The Adaptive Immune Response

Front 1

What are the five stages of an adaptive immune response?

Back 1

Antigen recognition, Lymphocyte activation, Antigen elimination, Contraction (homeostasis), Memory

Front 2

What happens during the stages of Lymhocyte activation, antigen elimination, and contraction?

Back 2

Lymphocyte activation = Clonal expansion and differentiation. Antigen elimination = Elimination of antigen. Contraction = Apoptosis

Front 3

How many antigen binding sites do TCRs have?

Back 3

One

Front 4

What do both TCRs and BCRs comprise of?

Back 4

Two different peptide chains and have variable regions for inding antigen, constant regions and hinge regions

Front 5

Which Cluster of differentiation is an accesory molecule for the T cell receptor?

Back 5

CD3

Front 6

Do B cells and T cells generally recognise similar antigens?

Back 6

No B cells recognise extracelluar antigens whilst T cells mostly recognise Intracellular antigens and needs helper cells to read the presented antigen

Front 7

What is adaptive immunity?

Back 7

An immune response that becomes more powerful following encounters with the same antigen

Front 8

What are the advantages of utilising highly specific antigen receptors.?

Back 8

Pathogens lacking stereotypical PAMPs can be recognised. Responses can be high specific for a given pathogen. The specificity of the response allows for immunological memory.

Front 9

How can specific immunity to a pathogen be achieved?

Back 9

Natural exposure, or artificially (vaccination)

Front 10

What do Pathogen assosiated molecular patterns (PAMPS), have to bind to?

Back 10

Pattern recognision receptors (PRRs)

Front 11

What is the main differences between an humoral and a T cell-mediated adaptive immunity?

Back 11

Humoral = Extracellular microbes, B-cells recognise the antigen, Secrete antibodies which either neutralise, Lysis (complement), Or phagocytosis. T cell = Intracellular microbes. Antigen presenting cell and helper T cell. Proliferation and activation of effector cells (cytotoxic T cells, natural killer cells, Macrophages). Lysis of infected cells

Front 12

Do Helper T cells also activate B cells?

Back 12

Yes

Front 13

Humoral adaptive immunity involves the production of what kind of antibodies by B cells?

Back 13

Antigen-specific

Front 14

How does the humoral adaptive immunity fight extracellular pathogens?

Back 14

The effector functions of antibodies

Front 15

What CD molecule does the Humoral adaptive response need to be exposed to in order to be activated?

Back 15

CD4+ T cells. Activate the B cells, induce memory and antibody production

Front 16

T cell-mediated adaptive immunity requires the gneration of what, in order to invoke a response?

Back 16

Involves the gneeration of antigen specific cytotoxic T cells (Tc)

Front 17

What are Cytotoxic T Cells also known as?

Back 17

CTL (cytotoxic T lymphocytes)

Front 18

What does T cell-mediated immunity, fight intracellular pathogens using?

Back 18

Effectgor functions of Tc Cells

Front 19

What CD molecule does the T cell-mediated immunity require and what does it induce?

Back 19

CD4+ and Helper T cells, in order to activate the Tc cells and induce memory

Front 20

An immune response by any cell is called what?

Back 20

Cell-mediated immunity

Front 21

T cells are either naïve, memory or effector cells. What is a naïve T cell?

Back 21

Cells have not been stimulated by antigen since leaving the thymus

Front 22

What is a memory Cell?

Back 22

Cells have had antigen presented to them and return to resting state. They are usually long-lived and can be subsequently reactivated

Front 23

What is an Effector T cell?

Back 23

T cells have specialised functions e.g. seretion of cytokines of lysis of target cells. Effector cells derive from naïve or memory cells, are short-lived, in an activated state but require further stimulation for full function

Front 24

Can memory cell be activated later on if neeed?

Back 24

Yes

Front 25

Where do naïve T cells circulate?

Back 25

Around the entrie body every one to two days

Front 26

Where are naïve cells constently sampling from?

Back 26

The lymph nodes

Front 27

Once a naïve cell has recognisesed an antigen, what happens?

Back 27

It becomes activated and undergoes clonal expansion (replicates). It then expands and differentiates into either memory or effectors

Front 28

Naive cells circulate around your body, how long does it take them to circulate?

Back 28

One to two days

Front 29

What are naive cells constantly doing when circulating?

Back 29

Constantly sampling the lymph nodes for antigen

Front 30

What happens to a naive cell when it recognises antigen?

