Mycobacterial Infections

Slide 1 · Mycobacterial infections

Bacterial persistence, host immunity, granulomatous inflammation and tissue injury

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning outcomes

Explain why mycobacteria are acid-fast and persist intracellularly.

Trace the Th1–macrophage response from inhalation to granuloma.

Recognize primary, postprimary and disseminated tuberculosis.

Select investigations for active versus latent tuberculosis.

Differentiate tuberculosis, NTM disease and the leprosy spectrum.

Slide 3 · Three major mycobacterial disease groups

An acid-fast genus; Markedly different reservoirs, host responses and organ distributions.

Tuberculosis

M. Tuberculosis complex; Human pulmonary/systemic infection

Nontuberculous mycobacteria

Environmental species; Opportunistic pulmonary and disseminated disease

Leprosy

M. Leprae / M. Lepromatosis; Skin and peripheral nerves

Slide 4 · Mycobacteria: Structural identity

Slender aerobic rods that may form straight or branching chains.

Waxy cell envelope is enriched in unusual glycolipids and lipids.

Mycolic acids underlie retention of acid-fast stains despite acid–alcohol decolorization.

They are weakly gram-positive; Routine Gram stain is not their defining laboratory feature.

Slide 5 · Why acid-fast staining works

This is a physicochemical staining property, not a species-level identification test.

Waxy envelope

Mycolic acid–rich wall

Apply stain

Cell retains primary dye

Acid–alcohol

Resists decolorization

Microscopic result

Acid-fast rods remain visible

Slide 6 · Acid-fastness is not species identification

A positive acid-fast smear demonstrates acid-fast organisms in the sampled material.

Different mycobacterial species require further microbiologic or molecular identification.

Culture and molecular testing establish organism identity and inform susceptibility.

A negative smear cannot reliably exclude disease in low-burden or immunocompromised cases.

Slide 7 · Tuberculosis: Core definition

Chronic pulmonary and systemic infection, usually caused by M. Tuberculosis.

In humans, infectious pulmonary cases release bacilli in sputum.

Spread occurs mainly through airborne organisms from people with active disease.

The clinical outcome is shaped by host cell-mediated immunity.

Slide 8 · Airborne transmission to alveolar macrophages

Source case

Active pulmonary TB with expelled bacilli

Airborne exposure

Inhalation by susceptible person

Distal airspaces

Initial pulmonary implantation

Macrophages

Early intracellular infection

Slide 9 · M. Bovis: A distinct ingestion route

Unpasteurized milk from infected cattle can transmit M. Bovis.

Oropharyngeal and intestinal tuberculosis may follow contaminated milk exposure.

This route is uncommon where milk pasteurization is routine.

It remains relevant where bovine tuberculosis and unpasteurized dairy coexist.

Slide 10 · Contexts favoring tuberculosis transmission

Poverty and crowded living conditions facilitate exposure.

Prisons, homeless shelters and long-term care settings are relevant examples.

Transmission risk depends on exposure to infectious individuals.

Host susceptibility additionally determines progression after acquisition.

Slide 11 · Conditions associated with progression

These factors raise susceptibility; They do not prove active tuberculosis.

Immune-related

HIV infection / advanced immunodeficiency

Glucocorticoids or transplant immunosuppression

Tumor necrosis factor inhibitors

Other clinical contexts

Diabetes mellitus and chronic renal failure

Silicosis or other chronic lung disease

Malnutrition, alcohol use and debilitating illness

Slide 12 · Infection is not the same as active disease

Latent infection

Immune response to mycobacterial antigens

No clinical evidence of active tuberculosis

Viable bacilli may persist for decades

Active tuberculosis

Organism-associated tissue disease

Pulmonary or extrapulmonary manifestations

May be transmissible when bacilli enter airways

Slide 13 · Outcomes after first exposure

Primary infection

Bacilli proliferate before adaptive response

Immune containment

Th1-activated macrophages restrict replication

Persistent focus

Fibrocalcific lesion may harbor viable bacilli

Later reactivation

Loss of host resistance permits disease

Slide 14 · Containment and damage are linked

Th1 cells activate macrophages to control M. Tuberculosis.

