CD4+ T Cells - Overview and Progress

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Questions and Answers

What is the primary function of the T cell receptor (TCR) in CD4+ T cells?

To recognize a specific peptide presented by an MHC molecule. (correct)

To regulate the activation of B cells.

To produce antibodies against pathogens.

To initiate apoptosis in infected cells.

Which of the following describes clonal expansion in CD4+ T cells?

The selective proliferation of T cells that recognize a specific antigen. (correct)

The process of generating a diverse repertoire of T cell receptors.

The mechanism by which T cells undergo apoptosis to maintain balance.

The activation of T cells by cytokines released from B cells.

Which molecules are essential for the full activation of a CD4+ T cell?

B cell signals and MHCI molecules.

Peptides alone suffice for activation.

TCR, co-stimulatory molecules, and cytokines. (correct)

MHC class II and IL-2.

What role does IL-2 play in the CD4+ T cell response?

It promotes the proliferation and differentiation of T cells. Signup and view all the answers

What is the role of Rag1 and Rag2 in T cell receptor diversity?

They are responsible for the recombination of gene segments to generate TCR diversity. Signup and view all the answers

What is the primary function of mature dendritic cells in the lymph nodes?

To present antigens to T cells Signup and view all the answers

What limits the number of total T cells in a mouse?

Thymic selection Signup and view all the answers

What is the estimated range of CD4+ T cells that can bind to the same peptide:MHCII molecule?

1 in 2e5 to 2e6 Signup and view all the answers

During T cell migration, what happens if a naive T cell does not encounter specific antigen?

It returns to circulation Signup and view all the answers

What is the role of CCR7 in mature dendritic cells?

To mediate trafficking to lymph nodes Signup and view all the answers

What is the typical time duration a naive T cell stays in a lymph node before returning to circulation?

Approximately 12-24 hours Signup and view all the answers

What initiates the migration of dendritic cells to lymph nodes during an infection?

Maturation of dendritic cells Signup and view all the answers

What can be inferred about T cells' encounter with specific antigens?

Very few T cells can recognize a single microbe. Signup and view all the answers

What is the primary function of IL-2 in T cell proliferation?

It acts as an autocrine growth factor binding to IL-2 receptors. Signup and view all the answers

What role does costimulation play in T cell activation?

It provides a safety mechanism to prevent inappropriate responses. Signup and view all the answers

Which type of T cell receptor expression change occurs upon activation of naïve T cells?

Upregulation of the α chain of the IL-2 receptor. Signup and view all the answers

What role does CTLA4 play in T cell proliferation regulation?

It transmits an inhibitory signal that downregulates IL-2 signaling. Signup and view all the answers

Which of the following cells expresses both MHC class II and B7?

Dendritic cells Signup and view all the answers

What does the TCR signal require for proper activation?

Interactions with antigen presenting cells and co-stimulatory signals. Signup and view all the answers

What is the expected outcome of IL-2 signaling inhibition by Tacrolimus?

Reduction in T cell activation and clonal expansion. Signup and view all the answers

How much can one activated T cell typically proliferate within a day?

What occurs if a T cell receives only Signal 1 without Signal 2?

The T cell undergoes anergy and becomes unresponsive. Signup and view all the answers

What ensures that T cells specifically respond to microbial antigens?

Co-stimulatory signals induced by pathogens. Signup and view all the answers

What is the maximum number of effector cells that can be generated from a precursor pool of 100 T cells in about a week?

1 million effector cells. Signup and view all the answers

Which type of T cell is primarily activated by MHC class II molecules?

CD4+ T cells Signup and view all the answers

Which drug is known to inhibit IL-2 production specifically?

Cyclosporine. Signup and view all the answers

What percentage of effector cells may be specific for the same peptide:MHC complex after clonal expansion?

50%. Signup and view all the answers

Which of the following best describes dendritic cells in the context of T cell activation?

They are the most potent antigen presenting cells. Signup and view all the answers

What happens when dendritic cells upregulate CD80 and CD86?

They become more mature and potent in T cell activation. Signup and view all the answers

What is the primary role of the CD4 co-receptor in T cell activation?

To decrease the number of MHC molecules required for activation Signup and view all the answers

Which of the following correctly describes the role of the T cell receptor (TCR)?

