Cell Mediated Immunity Activation of T Lymphocytes and Elimination of Intracellular Microbes

Slide 1 · Cell-Mediated Immunity

Activation of T lymphocytes and elimination of intracellular microbes

Antigen recognition

T-cell activation

Effector response

Antigen-bearing cells → activated T cells → infected-tissue defense

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning outcomes

Trace antigen capture, lymphoid activation, and effector-cell deployment.

Explain how peptide–MHC recognition and costimulation activate naive T cells.

Contrast Th1 macrophage activation with CD8⁺ cytotoxic killing.

Relate helper-T-cell subsets to their cytokines and dominant functions.

Slide 3 · Why cell-mediated immunity is required

Intracellular problem

Microbes can survive within phagocytes or infected host cells.

A cell may conceal microbial antigens from circulating antibodies.

T-cell solution

CD4⁺ T cells activate microbe-containing phagocytes.

CD8⁺ CTLs destroy infected cells harboring cytosolic microbes.

Slide 4 · Antigen location selects the effector route

Microbial antigen inside cells

Engulfed by phagocyte

CD4⁺ Th1 response

Activate the macrophage

Present in cell cytosol

CD8⁺ CTL response

Kill the infected cell

Slide 5 · Cell-mediated immunity has four linked phases

Capture antigen in tissues

Activate naive T cells in lymphoid organs

Expand and differentiate clones

Eliminate microbial reservoirs in tissues

Location and timing separate T-cell priming from tissue-level effector function.

Slide 6 · Naive T cells cannot inspect every tissue

A rare antigen-specific naive T cell is unlikely to meet its antigen by random tissue patrol.

Antigens are concentrated

Naive cells recirculate through nodes

Encounter becomes probable

Secondary lymphoid organs solve the encounter problem.

Slide 7 · Dendritic cells bring antigen to lymph nodes

Microbe enters tissue

Resident dendritic cell captures antigen

Dendritic cell migrates

Peptide–MHC displayed to naive T cells

This is the bridge from a peripheral infection to adaptive T-cell activation.

Slide 8 · Dendritic-cell maturation links innate and adaptive immunity

In tissue

DC captures microbial antigen.

Innate stimuli activate the presenting cell.

In lymph node

DC displays peptide–MHC complexes.

MHC and costimulatory expression is enhanced.

Slide 9 · Priming and defense occur in different places

Peripheral tissue: Antigen capture

Draining node: T-cell activation

Blood: Effector-cell migration

Infected tissue: Microbial elimination

Effector cells are generated in lymphoid organs and then move to antigen-bearing tissues.

Slide 10 · T cells recognize processed protein antigens

T-cell receptor recognition

T-cell receptor binds a peptide displayed by an MHC molecule.

T cells do not recognize intact soluble proteins as B cells do.

Consequence

Antigen recognition is restricted by self MHC.

The presenting route determines which T-cell class responds.

Slide 11 · MHC class I guides CD8⁺ responses

Cytosolic protein antigen

Peptide bound to MHC class I

CD8⁺ T-cell recognition

CTL-directed killing

Class I presentation provides immune surveillance for cytosolic infection and tumor-derived abnormal proteins.

Slide 12 · MHC class II guides CD4⁺ responses

Internalized microbial antigen

Peptide bound to MHC class II

CD4⁺ helper-T recognition

Macrophage or B-cell activation

Professional antigen-presenting cells, including DCs, macrophages and B cells, express class II MHC.

Slide 13 · MHC class I and II have different tasks

Feature

MHC class I / CD8⁺

MHC class II / CD4⁺

Typical source

Cytosolic proteins

Internalized proteins

Responding T cell

Cytotoxic T cell

Helper T cell

Effector outcome

Kill infected cell

Activate phagocyte / aid B cell

Immune problem

Cytosolic microbes

Ingested microbes

Slide 14 · Innate stimuli license antigen presentation

Antigen display alone is not the full activation signal for naive T lymphocytes.

Microbe stimulates innate sensors

APC increases costimulators

T cell receives coordinated signals

Adaptive activation is coupled to signs of microbial encounter.

Slide 15 · Signal 1 confers antigen specificity

Antigen-presenting cell

Naive T lymphocyte

Peptide–MHC ⇄ T-cell receptor

Signal 1: Antigen-specific recognition

Signal 1 selects the responding T-cell clone.

Slide 16 · Signal 2 provides costimulation

Antigen-presenting cell

Naive T lymphocyte

B7 (CD80/CD86) ⇄ CD28

Signal 2: Costimulatory input

B7 expression increases on APCs during innate immune activation.

Slide 17 · Both signals cooperate during T-cell priming

Naive T-cell activation

Signal 1

Specific peptide–MHC

Which clone responds?