Back 30

Undergoes clonal expansion

Front 31

What happens to a naive cell once it has undergone clonal expansion?

Back 31

It differentiates into either memory or effector cells

Front 32

In what organ do the stages of antigen recognition, activation, clonal extension and differentiation happen?

Back 32

Lymphoid organs

Front 33

Where does the stage of effector functions occur?

Back 33

Peripheral tissues

Front 34

What do Effector CD4+ T cells activate??

Back 34

Macrophages, B cells and other cells

Front 35

How do Effector CD8+ T cells (CTL) kill infected cells?

Back 35

Macrophage activation

Front 36

When do T cells recognise antigen?

Back 36

Only when presented to them by an APC in association with the correct MHC molecules

Front 37

What do Helper T cells do?

Back 37

Assist other white blood cells

Front 38

What CD molecule do Helper T cells express?

Back 38

CD4+

Front 39

Which MHC do Helper T cells recognise if they have CD4+ on their cell surface?

Back 39

MHC class 2

Front 40

When do Helper T cells only recognise antigen?

Back 40

When presented by an APC

Front 41

What do cytotoxic T cells kill?

Back 41

Intracellular pathogens

Front 42

What CD molecule do Cytotoix T cells express?

Back 42

CD8+

Front 43

If cytotoxic T cells express CD8+, what MHC molecule do they recognise?

Back 43

MHC class 1

Front 44

If cytotoxic T cells have a CD 8+ and recognise MHC class 1, what type of cell can they be activated by?

Back 44

All nucleated cells as they all express MHC class 1

Front 45

How many signals does the activation of a T cell require?

Back 45

Two

Front 46

What does the first signal to activate a T cell do?

Back 46

TCR/MHC with antigen bind. Stabilised by adhesion milecules

Front 47

What does the Second signal to activate a T cell do?

Back 47

Co-stimulatory molecules (principally B7 on the APC which bins to CD28 on the T cells). With both signals present, the T cell starts to undergo “clonal proliferation”

Front 48

What is proliferation of naive T cells induced by?

Back 48

Cytokines (Mostly IL-2)

Front 49

What are cytokines produced by?

Back 49

A T cell that has undergone recognition and activation by the two signals

Front 50

What mechanism primarily acts on T cell proliferation?

Back 50

Autocrine

Front 51

How does the autocrine mechanism work for T cell proliferation?

Back 51

Secretion of cytokines that act on self, since T cells also expresses the cell surface receptors for these cytokines (E.g. I-2R/CD25

Front 52

What happens to T cells if the second signal need for their activation were to not occur?

Back 52

State of “anergy” is induced (No proliferation of T cells but also tells cell to never produce that cell)

Front 53

If a State of anergy is induced, what happens to the T cells response?

Back 53

It would no longer recognise the antigen if they were to see it again

Front 54

If pressed on the T cell, What can CTLA-4 engage and induce?

Back 54

Engages with B7 instead of CD28, which can induceanergy

Front 55

Do all T cell express CTLA-4?

Back 55

No

Front 56

Why are there two signals for T cell activation?

Back 56

Expression of co-stimulators is regulated and ensures that T cells respond at the correct time and place,

Front 57

How is B7 expression induced?

Back 57

By microbial products and cytokines (INF-Gamma)

Front 58

Which cell expresses the highest levels of co-stimulators?

Back 58

Dendritic cells, therefore are the most potent stimulators of naive T cells

Front 59

Do immature Dendritic cells express MHC more or less than when mature, Are they more or less motile, more or less phagocytotic, and do they express more or less B7?

Back 59

Non-motile, MHC low, Highly phagocytic, B7 low

Front 60

In addition to the two signals which activate a naive T cell and causes them to proliferate, there is a third. What does this third signal cause the T cells to do?

Back 60

Directs T cell differentiation into different subsets

Front 61

What is it, which causes induces the third signal, and causes differentiation of T Cells?

Back 61

Cytokines made by the same APC that provide MHC2 and co-stimulation and both other cells “cytokine environment"

Front 62

With Helper T cell activation, what do different cytokines cause?

Back 62

Different cytokines in the cytokine environment produce a different type of effector Helper T cell

Front 63

What are the different T helper cell subsets?

Back 63

Pro-inflammatory, B cell activation and Ab production, Anti-inflammatory, B cell activation in follicles

Front 64

Name a cytokine which can induce one of the T helper cell subunits?