The TCR requires CD3 proteins to transmit signals Signup and view all the answers

What does the term ITAM refer to in T cell signaling?

Immunoreceptor tyrosine-based activation motif Signup and view all the answers

How does the binding of CD4 to MHC II affect T cell activation?

It enhances TCR affinity for MHC molecules Signup and view all the answers

Which of the following best describes the immunological synapse?

The junction where adhesion molecules and TCR/MHC meet Signup and view all the answers

What is the function of the enzymes activated during TCR signaling?

To facilitate transcription of genes for T cell proliferation Signup and view all the answers

What determines the decrease in the number of MHC molecules required for naïve T cell activation?

The presence of co-stimulatory molecules like CD28 Signup and view all the answers

Which transcription factors are activated during the signaling cascade initiated by TCR engagement?

NF-Kb, NFAT, and AP-1 Signup and view all the answers

Study Notes

CD4+ T Cells - Part I

Brian Rudd is from the Department of Microbiology and Immunology at Cornell University.
His contact information, including office hours are provided
The covered text for the next three lectures is detailed. Callahan & Yates (Chapter 10), Parham #3 (pages 75-83, 212-245, 305-307, 311-315), and Abbas #7 (Chapters 9, 10, and 11) are all optional readings.

Overview of the Immune System

The immune system is divided into innate and adaptive immunity.
Innate immunity includes Physical barriers, PRR, macrophages, neutrophils, phagocytosis, killing, and NK cells.
Adaptive immunity involves vaccines, MHC/TCR, CD4 T cells, dendritic cells, CD8 T cells, B cells, antibodies, and BCR.
Malfunctions in the immune system can lead to chronic inflammation, hypersensitivity, immune deficiency, and autoimmunity.

Progress in Adaptive Immunotherapy for Cancer in Companion Animals

This review discusses the progress in adaptive immunotherapy for cancer in companion animals with a goal of curing cancer.

Forest and Trees

This slide shows an image of a forest with trees.

CD4+ T Cell Response

The CD4+ T cell response has a typical activation, expansion, contraction, and maintenance cycle overtime.
The response is seen from a population/individual cell level.

Learning Objectives

The learning objectives for the course are based on the minimum knowledge needed to pass.
They cover activating CD4+ T cells, molecular interactions, the role of IL-2, clonal expansion, and turning off T cell signaling.

Big Picture View of T Cell Activation

This is a high-level overview of T-cell activation.

Back to the Basics

Every T cell is unique and expresses a single type of T cell receptor (TCR).
The TCR recognizes a specific peptide presented by an MHC molecule on another cell's surface.

The Immune System Generates a Diverse Repertoire of T Cells

The diverse repertoire of T cells is generated through recombination/rearranging V-(D)-J germline segments by enzymes RAG1 and RAG2.
Also involves the addition of N-nucleotides, and pairing different alpha and beta chains.

T Cells - by the Numbers

The number of possible TCRs is very high (~10^15).
This possibility is linked to size and thymic selection.
Total T cells in a mouse are on the order of ~8 x 10^7, and significant amounts reside in lymph nodes, with ~5M in the blood.
The number of CD4+ T cells specific for a peptide varies.
Different individuals may respond to different or some of the peptides from a pathogen.

Very Few T Cells Are Specific for Any One Microbe

The number of CD4+ T cells specific for a given peptide:MHCII molecule is low (1 in 2e5 to 2e6)

Key Question: How Do These Few T Cells Patrol All Tissues Where Antigen May Be Present?

This focuses on the need to bring antigen and lymphocytes together in lymph nodes.

Antigen and Lymphocytes Must Be Brought Together in Lymph Nodes

Dendritic cells take up antigens and migrate to lymph nodes.
This helps bring the antigen and lymphocytes (T Cells) together in the lymph nodes needed for response

What Initiates Migration of Dendritic Cells to Lymph Nodes During Infection?

Dendritic cells are immature in sites of infection and mature in lymph nodes.
Immature DCs prioritize antigen uptake and are low in MHC, B7, and CCR7 expression. Mature DCs prioritize antigen presentation with high expression in MHC, B7, and CCR7.
Immature DCs have high antigen uptake but mature DCs have low antigen uptake.

