Lecture 11 - T-cell Subsets (Gallucci)

Obj. 1

Define the terms “mature” and “naive” relative to T cells.

Naive

If the Ag has NEVER been seen before, there are very few T-cells that will recognize it

• “Ready, but unexperienced”

Mature

Fully developed T-lymphocytes that have completed their maturation, positive selection, and negative selection in the Thymus.

• Th0 cells require activating cytokines (IL-12, IL-2, IL4) to differentiate

• “Graduated from training school”

⚡ Key Relationship

👉 Most naive T cells are actually:

Mature + Naive

Meaning:

• Fully developed ✔

• But haven’t been activated yet ✔

Obj. 2

Contrast Th cells with T Killer (CTL) cells regarding their function.

CD4+ T Cells (Th): MHC Class II Restricted

• T-helper cells mostly

• Cytokine factors:

  • CD4⁺ cells work by releasing cytokines (chemical signals)

• Involved in Delayed Type Hypersensitivity (DTH):

  • A T-cell–mediated immune response

  • Takes 24–72 hours → “delayed”

CD8+ T Cells: MHC Class I Restricted

• Cytotoxic Lymphocytes (CTL) or T-killers

• Cellular assassins

• Can kill specific target cells (e.g., virus infected, tumor, etc.)

• Primarily kills via apoptotic processes

Obj. 3

Contrast Th cells with CTL with regard to surface markers.

Th cells

Th cells express CD4+ (binds MHC II)

CTL

CTL express CD8+ (binds MHC I).

Obj. 4

List the different types of T helper cells.

Th0 cells can differentiate into:

Th1, Th2, Treg, Th17, Tfh

• Each cell type steers the immune response to meet a specific pathogen type

• Most mature CD4+ T cells are Th1 or Th2

Obj. 5

Recognize the defining cytokines each Th type PRODUCES.

1. Th1 →

• Cytokines that INDUCE Differentiation:

  • IFN-γ & IL-12

• Makes/produced:

  • IFN-γ (& IL-2; associated w/ cell-mediated immunity)

2. Th2 →

• Cytokines that INDUCE Differentiation:

  • IL-4

• Makes/produced:

  • IL-4 (IL-4, 5, 13)

3. Th17 →

• Cytokines that INDUCE Differentiation:

  • IL-23 (& IL-6 + TGF-β)

• Makes/produced:

  • IL-17 (& IL-22)

4. Tfh →

• Cytokines that INDUCE Differentiation:

  • IL-21 (& IL-6)

• Makes/produced:

  • IL-21

5. Treg →

• Cytokines that INDUCE Differentiation:

  • TGF-β

• Makes/produced:

  • TGF-β & IL-10

Obj. 6

Name at least one characteristic cytokine to each Th type produces.

1. Th1 → IFN-γ (& IL-2)

2. Th2 → IL-4 (& IL-5)

3. Th17 → IL-17 (& IL-22)

4. Tfh → IL-21

5. Treg → TGF-β + IL-10

Obj. 7

Describe the principal pathogen(s) each Th cell targets.

1. Th1 → Activate Macrophages (& NK cell, CTL, ANTI-VIRAL, anti-tumor, & TB responses)

• viral or bacterial infection (cell-mediated immunity)

2. Th2 → Anti-parasitic, allergy

3. Th17 → Enhance Neutrophil responses/Recruit neutrophils/Inflammatory

• GOOD: Inflammatory responses - bacteria, fungus, myobacteria

• BAD: Involved in autoimmune disease (e.g., RA, MS, IBS, asthma)

4. Tfh → Activate B-cells to refine the Ab response

5. Treg → Anti-inflammatory; suppress other effector T-cells

• Cancer, immune regulation (mucosal immunity, autoimmunity)

Obj. 8

Describe what and how a specific cell type helps a Th0 cell to decide what type of Th cell it becomes.

APC interaction determines differentiation

• The cytokines APC makes helps Th differentiate

Obj. 9

Contrast in basic terms a Treg with an “ordinary” T helper cell.

Treg

• Regulatory helper subset

• Primarily immunosuppressive

• Maintains mucosal immunity

• Suppress other effector cells

Ordinary T-cells

• Promote immune activation via cytokines

• Drive pathogen specific responses

Obj. 10

What defining characteristics helped researchers differentiate Treg cells from activated T cells?