The same cellular response produces granulomas and caseous necrosis.

Effective containment often leaves limited residual tissue damage.

Dysregulated or sustained inflammation may produce cavities and impaired lung function.

Slide 15 · Phase 1: Bacillary entry into macrophages

Inhaled bacilli

Reach distal airspaces

Receptor-mediated uptake

Mannose-binding lectin; Complement receptor CR3

Infected phagocytes

Alveolar macrophages migrate into interstitium

Local propagation

Additional macrophages and dendritic cells infected

Slide 16 · Macrophage uptake does not ensure microbial killing

M. Tuberculosis enters phagocytic vesicles within macrophages.

It interferes with phagosomal maturation and lysosomal fusion.

Bacilli thereby avoid the destructive environment of an effective phagolysosome.

This intracellular refuge permits replication before acquired immunity develops.

Slide 17 · Phagosome–lysosome blockade

Bacillus in phagosome

Phagocytic uptake

Coronin recruitment

Host protein recruited to phagosome membrane

Calcineurin activation

Interferes with normal vesicle fusion

Failed phagolysosome

Intracellular bacillary persistence

Slide 18 · The initial weeks may be clinically silent

Before effective T-cell immunity, bacilli multiply within alveolar macrophages.

Early transient bacteremia can seed multiple distant sites.

Most immunocompetent hosts are asymptomatic or experience mild flu-like symptoms.

Subsequent immune containment usually prevents clinically overt dissemination.

Slide 19 · Innate recognition of mycobacteria

Mycobacterial ligands

Lipoarabinomannan and unmethylated CpG DNA

Innate sensors

TLR2 and TLR9

Dendritic cell response

Proinflammatory and antigen-presenting activity

Adaptive immunity

Promotion of antimycobacterial T-cell response

Slide 20 · Neutrophils are not uniformly protective

M. Tuberculosis can infect neutrophils and resist their killing.

After intracellular replication, infection can lead to neutrophil death.

The resulting inflammation is distinct from the later organized Th1 granuloma.

In NTM infection, neutrophil products may worsen preexisting lung injury.

Slide 21 · Dendritic cells initiate the Th1 response

Antigen uptake

Infected pulmonary dendritic cells

Node migration

Transport antigen to draining lymph nodes

IL-12 and IL-18

Promote Th1 differentiation

Specific Th1 cells

Return immune activation to infected tissue

Slide 22 · Th1 immunity becomes effective after a delay

In a previously unsensitized host, the Th1 response emerges at about 3 weeks.

Antigen-presenting cells produce IL-12 and IL-18.

Th1 cells secrete interferon-γ (IFN-γ).

IFN-γ is the critical activator of antimycobacterial macrophage effector functions.

Slide 23 · IFN-γ: Macrophage killing mechanisms

IFN-γ receptor signaling

Activation of infected macrophage

Reactive mediators

Nitric oxide and reactive oxygen species

Antimicrobial peptides

Defensins, including cathelicidin

Autophagy

Sequestration and disposal of intracellular bacteria

Slide 24 · Activated macrophages build granulomas

IFN-γ-stimulated macrophages become epithelioid histiocytes.

Epithelioid histiocytes aggregate into organized cellular foci.

Some macrophages fuse to form multinucleated giant cells.

Lymphocytes and fibrosis develop around the lesion over time.

Slide 25 · Granuloma: An organized cellular barrier

Central caseous necrosis

Epithelioid cell zone

Lymphocytic / fibrotic rim

Schematic, not histology

Slide 26 · Caseation reflects immune-mediated injury

Granuloma formation contains organisms but does not completely eliminate them.