Signal 2

B7–CD28 costimulation

Is APC activated?

Slide 18 · Costimulation limits indiscriminate responses

The innate response induces APC costimulators after microbial recognition.

Naive T cells require antigen recognition together with costimulation.

This requirement helps prevent vigorous responses to innocuous antigens.

Other control mechanisms also restrain anti-self responses despite APC activation.

Slide 19 · Lymphoid compartments organize encounters

T-cell zone

Naive T cells encounter antigen-presenting dendritic cells.

Peptide–MHC and costimulators initiate T-cell activation.

B-cell follicle

B lymphocytes and Tfh interactions support antibody responses.

Distinct localization allows specialized helper functions.

Slide 20 · Activation selects rare antigen-specific clones

Naive repertoire

Specific peptide–MHC recognized

Antigen-reactive T cells activated

Expanded effector population

Proliferation increases the number of T cells specific for the encountered antigen.

Slide 21 · IL-2 is produced early by activated helper T cells

Activated CD4⁺ helper T lymphocytes secrete IL-2.

They also increase expression of high-affinity IL-2 receptors.

The same activated clone can respond to the IL-2 it produces.

The resulting growth signal drives T-cell proliferation.

Slide 22 · High-affinity IL-2 receptors amplify responsiveness

Receptor upregulation makes activated T cells highly responsive to IL-2.

Antigen-driven activation

High-affinity IL-2R expression

IL-2-dependent proliferation

The growth-factor receptor is part of the activation program.

Slide 23 · IL-2 creates an autocrine proliferation loop

Activated CD4⁺ T cell

IL-2 secretion

IL-2R binding

Clonal proliferation

Slide 24 · Clonal expansion increases effector capacity

Before activation

Few naive cells are specific for any one microbial antigen.

The clone has not yet acquired its tissue-defense program.

After activation

Antigen-specific cell numbers rise.

Proliferating cells acquire helper or cytotoxic effector functions.

Slide 25 · Differentiation produces distinct T-cell fates

Activated naive T lymphocyte

Effector cells

Act during current infection

Migrate to infected tissues

Memory cells

Persist after response

Enable faster secondary responses

Slide 26 · Effector T cells leave lymphoid organs

Expansion in lymph node

Effector differentiation

Entry into circulation

Migration to antigen-bearing tissue

Local tissue defense is performed by differentiated cells generated during priming.

Slide 27 · CD4⁺ helper cells act through two mechanisms

Antigen-recognizing CD4⁺ T cell

Membrane-bound CD40 ligand

CD40 on target cells

Direct cell-contact activation

Secreted cytokines

Signal through cytokine receptors

Functional programming of target cells

Slide 28 · CD40L–CD40 is a contact-dependent signal

CD4⁺ helper T cell

Macrophage / B lymphocyte

CD40 ligand ⇄ CD40

Cell contact activates the antigen-presenting target

Helper T cells express CD40L when recognizing antigen displayed by the target.

Slide 29 · Helper-T-cell cytokines program target cells

Cytokines are secreted proteins that mediate immune-cell communication.

Their effects may be autocrine or paracrine; Endocrine actions are less common.

Distinct helper subsets secrete different cytokine combinations.

Cytokines collaborate with cell-contact signals such as CD40L.

Slide 30 · CD4⁺ helper T cells diversify into subsets

Activated CD4⁺ T cell

Signals at antigen recognition

Subset differentiation

Distinct cytokines and effector functions

Functional differentiation is matched to the microbial challenge.

Slide 31 · Major helper-T-cell programs are distinct

Subset

Key cytokine / induction

Principal function

Th1

IFN-γ; Induced by IL-12

Classical macrophage activation

Th2

IL-5; IL-4; IL-13

Eosinophils; Alternative macrophage activation

Th17

IL-17

Neutrophil / monocyte recruitment

Tfh

CD40L and cytokine help

High-affinity B-cell antibody responses

Slide 32 · IL-12 favors Th1 differentiation

Intracellular microbe encountered

Macrophage / DC produces IL-12

CD4⁺ cell differentiates to Th1

Th1 response directed to phagocytes

Microbial context shapes the responding helper-cell population.

Slide 33 · Th1 cells produce interferon-γ

Th1 is the principal helper subset for activation of microbe-containing macrophages.

Its characteristic cytokine is interferon-γ (IFN-γ).

IFN-γ delivers a potent activating signal to macrophages.

Contact signals reinforce the cytokine-driven response.

Slide 34 · Th1 cells and macrophages form a functional pair

Th1 effector cell

Microbe-containing macrophage

IFN-γ + CD40L–CD40

Classical macrophage activation

The macrophage presents antigen from its ingested microbes to the helper cell.

