Chapter IX: adaptive immunity - T cell responses

CTLA-4, which has a higher affinity than CD28, competes for binding of ___ on the APC

B7

During infection, the co-stimulatory molecule, ___ is expressed by professional antigen-presenting cells

B7

___ indicates that an immune response should be produced against the nonself antigen being presented

B7

Intracellular signal 2 is produced when B7 binds to ___ on the naïve T cell

CD28

CR is associated with the ___ complex, which is comprised of several membrane-embedded proteins (delta, gamma, epsilon and zeta)

CD3

When a peptide antigen is presented to the T-cell receptor, an intracellular signal is generated through the ___ complex. This represents signal 1 of 3 for T-cell activation.

CD3

CD40 ligand binds to its receptor, ___ on the APC

CD40

Activation of mature naïve ___ T cells leads to the development of the cytotoxic T lymphocyte (CTL) response

CD8

___ cell will differentiates into cytotoxic T cells and memory CD8 T cells.

CD8 T

Another mechanism for developing tolerance is through the use of the inhibitory molecule, ___, which is expressed by activated T cells and TREG cells

CTLA-4

Granzymes can also promote destruction of nuclear ___

DNA

Virus-infected cells express ___ (first apoptosis signal), also known as the "death receptor"

Fas

An alternative mechanism for killing infected host cells, called ___ cytotoxicity, is used by CTLs, as well as natural killer (NK) cells

Fas-mediated

With MHC I inhibition is removed, ___ cytotoxicity and ___ by NK cells can now occur to compensate for the lack of CTL activation

Fas-mediated, ADCC

CTLs express ___, which binds to Fas and activates a caspase cascade to trigger apoptosis

FasL

___ expression is increased in response to pro-inflammatory cytokines (IL-1 and TNF-α), which makes the TCR-antigen interaction more likely to occur during infection

ICAM-1

molecular interactions between the CD8 co-receptor and the MHC I molecule are strengthened by accessory molecules, including LFA-1 binding to ___ and CD2 binding to ___ (on T cell and APC, respectively)

ICAM-1, LFA-3

TH1 expression of ___, which enhances the activities of innate cells, such as natural killer (NK) cells and macrophages, as well as adaptive cells, such as B cells and cytotoxic T cells

IFN-y

Cell-to-cell contact and ___ secretion is required for suppressor function, which is mediated through the transcription factor Foxp3

IL-10

During bacterial infection, ___ induces expression of numerous pro-inflammatory cytokines (e.g. IL-6), chemokines and antimicrobial peptides from a variety of cell types, including fibroblasts, endothelial cells and macrophages

IL-17

IL-6 binding to its receptor on T cells activates the TH17-specifc transcription factors leading to expression of the cytokines ___

IL-17

___ has also been implicated in a number of autoimmune inflammatory conditions, such as psoriasis and rheumatoid arthritis

IL-17

___ binds to its receptor on an activated T cell and generates an intracellular signal that activates the TH2-specific transcription factor leading to ___ and ___ expression

IL-4, IL-4, IL-5

TH2 responses can also become misdirected; Increased ___ expression and ___ production are also hallmarks of allergies, or type I hypersensitivities

IL-4, IgE

___ is also involved in stimulating eosinophil production from the bone marrow and promoting their survival

IL-5

Since most parasitic infections focus on mucosal surfaces, such as the intestines, secretion of the mucosal antibody, ___, can inhibit attachment of the parasite to these surfaces

IgA

IL-4 and IL-5 are involved in class-switching in B cells for production of ___ and ___ antibodies, respectively

IgE, IgA

Since some viruses inhibit ___ expression in infected cells, alternative targeting mechanisms must be available

MHC I

___ cells improve B cell class-switching for immunoglobulin production and guide B cells into germinal centers by chemotaxis mediated by CXCR5 signaling

TFH

In response to PAMPs of intracellular pathogens, NK and dendritic cells produce IFN-γ (interferon-gamma), which binds its receptor on an activated CD4 T cell and activates the ___-specific transcription factor

TH1

___ cells also activate antigen-specific naïve B cells in a T-dependent fashion, and then promote antibody class-switching to yield high-affinity IgG

TH1

___ cells are produced in response to viruses and other intracellular pathogens

TH1

___ cells help activate antigen-specific naïve CD8 T cells to differentiate into CTLs

TH1

___ cells provide protection against bacteria and fungi at mucosal surfaces and assist in the clearance of certain microbes not targeted by TH1 or TH2 responses

TH17

___ differentiation occurs when IL-6, IL-23, and TGF-β are present during inflammation, but in the absence of the TH1 or TH2-inducing cytokines, IL-4 or IL-12, respectively

TH17

___ cells also intensify the innate immune response through activation of macrophages to express pro-inflammatory cytokines

TH2

___ cells are produced in response to extracellular parasite infections, particularly helminths

TH2

___ cytokines stimulate the production and activity of inflammatory cells and influence antibody class-switching in B cells

