5: Cell-Mediated Immune Responses

What is the overall purpose of helper T-cell activation?

To activate and multiply antigen-specific helper T cells

What does an APC do during helper T-cell activation?

It displays an antigen fragment on MHC II for the T cell to recognize

What does the TCR recognize in Helper T-Cell Activation?

The antigen fragment presented by MHC II on the APC

What is the role of CD4?

CD4 helps the helper T cell interact with and stabilize its connection to MHC II

What is the first activation signal for a helper T cell?

The TCR recognizes an antigen presented on MHC II

What is co-stimulation in Helper T-Cell activation, and why is it needed?

It is a second activation signal that confirms the T cell should become activated.

What two proteins provide the co-stimulation signal?

CD28 on the T cell binds to B7 on the APC

What does an activated helper T cell produce?

IL-2, a cytokine that promotes T-cell growth and division

What happens when IL-2 binds to IL-2R, which is also located on a T-Cell?

It signals the T cell to grow and divide

What is clonal expansion?

The rapid multiplication of activated T cells that recognize the same antigen

What are the two signals required for helper T-cell activation

Signal 1: TCR recognizes antigen-MHC II

Signal 2: CD28 binds B7

What is the relationship between IL-2 and IL-2R?

The T cell releases IL-2, which binds IL-2R on the T cell and promotes its division

What is the sequence of helper T-cell activation?

Antigen presentation → TCR recognition → CD28/B7 co-stimulation → IL-2 production → T-cell division

What happens is there are no dendritic cells?

There is no adaptive immunity

What does "intracellular microbe" mean

A microbe that lives inside a host cell.

What are the two major locations of intracellular microbes?

Inside phagocytes and inside nonphagocytic cells

What is a phagocyte?

An immune cell that engulfs and takes microbes inside itself

What happens to a microbe after a phagocyte engulfs it?

It is placed inside a compartment called a phagosome, compartment formed when a phagosome combines with a lysosome

What normally happens to microbes inside phagolysosomes

They are broken down and destroyed

How can some microbes survive inside phagocytes?

They can survive inside phagolysosomes or escape into the cytoplasm

What does it mean when a microbe escapes from a phagolysosome?

It leaves the phagolysosome and enters the cell's cytoplasm, meaning that it is no longer susceptible to the microbicidal mechanisms of the phagocytes

What is a nonphagocytic cell?

A cell that does not specialize in engulfing microbes

• ex: epithelial cell

Why are intracellular microbes important in T cell–mediated immunity?

They live inside cells, so T cell responses are important for combating them

What is a latent infection?

A latent infection is when a virus or microorganism stays inside your body without causing any symptoms or making you sick

How do viruses replicate in nonphagocytic cells?

1. Viruses must bind to a specific receptor or protein on the host cell’s outer membrane

2. Once bound, it can enter the cell through direct diffusion or endocytosis

3. Once inside the cell, the virus can replicate

What is the main purpose of cell-mediated immunity (CMI)?

To fight microbes that live inside host cells

What cell initiates the CMI response and what does it do?

A dendritic cell (DC)

• It presents antigen to T cells and helps activate them

Where does initial T-cell antigen recognition occur?

In lymphoid organs such as lymph nodes.

What happens after a T cell recognizes its specific antigen?

It becomes activated, multiplies, and differentiates into an effector T cell

What does T-cell expansion mean?

Activated T cells rapidly multiply to produce many antigen-specific cells

What does T-cell differentiation mean?

T cells develop into specialized cells that can carry out immune functions

What is an effector T cell?

An activated T cell specialized to perform an immune response

Where do differentiated effector T cells go after activation?

They enter circulation and travel toward the infected tissue

• They want to get to the actual site of infection!

What happens when effector T cells encounter their antigen in the peripheral tissues?

They become activated and carry out their specialized effector functions

What is the main function of CD4⁺ effector T cells in CMI?

They activate other immune cells, especially macrophages, using cytokines

How do CD4⁺ T cells help macrophages fight intracellular microbes?

They release cytokines that contribute to inflammation and activate macrophages, improving microbial killing

What is the main function of CD8⁺ T cells in CMI?

hey become CTLs (Cytotoxic T lymphocyte) that kill infected cells.

How to naive T-Cells enter the lymph node?

Naive T Cells Enter via High Endothelial Venules (HEVs)

How do dendritic cells enter the lymph node?

Dendritic Cells Enter via Afferent Lymphatic Vessels

Which MHC class is recognized by CD4⁺ T cells?

MHC II

Which MHC class is recognized by CD8⁺ T cells?

MHC I

What happens after a naive T cell receives the necessary activation signals?

It produces cytokines, expresses cytokine receptors, proliferates, and differentiates

What is IL-2, and what does it do?

IL-2 is a cytokine that stimulates activated T-cell growth and division

What is IL-2R?

The IL-2 receptor on a cell's surface that binds IL-2 and receives its signal

What happens when IL-2 binds to IL-2R?

It triggers signals that encourage the activated T cell to grow and divide

• PROLIFERATION

What is autocrine signaling?

When a cell releases a chemical messenger that acts on the same cell.

What are the two major outcomes of T-cell differentiation?

Effector T cells and memory T cells.

• Both helper T cells and killer T cells can be an effector or memory cell

Where do effector T cells perform their main functions?

In peripheral tissues where the infection is occurring

What is the difference between proliferation and differentiation?

Proliferation increases the number of cells; differentiation gives cells specialized functions.

