Injurious Effects of Host Immunity

Slide 1 · Injurious Effects

of Host Immunity

Mechanisms and clinicopathologic examples

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning outcomes

Explain why a protective antimicrobial response may also destroy host tissue.

Connect T-cell, antibody, immune-complex, and cytokine effectors to lesions.

Interpret the characteristic infectious and postinfectious examples.

Distinguish direct microbial injury from host-response injury.

Slide 3 · The central paradox: Defense can cause disease

Microbial antigen

Triggers recognition and antimicrobial effectors

Host immunity

Contains organisms or eliminates infected cells

Collateral injury

Inflammation damages functional tissue

Clinical sequelae

Necrosis, dysfunction, fibrosis, or systemic illness

Slide 4 · Three mechanisms of microbial tissue damage

Direct cellular damage

Entry, replication, or direct cytopathic effects

Microbial toxins / enzymes

Toxin-related cell injury and tissue destruction

Host immune response

Immune effectors harm infected or bystander tissue

Slide 5 · Immune injury is mechanistically diverse

Cellular immunity

CD8+ T cells kill infected cells

Th1 cells activate macrophages

Th17 cytokines recruit inflammatory leukocytes

Humoral and soluble effectors

Cross-reactive antibody can bind host tissues

Antigen–antibody complexes activate inflammation

Cytokines can produce systemic damage

Slide 6 · Protective and destructive outputs share effectors

Antigen recognition

Specificity directs immune response

Effector activation

T cells, phagocytes, antibodies, complement

Useful effect

Microbial clearance or containment

Injurious effect

Host-cell loss and inflammatory tissue destruction

Slide 7 · Why persistent antigen changes the outcome

Poorly eradicated microbe

Antigen remains in tissue

Continued activation

Macrophages and lymphocytes persist

Chronic inflammation

Concurrent injury and attempted repair

Fibrosis / dysfunction

Parenchyma replaced or structurally altered

Slide 8 · T cells create two distinct injury patterns

CD8+ cytotoxicity

MHC I presents intracellular microbial peptide

Cytotoxic lymphocytes eliminate infected target cells

Hepatocytes are targets in viral hepatitis

CD4+ inflammatory pathways

Th1-derived IFN-γ activates macrophages

Th17-derived mediators recruit myeloid cells

Granulomas and chronic inflammation may result

Slide 9 · Antibody-related injury: Two mechanisms

Cross-reactive antibody

Microbial epitope resembles a host determinant

Antibody recognizes host tissue

Rheumatic carditis provides the exemplar

Immune-complex deposition

Microbial antigens associate with antibody

Complexes deposit or form in tissue

Poststreptococcal nephritis provides the exemplar

Slide 10 · Local injury and systemic inflammation differ

Local tissue reaction

Destruction confined to infected or targeted tissue

Granuloma, hepatitis, carditis, nephritis

Repair can replace tissue with scar

Systemic response

Inflammatory mediators reach distant organs

Cytokine excess can accompany severe viral illness

Severe COVID-19 illustrates systemic injury

Slide 11 · Morphology records the dominant effector

Macrophage-rich

Granuloma with epithelioid macrophages and lymphocytes

Cytotoxic / mononuclear

Inflammatory hepatocyte injury with cell death

Neutrophilic / proliferative

Immune-complex nephritis with leukocyte influx

Slide 12 · Three questions to ask at the microscope

What effector dominates: Activated macrophages, lymphocytes, or neutrophils?

What structure is injured: Parenchymal cell, vessel, valve, or glomerulus?

Is the insult ongoing, or is the lesion postinfectious?

Which microbial tests can establish the specific cause?

Slide 13 · Tuberculosis: The classic containment–injury trade-off

Persistent M. Tuberculosis

Hard-to-eradicate microbial stimulus

Th1 / macrophage response

Forms a focused granulomatous reaction

Containment

Restricts dissemination of bacilli

Cost

Necrosis and subsequent fibrosis

Slide 14 · Th1 cells provide the signal for granulomas

Antigen-presenting cell

IL-12 favors Th1 differentiation

Th1 lymphocyte

Releases IFN-γ

Activated macrophage

Increased microbicidal and inflammatory activity

Organized aggregate

Granulomatous inflammatory focus

Slide 15 · Macrophages can injure the tissue they defend

IFN-γ promotes macrophage antimicrobial functions and inflammatory activity.