TH2

In ___ cells, CTLA-4 is expressed to inhibit T-cell responses against autoantigens and nonharmful antigens

TREG

Reduced ___ numbers and diminished effector function are known to occur in autoimmune diseases

TREG

Which one is signal 2 of CD8 T cell activation? a. B7, the co-stimulatory molecule expressed by the APC, will bind to CD28 on the CD8 T cell b. a positive feedback loop from autocrine signaling via Il-2/IL-2R interaction c. the licensed DC will, subsequently or simultaneously, present the exogenous viral peptide with MHC I to a naïve CD8 T cell

a. B7, the co-stimulatory molecule expressed by the APC, will bind to CD28 on the CD8 T cell

Which inhibitory molecule is expressed by activated T cells and T-reg cells to down-regulate and terminate immune responses and to inhibit responses against autoantigens and nonharmful antigens? a. CTLA-4 b. CD28 c. CD40L d. CD3 e. ICAM-1

a. CTLA-4

Match the helper T subset with its description. produces IFN-gamma to stimulate CTL and NK activity and IgG production a. TH1 b. TH2 c. TH17 d. TFH e. Treg

a. TH1

When naive T cells are activated, they secrete a cytokine called interleukin-2 (IL-2). IL-2 binds to receptors (IL-2R) on the T cell, which stimulates the secretion of more IL-2 and an increased expression of IL-2R. What type of signalling is responsible for this positive-feedback loop that leads to proliferation of activated T cells? a. autocrine b. endocrine c. exocrine d. paracrine

a. autocrine

TH1 cytokines act on all the following immune cells except: a mast cells b. NK cells c. B cells d. macrophages e. CTLs

a. mast cells

Match the T cell molecule with the molecule it binds on the professional APC. TCR a. peptide antigen + MHC b. MHC II c. MHC I d. B7 e. ICAM-1

a. peptide antigen + MHC

Match the cytotoxic factor with its role during intracellular infection. antimicrobial peptide that is useful against intracellular bacteria and parasites a. serglycin b. perforin c. granzymes d. granulysin

a. serglycin

Antigen presentation can still occur without the co-stimulatory signal, but instead of activation, this single signal will either cause the T cell to become ___ (unable to be activated by further antigen presentation) or to differentiate into a ___ cell

anergic, regulatory T

Three intracellular signals are required for activation of naïve T cells during antigen presentation: ___-specific signal, ___ signal and ___ and ___ signal

antigen, co-stimulatory, paracrine, autocrine

The CTL releases the contents of its cytotoxic granules, which trigger ___ in the virus-infected cell

apoptosis

Match the T cell molecule with the molecule it binds on the professional APC. CD4 a. peptide antigen + MHC b. MHC II c. MHC I d. B7 e. ICAM-1

b. MHC II

Match the helper T subset with its description. produces IL-4 and IL-5 to stimulate eosinophil and IgE production a. TH1 b. TH2 c. TH17 d. TFH e. Treg

b. TH2

Which helper response would likely be stimulated by an extracellular helminth infection? a. TH1 b. TH2 c. TH17

b. TH2

Which one is signal 3 of CD8 T cell activation? a. B7, the co-stimulatory molecule expressed by the APC, will bind to CD28 on the CD8 T cell b. a positive feedback loop from autocrine signaling via Il-2/IL-2R interaction c. the licensed DC will, subsequently or simultaneously, present the exogenous viral peptide with MHC I to a naïve CD8 T cell

b. a positive feedback loop from autocrine signaling via Il-2/IL-2R interaction

When professional APCs present antigens to mature naive T cells, intracellular signals cause the antigen-specific T cells to undergo rounds of mitosis. This is called clonal: a. deletion b. expansion c. differentiation d. apoptosis e. memory

b. expansion

Match the cytotoxic factor with its role during intracellular infection. protein that forms pores in host membrane to allow entry of other cytotoxic factors a. serglycin b. perforin c. granzymes d. granulysin

b. perforin

Which co-stimulatory pairing is used by a TH cell as it helps a naive CD8 T cell become activated? a. CD4 - MHC I b. CD4 - CD8 c. CD40 - CD40L d. CD8 - MHC II e. CTLA-4 - CD28

c. CD40 - CD40L

Match the T cell molecule with the molecule it binds on the professional APC. CD8 a. peptide antigen + MHC b. MHC II c. MHC I d. B7 e. ICAM-1

c. CD8

Match the helper T subset with its description. produces IL-17 to stimulate recruitment of neutrophils a. TH1 b. TH2 c. TH17 d. TFH e. Treg

c. TH17

Match the cytotoxic factor with its role during intracellular infection. enzymes that cause damage to mitochondria and activate apoptosis via caspases a. serglycin b. perforin c. granzymes d. granulysin

c. granzymes

Which one is signal 1 of CD8 T cell activation? a. B7, the co-stimulatory molecule expressed by the APC, will bind to CD28 on the CD8 T cell b. a positive feedback loop from autocrine signaling via Il-2/IL-2R interaction c. the licensed DC will, subsequently or simultaneously, present the exogenous viral peptide with MHC I to a naïve CD8 T cell

c. the licensed DC will, subsequently or simultaneously, present the exogenous viral peptide with MHC I to a naïve CD8 T cell

