MECHANISM OF

INFECTION AND
INFLAMMATION
BY DR.MADIHA EHSANSULHAQ
CONTENT
• Infectious disease – stages
• Systemic manifestation of infectious disease
• Inflammation
• Cardinal signs of inflammation
• Hemodynamic and cellular phases of inflammatory process
• Chronic and acute inflammation
INFECTION
• Invasion of human body by microorganisms producing harmful and
potential lethal consequences
• Consequences of invasion is called infectious diseases
TERMINOLOGY
HOST- any organism capable of supporting the nutritional and physical
growth requirements of another
Humans supporting the growth of microorganisms
INFECTION-presence and multiplication within another living organism
COLONIZATION- act of establishing a preence
• MICROFLORA- normally harmless bacteria that inhabit human body
• COMMENSALISM-relationship with commensal flora
MUTALISM
• PARASITIC RELATIONSHIP- infecting organism benefits from the
relationship and the host either gains nothing from the relationship or
sustains injury from the interaction.
MECHANIM OF TRANSMISSION
• Portal of entry- penetration, direct contact,ingestion,inhalation
• Source
MECHANISM OF DISEASE
PRODUCTION
• Virulence factors-toxins,adhesions,invasive factors, evading factors
STAGES OF INFECTION
SYSTEMIC MANIFESTATION OF
INFECTION
• FEVER – IL1, TNF, PGE2
• LEUKOCYTOSIS
• ELEVATED ACUTE PHASE PROTEINS – CRP , SAA
• INCREASE PULSE
• INCREASE BLOOD PRESSURE
• RIGORS
• CHILLS
• ANOREXIA, MALASIEE
• SEPSIS/ SEPTIC SHOCK
• ANEMIA
INFLAMMATION
• Defensive/reactive process that a living body initiates against
tissue damage.
• Suffix- it is denotes inflammation
• Derived from a latin word meaning flaming, burning

• It is a response of vascularized tissues that delivers

leukocytes and molecules of host defence from the
circulation to the sites of infection and cell damage in order
to eliminate the offending agents
EXAMPLES OF INFLAMMATION
• Appendicitis
• Pancreatitis
• Nephritis
Clinical significance
• It is a protective and defensive response
• It removes or destroys causative agents
• Repairs tissue damage
• Inactivates toxins
• Repair tissue and organ for healing and repair

• Disadvantages- destruction of normal tissue

ETIOLOGY OF INFLAMMATION
• Physical agents
mechanical injury,radiation,extreme temperature
• Inert agents-Foreign body
• Chemical agents-
drugs,acids
TISSUE NECROSIS
• Biological agents-
INFECTIONS-microorganisms
IMMUNE REACTIONS-immune cells and complexes
CARDINAL SIGNS OF INFLAMMATION
• RUBOR- Redness
• DOLOR-Pain
• TUMOR- Swelling
• CALOR- hot ,heat
• FUNTIO LAESA- Loss of funtion
TRIPLE RESPONSE
• Lewis in 1942 noted that firm stroking of human skin results in triple
response
• Features:
• RED LINE- Sharply demarcated red ine at the site of stroking due to
capillary dilation
• THE FLARE-after 15- 30 seconds,flare appears surrounding a line due
to arteriolar dilations
• THE WEAL- on the site of red line,a wheel appeards due to exudation
of fluid through the vessel wall
Triple response
TYPES OF INFLAMAMTION
On the basis of severity, duration , onset and other factors

ACUTE
CHRONIC
SUBACUTE
ACUTE AND CHRONIC
INFLAMMATION
INFLAMMATORY
PROCESS
VASCULAR EVENTS

CELLULAR EVENTS
VASCULAR EVENTS
• Changes in caliber of blood vessels
• Changes in blood flow
• Increased vascular permeability and fluid exudation
Changes in caliber of blood vessels

• Initial vasoconstrition- earliest response , transient

constriction in small blood vessels
• Persistent vasodilation- rapidly follows, persists for the
duration of inflammatory process
• Mediates- histamine, prostacyclin and nitric oxide
Changes in blood flow-STASIS
• Initially increase in blood velocity due to dilatation of terminal
arterioles-short time
• STASIS- slowing of blood stream
• Main factor- increased vascular permeability
Increased vascular permeability and
fluid exudation
• Immediate marked increase in permeability of cappilaries and venules
• Due to contraction of endothelial cells
• Widening of intercellular junction which allows passage of large
molecular weight proteins and fluid
• This is called exudation
• This produces tissue swelling-edema