Does the TCR generally recognize a free-floating antigen by itself?

No. It recognizes a specific peptide antigen presented by an MHC molecule

What is CD4/8, and what does it do?

• CD4/8 is a coreceptor—a protein on the surface of helper T cells that helps it interact with APCs

• CD4/8 binds MHC II and helps stabilize the interaction and strengthen signaling inside the T cell

(THE TCR RECOGNIZES THE SPECIFIC ANTIGEN PRESENTED ON MHC, BUT THE CD4/8 HELPS THEM BIND) (CD4 —> HELPER, CD8—> KILLER)

What can happen if a naive T cell recognizes antigen without adequate costimulation?

It may fail to activate fully or become anergic, meaning it responds poorly to the antigen

What are the second signals provided by APCs during T-cell activation?

Costimulatory signals, classically B7 on the APC binding to CD28 on the T cell.

What is an immunological synapse?

An organized contact area between an APC and a T cell where antigen recognition and activation signals occur

What does pMHC class II mean?

Peptide-MHC class II; an MHC II molecule displaying an antigen fragment.

What is the role of CD4 at the immunological synapse?

It binds MHC II and helps stabilize the interaction and support T-cell signaling

What is the role of CD3 in T-cell activation?

It transmits antigen-recognition signals from the TCR into the T cell.

What is CD247?

Another name for the CD3 zeta chain, which helps transmit TCR activation signals.

What are CD80 and CD86 also called?

B7-1 and B7-2, respectively; they are costimulatory molecules on APCs.

What is the role of CD28 in terms of CD80/CD86?

It binds CD80/CD86 on the APC to provide the costimulatory signal.

What is the role of LFA-1/CD11a/CD18 and ICAM-1/CD54?

They bind to help the APC and T cell adhere and maintain stable contact.

What is the role of CD2 and LFA-3?

They provide additional adhesion that helps stabilize the APC-T-cell interaction

What makes up LFA-3?

CD58

How does the immunological synapse connect to IL-2 production?

TCR signaling and costimulation help activate the T cell, enabling it to produce IL-2 and respond to it.

What is the difference between CD4 and CD28?

CD4 binds MHC II as a coreceptor; CD28 binds B7 molecules to provide costimulation.

What is the difference between CD28-B7 and LFA-1-ICAM-1?

CD28-B7 provides costimulation; LFA-1-ICAM-1 mainly provides adhesion and stable contact.

Function of TCR?

Antigen recognition

What ligand to TCRs bind to?

Peptide- MHC

What cells present peptide- MHC?

All antigen-presenting cells

Function of ζ molecule?

Signal transduction by TCR complex

Function of CD4 molecule?

Signal transduction

What ligand does CD4 bind to?

Class II MHC

Where are Class II MHC ligands expressed?

All APCs

Function of CD28?

Signal transduction

Function of CTLA-4?

Signal transduction (costimulation)

Function of PD-1?

Negative regulation

Function of LFA-1?

Adhesion

What ligand(s) does CD8 bind to?

Class I MHC

What ligand(s) does CD28 bind to?

B7-1/B7-2

What ligand(s) does CTLA-4 bind to?

B7-1/B7-2

What ligand(s) does PD-1 bind to?

PD-L1/PD-L2

What ligand(s) does LFA-1 bind to?

ICAM-1

What cells express CD*?

All nucleated cells

What cells express B7-1/B7-2?

APCs

What cells express PD-L1/PD-L2?

APCs, tissue cells, tumor cells

What cells express ICAM-1?

APCs, endothelium

What is signal transduction during T-cell activation?

The process of converting antigen recognition at the cell surface into internal signals that help activate the T cell.

Why does the TCR need the CD3 complex?

The TCR recognizes the antigen, while CD3 provides signaling components that help carry the message into the cell

What is Lck?

A protein tyrosine kinase that helps initiate TCR signaling by phosphorylating proteins associated with the TCR-CD3 complex.

What is a protein tyrosine kinase?

An enzyme that adds phosphate groups to tyrosine residues in proteins, changing their signaling activity.

What is the role of Lck in T-cell activation?

Lck phosphorylates ITAMs associated with CD3 proteins, helping initiate downstream signaling

What is an ITAM?

A specific region of a signaling protein that can be phosphorylated to help transmit an immune activation signal

Where are ITAMs found in the TCR complex?

In the cytoplasmic portions of CD3-associated signaling proteins

What happens when Lck phosphorylates ITAMs?

The phosphorylated ITAMs help recruit and activate additional signaling proteins, allowing the signal to continue

What does cross-linking mean in TCR signaling?

Bringing multiple TCR molecules close together through interactions with antigen-bearing structures, helping initiate signaling.

What do the first signals of antigen recognition produce?

First signals will lead to translation and transcription, making IL-2 (inflammatory signals)

What do CD40 and CD40L do in antigen recognition?

CD40–CD40L engagement triggers the APC to secrete inflammatory cytokines (like IL-12) and helps drive robust cellular immunity and humoral immunity

What is a resting APC?

An antigen-presenting cell that has not received sufficient activation signals and generally expresses low levels of costimulatory molecules.

Can a resting APC present an antigen without fully activating a naive T cell?

Yes. It can present antigen and provide Signal 1 without providing enough costimulation for full activation.

What happens when a naive T cell recognizes antigen without adequate costimulation?

It may fail to activate or become functionally unresponsive, depending on the circumstances.

• Naive T cells may become unresponsive to subsequent exposure to the antigen, even if costimulators are present