Components of Innate Immunity

Slide 1 · Components of Innate Immunity

Barriers • Cells • Soluble mediators

Epithelial

defense

Cellular

effectors

Humoral

effectors

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning outcomes

Identify anatomic, cellular, and soluble constituents of innate immunity.

Explain the principal functions of phagocytes, dendritic cells, NK cells, and ILCs.

Distinguish complement, pattern recognition, and antiviral defense.

Integrate the components in infection and tissue-injury scenarios.

Organizing question

Which component detects a threat, which eliminates it, and which connects innate defenses to adaptive immunity?

Slide 3 · Innate immunity is present before exposure

Intrinsic host mechanisms are poised to act immediately.

Conserved microbial products and injury-related signals initiate responses.

Principal purposes: Limit infection and clear damaged cells.

It serves as the first defensive tier, not a delayed clonal response.

Contrast with adaptive immunity

Innate responses depend on germline-encoded recognition; Adaptive lymphocyte receptors undergo somatic recombination.

Slide 4 · Response timing: Immediate versus induced

Microbe enters

Tissue

Innate reactions

Hours

Adaptive response

Days

Early protection

Barrier defense, complement activation, phagocytosis, and NK-cell activity.

Later antigen-specific expansion

T- and B-lymphocyte activation, proliferation, and differentiation.

Slide 5 · Microbial and damage signals initiate defense

Microbial structures

PAMPs

Injured / necrotic cells

DAMPs

Pattern-recognition receptors

On host cells

Cytokines • Phagocytosis • Antiviral programs

Slide 6 · Defense is organized in complementary layers

Barrier exclusion

Surface epithelium restricts microbial entry before local tissue penetration.

Cellular effector defense

Resident sentinels, recruited phagocytes, NK cells and ILCs respond to danger.

Soluble effector defense

Complement and antimicrobial proteins support elimination concurrently with cellular responses.

Network principle: These components cooperate; They are not strictly sequential modules.

Slide 7 · Cellular and humoral arms of innate immunity

Cellular arm

Neutrophils, macrophages, dendritic cells, NK cells, innate lymphoid cells, and additional tissue sentinels.

Acts through recognition, phagocytosis, cytokine production, and target-cell killing.

Humoral arm

Complement, mannose-binding lectin, C-reactive protein, and local soluble factors such as surfactant.

Acts through microbial coating, complement-mediated injury, and inflammatory amplification.

Slide 8 · Main constituents: A functional classification

Barrier and tissue interface

Cell populations

Soluble proteins

Skin, gastrointestinal and respiratory epithelia

Neutrophils and monocyte–macrophage lineage

Complement proteins

Epithelial antimicrobial molecules

Dendritic cells and natural killer cells

Mannose-binding lectin

Epithelial resident lymphocytes

ILCs; mast cells; responsive endothelial cells

C-reactive protein; pulmonary surfactant

Slide 9 · Epithelial surfaces block microbial entry

Skin

Continuous epithelial surface separates microbes in the external environment from deeper tissues.

Gastrointestinal tract

Epithelial lining restricts microbial penetration at a heavily exposed interface.

Respiratory tract

Epithelial surface blocks entry of inhaled microbes; Local soluble factors add protection.

Functional principle: Mechanical exclusion is protective before any leukocyte recruitment occurs.

Slide 10 · Barrier protection is not only mechanical

Epithelial barrier

Physical separation

Antimicrobial defensins

Intraepithelial lymphocytes

Result: Parallel mechanical, molecular, and cellular protection at exposed surfaces.

Slide 11 · Defensins: An epithelial antimicrobial product

Epithelial cells synthesize defensins as part of local innate defense.

Defensins act at the exposed tissue interface.

Antimicrobial production complements the epithelial physical barrier.

Barrier-derived defense operates even before recruited phagocytes arrive.

Teaching distinction

A protective barrier is an active host tissue, not simply an impermeable covering.

Slide 12 · Intraepithelial lymphocytes defend surface tissues

External microbial challenge

Epithelium

Local lymphocyte

Lymphocytes positioned in epithelia combat microbes where they first encounter the host.

