UNIT TWO

ALTRATION IN BODY DEFENCE

Inflammation

Definition:
is a local response (reaction) of living vascularized tissues

to endogenous and exogenous stimuli (the same stimuli

causing cell injury).
The term is derived from the Latin "inflammare" meaning

to burn.
Inflammation is fundamentally a protective (Physiologic)

response destined to localize and eliminate the causative

agent and to limit tissue injury

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Causes:
The same as causes of cell injury or diseases.

Nomenclature:
The name of the inflamed tissue or organ is suffixed with

'itis'.

Thus inflammation of appendix is called appendicitis and of

meninges as meningitis, etc.

Exceptions = Pleura -- pleurisy, rectum – proctitis, lung –

pneumonia, etc.

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Inflammation accomplishes its missions by
trying to dilute,

destroy or

otherwise neutralize the offending agents.

The inflammatory response is followed by a

set of repair processes designed to

regenerate the damaged tissue and/or fill the
gaps with fibrous tissue (scar).
Components of the Inflammatory Response
Acute Inflammation
 Transient and early response to injury (e.g., bacterial infection)

 Involves release of chemical mediators, causing stereotypic

vessel and leukocyte responses.

Cardinal signs of inflammation

 Rubor (redness): histamine-mediated vasodilation of arterioles

 Calor (heat): histamine-mediated vasodilation of arterioles

 Tumor (swelling): histamine-mediated increase in permeability

of venules
 Dolor (pain): caused by prostaglandin E2 and bradykinin
Vascular events
1. Transient vasoconstriction of arterioles
 lasts only seconds

2. Vasodilation of arterioles
 mast cells release histamine, which acts on vascular smooth
muscle and causes increased blood flow.

3. Increased permeability of venules:

 histamine contracts endothelial cells of the vessels, causing
movement of a transudate into interstitial tissue.

4. Swelling of tissue:
 outflow of fluid surpasses lymphatic ability to remove fluid.

5. Reduced blood flow:

 caused by outflow of fluid from blood vessels
Cellular events

1. Margination:
 Red blood cells (RBCs) aggregate into rouleaux ("stacks of
coins") in venules, with the neutrophils pushed to the
periphery.

2. Rolling:
 Selectin molecules on the cell surfaces cause the neutrophils
to "roll" along the endothelium or to adhere to it temporarily.

3. Adhesion:
 neutrophils adhere to endothelial cells.
4. Transmigration:
 neutrophils move through the basement membrane
of venules and release type IV collagenase,
producing an exudate in the interstitial tissue.

5. Chemotaxis:
 neutrophils migrate toward bacteria.

6. Phagocytosis:
 neutrophils ingest opsonized bacteria.

7. Bacterial killing by neutrophils

PNEUMONIA
 Microbial invasion of the lung parenchyma evoking exudative solidification
(consolidation) of the lung tissues.
 Etiology: Pneumonia can be caused by bacteria, viruses, fungi, parasites,

chemicals etc...
 Classification

 Based on etiologic agents

 bacterial: pneumococcal, staphylococcal, mycoplasma, etc:

 viral: iffluenza, respiratory syncythial virus etc

 fungal: Histolasopasma captulatum, Aspagilla Fumigatus, etc

 paracytic:

 chemicals:

 Based on the gross anatomic distribution of the disease

 broncho pneumonia and lobar pneumonia

PATHOGENESIS
 The resparatory airways and alveoli are exposed air containing
hazardous dusts,chemicals and micro-organisms.
 Small particles about the size of most bacteria 1-5µm are
deposited in the terminal airways and alveoli.
 The normal lung is free from bacteria

 There are potent defence mechanisms that clear or destroy

any bacteria inhaled with with air.
 Nasal clearance-
 Sneezing,or blowing.
 Tracheo-brnchial clearance

 Mucocilliary action that eventually expectoriated or swallowed.

 Alveolar clearance
 Bacteria or solid particles deposited in alveoliare phagocytosed by
alveolar macrophages.
Pneunonia can result whenever
these defencesmechanisms are impaired or

the resistance of the host in general is lowered.

Factors that affect the resistance in general include

 chronic diseases,

immunologic deffieciencies,

treatment with immunosuppressive agnts and

unusal virulent infections

The Clearance mechamims can be interfered by

many factors including

 Loss or suppression of cough reflex, as a result of

 coma,
 anesthsea,
 neuromuscular disorders,
 drugs or chest pain (this may lead to aspiration of gastric
contents).