Activated macrophages also release cytokines that sustain local leukocyte recruitment.

Persistent activation couples microbial containment to continuing collateral damage.

Repair of destroyed tissue may culminate in fibrosis.

Slide 16 · Granuloma architecture is a tissue-level strategy

Schematic — cellular organization, not histology

Central focus

May contain caseous necrosis

Inner cellular zone

Epithelioid macrophages and giant cells

Peripheral reaction

Lymphocytes and later fibroblasts

Slide 17 · Epithelioid transformation signifies sustained activation

Activated macrophages acquire abundant cytoplasm and an epithelial-like appearance.

Cells aggregate into a compact granulomatous focus.

Fusion of macrophages can produce multinucleated giant cells.

Lymphocytes commonly surround or intermix with the macrophage population.

Slide 18 · Caseation links immune reaction to irreversible loss

Persistent tubercle bacilli

Sustained cellular response

Granulomatous focus

Macrophage-rich inflammation

Central necrosis

Destruction of local tissue

Healing response

Collagen deposition and scar

Slide 19 · A granuloma is not synonymous with tuberculosis

Infectious granuloma

Tuberculosis: Classic caseating reaction

Other microbes can form granulomas

Specific organism must be demonstrated

Noninfectious granuloma

Foreign material may stimulate giant cells

Sarcoidosis and Crohn disease are examples

Similar morphology has different etiologies

Slide 20 · Proving the cause of a granulomatous lesion

Recognize granuloma

H&E suggests an inflammatory pattern

Search for agent

Acid-fast / fungal stains as indicated

Microbiologic confirmation

Culture or molecular detection

Clinicopathologic synthesis

Use the full context; Avoid morphology alone

Slide 21 · Containment and scarring are simultaneous outcomes

Protection

Focal cellular response encases persistent bacilli

Activated macrophages constrain infection

Damage

Necrosis interrupts tissue architecture

Fibrosis may persist after inflammation resolves

Organ function reflects both infection and repair

Slide 22 · Granulomatous injury: Mechanistic synthesis

Persistent microbial antigen

Continued Th1 recognition

IFN-γ / macrophages

Containment and inflammatory mediator release

Tissue necrosis

Loss of normal structures

Fibrotic repair

Long-term architectural distortion

Slide 23 · Viral hepatitis: Cytotoxic defense damages parenchyma

HBV or HCV infection

Viral antigen in hepatocytes

Cell-mediated recognition

Antiviral lymphocyte response

Infected-cell killing

Hepatocyte injury / death

Functional impact

Hepatitis, with possible persistent injury

Slide 24 · CD8+ T-cell specificity follows MHC class I

Infected hepatocyte

Viral peptide generated intracellularly

MHC class I presentation

Displays viral peptide at cell surface

CD8+ effector T cell

Recognizes antigen-bearing target

Cytolysis

Removes infected hepatocyte

Slide 25 · HBV pathology depends strongly on host immunity

The immune response is a major determinant of HBV outcome.

Most hepatocyte injury results from attack by virus-specific CD8+ cells.

Viral replication and proteins can also produce cytopathic changes.

An effective antiviral response may clear infection but still generate acute hepatitis.

Slide 26 · HCV persistence prolongs the inflammatory exposure

High viral variability

Emergent variants escape immune pressure

Failure of elimination

Persistent HCV infection

Repeated immune attack

Ongoing necroinflammatory activity

Repair and scarring

Progression to fibrosis or cirrhosis

Slide 27 · T-cell injury is not equivalent to viral cytotoxicity

Direct virus-associated change

A virus may alter synthesis, metabolism, or viability

Cytopathic mechanisms depend on virus and cell

Immune-mediated hepatitis

T cells recognize infected hepatocytes

Cell death arises during attempted clearance

Both processes can coexist in viral diseases

Slide 28 · Morphology of ongoing hepatitis follows cell loss

Hepatocellular injury occurs amid an inflammatory lymphocytic response.

Repeated death and regeneration can distort the architecture of liver parenchyma.

Sustained injury promotes progressive deposition of fibrous tissue.

Advanced scarring impairs the structure and function of the liver.