Slide 35 · Classical macrophage activation requires cooperation

Macrophage presents ingested antigen

Th1 recognizes peptide–MHC II

CD40 activation + IFN-γ

Enhanced intracellular microbicidal activity

Cooperative contact and cytokine signals induce the classical activation program.

Slide 36 · Why activate the macrophage rather than kill it?

Macrophage harbors ingested microbes

Microbes may be contained within phagocytic compartments.

The infected phagocyte can remain an antimicrobial effector.

Th1 response enhances killing

IFN-γ and CD40 signals increase microbicidal function.

The macrophage eliminates microbes it has ingested.

Slide 37 · The Th1 response operates at the infection site

Primed Th1 cell migrates

Recognizes local macrophage antigen

CD40L and IFN-γ delivered

Ingested microbes destroyed

Antigen recognition and effector activation are linked in the infected tissue.

Slide 38 · Th2 differentiation reflects epithelial danger signals

Epithelial injury or stress

IL-25, IL-33 and TSLP

Th2 differentiation favored

Barrier-associated type 2 response

The source links this subset to epithelial interfaces and their characteristic stimuli.

Slide 39 · Th2 IL-5 promotes eosinophil responses

Th2 effector cell

IL-5 secretion

Eosinophil activation

Defense against helminthic parasites

Helminth defense is a distinct helper-cell function, not the principal Th1 route.

Slide 40 · Th2 IL-4 and IL-13 alter macrophage programs

Th2 cell

IL-4 and IL-13

Alternative macrophage activation

Tissue repair and fibrosis

Alternative and classical activation represent different functional responses.

Slide 41 · Classical versus alternative macrophage activation

Feature

Classical activation

Alternative activation

Associated helper cell

Th1

Th2

Signals

IFN-γ + CD40

IL-4 / IL-13

Principal function

Kill ingested microbes

Tissue repair / fibrosis

Teaching distinction

Host defense inside phagocyte

Remodeling and repair

Slide 42 · Th17 cells arise during fungal and bacterial responses

Fungi or some bacteria encountered

Macrophage / DC cytokines

Th17 differentiation

Recruitment of inflammatory leukocytes

The extracted section does not list specific Th17-inducing cytokines; None are inserted.

Slide 43 · IL-17 recruits neutrophils and monocytes

Activated Th17 cell

IL-17 secretion

Neutrophil / monocyte recruitment

Defense against extracellular microbes

Th17 functions differ from Th1 macrophage activation and Th2 eosinophil recruitment.

Slide 44 · Helper subsets align with pathogen biology

Challenge

Preferred helper activity

Effector outcome

Ingested intracellular microbes

Th1 → macrophage activation

Microbicidal killing

Helminthic parasites

Th2 → IL-5 / eosinophils

Parasite defense

Extracellular bacteria / fungi

Th17 → leukocyte recruitment

Neutrophil-rich defense

Protein antigens in follicles

Tfh → B-cell help

Higher-affinity antibody

Slide 45 · Helper-cell identities are not absolute

Th1, Th2, and Th17 describe characteristic cytokine and functional programs.

Some activated T cells produce multiple cytokines.

Other activated cells do not fit perfectly into a single canonical subset.

Use the subsets as mechanistic patterns, not mutually exclusive boxes.

Slide 46 · T follicular helper cells remain near B cells

Migrating helper cells

Th1, Th2, and Th17 effectors move toward peripheral sites.

They activate leukocytes in infected or inflamed tissues.

T follicular helper cells

Concentrate in lymphoid follicles with B cells.

Provide signals for high-affinity antibody responses.

Slide 47 · Tfh cells connect T-cell help to antibodies

Protein-antigen recognition

Tfh–B-cell interaction

CD40L + cytokine help

High-affinity antibody production

This is a lymphoid-organ function of CD4⁺ cells rather than direct intracellular killing.

Slide 48 · Helper effector location reflects function

Subset

Typical site of action

Immediate target

Th1

Infected tissues

Antigen-bearing macrophage

Th2

Barrier / infected tissues

Eosinophil; Macrophage

Th17

Inflamed infected tissues

Recruitable leukocytes

Tfh

Lymphoid follicle

B lymphocyte

Slide 49 · CD8⁺ T cells undergo antigen-driven activation

The early activation steps resemble those of CD4⁺ T cells.

Peptide–MHC class I recognition provides antigen specificity.

Costimulation and IL-2 support their proliferative response.

Activated CD8⁺ cells differentiate into cytotoxic T lymphocytes (CTLs).

Slide 50 · CD8⁺ clones expand extensively

Activated CD8⁺ lymphocytes proliferate especially strongly.

Peptide–MHC I and costimulation

IL-2-supported expansion

Large antigen-specific CTL population

The Robbins source describes more extensive CD8⁺ than CD4⁺ proliferation.