Slide 13 · When epithelia are breached, deeper defenses engage

Microbes breach

Epithelium

Tissue sentinels

Recognize danger

Leukocytes are

Recruited

Microbes are

Ingested / killed

Mechanism: Barrier failure changes the response from exclusion to recognition and clearance.

Slide 14 · Principal phagocytes circulate and enter tissues

Neutrophils

Circulating granulocytes that can be rapidly recruited into sites of infection.

Provide strong short-lived antimicrobial responses.

Monocytes → macrophages

Blood monocytes enter tissues and mature into macrophages.

Macrophages phagocytose organisms and coordinate longer inflammatory responses.

Slide 15 · Neutrophils: Rapid recruited phagocytes

Present in blood before tissue infection develops.

Rapid recruitment brings microbicidal activity into infected tissue.

Phagocytosis, granule products, and reactive oxygen species eliminate microbes.

Predominate in the early inflammatory leukocyte infiltrate.

Relation to inflammation

Neutrophils are a hallmark effector of acute inflammation; Their destructive molecules may also injure host tissue.

Slide 16 · Monocytes differentiate into tissue macrophages

Blood

Monocyte

Extravasation

Into tissue

Differentiation

Into macrophage

Microbial clearance

And cytokine response

Macrophages remain important after early neutrophil-dominant inflammation and contribute to chronic inflammatory responses.

Slide 17 · Tissue-resident macrophages occupy sentinel niches

Tissue

Resident macrophage population

Functional relevance

Liver

Kupffer cells

Local tissue surveillance and clearance

Central nervous system

Microglia

Resident immune sentinel population

Lung

Alveolar macrophages

Defense within the respiratory compartment

Slide 18 · Macrophage origins include embryonic precursors

Developmental resident pool

Some long-lived tissue-resident macrophages originate from progenitors in the yolk sac or fetal liver early in development.

Recruited inflammatory pool

Circulating monocytes from hematopoietic production enter tissues and generate macrophages during inflammatory reactions.

Implication: Macrophages in tissue are not all recently recruited from blood.

Slide 19 · Phagocytes carry out a three-stage program

Recognition and

Attachment

Engulfment

→ phagosome

Intracellular killing

And degradation

Biological purpose

Capture a threat, isolate it in an intracellular compartment, then destroy and digest the material.

Slide 20 · Leukocyte recruitment is a multistep process

Selectin-dependent

Rolling

Integrin-dependent

Firm adhesion

Migration across

Endothelium

Chemotaxis toward

The offending agent

Coordination: Cytokines and chemokines generated in tissue regulate each recruitment step.

Slide 21 · Inflammatory cytokines activate the vascular gateway

Tissue macrophage / sentinel

Responds to microbes

TNF, IL-1 and chemokines

Endothelial adhesion +

Leukocyte migration

Selectins support rolling; Activated integrins support firm adhesion; Chemoattractants direct migration.

Slide 22 · Phagocytic receptors recognize microbial surfaces

Receptor group

Recognized feature

Result

Mannose receptors

Terminal mannose/fucose on microbial structures

Preferential microbial recognition

Scavenger receptors

Diverse microbial ligands

Binding and uptake

Opsonin receptors

Microbes coated with IgG or complement fragments

Efficient phagocytic attachment

Slide 23 · Opsonization increases phagocytic efficiency

Microbe

C3b / IgG / lectin

Coat microbial surface

Phagocyte receptor

Engagement

An opsonin provides a recognizable ligand for the phagocyte, converting weaker attachment into effective engulfment.

Slide 24 · Engulfment produces an intracellular phagosome

Bound particle at

Cell surface

Actin-dependent

Membrane extension

Closure of membrane

Around particle

Intracellular

Phagosome

Mechanism: Receptor-initiated signals reorganize membrane and cytoskeleton during particle uptake.

Slide 25 · Phagosome–lysosome fusion enables degradation

Phagosome

With microbe

Lysosome

Hydrolytic enzymes

Phagolysosome

Killing + digestion

Controlled compartmentalization limits damage to the phagocyte

Slide 26 · Phagocytes use multiple microbicidal effectors

Reactive oxygen species

Phagocyte oxidase generates oxidative intermediates for antimicrobial action.