Slide 29 · Hepatitis can convert defense into chronic fibrosis

Persistent viral infection

Antigen remains available

Recurrent immune injury

Hepatocytes are repeatedly lost

Stellate-cell / repair response

Extracellular matrix accumulates

Advanced architectural change

Bridging fibrosis and cirrhosis

Slide 30 · Hepatitis-related cancer reflects more than one route

Chronic inflammatory setting

Hepatocyte turnover and scarring accompany persistence

HCV-related cancer often follows chronic disease

Viral contribution beyond inflammation

HBV proteins, including HBx, are implicated in cancer

Direct and indirect mechanisms should not be conflated

Slide 31 · Rheumatic heart disease: An immune response without bacteria in lesions

Group A streptococcal infection

Immunizing M-protein antigens

Cross-reactive response

Antibodies and CD4+ cells recognize heart antigens

Cardiac inflammation

Valvulitis, myocarditis, or pericarditis

Healing / fibrosis

Potential deforming valve disease

Slide 32 · Molecular mimicry explains the target mismatch

Intended recognition

Antibody generated against streptococcal M protein

Immune response directed at microbial material

Unintended recognition

Cross-reactive determinants on host tissues

Heart is injured even when bacteria are absent in lesions

Slide 33 · The postinfectious delay is mechanistically important

Streptococcal pharyngitis

Initial antigenic exposure

Immune response develops

Cross-reactive B- and T-cell responses

After a latent interval

Acute rheumatic inflammatory syndrome

Healing phase

Valvular remodeling may follow

Slide 34 · Rheumatic carditis combines immune effectors

Antibody

Cross-reactivity with cardiac antigens

Complement / Fc cells

Inflammation after antibody binding

CD4+ T cells

Cytokines activate macrophages in lesions

Slide 35 · Acute rheumatic carditis has a distinctive lesion

Schematic — cellular organization, not histology

Aschoff body

Focal inflammatory nodule

Cellular composition

T cells, plasma cells, activated macrophages

Anitschkow cells

Macrophages with wavy nuclear chromatin

Slide 36 · Chronic rheumatic injury deforms the valve

Acute immune valvulitis

Fibrinoid damage and small verrucae

Organization

Postinflammatory repair and neovascularization

Fibrosis

Leaflet / chordal thickening, commissural fusion

Hemodynamic outcome

Mitral stenosis or mixed valve dysfunction

Slide 37 · Rheumatic valvulitis is not infective endocarditis

Rheumatic inflammatory lesion

Poststreptococcal immune pathogenesis

Bacteria absent from characteristic cardiac lesions

Small verrucae along closure lines

Infective endocarditis

Organism-driven infection of endocardial surface

Vegetations contain microbial infection

Distinct clinical and microbiologic work-up

Slide 38 · Cardiac sequelae may outlast the trigger

The streptococcal episode may have resolved before the cardiac lesion is apparent.

Repeated or healed inflammation can result in leaflet and commissural fibrosis.

The chronic valve defect expresses accumulated tissue remodeling, not ongoing streptococcal infection.

Clinical assessment must distinguish active inflammation from fixed stenotic disease.

Slide 39 · Poststreptococcal nephritis: Immune complexes localize injury

Nephritogenic streptococcal infection

Microbial antigens elicit antibody response

Immune complexes

Circulating or in-situ antigen–antibody binding

Glomerular deposition

Complement and leukocyte recruitment

Inflammatory GN

Capillary injury and filtration dysfunction

Slide 40 · An infection may be gone when nephritis appears

Poststreptococcal glomerulonephritis often follows pharyngeal or skin infection.

The latent interval is consistent with antibody development and complex formation.

Renal pathology is not the result of local invasive streptococcal growth.

Immunologic evidence of antecedent infection informs diagnosis.