 Injury of mucocilliary apparatus

 Owing to cigarette smok

 Inhalation of hot or corrosive gases,
 Viral diseases
Intrefrance with phagocytic or bactericidal

action of alveolar macrophages

 Alcohol

Tobacco s

anoxia
 LOBAR peumonia Brochopeumonia
Route First L ung infection First bronchi and
bronchioles then lung
parenchyma
Age Young adult Extremes of age

Organisms Pnumococci, and Any organism

occasionally Klebssella

Health status Healthy Predisposed by viral

(previous)   infection, bronchitis,
cancer etc..
Site any lobe Most lower lobes or
bilaterally
Gross Consolidative Patchy (3 - 4 cm
elevatel, granular)
 
Prognosis Bad Worse
Resolution Common Uncommon, with
complications
Morphology of lobar pneumonia
 Pneumooococci and Klebsiela mainly cause lobar pneumonia

 Lolar pneumonia is characterized by four stages.

 Acute congesition
 lasts - 2 days.
 The lung heals, dark and firm.
 The alveoli are filled with eosinophilic edema, containing many gram-
positive diplococci and PMNs

 Red hepatization
 lasts 2nd to 4th day.
 Lung is dry, firm, red and granular.
 The pleural surface, grey-white and friable.
 The capillaries engorged, filled with fibrin exudates, RBC and numerous
neutrophils.
  Grey hepatization –
 lasts 4th - 8th day:
 Cut surface is dry, granular and grey.
 Alveoli contain fibrins, dead and live neutrophiles and occasionally
degenerating erythrocytes.
 Resolution –
 after 8th day:
 migration of macrophages from the alveolar space into the exudate,
which latter liquefied by fibrinolytic system
 Complete resolution and aeration takes 1-3 weeks, but pleural
adhesion between the two layers usually persists.

 These classic stages (phases) of lobar pneumonia are now

infrequent owing to effective antibiotic thrapy that prevent the
deveopment of full blown lobar consolidations.
Malaria
Mosquito- born, hemolytic, febrile illness.
It infects over 200 million persons per year and kills
more than 1 million
Four species of plasmodium cause malaria:
 P. falciparum

 P. Vivax

 P. Ovale

 P. Malariae

P. falciparum causes more severe disease than the

others.
 
Epidemiology
Common in tropical and subtropical areas

especially in African, South and central

America, and South East Asia.
If is transmitted by the bite of female

Anopheles mosquito.
P. fellciparum and P. Vivax are the most

common causes in Ethiopia

Pathogenesis
Sporozoites inside
Anopheles mosquito

Human skin

Sporozoites

Liver

Gametocytes
Schizonts
Merozoites

Rupture of
RBCs Schizonts
RBCs
Inside RBCs

 
 P. Falciparum
 the cause of severe malaria

 is distinguished from other malarial parasites in four

aspects:
 has no secondary hepatic stage.
 there is high parasitemia and anemia.
 there may be several parasites in a single RBC.
 it charges the flow characteristics and adhesive qualities
of infected RBC so that
 they adhere to the endothelial cells of small blood vessels.
 The obstruction of small blood vessels frequently produces
severe tissue ischemia,
 which is probably the most important factor , in the
virulence of P. falciparum
Pathology
 Enlargement of the liver & spleen by sequestered red
blood cells.
 These organs appear dark because of macrophages filled
with hemosiderin and malarial pigment.
 Obstruction of Capillaries of deep organs by P.

falciparum infected RBCs leading to ischemia of different

organs ( Kidneys, lungs, brain, etc)
 Intravascular hemolysis causes hemoglobinuric
nephrosis (“ black water fever”)
 In the lungs damage to alveolar Capillaries leads to
pulmonary edema and acute alveolar damage.
 Clinical Feature
 High grade intermittent fever

 Chills

 Headache

 nausea, Vomiting and abdominal Pain

 Hypotension

 hepatosplenomegally

 anemia

 P. falciparum:-
 Ischemic injury to the brain

 Somnolence

 Hallucinations

 Seizure & coma.

 the mortality is 20 % to 50 %
Chronic Inflammation
 Inflammation of prolonged duration (weeks to years)

 most often results from persistence of an injury-

causing agent.
 Injurious agents include infectious diseases (e.g.,

hepatitis C, tuberculosis) and alcohol.

