop that drives more division

IL-2= proliferation

19
Q

T cell expansion and decline

A

Clonal expansion, contraction, only memory cells left behind (non memory cells die)

20
Q

Vaccines

A

Live-atenuated: robust response probs

Flu: shot is dead inactivated, intranasal is live attenuated and stays in upper respiratory tract, doesn’t make it to lungs

Intranasal: get serum and mucosal protection, better memory

Shot dead inactive is only serum protection

21
Q

Helper T cell subtypes?

A

TH1: activates macrophages and B cells, standard pro-inflammatory response, works back&forth with innate

TH2: anti-inflammatory, antagonistic to TH1 (prevent each other) because cytokines inhibit each other’s pathway

TH17: similar to TH1, mediate neutrophil response, guide them to sit and for their action, pro-inflammatory

1&17 can work together (pro-inflammatory and activate innate cells

T1&T2 are mutually exclusive in the same region

22
Q

What dictates what type of helper T cell it will become?

A

Cytokines

23
Q

Cytokines secreted by APC and resulting TH cell. What they secrete, and pro-anti inflammatory

A

IL-12 and IFN-y –> TH1 –> secretes IFN-y–> macrophage activation, proinflammatory

IL-4 –> TH2 –> secretes IL-4 (leads t B cell class switch to IgE: mast cell de granulation and allergies) and IL-5 (eosinophils activation), anti inflammatory.

TGF-B & IL-6 –> TH17–> secretes IL-17–> proinflammatory and increased neutrophil response

24
Q

What do T cell secreted cytokines tell B cells to do?

A

Class switch (antibodies). Tells them what to class switch to

Antibodies if B cells have effector functions. Not the B cells themselves!!

25
Q

TH1 vs TH2 balance

A

Their cytokines negatively inhibit each other

Vs some pathogens this causes differing results:

Tuberculoid leprosy is isolated (granules surrounded by T cells: TH1 normal response) whereas lepromatous leprosy cannot be contained (defective TH1)

Recall TH1 leads to normal macrophage activation

26
Q

CTLs at work (CD8 here): effector function

Perforin and granzyme function

A

CD8 only has one effector function: look for cells infected with same antigen that activated them and kill them

Perforin: creates pore

Granzyme: activate apoptosis, cell death cascade, tells target cell to self destruct

One cell at a time only

27
Q

When is complement activation required

A

Only to activate the b and T cells

Once activated, CD8s no longer need complement, only MHC and antigen

28
Q

NK cells activation and inhibition

A

If inhibitory receptor engaged –> not activated and no killing

If not engaged–> activated and kills infected cell

NK is not antigen specific

Takes care of the cells that cannot talk to CD8, such as when a virus turns off a cells ability to say it’s infected

29
Q

T cell activation summary

A

APC: MHC&peptide, B7, adhesions (ICAM-1) hold them together long enough for rxn to take place

T cell: TCR w/ CD3&4/8, CD28, integrins (LFA-1) –> both MHC and antigen recognized =activation

CD4 tells other cells what to do, CD8 just kills infected

30
Q

What are gamma-delta T cells?

A

Small (10%) subset of T cells that can bind w/o MHC restriction. Appear to have more of an innate function, recognize broad antigens

Found in intestinal and pulmonary epi

Epi surveillance for UV damage, infection, and cancer

31
Q

How do T cells tell other cells what to do?

A

CD40 ligand (on T cell) binds to CD40 (on target cell) binding activates the target cell

Macrophages: are activated and start killing phagocytosed microbes (cell-mediated), cytokines as well

B cells: activate via CD40, T cell cytokines tell them which Ig to make

T cell is SENDING the signal now!

32
Q

Cell mediated immunity overview

A

CD4 TH1&17 recognize antigen on APC, cytokine secretion, macrophage activation and inflammation

CD8recognizes activates and tells cell to die

33
Q

What do you need cell mediated response for?

A

Intracellular pathogens

Such as Listeria, an intracellular bacteria

34
Q

Does serum transfer specific immunity?

A

No, need a cell mediated response to deal with intracellular pathogens

Serum=do not fight off listeria

Serum= antibodies/humoral response

35
Q

What type of cell must be used to fight intracellular pathogens?

A

T cell response is needed, so that they can activate macrophages which do the killing

CD4s activate macrophages

CD4 doesn’t kill listeria itself, but it activates the cells that can

36
Q

When a T cell TH1 for example, activates its target cells it…

A

Gets them to work harder

37
Q

What are responsible for pulling naive T cells to get into lymph?

A

CCR7, L-selection, and sphingosine-1P

S-1P is high in blood and lymph, low in nodes, this gradient pulls it in, then pulls it back out

These are turned off once the cells become effector cells

HEV has ligand for L-selectin
Chemokines that bind CCR7 only made in lymph tissues

38
Q

Once activated, how do T cell receptor expressions change?

A

Once they enter through the HEV, and become activated, they turn off CCR7 and L-selectin and turn in receptors that correspond to tissue

Remember: T cells exert effector functions at the site of infection, so once activated they want to leave lymph

39
Q

How do T cells get out of lymph tissue?

A

S1P is high in blood/lymph and low in nodes

Binding to its receptor reduces expression of receptor

If not activated: receptor expression increases and it leaves through efferent lymph vessel

If activated: receptor expression is repressed

Eventually expression is restored and l-selection and CCR7 are turned off, drawing cell out of lymph

40
Q

Effector T cell migration summary

A

Effector cells migrate to site of infection

They do NOT express L-selectin or CCR7 (naive off)

Endothelium expresses: E&P-selectins and ICAM1&VCAM1
Activated T cell expresses: propor E&p-selectin ligands and integrins LFA-1&VLA-1

E&P selectin and ICAM1&VCAM1= effector ON
L-selectin and CCR7= naive OFF

41
Q

How cells stop at tissue

A 
Rolling adhesion: selections
Integrins activation by chemokines--> to high affinity state
Stable adhesion (high affinity integrins) 
Migrate through Endo cells to infection site
42
Q

How do Cd4/8 work together?

A

CD4 tells macrophages to work harder, if macrophage can’t kill an infected cell it ingested, then CD8 kills it

43
Q

Resistance to CMI

Herpes and mycobacterium

A

Herpes shits down process of cell destruction, such as shutting down MHC class 1 presentation

Mycobacteria: inhibit phagolysosome fusion

True pathogens find a way to avoid immune response: escape recognition, colonize, before immune system recognizes

44
Q

Clonal selection

A

Only activate antigen-specific T cells, so only clones that recognize specific antigens

Fundamentals Of Immunology (11 decks)

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