Ongoing cellular inflammation may generate central caseous necrosis.

Necrotic tissue can subsequently liquefy and communicate with a bronchus.

Cavity formation promotes further airway spread of infectious bacilli.

Slide 27 · Tumor necrosis factor sustains containment

Activated macrophage

Secretes TNF and chemokines

Monocyte recruitment

Reinforces granulomatous response

Organism containment

Helps maintain control of residual bacilli

TNF blockade

Raises risk of reactivation

Slide 28 · Why immunosuppression changes morphology

Impaired Th1 signaling weakens activation of bactericidal macrophages.

Bacillary proliferation can become extensive while granulomas are poorly formed.

Tissue sections may contain numerous bacilli even without classic tubercles.

Extrapulmonary and disseminated infection become more frequent.

Slide 29 · Mendelian susceptibility to mycobacteria

Rare inherited defects impair IL-12 / IFN-γ host-defense pathways.

Examples include loss of IL-12 receptor β1 function.

Affected patients may develop severe tuberculosis.

Even normally low-virulence mycobacteria or BCG vaccine strains can cause disease.

Slide 30 · A spectrum of pulmonary tuberculosis

Primary disease

First infection in previously unsensitized host

Controlled infection

Fibrotic/calcified residual focus

Postprimary disease

Reactivation or reinfection in sensitized host

Progression

Cavitation, pulmonary or systemic dissemination

Slide 31 · Primary tuberculosis begins subpleurally

Inhaled organisms usually implant in distal airspaces.

Typical site: Lower upper lobe or upper lower lobe, close to pleura.

A discrete gray-white inflammatory focus forms as immunity develops.

The focus often develops central caseous necrosis.

Slide 32 · Ghon focus and Ghon complex

Parenchymal focus

Hilar node involvement

Together: Ghon complex

Schematic lung-location diagram

Slide 33 · The Ghon complex evolves with immunity

Parenchymal focus

Gray-white lung consolidation

Regional node

Drainage of infected phagocytes; Caseation

Immune control

Macrophage response restricts infection

Healing

Fibrosis with possible calcification

Slide 34 · Fibrocalcific healing does not guarantee sterilization

Most primary infections are controlled by cell-mediated immunity.

Granulomas gradually fibrose; Calcification may make lesions visible radiologically.

Dormant bacilli can persist within some healed lesions.

Loss of resistance may reactivate these foci many years later.

Slide 35 · Progressive primary tuberculosis

A minority of newly infected people develop clinically important primary disease.

Lobar consolidation may resemble acute bacterial pneumonia.

Hilar lymphadenopathy and pleural effusion are relatively prominent.

Hematogenous spread can cause meningitis or miliary tuberculosis.

Slide 36 · Postprimary tuberculosis arises in a sensitized host

May follow reactivation of persistent organisms after months or years.

Reinfection also contributes where tuberculosis exposure is common.

Preexisting hypersensitivity produces rapid local inflammatory injury.

The initial focus classically favors the apical lung.

Slide 37 · Apex-predominant postprimary disease

Apical focus

Caseation ± fibrosis / cavitation

Schematic lung-location diagram

Slide 38 · The secondary focus can heal or progress

Apical focus

Small, circumscribed consolidation

Immune containment

Caseation with peripheral fibrosis

Scar formation

Fibrocalcific, inactive lesion

Progression

Expansion, airway erosion and cavitation

Slide 39 · Cavitation: A structural consequence of necrosis

Coalescent caseation

Necrosis of infected lung parenchyma

Airway erosion

Caseous material drains into bronchus

Irregular cavity

Poorly walled off by fibrous tissue

Bacilli in sputum

Greater opportunity for transmission

Slide 40 · Why cavitary tuberculosis produces hemoptysis

Progressive necrotizing lesions erode nearby bronchi and vessels.

Vascular injury allows blood to enter the bronchial tree.

A cavitary patient may expectorate bacilli-rich sputum.