Morphology

1. Cell types:
 Monocytes and/or macrophages,
 Lymphocytes and/or plasma cells, eosinophils, fibroblasts,
endothelial cells
 2. Necrosis:
 not as prominent a feature as in acute inflammation

3. Destruction of parenchyma:
 loss of functional tissue,with repair by fibrosis

Granulomatous inflammation
1. Causes
 Infectious agents
 include tuberculosis and systemic fungal infection;
 usually associated with caseous necrosis
 Noninfectious causes include
 sarcoidosis and Crohn's disease;
 associated with noncaseating necrosis
2. Morphology
Gross: pale
 white nodule with or without central caseation

Microscopic
 Usually well-circumscribed
 Cell types:
 epithelioid cells (activated macrophages),
 mononuclear (round cell) infiltrate(CD4 helper T cells,
or TH cells of the TH 1 type)
 Multinucleated giant cells:
 fusion of epithelioid cells; nuclei usually at the
periphery
TUBERCULOSIS
 Tuberculosis is a chronic communicable
disease
 Etiology
 M. tuberculosis (Principal)

 M. bovis (rare)

 M. hominis (rare)

The lungs are the prime target, but any organ may
be infected.
M. tuberculosis is a slender beaded, non- motile
acid fast bacillus.
Epidemiology
 Disrupted through out the world

 Annual incidence:
 USA: 12/100,000

 Some developing countries 450/100.000

 It is transmitted by aerosolized depletes during coughing,

sneezing and talking all create aerosolized respiratory
droplets.
 Tuberculosis can also be caused by
 M. bovis

 Humans acquire infection by these rare organisms following

ingestion of raw milk

Generally, tuberculosis infection is divided into two.

1. Primary infection

This is an infection of persons who have not had prior

contact with the tubercle bacillus.

Pathogenesis

1. Inhaled droplets containing M. tuberculosis are

deposited in the alveoli.

2. The organisms are phagocytosed by alveolar

macrophages but resist Killing by these unsensitized cells.
3.Proliferation of the organisms with in the macrophage
4.Degeneration of macrophages and release of organisms
attracting additional macrophages and lymphocytes and
eventually producing inflammation.
5.Some macrophages carry organisms from the lung to
regional (hilar or mediastinal) lymphondes, and from their
they may be disseminated by the blood stream to other
sites in the body (kidneys, meninges, bones and other parts
of the lungs)
6.Infected macrophages present tuberculous antigens to
lymphotytes, which are then transformed and produce
cytokines.
7. Cytokines activate macrophages
increasing their concentration of lytic
enzymes and augmenting their capacity to
kill mycobacteria.
The lytic enzymes also destroy host tissues.

Epithelioid cells and Langhan’s giant cells are

activated macrophages.
The development of a population of activated

lymphocytes constitutes the hypersensitivity

response to the organism.
The related development of activated

macrophages capable of ingesting and

destroying the organism comprises the cell
medicated immune responses.
Pathology 
Macroscopic:
 Ghon focus is a small ill- defined area of inflammatory
consolidation which is found on the lower lobe.
 Ghon complex is the combination of Ghon focus and
involved hilar or mediastinal lymph node.
Microscopic
 Caseous granuloma is the classic lesion.

 It has soft Semisolid core surrounded by epithelioid

cells, Langhan’s giant cells, lymphocytes and peripheral
fibrous tissue.
Out Come:
> 90% have a self- limited course

Progressive primary tuberculosis in which the immune

system fails to control the primary infection

Miliary tuberculosis refers to infection at disseminated

sites that produces multiple, small, yellow and

nodular lesions in several organs.

Clinical Picture of Primary Tuberculosis

Primary tuberculosis is generally asymptomatic.
2. Secondary (Cavitary) Tuberculosis
This results from the proliferation of the organisms
in a person who has been previously infected and
has mounted an immunologic response.
The sources of infection are:
Dormant organisms from old granuloma.

Newly acquired bacilli.

Causes: - Cancer,Chemotherapy, AIDS,

Malnutrition, Old age & Others
Pathology
 The lungs are the commonest sites

 The apical lobe is mainly affected

 Hypersensitivity and cell-mediated immunity lead to tissue

necrosis and the production of tuberculous cavities.

 Cavities are typically 2 to 4cm in diameter.

Clinical picture
 Cough, low grade fever, malaise, fatigue, anorexia, weight

loss night sweats.

 Hemoptysis (Coughing up of blood)

 Chest x- ray shows apical cavities.

Leprosy (Hansen’s Disease)
 Is a chronic slowly progressive, distractive process involving

peripheral nerves, skin, and mucous membranes.

