PCB 3233 Module 4 Exam Review: Chapters 7 and 8

Comprehensive practice flashcards covering Chapter 7 (T-cell development in the thymus) and Chapter 8 (T-cell activation, homing, and effector functions) based on the PCB 3233 Exam Review.

Where do T cells and B cells develop, and what term describes these anatomical sites?

T cells develop in the thymus and B cells develop in the bone marrow; together, these locations are known as primary lymphoid tissues.

What are the two lineages of T cells, and which receptor type is the most abundant?

The two lineages are $\alpha:\beta$ and $\gamma:\delta$, with $\alpha:\beta$ being the most abundant type found on T cells. A single T cell cannot express both receptors simultaneously.

Are T cells activated in the thymus?

False. T cells are not activated in the thymus; immature T cell precursors develop there and are later activated in secondary lymphoid tissues.

Through what route do T cell precursors enter the thymus and mature T cells exit?

Blood is the only route through which T cells enter and exit the thymus.

What are the two structural regions of the thymus, and in which direction should T cell development be visualized?

The two regions are the cortex and the medulla, and development should be visualized in a north-to-south direction.

What are immature T cells called ?

Thymocytes

True or false :Blood is the only route through which T cells enter and exit

True

What is the function of macrophages and are they located in the the cortex and medulla?

Macrophages in both areas and they remove cells that fail to mature properly.

Where are Hassall's corpuscles found and what is their suspected function?

found in the medulla and are possibly sites of cell destruction.

Which cell surface markers distinguish an uncommitted progenitor cell from a committed T-cell precursor?

An uncommitted progenitor cell expresses CD34 and CD44, whereas a committed cell expresses CD2 and CD5.

What is a "double-negative" thymocyte?

A committed T cell that does not yet express the CD4 or CD8 co-receptors.

What is the role of IL-7 and Notch-1 in early T-cell development?

The IL-7 receptor on T cells binds IL-7 on thymic stromal cells to guide subsequent developmental steps, while Notch-1 signaling keeps the T cell committed on the T-cell developmental pathway.

Which TCR chain rearranges first, and how do the gene segments of the $\alpha$-chain and $\beta$-chain compare?

The $\beta$-chain rearranges first. The $\beta$-chain contains V, D, and J segments (similar to the heavy chain), whereas the $\alpha$-chain contains only V and J segments (similar to the light chain).

Do T cells rearrange their $\beta$, $\gamma$, and $\delta$-chain genes at roughly the same time?

True. T cells rearrange their $\beta$, $\gamma$, and $\delta$-chain genes at approximately the same time.

True or false :The delta chain locus is located within the a-chain locus

True: The $\delta$ -chain locus is located entirely within the $\alpha$-chain locus.

True or false : Cells committed to one lineage can contain productive rearrangement for the TCR genes of the other lineages (except for a-chain)

True

What molecular event occurs during allelic exclusion of the TCR $\beta$-chain?

The RAG-1 and RAG-2 genes are repressed to halt further rearrangement.

How many times can recombination occur per cell on the TCR $\beta$-chain compared to the heavy-chain ?

Recombination can occur $4$ times per cell for the $\beta$-chain , compared to only $2$ times per cell for the heavy-chain .

Can the TCR $\alpha$-chain undergo more than one gene rearrangement?

Yes; unlike the immunoglobulin heavy chain, the TCR $\alpha$-chain can undergo multiple successive rearrangements to rescue an unproductive gene rearrangement.

What do we call it when we try to “save” an unproductive gene rearrangement?

Rescue

What components make up the pre-TCR?

The rearranged $\beta$-chain assembles with the surrogate $\alpha$-chain, known as $\text{pT}\alpha$.

What are the four downstream signals generated by the pre-TCR, in order?

$1$. Allelic exclusion ($\beta$-chain stops rearrangement); $2$. Proliferation;

$3$ . Expression of CD4 and CD8 co-receptors (yielding "double-positive" thymocytes);

$4$ . Permitting the $\alpha$-chain to rearrange.