Slide 41 · Circulating and in-situ complexes converge

Preformed circulating complex

Antigen and antibody associate before deposition

Circulating complexes lodge in receptive tissue

In-situ immune complex

Antigen becomes localized in glomerulus first

Antibody binds the deposited microbial antigen

Both pathways elicit inflammatory injury

Slide 42 · Glomeruli are vulnerable to immune-complex injury

Antigen + antibody

Immune complexes form

Glomerular capillary network

Complexes deposit or assemble locally

Complement activation

Inflammatory fragments and consumption

Leukocyte recruitment

Capillary injury and cell proliferation

Slide 43 · Postinfectious glomerulonephritis has a pattern triad

Light microscopy

Diffuse endocapillary hypercellularity with leukocytes

Immunofluorescence

Granular deposits of immunoglobulin and complement

Electron microscopy

Characteristic subepithelial humplike deposits

Slide 44 · Granular versus linear immunofluorescence matters

Immune-complex GN

Granular staining corresponds to immune deposits

Postinfectious GN is an example

Anti-GBM nephritis

Linear staining follows binding along GBM

Different immune mechanism and disease context

Slide 45 · Why immune nephritis produces nephritic syndrome

Inflamed glomerular tuft

Leukocyte accumulation and hypercellularity

Glomerular barrier damage

Erythrocytes and protein enter urine

Filtration impairment

Retention of salt and water

Clinical syndrome

Hematuria, edema, hypertension, azotemia

Slide 46 · Evidence should triangulate immune pathogenesis

Clinical timing and preceding streptococcal infection support the context.

Complement consumption can be reflected in reduced serum C3.

Granular glomerular deposits argue for immune-complex injury.

Morphology and microbiologic evidence must be reconciled before attributing causality.

Slide 47 · Antibody cross-reactivity is not immune-complex nephritis

Rheumatic fever

Molecular mimicry redirects response at cardiac antigens

Antibody binding and T cells cause cardiac inflammation

Poststreptococcal GN

Microbial antigen and antibody form complexes

Glomerular deposition activates complement and leukocytes

Slide 48 · Inflammatory bowel disease: Disturbed host–microbe dialogue

Intestinal luminal microbes

Antigenic exposure at mucosal surface

Susceptible host

Immune regulation and barrier function altered

Persistent mucosal inflammation

Immune-mediated epithelial injury

Feedback cycle

Barrier injury sustains inflammation

Slide 49 · IBD is not simply infection by one organism

Conventional infection

A defined invasive or toxin-producing pathogen

Direct microbial cause may be demonstrated

IBD host–microbe dysregulation

Microbiota contribute within a susceptible host

Immune regulation and epithelium are also implicated

Avoid claiming a single causative infectious agent

Slide 50 · Epithelial injury can amplify mucosal inflammation

Immune activation

Inflammatory mediators damage mucosa

Epithelial barrier injury

Luminal exposures change

Immune stimulation persists

Further chronic inflammatory recruitment

Recurrent injury

Ulceration and incomplete repair

Slide 51 · Chronic inflammation provides a carcinogenic setting

Persistent infection

Long-lived inflammatory stimulus

Repeated tissue injury

Cell loss and repair

Inflammatory microenvironment

Cellular signaling and turnover

Neoplastic evolution

Increased opportunity for cancer development

Slide 52 · H. Pylori: Inflammation modifies gastric cancer risk

Persistent H. Pylori

Chronic gastritis

Injury and tissue remodeling

Atrophy in a subset of patients

Intestinal metaplasia

Altered gastric epithelial phenotype

Cancer-associated milieu

Risk of gastric adenocarcinoma

Slide 53 · Infection-related oncogenesis needs causal precision

Cancer-promoting inflammatory environment

H. Pylori gastritis and chronic viral hepatitis

Long-term repair, cell turnover, and inflammation

Direct microbial oncogenic contribution

Some viruses encode transforming or regulatory proteins

HBV-associated cancer may involve HBx

Do not assert all infection-associated cancers share one mechanism

Slide 54 · Severe viral illness can become systemic immunopathology

Viral infection

Triggers innate and adaptive responses

Hyperinflammatory state

Excess or dysregulated inflammatory mediators

Organ-wide effects

Vascular, pulmonary, and other tissue dysfunction

Severe illness

Damage reflects infection plus host response

Slide 55 · COVID-19 illustrates cytokine-associated injury

Severe COVID-19 may involve a hyperinflammatory response.

Increased cytokines, including TNF and IL-6.

Abnormal myeloid-cell responses and lymphopenia accompany immune dysregulation.

These observations support host-response injury but do not exclude direct viral effects.