Etiology:
 M. leprae (slender, acid- fast rod)

Epidemiology:
 M. leprae is shed in nasal secretions or from ulcerated lesions

of an infected person.
 The mode of infection is unclear, but it probably involves

inoculation of bacilli into the respiratory tract or into open

wounds.
 Years of close contact with an infected person are required for
successful transmission of the disease.
 15 million people are infected world wide
Pathogenesis
 M. leprae multiplies best at temperatures colder than

core human body temperature and lesions tend to occur

in coaler parts of the body (e.g, the hands and the face)
 Depending on the differences in immune reactivity, the

lesions of leprosy may vary from small, insignificant and

self healing macules of tuberculosis leprosy to the
diffuse, disfiguring lepromatous.
 95% of all persons have a natural protective immunity

to M. lepae and are not infected even though there is

intimate and prolonged exposure.
Susceptible people (5%) may develop any one of the
following three clinical varieties of leprosy:

1. Anergic patients (those with little or no

resistance) have lepromatous leprosy.

2. Hyperegic patients (those with high resistance)

develop tuberculous leprosy.

3. Border line leprosy falls in between. The majority

of patients belong to this group.
1. Tuberculosis leprosy
 This occurs in infected persons who manifest an effective graunlomatous

response that limits the proliferation of the bacillus and the extent of the
disease.

Pathology
  Single lesion or very few lesions on the skin are characteristics.

 The lesions appear on the face, trunk or extremities.

  Microscopic :

 Well- formed, circumscribed. dermal granulomas.

 Composed of epitheliod cells, Langhans giant cells, and lymphocytes.

 There is no caseaus necrosis.

 Neurons are swollen and infiltrated with lymphocytes which is

responsible for sensory loss.

 Bacilli are rare and often not found with acid fast stain.
Clinical picture.
 Skin:
 Well- demarcated hypopigmented or erythematous, dry, hair-less

patches with raised outer edges.

 There is diminished sensation with in the patches.

 The lesions are not infectious.

 They cause only minimal disfigurement.

2. Lepromatous leprosy
 Occurs in persons who fail to develop adequate immune
response to the bacteria.
 There are progressive destructive lesions filled with
mycobacteria.
 
Pathology
Multiple tumor- like lesions of the skin eyes, testes,

nerves, lymph nodes, and spleen.

There is nodular or diffuse infiltrates of foamy

macrophages which contain the bacilli.

The epidermis stretched thinly over the nodules

There is a clear- zone of dermis between the tumor

and the epidermis.

Globi is the name given to aggregates of acid- fast

materials with in the foamy macrophages.

Clinical picture
 Nodular skin lesions with or without ulceration

 Claw- shaped hands

 Hammer toes

 Saddle- nose

 Pendulous ear lobes

 Lion- like appearance (leonine facies)

 Chronic nasal discharge & voice change

 Blindness.

3. Border line leprosy

 These patients have variable combination of features of
both lepromatous and tuberculoid leprosy.
Wound Healing
Demonstrates
 Epithelial regeneration (healing of the epidermis) and

 Repair by scarring (healing of the dermis).

Two patterns of wound healing

1. Healing by first intention (primary union)

 Occurs with clean wounds when there has been little

tissue damage and

 The wound edges are closely approximated

 The classicexampleis asurgicalincision 

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 Day 1:
 fibrin clot (hematoma) develops.

 Neutrophils infiltrate the wound margins.

 There is increased mitotic activity of basal cells of squamous

epithelium in the apposing wound margins.

 Day 2:
 squamous cells from apposing basal cell layers migrate under the

fibrin clot and seal off the wound after 48 hours

 Macrophages emigrate into the wound.

 Day 3:
 granulation tissue begins to form.

 Initial deposition of type III collagen begins but does not bridge the

incision site.
 Macrophages replace neutrophils.

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 Days 4-6:
 granulation tissue formation peaks, and collagen bridges

the incision site.

 Week 2:
 collagen compresses blood vessels in fibrous tissue,

resulting in reduced blood flow.

 Tensile strength is about 10%.

 Month 1:
 collagenase remodeling of the wound occurs, with

replacement of type III collagen by type I collagen

 Tensile strength increases, reaching 80% within 3 months.

 Scar tissue is devoid of adnexal structures (e.g., hair, sweat

glands) and inflammatory cells

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48
2. Secondary union (healing by secondary intention)
Occurs in wounds that have large tissue defects and when

the two skin edges are not in contact

requires larger amounts of granulation tissue to fill in the

defect
Often accompanied by significant wound contraction

Often results in larger residual scars

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Factors affecting Healing:
Systemic Local
Nutrition necrosis
Vitamin def.
Infection
Age
apposition
Immune status
Other diseases
Blood supply
Mobility
Foreign body