What are the two major checkpoints in T-cell development?

Checkpoint $1$ checks the $\beta$-chain with the surrogate $\alpha$-chain (pre-TCR); Checkpoint $2$ checks the newly rearranged $\alpha$-chain with the $\beta$-chain (mature TCR).

One of the signals of the pre-TCR is the expression of ____ and ____ co-receptors.Because the T cell has both of these co-receptors ,it is called ?

CD4 and CD8 and these are called double -positive thymocytes

The second phase of T cell development is known as _______ ? What is this ?

Positive selection and this makes sure T cells can recognize your MHC and binds “moderately”

What is positive selection, and which cells mediate this process?

Positive selection ensures developing T cells can recognize self-MHC molecules by binding moderately to them; it is mediated by cortical epithelial cells in the thymic cortex.

True or false:Positive selection involves both alpha and beta T cells and y delta T cells ?

False

Which complementarity-determining regions (CDRs) of the TCR interact with MHC versus peptide?

CDR1 and CDR2 (encoded by V gene segments) bind directly to the MHC molecule, while CDR3 binds directly to the presented peptide.

How many self-peptides and MHC molecules can present antigen in an individual heterozygous for the six major HLA genes?

About $180{,}000$ self-peptides can be presented across $18$ different MHC class I and class II molecules.

How is positive selection mediated ?

Cortical epithelial cells

In positive selection,we also determine if the T cell matures into a ____ or ______ T cell , this is also known as “_____”thymocytes

CD4 and CD8 …. Single positive

MHC I recruit ____ and excludes ____ . MHC I is for ______ pathogens and is used by all ______ /PAPC’s

CD8 and CD4 …. Intracellular and nucleated

MHC II recruit _____ and excludes ____. MHC II is for ______ pathogens and is used by all nucleated cells /______

CD4 and CD8 ….. extracellular and PAPC’s

Rearrangement of ____-chain stops genes once a cell has been positively selected .

Alpha

All the stages from a-h occur in the ____ of the thymus

Cortex

What is negative selection, and which thymic cells mediate it?

Making sure your T cell doesn’t bind too strongly to the MHC :peptide complex ; it is mediated by bone marrow-derived dendritic cells and macrophages.

Can negative selection occur concurrently with positive selection?

True. Negative selection can occur at the same time as positive selection.

What is AIRE, and which specific thymic cells utilize it?

AIRE (Autoimmune Regulator) allows medullary thymic epithelial cells (MTECs) to express self-peptides not normally present in the thymus, this leading to central tolerance in the primary lymphoid tissue.

Most T cells die in ______ selection

Positive

After negative selection,T cells are now _____ T cells ?

Naive

What percentage of the primary $\alpha:\beta$ T-cell repertoire successfully exits the thymus into circulation?

Only $1\text{-}2\%$ of the primary repertoire survives both selections and exits into the bloodstream.

T cells undergo further differentiation in ____ lymphoid tissue

Secondary

The term “CD4 T cell” refers to a ______ T cell

Naive

CD4 effector cells include

TH1 , TH2 , TH17 , TFH and Treg

What is the function of TH1?

Secrete IFN-Y to recruit macrophages

What is the function of TH2

Secrete IL-4 and IL-5 to activate B cells and antibodies response

What is the function of Treg?

Secrete TGF-Beta and IL-10 to suppress the immune response

What is the function of TFH?

Help B cells become activated,switch isotype , and increase affinity

What is the function of TH17 ?

Secrete IL-17 to enhance the neutrophil response

What do Treg cells express ?

FoxP3 and CD25

What is the role of CD8 T cells ?

To become activated cytotoxic T cells

Which of the following surface molecules remains “on” once it is placed on the T cell surface ?

CD3 complex

What is the genetic cause and clinical consequence of DiGeorge's syndrome?