Back 64

TH1 = IL-12, IFN gamma, IL-18. TH2 = IL-4. Treg = TGF beta, IL-2. Th17 = IL-1, IL-6, TGF beta, TfH (T follicular) = IL-6, IL-21

Front 65

T helper cell 1 is a CD4+ T cell subset. What does Th1 do?

Back 65

Inflammatory T cells, produce TNF alpha/IFN gamma. Medicate inflammatory immune responses (through activation of macrophages and cytotoxic T cells)

Front 66

T helper cell 2 is a CD4+ T cell subset. What does it produce and is involved in?

Back 66

Produces IL-4, iL-5 and IL-13. Involved in the clearance of parasitic infections and enhanced eosinophil/mast cell response

Front 67

T helper cell 17 is a CD4+ T cell subset. What does it produce and what is it involved in?

Back 67

Produces IL-17, and IL-22. Thought to play a role in inflammation and tissue injury

Front 68

Treg, is a CD+ t cell subset, what does it produce and what is it involved in?

Back 68

Produces IL-10, TGF beta. Regulatory T cell. Plays a suppressive or regulatory role. Can be natural or inducible

Front 69

Tfh is a CD4+ T cell subset. What does it produce and what is it involved in?

Back 69

Produces IL-4 and IL-21. Is a follicular helper T cell, found in 2o lymphoid follicles. Activate B cells

Front 70

Th3 is a CD4+ T cell subset. What does it produce and what is it involved in?

Back 70

Non inflammatory IgA. A type of inducible Treg (involved in mucosal immunity and tolerance)

Front 71

What can the presence of Th1 cells and Th2 cells suppress?

Back 71

Th1 suppresses the production of Th2 and vice versa

Front 72

The effect of the which Th molecule is made is at the transcriptional level. What is this due to?

Back 72

The interaction of the master regulators T-Bet and GATA-3

Front 73

Is the Th subset fixed?

Back 73

No, it can change as an immune response develops

Front 74

CD8+ T cytotoxic cells, recognise antigen presented by what MHC molecule?

Back 74

MHC class 1 (e.g. virally infected cells)

Front 75

Is the activation process for Tc cells the same as Th?

Back 75

Yes but require more co-stimulation

Front 76

What can be the co-stimulators for the activation of Tc cells?

Back 76

Highly activated Dendritic cells, more commonly provided by effector CD4+ Th (Th1 or Th17_ cells that have recognised related antigen on the APC

Front 77

CD4+ Th cells help to activate Tc cells by providing what?

Back 77

Cytokines and DC40L

Front 78

When the CD4+ Th cell is activated by the APC< what does it secrete?

Back 78

IL-2 and Express CD40L

Front 79

What does IL-2 act directly on in T cells

Back 79

CD8

Front 80

What does CD40L bind to, what does it stimulate, and what does this enhance?

Back 80

Binds to CD40 on the APC< stimulating it to produce more co-stimulatory B7, enhancing activation of the CD8 T cell

Front 81

Because Tc Cells require more co-stimulation to become activated, what must the T cells be activated by?

Back 81

Related antigens presented by both MHC1 and MHC2 on the same APC

Front 82

On what type of cell is CHC2 only present on?

Back 82

Antigen presenting cells

Front 83

What is cross presentation?

Back 83

The presentation of exogenous antigens on MHC class 1 by an unknown mechanism

Front 84

How many signals does T cell activation require?

Back 84

2

Front 85

For Th cells, how many activation signals are needed?

Back 85

B7-CD28 is enough

Front 86

What does the cytokine environment (3rd signal for the activation of T cells) do?

Back 86

Defines the type of T effector you get

Front 87

To activate a Tc cell what do you need?

Back 87

Th Help, activated and bound by the same APC (CD40-CD40L)

Front 88

What is important for Tc activation?

Back 88

Cross presentation of exogenous antigens to MHC1

Front 89

Many T cell effector functions occur where?

Back 89

IN the periphery, at the sites of infection

Front 90

T cells in circulation are directed to the right part of the body by what?

Back 90

The interaction between molecules on the T cells and on endothelial cells lining blood vessels

Front 91

What do cytokines do during T cell migration?

Back 91

Up-regulate adhesion molecule expression on endothelium to initiate migration

Front 92

During T cell migration, they bind loosely, roll and then enter tissue by what method?