Persistent cavities and fibrotic healing can distort lung architecture.

Slide 41 · Primary and postprimary tuberculosis

Feature

Primary

Postprimary

Host

Previously unsensitized

Previously sensitized

Typical location

Subpleural middle lung zones

Upper-lobe apex

Lymph nodes

Prominent hilar involvement

Less prominent early

Progression

Consolidation / pleural effusion

Cavitation more typical

Potential sequel

Fibrocalcific Ghon complex

Apical scar or progressive cavity

Slide 42 · Clinical onset can be indolent

Localized secondary infection may initially be asymptomatic.

Constitutional symptoms include malaise, anorexia, fever and weight loss.

Low-grade remittent fever and night sweats are characteristic presentations.

Cytokines produced by activated macrophages contribute to systemic illness.

Slide 43 · Pulmonary symptoms reflect lesion progression

Cough and increasing sputum accompany pulmonary progression.

Sputum may evolve from mucoid to purulent.

Hemoptysis suggests tissue or vascular destruction.

Pleural involvement can cause pleuritic chest pain and effusion.

Slide 44 · Histology: Tuberculoid granulomatous reaction

Microscopic tubercles contain epithelioid histiocytes.

Multinucleated giant cells are commonly present.

Lymphocytes and fibroblasts form a peripheral rim.

Granulomas may be necrotizing or nonnecrotizing.

Slide 45 · Noncaseating granulomas do not exclude tuberculosis

Tuberculous lesions do not invariably contain demonstrable caseous necrosis.

Histologic pattern is influenced by lesion stage and host immune competence.

A granuloma pattern alone is not species-specific.

Acid-fast stains and microbiologic evaluation remain indicated when tuberculosis is plausible.

Slide 46 · High bacillary load may coexist with weak granulomas

Cell-mediated immunity preserved

Organized epithelioid granulomas

Caseation may be prominent

Few detectable bacilli in late fibrotic lesions

Severe immune compromise

Poorly organized or absent granulomas

Macrophages may harbor numerous bacilli

Dissemination and atypical distribution more likely

Slide 47 · Acid-fast stain interpretation in tissue

Acid-fast bacilli may be found in early exudative or caseous lesions.

Late fibrocalcific lesions often have very low demonstrable bacillary burden.

A stain-negative granuloma does not rule out tuberculosis.

Correlation with culture or molecular assays is needed for pathogen identification.

Slide 48 · Airway, lymphatic and bloodborne dissemination

Progressive pulmonary focus

Active parenchymal infection

Airway spread

Bronchial and laryngeal involvement

Lymphovascular spread

Return to lung or systemic arterial circulation

Distant lesions

Miliary or isolated extrapulmonary tuberculosis

Slide 49 · Pulmonary miliary tuberculosis

Widespread tiny parenchymal foci

Unlike one dominant cavitary focus, miliary disease distributes numerous lesions through the lungs.

Schematic, not radiology or gross pathology

Slide 50 · Systemic miliary dissemination

Hematogenous escape

Organisms enter systemic arterial circulation

Multiple organ seeding

Liver, spleen, marrow and adrenal glands

Additional targets

Meninges, kidney and reproductive tract

Clinical result

Multiorgan tuberculosis

Slide 51 · Extrapulmonary tuberculosis can dominate presentation

Hematogenous seeding can establish isolated organ disease.

Meningeal infection produces tuberculous meningitis.

Osteomyelitis, genitourinary lesions and adrenal disease may occur.

The presenting complaint may not be respiratory.

Slide 52 · Cervical tuberculous lymphadenitis

Lymphadenitis is the most frequent extrapulmonary presentation.

Cervical nodes are a common site: Traditionally called scrofula.

In HIV-negative hosts, disease is often localized and unifocal.

In HIV-associated immunodeficiency, multifocal nodal and systemic disease are common.