Slide 51 · CTL differentiation creates a killing effector

Naive CD8⁺ T cell

Antigen + costimulation

Clonal proliferation

Cytotoxic T lymphocyte

The central new function is selective destruction of cells expressing the target antigen.

Slide 52 · CD8⁺ CTLs detect cytosolic infection

CD8⁺ cytotoxic T cell

Cytosol-infected target cell

T-cell receptor ⇄ peptide–MHC class I

Recognition of infected cell → directed killing

The infected cell displays peptides derived from its intracellular proteins.

Slide 53 · CTLs eliminate infected host cells

Microbe persists in host cytosol

Target presents microbial peptide

CTL recognizes target

Infected host cell killed

Eliminating the host cell also eliminates a cellular reservoir of infection.

Slide 54 · Killing the reservoir is the CTL strategy

If infection is cytosolic

The pathogen occupies a host-cell compartment.

Macrophage activation alone may not remove the infected reservoir.

CTL effect

The antigen-bearing host cell is destroyed.

The intracellular reservoir is removed from the tissue.

Slide 55 · Tumor cells can also be CTL targets

Mutated / abnormal cytosolic protein

Tumor-derived peptide–MHC I

CTL antigen recognition

Tumor-cell killing

This is a second biological application of class I–restricted cytotoxicity described in the source.

Slide 56 · CD4⁺ and CD8⁺ T cells solve different problems

Dimension

CD4⁺ helper T cell

CD8⁺ CTL

Antigen display

Peptide–MHC class II

Peptide–MHC class I

Effector mechanism

CD40L + cytokines

Kill target cell

Principal target

Macrophage / B cell

Infected or tumor cell

Microbial focus

Ingested microbes

Cytosolic microbes

Slide 57 · Two intracellular niches, two effector strategies

Where is the microbial reservoir?

Within a phagocyte

Th1 sees MHC II–peptide

Amplify phagocyte killing

Within a cytosol-infected cell

CTL sees MHC I–peptide

Destroy infected cell

Slide 58 · An integrated timeline links priming and defense

Innate recognition and antigen capture

Peptide–MHC + B7–CD28 priming

IL-2-driven clonal expansion

Th1 activation / CTL killing

The early events are shared; The later effector paths diverge by antigen location.

Slide 59 · Innate and adaptive immunity reinforce one another

Microbial innate response

APC costimulation / cytokines

T-cell activation

Enhanced microbial elimination

Slide 60 · Effector cytokines can also drive immunopathology

Protective function

Helper subsets coordinate inflammation appropriate to the pathogen.

IFN-γ, IL-5 and IL-17 mobilize different effectors.

Clinical implication

The same cytokine programs may participate in inflammatory disease.

Biologics can block selected inducing or effector cytokines.

Slide 61 · Therapeutic cytokine blockade is subset-specific

Helper subsets differ in inducing stimuli and secreted effector cytokines.

Antibodies that block these pathways are used in diseases driven by the respective subset.

Blocking a cytokine targets an immune program, not a universal inflammatory switch.

The selected Robbins passage does not specify particular drugs or indications.

Slide 62 · Case: Ingested intracellular microbe

A macrophage has phagocytosed a microbe but needs enhanced intracellular killing. Which T-cell subset provides the characteristic activating signals?

A. Th2: IL-5-driven eosinophil response

B. Th1: IFN-γ plus CD40L–CD40

C. Th17: IL-17-driven leukocyte recruitment

Slide 63 · Case: Virus in the cytosol

A host cell is producing microbial proteins in its cytosol. Which antigen-display and effector combination directly eliminates this infected cell?

A. MHC II → Th1-dependent macrophage activation

B. Th2 → eosinophil activation

C. MHC I → CD8⁺ cytotoxic T lymphocyte

Slide 64 · Case: Inflammatory leukocyte recruitment

A T-cell response is characterized by IL-17 and recruitment of neutrophils and monocytes. Which helper lineage best explains the pattern?

A. Th1

B. Th17

C. Tfh

Slide 65 · Three causal relationships to retain

B7–CD28 + peptide–MHC → activation

IL-2 / IL-2R → clonal expansion

Th1 / CTL → intracellular microbial control

Differentiate signals that activate T cells from effector mechanisms that eliminate infection.

Slide 66 · Primary source and figure context

Robbins, Cotran & Kumar: Pathologic Basis of Disease. 11th edition (2026). Chapter 6, pp. 175–179.

“Display and Recognition of Antigens” and “Cell-Mediated Immunity: Activation of T Lymphocytes and Elimination of Intracellular Microbes.”

Conceptual sequences grounded in the explanatory text and captions of Figures 6.10 and 6.11.