Reactive nitrogen species

Nitric oxide-derived chemistry contributes to killing of ingested microbes.

Lysosomal enzymes

Degradation proceeds inside phagolysosomes through enzyme-rich compartments.

Slide 27 · Respiratory burst links oxygen use to microbicidal ROS

NADPH oxidase

Assembly

Oxygen is reduced

To superoxide

Oxidative products

Attack ingested microbes

Why compartmentalization matters

Phagocytes generate potent toxic mediators; Concentrating them in microbicidal compartments helps preserve host-cell integrity.

Slide 28 · Neutrophils and macrophages are not interchangeable

Characteristic

Neutrophils

Macrophages

Response profile

Rapid; short-lived

Sustained; gene-expression dependent

Granule release

Prominent

Less prominent

Cytokine production

Limited compared with macrophages

Major functional activity

Reactive intermediates

Rapid oxidase assembly / ROS

iNOS-derived nitric oxide; ROS

Slide 29 · Acute cellular defense evolves over time

Injury or

Infection

Neutrophil-rich

Early response

Monocyte entry

And maturation

Macrophage-rich

Continued response

Clinical link: Neutrophils dominate many early acute lesions; Macrophages are important in persistent inflammation.

Slide 30 · Dendritic cells are distributed tissue sentinels

Epithelial sites

Dendritic cells position microbial sensing near the host–environment interface.

Peripheral tissues

They sample antigens and danger signals in most tissues.

Lymphoid organs

They display captured peptide antigens to T lymphocytes.

Slide 31 · Dendritic cells detect danger and signal it

Microbes or cell

Damage

Dendritic-cell

Sensing receptors

Cytokine production

Inflammatory / antiviral

Immune signaling

Key contrast: Dendritic cells are chiefly sentinels and coordinators, not the main cells that digest and destroy microbes.

Slide 32 · Dendritic cells connect innate and adaptive immunity

Capture protein

Antigen

Process / display

Peptide antigen

T lymphocyte

Recognition

Adaptive immune

Activation

Two roles in one cell

Innate detection of danger and presentation of antigen to adaptive lymphocytes are coordinated in dendritic cells.

Slide 33 · Macrophages and dendritic cells: Division of labor

Macrophage emphasis

Engulfment and destruction of offending agents; Secretion of inflammatory cytokines; Clearance of damaged tissue.

Dendritic-cell emphasis

Environmental sensing, cytokine signaling, antigen capture, and display of peptides to T lymphocytes.

Slide 34 · Innate lymphoid cells respond without antigen receptors

ILCs are tissue-resident lymphocytes lacking T-cell antigen receptors.

They respond to cytokines and local mediators associated with tissue injury.

They provide early sources of cytokines during immune reactions.

They are distinct from antigen-specific T lymphocytes.

Slide 35 · ILC groups parallel helper-T-cell functional profiles

Innate lymphoid group

Corresponding helper-T subset

Shared organizing principle

Group 1 ILCs

Th1

Related dominant cytokine patterns

Group 2 ILCs

Th2

Related dominant cytokine patterns

Group 3 ILCs

Th17

Related dominant cytokine patterns

Boundary: Functional parallels do not mean ILCs carry T-cell antigen receptors.

Slide 36 · NK cells detect abnormal host cells

Virus-infected cells

Early surveillance detects altered self surfaces during viral infection.

Other stressed cells

Activating ligands can appear following injury or DNA damage.

Neoplastic cells

Tumor transformation may reduce self MHC class I and raise activating ligands.

Slide 37 · NK activity balances two receptor inputs

Activating receptor

Stress ligand

Inhibitory receptor

Self MHC class I

Net signal determines

NK-cell killing

Slide 38 · Normal MHC class I restrains NK-cell cytotoxicity

Healthy cell displays

Self MHC class I

NK inhibitory

Receptor engaged

Activation suppressed;

Healthy cell spared

Logic: Inhibitory recognition prevents the immune system from destroying ordinary healthy cells.

Slide 39 · Stressed cells can escape NK inhibition

Viral infection or

Neoplastic change

Reduced MHC I +

Increased stress ligands

Activating signals

Prevail

NK-cell-mediated

Target-cell killing

Distinction: NK cells kill abnormal host cells rather than engulfing free extracellular microbes.