DiGeorge's syndrome is caused by a deletion in chromosome $22$, leading to failure of the thymus to develop, which can result in severe combined immunodeficiency disease (SCID).

True or false :The thymus is fully developed before birth and atrophies(declines) with age

True

Who is more likely to produce a lot of T cells : a 12yr old child or 41 year old adult ?

A 12yr old child

Are T cells short-lived cells requiring constant replenishment, or long-lived and self-renewing?

T cells are long-lived and self-renewing, meaning mature T-cell populations can persist for decades after thymic involution, whereas B cells are short-lived and constantly replenished.

How is AIDS defined according to Prof. Weigel?

It is defined as having a CD4 T cell count of $<200$ microliters.

T-cell activation =

T-Cell priming

Does the adaptive immune response initiate directly at the site of infection?

False. The immune system initiates the adaptive immune response in secondary lymphoid tissues, not at the site of infection.

What happens when a naïve T cell interacts with an antigen presented by a non-PAPC cell?

The interaction leads to inactivation .

Dendritic Cells carry antigens from sites of infection.They are the only cell we know that can be used to activate ___ T cells and trigger the T cell response

Naive

In tissue ,dendritic cells are considered ____ and are in the process of capturing and processing antigen . What is the model for this type of dendritic cell and what receptor is found on this cell ?

Immature,langerhans cells , DEC205

True or false :These dendritic cells can use receptor-mediated endocytosis OR nonspecific macropinocytosis

True

In secondary lymphoid tissues ,dendritic cells are considered _____ and gain the capacity to interact with T cells, what is the model for this type of dendritic cell , what receptor is found on this cell ?

Mature, Interdigitating reticular cells , DC-SIGN

Which chemokine is secreted by mature dendritic cells and attracts naïve T cells, and what does DC-SIGN bind to on the T cell?

Mature dendritic cells secrete CCL18 to attract naïve T cells, and their DC-SIGN surface receptor binds ICAM-3 on the naïve T cell.

Which chemokines draw naïve T cells through HEVs into secondary lymphoid tissue, and what is the corresponding receptor on the T cell?

Chemokines CCL19 and CCL21 recruit naïve T cells by binding to the CCR7 receptor on the T cell surface.

Naive T cells enter lymphoid tissues via blood capillaries or from the _____ lymph.The T cells in the blood will bind to the ____ and squeeze through the wall

Afferent and HEV

Efferent = ….. afferent =

Exiting and arriving

What molecule guides a naïve T cell out of the lymph node if it does not encounter its cognate antigen, and is it a chemokine?

Sphingosine 1-phosphate (S1P) draws the T cell out into the efferent lymph; S1P is a chemotactic lipid molecule, not a chemokine.

The movement into the lymph node cortex is controlled by a cell -surface molecule and endothelial cells called leukocytes _____ molecules

Adhesion

What are the four classes of leukocyte adhesion molecules and their primary examples in T-cell homing?

$1$. Selectins (L-selectin)

; $2$ . Vascular addressins (GlyCAM-1, CD34, MAdCAM-1);

$3$. Integrins (LFA-1)

; $4$. Immunoglobulin superfamily (ICAMs).

True or false :L-lectin can bind to GlyCAM-1

True

Chemokines activate ____ on the T cell (or B cell) , which allow it to bind strongly to ____ on the endothelial.This will suppress of ___ receptors (stopping the lymphocytes from being drawn out of the lymph node cortex)

LFA-1 ,ICAM-1,S1P

What are the four sequential steps of leukocyte extravasation across high endothelial venules?

Rolling adhesion, Tight binding, Diapedesis, and Migration.

Which receptor-ligand pairing delivers the necessary co-stimulatory signal to naïve T cells, and which molecule acts as an inhibitory brake?

B7 molecules on APC’s bind CD28 on the T cell to drive proliferation; CTLA-4 binds B7 with higher affinity to deliver inhibitory signals and limit proliferation.