Slide 53 · Vertebral tuberculosis and cold abscesses

Tuberculosis may seed vertebrae and produce destructive osteomyelitis.

Vertebral infection is referred to as Pott disease.

Paraspinal collections may track along fascial planes.

A cold abscess can present at a site distant from the original spinal lesion.

Slide 54 · Intestinal tuberculosis: A route-to-morphology link

Enteric exposure

M. Bovis in unpasteurized milk or swallowed sputum

Lymphoid aggregates

Organisms seed ileal or colonic mucosa

Granulomatous injury

Superficial transverse ulcers

Healing

Fibrosis and stricture formation

Slide 55 · Pleural and airway complications

Parenchymal spread can involve the pleura and produce effusion.

Progressive cases may lead to empyema or fibrous pleuritis.

Endobronchial, tracheal or laryngeal lesions may follow drainage or direct seeding.

Mucosal granulomas may be microscopic rather than grossly obvious.

Slide 56 · HIV profoundly alters the phenotype

All stages of HIV infection confer increased tuberculosis risk.

Low CD4 T-cell count is a risk for subsequent active disease.

Pulmonary findings range from focal lesions to multifocal infiltrates or cavitation.

Severe immune compromise substantially increases extrapulmonary involvement.

Slide 57 · Why HIV-associated TB can be smear-negative

Advanced T-cell deficiency impairs granuloma and cavity formation.

Less bronchial destruction may reduce expulsion of organisms into sputum.

Sputum acid-fast smear may therefore be negative despite high tissue bacterial burden.

Histology may show organisms without organized granulomatous inflammation.

Slide 58 · Diagnostic questions must be kept separate

Is there active disease?

Examine sputum or involved tissue

Acid-fast microscopy and culture

Rapid nucleic-acid amplification

Is there immune sensitization?

Tuberculin skin test (PPD / Mantoux)

Interferon-γ release assay (IGRA)

Neither establishes active disease alone

Slide 59 · Acid-fast sputum smear: What it can show

Demonstrates acid-fast bacilli when present above the assay’s detection threshold.

A positive result is not equivalent to M. Tuberculosis species confirmation.

Sensitivity falls with low sputum bacillary burden.

Smear must be interpreted alongside molecular tests, culture and the clinical context.

Slide 60 · Culture: Identification and susceptibility

Mycobacterial cultures can detect viable organisms.

The source reports solid-medium growth over approximately 3–6 weeks.

Liquid culture media can provide results sooner, sometimes within 2 weeks.

Culture permits comprehensive phenotypic drug susceptibility testing.

Slide 61 · Molecular testing accelerates active-TB evaluation

PCR detects M. Tuberculosis DNA much faster than culture.

Some assays also identify mutations associated with drug resistance.

Sensitivity is lower in smear-negative disease and especially in children.

Molecular results complement rather than wholly replace culture.

Slide 62 · Drug-resistance determination

Clinical suspicion

Active tuberculosis suspected

Rapid molecular assay

Identify organism and selected resistance markers

Mycobacterial culture

Obtain isolate

Phenotypic testing

Comprehensive drug susceptibility evaluation

Slide 63 · TST and IGRA detect an immune response

Characteristic

Tuberculin skin test

IGRA

Biologic basis

Delayed-type skin induration

Ex vivo T-cell IFN-γ release

Readout

Induration at 48–72 h

Antigen-triggered IFN-γ assay

BCG effect

May produce false positive

False positives uncommon

Active vs latent

Cannot distinguish

Cannot distinguish

Slide 64 · Negative immunologic tests can be misleading

A negative TST or IGRA is not definitive evidence against tuberculosis.

Immunosuppression or severe disease can weaken detectable T-cell responses.

Other associated false-negative contexts include malnutrition and Hodgkin lymphoma.

Active disease demands direct organism testing and clinicopathologic correlation.

