This document provides an overview of inflammatory responses. It defines inflammation as the protective response by host cells to eliminate the initial cause of cell injury and restore homeostasis. The document then describes the types of inflammation as acute or chronic, and the key cellular and vascular changes involved in each. It also discusses the various mediators of inflammation, systemic effects like fever and acute phase reactions, and common anti-inflammatory pharmacology treatments.
2. What is inflammation?
A protective response by host cells intended to
eliminate the initial cause of cell injury as well as
necrotic tissues and restore normal homeostasis.
4. Overview
• Occur as a consequences of local or systemic release of
chemical mediators by various host cells
• in responses to invading pathogens or tissue injury
• to mobilize the necessary resources required for the
restoration of homeostasis.
5. • Invloves
– Host cells
– Blood vessels
– Proteins
– Chemical mediators and their receptors.
6.
7. • Is it always protective?
– No
– Capable of causing considerable host tissue damage.
– There are many known autoimmune conditions too.
8. • So, why is it important?
– Without inflammation, cell injury would go
unchecked and wounds or tissue injury would
never heal which leads to continuous progression
of the disease.
9. What cause inflammatory responses to be
activated?
• According to Matzinger’s Danger hypothesis
– Immune system is activated by a broad categories of
signalling molecules termed “ Danger Associated
Molecular Patterns”(DAMP).
– Microbes elaborate similar molecules: Pathogen
Associated Molecular Patterns or PAMP( a subset of
DAMP molecules)
– Tissue necrosis secondary to injury release: Alarmins –
these are not released in apoptosis.
10. • These molecules such as PAMP and Alarmins are recognised
by Toll-like receptors(TLR) present in the immune cells which
ultimately initiate the cascade of inflammatory responses.
11. Types of inflammation
• Broadly classified as
– Acute inflammation
– Chronic inflammation
• But sometimes, these can be found coexisting
in clinical scenarios.
13. Acute inflammation
• Rapid delivery of WBC and plasma proteins to the
site of injury.
• 2 major components:
– Vascular
– Cellular
14. Vascular changes in Acute inflammation
– Changes in vascular caliber and flow
– Transient vasoconstriction
– Arteriolar vasodilation
– Increased permeability of microvasculature
– Stasis of blood
15.
16. Cellular events mainly include Leukocytes
recruitment and activation.
• Recruitment
– Margination and rolling along the vessel wall
– Firm adhesion to endothelium
– Transmigration between endothelium cells
– Migrations to interstitial tissues toward a chemotactic
stimulus.
22. Leukocytes induced tissue injury:
– Bystander tissues injured as a part of normal defense
reactions, in infections that are difficult to eradicate.eg TB,
some viral diseases
– As a normal attempt to remove damaged tissues, inflm
may prolong and exacerbate
– As in certain autoimmune reactions
25. Outcomes of acute inflammations
• Resolution: regeneration and repair
• Chronic inflammation
• Scarring
26.
27. Chronic inflammation
• Of prolonged duration (weeks to years)
• continuing inflammation, tissue injury and healing,
often by fibrosis, proceed simultaneously
• Characterized by
– Infiltration with mononuclear cells,
– Tissue destructions, largely induced by the products of the
inflammatory cells.
– Repair involving new vessel proliferation and fibrosis
28. When does chronic inflammation arise?
• Persistent infections
• Immune related inflammatory diseases
• Prolonged exposure to potentially toxic agents
33. Granulomatous inflammation
• Distinct pattern of chronic inflammation
• Under 3 settings
– Persistent T-cell responses to MTB,T. pallidum or fungi,etc,
T-cell derived cytokines cause chronic macrophage
activation
– Immune mediated diseases- Crohn disease
– Idiopathic disease – Sarcoidosis
• Also in response to inert foreign bodies eg suture or splinters, so
called foreign body granulomas
34. Systemic effects of inflammations
• Collectively called as SIRS or acute phase reactions.
• Important cytokines produced by leukocytes:
– TNF
– IL-1
– IL-6
35.
36.
37. • Several clinical and pathologic changes
– Fever
• in response to pyrogens act by stimulating
prostaglandin (PGE2)synthesis in the vascular and
perivascular cells of hypothalamus.
• LPS (exogenous pyrogens) stimulate leukocytes to
produce IL-1 and TNF(endogenous pyrogens)
38. – Elevated plasma levels of acute phase reactants
• Most are produced in liver, stimulated by IL-6
– Best known proteins- CRP, fibrinogen, serum amyloid a(SAA)
– These also act as opsonin and to fix complement
– Firinogen cause rouleax formations – increase ESR
39. – Leukocytosis or leukopenia
• extremes- 40000 to 100000 leukemoid reactions
• shift to left
– Increased HR and BP, chills and rigors, loss of
sweating, anorexia somnolence and malaise 2* to
cytokines on brain cells
40. – In severe reactions:
• TNF can cause DIC, metabolic disturbances including
acidosis and hypotensive shock, this triad: septic shock