Slide 40 · NK-cell IFN-γ helps macrophage control infection

Intracellular

Microbial challenge

NK-cell activation

IFN-γ secretion

Macrophage activation

And microbe killing

Innate cytotoxic lymphocytes also influence the antimicrobial programs of phagocytes.

Slide 41 · NK cells can mediate antibody-dependent cytotoxicity

IgG antibody coats

Target cell

NK CD16 binds

IgG Fc region

NK cell lyses

Antibody-coated cell

Important connection: This is antibody-dependent cellular cytotoxicity (ADCC): An innate effector cell uses an adaptive antibody.

Slide 42 · Mast cells serve as innate inflammatory sensors

Microbial / damage-related

Local cues

Mast-cell mediator

Release

Vascular and

Inflammatory effects

Complement cooperation

C3a and C5a can trigger mast-cell mediator release, linking plasma proteins to vascular changes.

Slide 43 · Epithelial and endothelial cells also react to microbes

Epithelial cells

Serve as a physical barrier and produce antimicrobial molecules; Can also sense microbial danger at the surface.

Endothelial cells

Respond to inflammatory mediators by expressing leukocyte adhesion machinery that permits recruitment into tissue.

Slide 44 · Soluble innate defense operates in tissue fluids

Complement cascade

Plasma proteins amplify recognition and mediate opsonization, inflammatory effects, and selected microbial lysis.

Opsonizing proteins

Mannose-binding lectin and C-reactive protein coat microbes for phagocytic recognition.

Pulmonary surfactant

A local component of respiratory innate defense against inhaled microbes.

Slide 45 · Complement connects innate and adaptive immunity

Activation route

Initiating recognition

Immune context

Alternative

Microbial surfaces without antibody requirement

Innate

Lectin

Mannose-binding lectin bound to microbial carbohydrates

Innate

Classical

Antigen–antibody complexes activating C1

Adaptive-linked

Slide 46 · Alternative complement activation is antibody-independent

Activation on

Microbial surface

C3 cleavage

Amplified

C3b deposition

On microbe

Enhanced clearance

And downstream effects

Principle: Antibody is not necessary for this pathway to participate in early host defense.

Slide 47 · Lectin pathway couples microbial sugar recognition to C3

MBL binds microbial

Carbohydrates

Lectin-associated

Protease activation

C3 convertase

Formation

Complement

Effector functions

Specificity: Recognition is directed at characteristic microbial carbohydrate patterns.

Slide 48 · Classical complement activation depends on antibodies

Antibody bound

To antigen

Complement C1

Engagement

C3 convertase

Formation

Shared downstream

Complement effects

Boundary: The classical pathway illustrates cooperation with adaptive immunity rather than purely innate triggering.

Slide 49 · All complement pathways converge at C3

Alternative

Lectin

Classical

C3 convertase

C3a + C3b

Slide 50 · Complement mediates three distinct host effects

Inflammation

C3a and C5a promote vascular changes; C5a also recruits leukocytes.

Opsonization

C3b and iC3b on microbes support phagocyte receptor binding.

Cell lysis

Terminal C5b–C9 membrane attack complexes can disrupt selected microbes.

Slide 51 · Complement regulators prevent self-injury

Complement cascade

Amplifies on surfaces

Regulatory proteins

Restrain activation

Normal host cells

Are protected

When regulation fails

Excess complement activation can contribute to tissue damage even though complement normally protects against microbes.

Slide 52 · Mannose-binding lectin supports two defenses

Mannose-binding lectin

Binds microbial carbohydrates

Coats microbes

For phagocytosis

Activates lectin pathway

Of complement

Slide 53 · C-reactive protein is an innate opsonin

Circulating

C-reactive protein

Binding / coating

Of microbes

Improved recognition

By phagocytes

Functional distinction

CRP is included here because of its host-defense role as a microbial coating protein, not solely because clinicians measure it during inflammation.

Slide 54 · Pulmonary surfactant has an immune-defense role

Inhaled

Microbes

Airway / alveolar

Surface

Surfactant-associated

Local protection

Scope: Surfactant is explicitly included among innate immune components protecting against inhaled microbes.