Slide 65 · Integrated diagnostic interpretation

Symptoms / lesions

Evaluate possible active infection

Direct organism tests

Sputum or biopsy; PCR, smear and culture

T-cell tests

Support sensitization, not activity

Final synthesis

Pathology + microbiology + clinical distribution

Slide 66 · Nontuberculous mycobacteria: Different ecology

NTM excludes the M. Tuberculosis complex and very fastidious M. Leprae.

Many species are environmental inhabitants of soil and water.

Routine person-to-person transmission is uncommon.

Species identification matters because pathogenicity and treatment differ.

Slide 67 · Important NTM pathogens

M. Avium complex

Includes M. Avium, M. Intracellulare and M. Chimaera

M. Abscessus complex

Often clinically relevant in structural lung disease

M. Kansasii

Another important human NTM pathogen

Slide 68 · NTM requires a susceptible host environment

Structural lung damage predisposes to chronic pulmonary NTM disease.

Examples include bronchiectasis, cystic fibrosis and pneumoconiosis.

Immune defects and immunosuppressive drugs increase disseminated disease risk.

IL-12 / IFN-γ pathway defects and anti–IFN-γ autoantibodies are relevant susceptibility mechanisms.

Slide 69 · NTM has several clinical presentations

Presentation

Characteristic context

Pulmonary disease

Bronchiectasis or preexisting structural lung disease

Lymphadenitis

Localized mycobacterial involvement

Skin / soft tissue

Trauma, surgery or medical-device infection

Disseminated infection

Marked T-cell deficiency, particularly advanced HIV

Slide 70 · NTM lung injury involves innate cells

MAC can stimulate neutrophil extracellular trap formation.

Infected airways show IL-8 signaling and neutrophil recruitment.

Neutrophil proteases and matrix metalloproteinases can increase inflammation.

The result may exacerbate existing structural lung damage.

Slide 71 · Disseminated MAC: Organisms without granulomas

In severe T-cell deficiency, MAC can multiply widely in macrophages.

Infected macrophages may fill lymph nodes, liver, spleen and other organs.

Abundant acid-fast bacilli are a characteristic tissue finding.

Well-formed granulomas and major tissue destruction may be uncommon.

Slide 72 · Tuberculosis versus pulmonary NTM disease

Dimension

Tuberculosis

NTM disease

Typical reservoir

Human pulmonary cases

Soil / water environments

Transmission

Airborne person-to-person

Usually environmental acquisition

Host pattern

May affect immunocompetent hosts

Structural damage / immunodeficiency often important

Clinical issue

Containment, reactivation, transmission

Species-specific pathogenicity and management

Slide 73 · Leprosy: Skin and peripheral nerve infection

Slowly progressive infection caused primarily by M. Leprae.

M. Lepromatosis is a less frequent cause.

Organisms favor cooler tissues, especially skin and distal extremities.

The host T-cell response determines the clinical spectrum.

Slide 74 · Leprosy: Distinctive biologic constraints

M. Leprae is obligately intracellular and cannot be cultured in vitro.

Growth is favored by temperatures near those of human skin.

Bacillary cell-wall lipid PGL-1 facilitates host-cell invasion.

Peripheral nerves are vulnerable because bacilli invade Schwann cells and associated macrophages.

Slide 75 · Immune polarity determines leprosy phenotype

Tuberculoid pole

Strong Th1 response; IFN-γ-mediated macrophage activation

Few demonstrable bacilli (paucibacillary)

Localized skin / nerve granulomatous injury

Lepromatous pole

Weak cell-mediated immunity

Numerous acid-fast bacilli (multibacillary)

Widespread lesions and symmetric nerve invasion

Slide 76 · Tuberculoid leprosy: Destructive nerve granulomas

Localized, dry and often anesthetic skin plaques are characteristic.

Granulomatous inflammation involves and can destroy peripheral nerve twigs.

Sensory loss exposes skin to repeated unrecognized trauma.