Back 92

Diapedesis/ extravasation

Front 93

During T cell migration, does the activated T cell interact with?

Back 93

Endothelial cell

Front 94

What is produced at the site of an infection, and what does it cause?

Back 94

Chemokines and produces a chemokine gradient that attracts the cell into the tissue

Front 95

CD4+ T helper cells produce cytokines to help what cells, and where is this function performed?

Back 95

B cells and other T cells and other cells to perform their functions, predominantly in the lymph node

Front 96

What is the function of each Th subset largely determined by?

Back 96

The cytokines they make

Front 97

What does the production of IFN gamma, IL-10, IL-17 and TGF beta, cytokines transcribing T cells, make what Th subsets?

Back 97

IFN gamma = Monocyte activation. IL-10 = anti-inflammatory. IL-17 = inflammation. TGF beta = Anti-inflammatory

Front 98

Apart from Th cell subset being largely determined by cytokines, what else can they promote?

Back 98

Immunoglobulin class-switching

Front 99

What IL-molecule is made by all T cells?

Back 99

IL-2

Front 100

Th1 cells in the periphery, which produce IFN-gamma, cause what when interacting with an APC?

Back 100

Macrophage activation (enhanced microbial killing)

Front 101

Th1 cells in the lymphoid, which produce INF-gamma, cause what?

Back 101

Bcell activation, Complement binding and opsonising antibodies, Opsonisation and phagocytosis.

Front 102

Th1 cells in the periphery, which produce TNF, cause what?

Back 102

Interact with neutrophil. Causes Neutrophil activation (enhanced microbial killing)

Front 103

Does interferon gamma make macrophages?

Back 103

No but does activate them

Front 104

What is Th2s effector function?

Back 104

IgE already bound to the surface of cells that express receptors. They circulate around the body and when they bind an antigen the eosinophil will then granulate

Front 105

Is CD8+ usually cytotoxic in nature?

Back 105

Yes

Front 106

When Tc cells kill, is it antigen specific?

Back 106

Yes. Target cell must bear the same antigen that activated the naive Tc presented on MHC class 1 on its surface

Front 107

Are adjacent cells laking a target antigen affected by Tc cells?

Back 107

No, Tc cell must contact the target cell and have the appropriate antigen in MHC class 1

Front 108

What happens to Tc cells once they have killed their target cell?

Back 108

Remain intact. Each Tc is capable of killing many target cells in sequence

Front 109

What are the two mechanisms for Cytotoxic lymphocyte (CTL) or Cytotoxic T cell killing, what are they?

Back 109

Fas-Fas Lingand. Granzyme/perforin

Front 110

What do both Fas-Fas ligand and Granzyme/perforin result in as a mechanism of CTL killing?

Back 110

Apoptosis

Front 111

Can apoptosis be phagocytosed, and if so, by what cells?

Back 111

Yes. Dendritic cells as the cell being killed is broken up into little vesicles

Front 112

What does it mean when the T cell response reaches contraction/homeostasis?

Back 112

Antigen is cleared, the similes for co-stimulation subsides and T cell responses decline

Front 113

During contraction/homeostasis of the T cell response, are new effector cells activated?

Back 113

No

Front 114

When the T cell response reaches contraction/homeostasis, what happens to effector cells?

Back 114

Age and die by apoptosis and are cleared by phagocytes

Front 115

What percentage of effector T cells die once the antigen is eliminated?

Back 115

Almost 95%

Front 116

What do some of the progeny of antigen-stimulated T cells develop into?

Back 116

Long-lived, functionally quiescent (resting) memory cells

Front 117

What are memory T cells responsible for?

Back 117

Accelerated and enhanced secondary immune responses on subsequent exposures to the same antigen

Front 118

Give an example of a marker used to identify effector memory T cells?

Back 118

CD45RO

Front 119

Once activated in the lymph node, many T effector cells do what?

Back 119

Leave and carry out their effector function in tissues

Front 120

Effector cells are attracted to the site of infection by what?

Back 120

Chemokines and adhesion monlecules

Front 121

Some Th cells carry out their function in the periphery, what do they activate?

Back 121

Other immune cells like monocytes, PMN, andEosinophils .

Front 122

What do the Th cells which have their effector function in the lymph node do?

Back 122

Activate B cells

Front 123

What are the two methods of killing which Tc cells use, when presented with the same Antigen/MHC12 on the cell surface?

Back 123

Fas-FasL or granmzyme/perforin