If a TCR binds to a peptide:MHC complex on this cell that does not express this molecule, the T cell will become _____ (which leads to no proliferation or differentiation)

Anergic

The signals from TCR and CO-Receptors alter the pattern of gene transcription in activated T cells .CD3 cytoplasmic tails contain sequences called ____ ,which associate with tyrosine kinases

ITAM’s

Kinases ____ phosphates while phosphatases ____ phosphates

Add and remove

What signaling molecules comprise the central supramolecular activation cluster (c-SMAC) versus the adhesion cluster (p-SMAC)?

c-SMAC contains signaling proteins (TCR, CD2, CD4, CD8, CD28)

; p-SMAC contains adhesion molecules (LFA-1, ICAM-1).

in a resting T cell , ITAM’s are not phosphorylated . Binding of MHC to the T-Cell receptor leads to phosphorylation by _____.ZAP70 will bind to the (phosphorylated) _____-chain and leads to activation of PLC-y.This will cleave PIP2 into DAG and IP3.

Lck , Zeta

This will cause ______,____ , and AP-1 (which are transcription factors ) to change the pattern of gene expression. This will lead to cell division, proliferation, and differentiation to effector T cells .

NFkB , NFAT

How does CD28 co-stimulation amplify IL-2 production in activated T cells?

CD28:B7 signaling stabilizes IL-2 mRNA, increasing cytokine synthesis by $20\text{-}30\times$.

True or false :Immunization of protein antigen alone always induces an immune response

False

What is the role of adjuvants in vaccination?

Adjuvants are microbial products that induce necessary co-stimulatory B7 activity on PAPCs, ensuring T cells are activated rather than tolerized.

What are the defining master transcription factors for TH1 cells ?

TH1: T-bet

What are the defining master transcription factors for TH2 cells?

TH2: GATA3

What are the defining master transcription factors for TH17 cells?

TH17: $\text{ROR}\gamma\text{T}$

What are the defining master transcription factors for TFH cells ?

TFH: Bcl-6

What are the defining master transcription factors for Treg cells?

Treg: FoxP3.

What are the characteristic functions and secreted cytokines of TH1 and TH2 subsets?

TH1 cells secrete $\text{IFN-}\gamma$, GM-CSF, and $\text{TNF-}\alpha$ to activate macrophages and fight intracellular pathogens (dominant in tuberculoid leprosy)

; TH2 cells secrete IL-4 and IL-5 to stimulate B cells and defense against tissue parasites (dominant in lepromatous leprosy).

What are the characteristic functions and secreted cytokines of TH17 subsets?

Recruits neutrophils to site of the infection

What are the characteristic functions and secreted cytokines of Tfh subsets?

Helps naive B cells become plasma cells

What are the characteristic functions and secreted cytokines of Treg subsets?

Regulate the immune response

Where are TH1 cytokines and TH2 cytokines present ?

Tuberculoid and lepromatous

Which CD4 effector T-cell subsets travel to the site of infection versus remaining in secondary lymphoid tissue?

TH1, TH17, and Treg migrate out to the site of infection, whereas TH2 and TFH remain within secondary lymphoid tissues.

true or false : effector T cells can be stimulated by antigen in the absence of co-stimulation

True.

True or false : Resting naive T cells express L-selectin and high level of CD2 and LFA-1

false

After L-selectin expression stops,_____ is expressed and guides activated T cells to the infection site.This binds to the cell adhesion molecules ____, which is selectively expressed on the endothelium of blood vessels in inflamed tissue.

VLA-4 and VCAM-1

Alter behavior of target cells (used by CD4 and CD8 cells ) , would that be cytokines or chemokine ?

Cytokines

Secreted cytotoxic proteins used to kill target cells (used in CD8T cells ); perforin , granulysin,serglycin, and granzymes

Cytotoxins