Marked cellular immunity makes bacilli difficult to identify in tissue.

Slide 77 · Lepromatous leprosy: Heavy bacillary burden

Diffuse skin thickening, papules and nodules may develop.

Lipid-laden lepra macrophages may contain aggregates of acid-fast bacilli (globi).

Ulnar and peroneal nerves can be symmetrically infiltrated.

Extensive skin and peripheral nerve involvement may cause deformity.

Slide 78 · Leprosy: Nerve dysfunction creates downstream injury

Schwann cell / nerve injury

Bacillary invasion and inflammation

Sensory loss

Reduced detection of tissue trauma

Repeated damage

Ulcers, atrophy and contractures

Functional sequelae

Motor deficits and digital tissue loss

Slide 79 · Leprosy spectrum: Morphologic distinctions

Feature

Tuberculoid pole

Lepromatous pole

Immunity

Strong Th1

Weak Th1

Skin

Discrete anesthetic plaques

Numerous / diffuse lesions

Nerves

Focal granulomatous destruction

Often symmetric invasion

Bacilli

Scant or undetectable

Abundant within foamy macrophages

Tissue pattern

Well-formed granulomas

Bacilli-filled lepra cells

Slide 80 · Clinicopathologic exercise: Apical cavitary lesion

CLINICAL STEM

A patient with weeks of night sweats, weight loss and productive cough has an apical lung cavity.

Question

Which disease pattern is most likely, and why is the patient potentially infectious?

Interpretation

Postprimary pulmonary tuberculosis; Erosion into an airway allows bacilli to enter sputum.

Apical location, caseous tissue breakdown and airway communication support postprimary disease.

Slide 81 · Clinicopathologic exercise: Weak granulomas

CLINICAL STEM

A markedly immunosuppressed patient has numerous acid-fast bacilli in tissue macrophages but poorly formed granulomas.

Question

Why can bacterial load be high while classical granulomas are absent?

Interpretation

Severe T-cell dysfunction impairs IFN-γ-dependent macrophage activation and granuloma formation.

The host response that contains organisms also produces much of the characteristic granulomatous injury.

Slide 82 · Clinicopathologic exercise: Numb skin plaque

CLINICAL STEM

A patient has an anesthetic plaque and a thickened peripheral nerve; Biopsy shows granulomatous neuritis with scant detectable organisms.

Question

Which end of the leprosy spectrum fits best?

Interpretation

Tuberculoid (paucibacillary) leprosy.

Strong cell-mediated immunity restrains bacilli but causes localized granulomatous nerve injury.

Slide 83 · How to discriminate the major entities

Feature

Tuberculosis

NTM disease

Leprosy

Reservoir / acquisition

Airborne infectious case

Environmental exposure

Likely respiratory; uncommon zoonosis

Main target

Lung ± systemic

Lung; skin; disseminated

Skin and peripheral nerves

Signature mechanism

Th1 granuloma ± caseation

Opportunistic growth in susceptible host

Immune-spectrum nerve injury

Important pitfall

Latent ≠ active

AFB ≠ M. tuberculosis

Scant bacilli in tuberculoid disease

Slide 84 · Major mechanisms to retain

Mycolic acid envelope

Acid-fast organisms

Phagosome persistence

Intracellular survival

Th1 / IFN-γ immunity

Containment with granulomatous damage

Host immune failure

Reactivation or dissemination

Slide 85 · Morphologic rules of interpretation

Caseating granulomas support but do not independently establish tuberculosis.

A noncaseating granuloma does not exclude mycobacterial infection.

Loss of T-cell immunity may increase bacilli while diminishing granuloma formation.

Direct microbial identification remains essential when clinical management depends on species.

Slide 86 · Primary source

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

Infectious Diseases: Mycobacterial Infections, Tuberculosis, Nontuberculous Mycobacterial Infections and Leprosy.

Original conceptual diagrams and tables were authored specifically for this lecture.