Slide 55 · Pattern recognition links constituents to danger

PAMPs: Shared microbial

Molecular structures

DAMPs: Signals from

Damaged / necrotic cells

Germline-encoded

Pattern-recognition receptors

Slide 56 · Recognition systems survey different compartments

Receptor location

What can be sensed

Biologic rationale

Cell surface

Extracellular microbial ligands

Signals before cellular entry

Endosomal vesicles

Products of internalized microbes

Detects ingested microbial contents

Cytosol

Microbes or intracellular danger signals

Detects danger within the cell

Slide 57 · Toll-like receptor signaling has two major outputs

TLR activation

NF-κB activation

→ cytokines + adhesion molecules

IRF activation

→ type I interferons

Outcome: Coordinated leukocyte recruitment and antiviral protection.

Slide 58 · Inflammasomes convert danger sensing into IL-1

Cellular damage /

Microbial stimuli

NLRP3 inflammasome

Assembly

Caspase-1

Activation

Pro-IL-1 cleavage

→ active IL-1

Inflammatory result

Active IL-1 contributes to recruitment of leukocytes and fever.

Slide 59 · Inflammation is a principal innate reaction

Microbes / tissue

Damage detected

Cytokines and

Complement products

Vascular / leukocyte

Inflammatory reaction

Microbe removal +

Debris clearance

After control: Inflammation also supports the subsequent repair of damaged tissues.

Slide 60 · Type I interferons establish an antiviral state

Virus detected

By innate receptors

Type I interferons

Produced

Antiviral enzymes

Induced in cells

Viral nucleic acid /

Replication inhibited

Complementary response: NK cells recognize and eliminate virus-infected host cells.

Slide 61 · Innate immunity provides activation cues to adaptive cells

Danger recognition +

Innate cytokines

Dendritic-cell

Antigen presentation

T / B-cell-dependent

Adaptive response

Two systems cooperate

Innate effector functions buy time and deliver inflammatory and antigen-presentation signals that support adaptive immunity.

Slide 62 · Case application: Contaminated skin wound

Clinical situation

A break in the skin is followed by microbial entry into deeper tissues and a neutrophil-rich early inflammatory response.

Loss of epithelial

Exclusion

Innate danger

Recognition

Endothelial

Recruitment signals

Neutrophil phagocytosis

And microbe killing

Slide 63 · Case application: Virus-infected cell with low MHC I

Clinical situation

An infected cell reduces surface MHC class I while displaying stress-induced activating ligands.

NK inhibition

Is reduced

Activating

Signals dominate

NK target-cell

Killing occurs

Virus-infected

Cell is eliminated

Parallel defense: Type I interferons also inhibit viral replication in nearby cells.

Slide 64 · Case application: Susceptibility to Neisseria infection

Mechanistic vignette

A patient with deficient terminal complement components cannot assemble an effective membrane attack complex.

C5b–C9 pathway

Is impaired

Membrane attack complex

Formation declines

Lysis of susceptible

Bacteria is reduced

Neisseria susceptibility

Is increased

Slide 65 · Synthesis: Match each component to its job

Constituent

Principal task

Primary outcome

Epithelium / defensins

Block access; local antimicrobial action

Exclusion

Neutrophils / macrophages

Engulf and kill microbes

Clearance

Dendritic cells / ILCs

Sense danger; produce signals; present antigen (DCs)

Coordination

NK cells

Recognize abnormal cells; cytotoxicity / IFN-γ

Infected-cell control

Complement / MBL / CRP

Opsonization, inflammation; sometimes cell lysis

Soluble protection

Slide 66 · Integrating the host-defense network

Epithelial barrier breached

Microbes enter tissue

Recognition by sentinels

Phagocytes

Engulf and kill

Complement / opsonins

Support clearance

DC / cytokine signals

Shape adaptive response

Slide 67 · References and source scope

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. (2026).

Normal Immune Response; Components of Innate Immunity.

Cellular Receptors; Natural Killer Cells; Reactions of Innate Immunity.

Leukocyte activation and phagocytosis.

Complement System.

Conceptual diagrams in this lecture are original editable teaching schematics.