• Treg were difficult to discover b/c they look like activated T-helper cells

• Express CD4+, CD25+ (IL-2Rα)

• Their defining characteristic was the expression of high levels of FoxP3 transcription factors - could not be seen w/ conventional flow cytometry

Obj. 11

Contrast how a follicular T helper cell (Tfh) differs from an “ordinary” T helper with regard to anatomic location.

Goes to lymphoid follicle after differentiation

• Activate B cells to refine Ab responses (T-dependent Ab production, meaning: Requires Tfh help)

• B-cell + Tfh → results in formation of the germinal center

• Promote class switch to IgG, especially IgG1

  • IgM → IgG/IgG1

🧠 Big Picture

👉 After activation, some B cells don’t just start pumping antibodies immediately.

They go to a lymphoid follicle to improve their antibodies.

• Think: “basic antibodies → upgraded, high-quality antibodies”

Obj. 12

Contrast how a follicular T helper cell (Tfh) differs from an “ordinary” T helper cell with regard to the cell it “helps.”

Follicular T helper (Tfh) cells

• Specifically localize to B cell follicles within lymph nodes and the spleen to provide essential help to B cells for germinal center formation, affinity maturation, and antiboday production.

Conversely, “ordinary” T-helper cells (e.g., Th1, Th2, Th17)

• Primarily operate in the T cell zones or tissues to assist macrophages, neutrophils, or other immune cells

Obj. 13

Name a follicular T helper cell (Tfh) characteristic cytokine.

IL-21

Obj. 14

Describe how a CTL kills an infected cell.

1. Recognition:

• APC presents antigen via MHC I + co-stimulation (B7 + CD28).

1. Proliferation and Differentiation:

• IL-2 drives proliferation → many CD8 clones.

3. Killing:

• Effector CD8 cells recognize infected cells → induce apoptosis.

Obj. 15

Identify the mechanism by which an APC activates a CTL.

1. Antigen presentation (processed peptide + MHC)

2. Co-stimulation (B7 on APC binding CD28 on T cell)

3. Cytokine signals (APC releases cytokines → tells T cell what type to become: Th1, Th2, etc.)

a. Without co-stimulation → anergy

b. Conundrum: T cells need an APC to activate them, but CTLs only see an antigen in the context of MHC I.

• 👉 Problem:

  • APCs usually present exogenous antigens on MHC II

  • CTLs need MHC I

  • So how does this work??

• 🔥 The Answer: Cross-Presentation

  • 🧬 Mechanism: Cross-presentation (cross-priming)

    • 👉 Specialized APCs (especially dendritic cells) can:

      • Take external (exogenous) antigen

      • AND present it on MHC Class I

Obj. 16

Describe at least two defining characteristics of γδT cells.

• MINOR population in peripheral blood.

• Major population in the intraepithelial lymphocytes.

• Do not go through thymic selection (perhaps).

• Does not use CD4 or CD8, therefore does not need an MHC.

• Ligands are different from ⍺/β T cells; not short peptides (e.g., small bacterial phosphoantigens).

• Produces cytokines.

• Are cytotoxic → especially certain tumor cells.

• Role in tissue maintenance and repair – looks for distressed cells.

Obj. 17

Describe at least one functional characteristic that makes NK cells different from T killer cells.

• Killing is not immunogen specific nor MHC restricted – sort of.

• Possess IL-2 receptors → lymphokine activated killer cells (LAK).

• Possess Fcg receptors (ADCC) - antibody dependent cell mediated cytotoxicity.

• Looking for cells W/OUT MHC; all ⍺β T cells will have MHC I unless the cell is virally infected.

Obj. 18

Describe the process of ADCC.

• ADCC = antibody-dependent cellular cytotoxicity – immune cells kill targets coated with antibody.

• Per Image:

  • Antibody binds CD20 on B-cell lymphoma.

  • NK cell Fc receptor binds antibody Fc region.

  • NK cell activation via Fc receptor cross linking.

  • Release of perforin/granzymes.

  • Cancer cell apoptosis.

• Antibody → tags; NK → assassinates.