T Cell Migration

Mature DCs enter lymph nodes via afferent lymphatics.
Naive T cells enter the nodes via the blood and stay for ~2-24 hrs
T cells that do not encounter specific antigen return to circulation.
T cells that DO encounter specific antigen become activated, proliferate, and differentiate into effectors (~3 days).
Dendritic cells in lymph nodes can contact up to ~5,000 naive T cells/hr

Live Cell Imaging of T Cells and DCs in a Lymph Node

Live cell imaging shows how dendritic cells and T cells interact in the lymph node
This is observed over time.

Key Question: How Do T Cells Know That It Is an Appropriate Time to Be Activated?

This question explores the need for specific activation signals

T Cell Activation Requires Interactions with Other Cells

T cells recognize antigens presented by MHC molecules on the surface of other cells.
CD4+ T cells recognize peptides in the context of MHC class II molecules on cells like dendritic cells, B cells, and macrophages.

Activation of T Cells Requires 2 Signals

T cell activation requires signal 1 (TCR/peptide) and signal 2 (CD28/B7)
Professional APCs (Dendritic cells, macrophages, B cells) express both MHCII and co-stimulatory molecules (B7)
Expression of CD80 and CD86 (which are B7 molecules) is upregulated during DC maturation. This is crucial for proper T cell activation

Possible Outcomes

Outcomes for T cells are dependent on signals received. Single signal 1 leads to anergy; signal 1 plus signal 2 leads to activation.

How is the TCR Signal Transduced?

TCRs recognize antigens, but need helper molecules (CD3) to transduce the signal.
Antigen binding triggers phosphorylation cascades that activate intracellular signaling pathways and gene expression.

What Does the Co-receptor Do?

CD4 co-receptor binds to MHC class II, increasing TCR affinity for MHC and lowering the threshold of activation.
Co-receptor binding significantly reduces the number of MHC molecules needed for effective activation of naïve T cells

The Immunological Synapse

The immune synapse is an area of close contact between two cells (e.g. T cell and antigen presenting cell).
The outer ring involves adhesion molecules whilst the inner ring is where TCR/MHC, CD28/B7, interact.

Key Question: What Signals Are Required for T Cells to Start Proliferating?

The key question explores how T cells know when to start and stop proliferating.
This is linked to expansion, maintenance and contraction cycles

Proliferation Is Driven by IL-2

Signal 1 and signal 2 are required for T cell activation
IL-2 released by activated T cells binds to IL-2 receptors on T cells (autocrine growth factor), driving further proliferation.

Activated T Cells Produce and Respond to IL-2

Activated T cells express the high-affinity IL-2 receptor, differing from naive T cells which only express the low-affinity receptor.
This increased expression along with IL-2 production drives proliferation.
IL-2 signaling is a target for many immunosuppressive drugs.

Activated T Cells Undergo Massive Clonal Expansion

T cells rapidly proliferate (2-3 times per day)
Individual precursor pools produce millions of effector cells in a week
A significant percentage of effector cells can be highly specific for the same peptide:MHC complex.

How Do We Turn T Cell Proliferation Off?

Cross-linking of CD28 delivers co-stimulation and then leads to CTLA-4 expression.
CTLA-4 binds B7 more strongly than CD28, delivering inhibitory signals, downregulating IL-2 signaling, stopping proliferation, and inducing apoptosis.

Why Do I Need to Learn This Stuff?

This section is focused on the motivation for learning this information.

Ipilimumab: CTLA-4 Inhibitor

Ipilimumab is a CTLA-4 inhibitor.
CTLA-4 is conserved in both dogs and humans.

Success! (Data on Ipilimumab)

This section likely depicts results of studies using ipilimumab, illustrating its clinical effect or efficacy.

And the Nobel Prize Goes To...

This section likely points out the researchers associated with a notable discovery related to T cell activation.

Summary

Multiple key questions are posed in relation to T cell activation, antigen recognition, infection, and proliferation.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

Explore the key concepts of CD4+ T cells and their roles in the immune system, particularly focusing on innate and adaptive immunity. This quiz also addresses adaptive immunotherapy advancements for cancer in companion animals, highlighting the importance of understanding immune functions and malfunctions.