Granzymes activate ___, which are proteolytic enzymes that cause damage to hundreds of cellular components, thus promoting cell death via apoptosis

caspases

___ CD4 T cells are not yet committed to a TH subset and their differentiation can still be determined by polarizing cytokine

central memory

T cell activation requires presentation of a peptide antigen by a professional antigen-presenting cell (pAPC), which is called...

clonal selection

in the absence of the ___ signal, a naïve CD4 T cell will not become activated

co-stimulatory

More often than not, a virus does not infect dendritic cells. So, in order to get MHC I presentation of viral antigens by pAPCs, ___ must occur

cross presentation

The combination of CD40 co-stimulation, PRR signaling from viral PAMPs, and MHC-TCR interaction will stimulate the ___ pathway

cross-presentation

Match the T cell molecule with the molecule it binds on the professional APC. CD28 a. peptide antigen + MHC b. MHC II c. MHC I d. B7 e. ICAM-1

d. B7

Cytotoxic T cells can trigger cell death in infected cells in two ways - (1) recognition of antigen-MHC I with the TCR or (2) the interaction of: a. CD40 - CD40L b. MHC I - CD4 c. CTLA-4 - CD28 d. Fas - FasL e. TCR-BCR

d. Fas - FasL

Match the helper T subset with its description. produces IL-21 to stimulate B cells to produce high-affinity class-switched antibodies a. TH1 b. TH2 c. TH17 d. TFH e. Treg

d. TFH

During cross presentation of a viral antigen by a DC, the ___ antigen is presented with ___ to a CD8 T cell. a. endogenous / MHC I b. endogenous / MHC II c. exogenous / MHC I d. exogenous / MHC II

d. exogenous / MHC II

Match the cytotoxic factor with its role during intracellular infection. protein that stabilizes cytotoxic granules by forming complexes with other cytotoxic factors a. serglycin b. perforin c. granzymes d. granulysin

d. granulysin

Match the T cell molecule with the molecule it binds on the professional APC. LFA-1 a. peptide antigen + MHC b. MHC II c. MHC I d. B7 e. ICAM-1

e. ICAM-1

Match the helper T subset with its description. produces IL-10 and TGF-beta to suppress immune responses and maintain tolerance a. TH1 b. TH2 c. TH17 d. TFH e. Treg

e. Treg

___ CD4 T cells have committed to differentiation into TH subset(s) and will always respond according to their helper designation

effector memory

For intracellular eukaryotic parasites, ___ delivers granzymes across the membranes of the parasites

granulysin

an antimicrobial peptide that inserts into and disrupts membrane

granulysin

When host cells are infected by intracellular bacteria, ___ is delivered across the host cell membrane via ___ pores

granulysin, perforin

a group of five proteases that activate host factors involved in cell death

granzymes

Activation of mature naïve CD4 T cells leads to the development of the ___ T cell response

helper

___ signals from CTLA-4 suppress further T cell activation and terminate immune responses that are no longer required, such as when the microbe has been cleared

inhibitory

Commitment to the TH1 lineage ___ TH2 development, and vice versa

inhibits

Antigen-specific TH1 cells will ___ DCs for that antigen when they bind to an exogenous viral peptide presented with MHC II which requires the expression of a co-stimulatory molecule on the ___ cell surface called CD40L

license, TH1

Granzymes also disrupt ___ function, which results in the production of toxic oxygen products

mitochondrial

Successive rounds of ___ are induced in the activated T cell. The proliferation of antigen-specific T cells is called ___

mitosis, clonal expansion

TH1 cells also produce TNF-α (tumor necrosis factor-alpha) and lymphotoxin, which are cytokines that stimulate ___ chemotaxis and ___ activation

neutrophil, macrophage

The combination of ___ and ___ signals provides intracellular signal 3, which is needed to reach threshold for activation

paracrine, autocrine

granulysin and perforin generate toxic oxygen responses to kill ___

parasites

a protein that aggregates in membranes and forms pores

perforin

Destructive granzymes are delivered into the infected cell by the membrane-active components, ___ and ___

perforin, granulysin

four main factors are released from CTL granules: ___, ___, ___ and ___

perforin, granzymes, granulysin, serglycin

Cytokines secreted by other nearby immune cells resulting from PAMP stimulation also influence the activation and differentiation of the T cell, which are called ___ cytokines because they influence the differentiation of the activated T cell into helper subsets

polarizing

Autocrine signaling via IL-2R increases expression of IL-2 and IL-2R creating a ___ feedback loop

positive

a chaperone protein that stabilizes granules

serglycin

___ response inhibits viral multiplication and NK cells target infected cells for killing

type I interferon

Once the T cell becomes activated, CTLA-4 expression is ___

upregulated