• Histamine, bradykinin, TNF, IL-1,lEUKOTRIENES

Mechanism of increased vascular
permeability
5 possible mechanism
• Endothelial contraction
• Endothelial cell retraction
• Direct endothelial injury
• Leukocyte mediated endothelial injury
• Leakage from regenerating capillaries
Patterns of increases vascular
permeability
• Immediate transient response- mild injury , onset 1-2 minutes,
persiss 15-30 minutes,mediated by histamine ,bradykinin and
leukotrienes,inury mediated by contraction of endothelial cells
• Delayed prolonged response-moderate injury , onset 30 minutes to
10 hours, peak 4-1 2 hours ,cause- sunburns ,bacterial toxins,injury
mediated by injury to endothelial cells
• Immediate prolonged response-severe Injury, due to necrosis of
endothelial cells, continues for several days
EXUDATION
• Passage of fluid from the vessel to the interstitial space
• Results due to increased capillary hydrostatic pressure and increased
vascular permeability
EXUDATE TRANSUDATE
Characteristics of acute inflammation Ultrafiltrate of plasma
Formed as a result of endothelial damage and Formed as aresult of increased vascular hydrostatic
increased permeability pressure
High protein content Low protein content
Specific gravity> 1.016 Specific gravity < 1.016

LDH> 200 LDH <200

RBCs present, fibrin seen RBCS never present
EXAMPLES EXAMPLES

TUBERCULOSIS PERITONITIS LIVER CIRRHOSIS

BACTERIAL INFECTION RENAL FAILURE
CANCER HEART FAILURE
TYPES OF INFLAMMATORY CELLS
• NEUTROPHILS
• MACROPHAGES/MONOCYTES
• LYMPHOCYTES
• EOSINOPHILS
CELLULAR EVENTS OF ACUTE
INFLAMAMTION
• MARGINATION/rolling
• ADHESION
• EMIGRATION/transmigration
• CHEMOTAXIS
• PHAGOCYTOSIS
MARGINATION

• Process in which leukocytes localize toouter margin of blood flow

adjacent to endothelium
• Normally ,they flow along central axis
• But in inflmamtion, vascular permeability Increasess which causes
stasis of blood flow leading to RBCs being stick together and displaces
WBCs to periphery
ADHESION
• Process in which leukocytes adhere to endothelial cells
• This is mediated by adhesion molecules on surface of leukocytes as
well as endothelium
EMIGRATION
• The adherent leukocytes leave the blod vessel by moving along the
endothelial surface and insert there pseudopodium like cytoplasmic
projections at the intercellular junction
• They squeeeze their way through the pore by passing the basement
membrane
• Reach the intertitial space
CHEMOTAXIS
• Process by which leukocytes are attracted to and move towards an
attractant usually a chemical substance at site of injury

• Chemotactic factors- substances which act as chemotactic agents for

WBC
Examples-bacterial products, complement components- C5a,
Arcachidonic acid metabolites –Prostaglandins and leukotrienes
Tumor necrotic factor and platelet activating factor
PHAGOCYTOSIS

• Process by which microorganisms and other foreign particles are

engulfed an destroyed by neutrophils and macrophaes
• 3 steps
• Recognition and attachment of particle to ingesting leukocyte –
opsonization- process by which some serum proteins coat the
microorganism which facilities recognition by receptos of leukocytes-
C3b IgG
• Engulfment and formation of phagocytic vacoule
• Killing and degradation of ingested material-by lysosomal acid
hydrolase enzyes and reactive oxygen species
ACUTE INFLAMMATION
• Immediate and early response to injury
• First line of defence against injury

• Short duration (lasting few minutes to days)

• Predominantly leukocyte /NEUTROPHILS
Outcome of Acute inflammtion
• Complete resolution- complete return to normal tissue following
acute inflammation
• Scarring and fibrosis/healing- fibrosis takes place
• Abscess formation
• Chronic inflammation
TYPES OF ACUTE INFLAMMATION
• Serous inflammation
• Fibrinous inflammation
• Suppurative inflammation
• Hemorrhagic inflammation
• Pseudomembranous inflammation
Serous inflammation
Clear (fibrin free ) serum like exudate
Sparse leukocytic infiltrate
Causes; hypersensitivity reaction,bacterial and viral tissue ijury,physical
and chemical tissue
n injury
CATARRHAL INFLAMMATION
• Occuring exclusively on mucous membranes of respiratory and
gastrointestinal tracts producing watery exudate of serum and mucus