Slide 56 · Inflammation and coagulopathy can reinforce harm

Inflammatory endothelial injury

Tissue-factor exposure may increase

Coagulation activation

Thrombotic tendency rises

Reduced fibrinolysis

Clot removal is impaired

Organ dysfunction

Microvascular and systemic consequences

Slide 57 · Local inflammatory control versus systemic spillover

Locally focused response

Antigen and effector cells concentrated in tissue

Potential containment of microbes

Risk of focal necrosis and fibrosis

Systemic dysregulation

Cytokines and vascular effects extend beyond the focus

Multiorgan dysfunction and coagulopathy possible

Requires clinicopathologic attribution

Slide 58 · Match tissue target to immune mechanism

Liver

Infected hepatocyte killed by antiviral T cells

Heart

Cross-reactive immune response after streptococci

Kidney

Glomerular immune complexes activate inflammation

Slide 59 · Tissue timing is diagnostic information

During persistent infection

Tuberculous granulomas

Chronic viral hepatitis

H. Pylori–related inflammation

Following microbial exposure

Acute rheumatic fever after streptococci

Poststreptococcal immune-complex nephritis

Immune damage may persist after organism clearance

Slide 60 · Do not infer the infectious agent from pattern alone

A granuloma identifies an inflammatory pattern—not uniquely tuberculosis.

Granular immunofluorescence indicates immune deposits—not uniquely streptococci.

Lymphocyte-rich hepatitis establishes a reaction pattern—not viral type.

Etiologic attribution requires appropriate organism-specific testing and context.

Slide 61 · Case: Necrotizing granulomatous lung lesion

Clinical reasoning exercise

A lung biopsy shows a macrophage-rich granuloma with central necrosis.

Which host effector is most closely related to its architecture?

Why is the lesion both protective and destructive?

What test category is needed before assigning tuberculosis?

Slide 62 · Case analysis: Cell-mediated containment

Mechanistic answer

Th1-derived IFN-γ activates macrophages

Organized reaction can contain resistant bacilli

Interpretive caution

Granulomatous inflammation itself damages parenchyma

Seek acid-fast stain, microbiologic culture, or molecular identification

Slide 63 · Case: Nephritis after sore throat

Clinical reasoning exercise

A child develops hematuria and edema after a recent sore throat.

Glomerular findings include hypercellularity and granular immune staining.

Identify the principal immune mechanism.

Predict the role of complement in producing the lesion.

Slide 64 · Case analysis: Immune complexes in glomeruli

Mechanistic answer

Streptococcal antigen and antibody associate

Immune deposits recruit complement and leukocytes

Expected corroboration

A preceding infection with an appropriate interval

Possible serum C3 consumption

Granular deposits and subepithelial humps

Slide 65 · Case: Mitral disease after streptococci

Clinical reasoning exercise

A patient develops inflammatory carditis weeks after group A streptococcal illness.

No organisms are found in the characteristic cardiac lesion.

What explains the tissue specificity?

How can the disease later produce fixed mitral stenosis?

Slide 66 · Case analysis: Mimicry followed by scar

Acute mechanism

Cross-reactive antibodies and CD4+ T cells

Inflammation and macrophage activation in heart

Chronic consequence

Repair replaces inflamed valvular tissue with fibrosis

Leaflet thickening and commissural fusion

Persistent dysfunction without active organisms

Slide 67 · Mechanism-based diagnosis: A compact decision path

Identify injured tissue

Organ and histologic reaction pattern

Determine effector type

T cells, macrophages, antibody or complexes

Connect infection history

Ongoing vs postinfectious timing

Confirm etiology

Specific microbiology and tissue evidence

Slide 68 · Comparative synthesis: Five injury pathways

Containment injury

TB: Granuloma → necrosis / fibrosis

Specific cell killing

HBV/HCV: Antiviral T cells → hepatitis

Misidentification

Rheumatic fever: Molecular mimicry → carditis

Slide 69 · Five statements to retain

Defense may contain microbes yet injure the tissue containing them.

CD8+ cytotoxicity is central to much viral hepatitis-related hepatocyte loss.

Rheumatic carditis and poststreptococcal GN are immunologically different.

Persistent inflammation can cause scarring and favor cancer development.

Clinical interpretation must integrate morphologic pattern and pathogen evidence.

Slide 70 · References and source boundaries

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. 2026. Ch. 8, p. 308 (primary assigned passage).

Mechanistic context: Ch. 3 (inflammation); Ch. 6 (hypersensitivity).

Organ-specific context: Ch. 12 (rheumatic heart disease); Ch. 18 (hepatitis); Ch. 20 (glomerulonephritis).

Additional context: Ch. 17 (IBD and H. pylori); Ch. 7 (cancer); Ch. 8 (COVID-19).

All mechanism and morphology graphics are editable, original PowerPoint schematics; no textbook figure is reproduced.