• Acute rhinitis , bronchitis

Fibrinous inflammation
• Exudative inflammation with exudation of fibrinogen/fibrin containing
serum that polymerizes to fibrin outside the blood vessels

• Lobar pneumonia
Suppurative (purulent) inflammation
• Inflammation with exudate consisting primarily of died neutrophils
and cellular debris

• Cause: empyema,abscess
ABSCESS
• Accumulation of pus with tissue destruction and a cavity formation

• Kidney abscess,cerebeal abscess, furuncles

HEMORRHAGIC INFLAMMATION
SUBACUTE INFLAMMATION
• Transition period separating acute and chronic inflammation.
• Evidence of hyperaemia and edema is regressing but evidence of
repair such as fibroplasia and angiogenesis is lacking.
• Time: varies from a few days to a few weeks.
• Vascular involvement: There is a decline in the magnitude of vascular
changes, compared to acute inflammation (less haemorrhage,
hyperaemia and edema).
• Inflammatory Cells: Characterised by a "mixed" or "pleocellular"
inflammatory infiltrate. This means that the inflammatory cell type
still may be primarily neutrophilic but usually it is also associated with
an infiltration by lymphocytes, macrophages and plasma cells.
• Fibrosis and neovascularization is not a feature of subacute
inflammation.
CHRONIC INFLAMMATION

• Inflammation which persists over a period of time.

• Chronic inflammation is often the result of a persistent inflammatory stimulus
in which the host has failed to completely eliminate the causative agent.
• -Inflammatory response usually is accompanied by an immune response. -
Chronic inflammation is characterized by evidence of host tissue response in
terms of repair - formation of scar and regeneration of damaged tissue
• Histology: mononuclear inflammatory cells, fibroblasts and collagen with
proliferating vasculature. C
• Cause: May follow an acute inflammatory phase. May develop as an insidious,
low-grade, subclinical process without history of a prior acute episode.
• Proliferations of capillaries and small blood vessels (angiogenesis/
neovascularization) resulting in edema, haemorrhage and congestion.
Host involvement: Parenchymal regeneration or repair by fibrosis
(scarring).
• Inflammatory Cells: Primarily Mononuclear Inflammatory Cells
Lymphocytes Macrophages - Cells responsible for phagocytosis and
tissue debridement Plasma cells Fibroblasts
TYPES OF CHRONIC INFLAMMATION
• GRANULOMATOUS
• NON GRANULOMATOUS
GRANULOMATOUS INFLAMMATION
• Type of chronic inflammation characterized by formation of granuloma

• GRANULOMA- microscopic aggregate of epithelioid cells surrounded by

collar of lymphocytes and plasma cells ,with rim of fibroblasts and
scattered multinucleated giant cells
• Epithelioid cells-activated macrophages
• Types of giant cells-Langhans type- in tuberculosis, nuclei arranged inn
periphery
-Foreign body type- nuclei scattered in cytoplasm,
may see foreign body
TYPES OF GRANULOMATOUS
INFLAMAMTION
• BACTERIAL – Tuberculosis , Leprosy , Syphilis, Cat scratch disease

• PARASITIC- Schistosomiasis

• FUNGAL- Histoplasma, blastomycosis

• FOREIGN BODY- Suture , prosthesis

• UNKNOWN- Sarcoidosis
NON GRANULOMATOUS
INFLAMMATION
• Accumulation of lymphocytes , macrophages and plamsa cells
• No granulomas
• Fibrosis my be seen

• EXAMPLE- Chronic viral hepatitis, Rheumatoid arthritis, Atopic

dermatitis
OUTCOME OF CHRONIC
INFLAMMATION
CHEMICAL MEDIATORS
• Any chemical / messenger that acts on blood vessels, inflammatory
cells or other cells to contribute to an inflammatory response
• Can be exogenous (endotoxins) or endogenous (from plasma,
leukocytes,endothelial cells)
CHEMICAL MEDIATORS
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