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9.1
Introduction
The most general and fundamental indicator of all pathological conditions initiates
with inflammation, a general form of resistance broadly defined as a non-specific
response to tissue malfunction, and it is employed by immune systems to combat
pathogenic invaders (Ashley 2012).The Roman encyclopaedist Aulus Cornelius
Celsus described four principal effects of inflammation which were rubor, tumor,
calor and dolor and finally loss of function which was added by Virchow.
Inflammation is initiated by the presence of physical agents, chemicals, microorganisms, inappropriate immunological responses and tissue death. An important
stimulus of inflammation is caused by the endotoxins of bacteria and viruses.
Viruses mediate inflammation by entering and destroying the cells of the body. Loss
of blood flow causes tissue death due to lack of oxygen or nutrients, which also
results in inflammation. Inflammation is a major problem associated with diseases
like rheumatoid arthritis, cancer, obesity, neurodegenerative diseases, type 2 diabetes, cardiovascular diseases and ageing.
Inflammatory processes are generally of two kinds, acute and chronic. Acute
inflammatory response will rapidly set in and last briefly. It may be accompanied by
systemic reaction known as acute-phase response. It will be characterized by a rapid
change in several plasma proteins levels. Chronic inflammation develops when an
antigen persists for a long time and is characterized by macrophage accumulation.
Chronically activated macrophages release cytokines which stimulate fibroblast
proliferation and collagen production.
9.1.1 Mechanism of Inflammation
Cytokines which regulate inflammation also regulate a series of immunological,
physiological and behavioural processes. Initial step of inflammatory cascade is the
identification of infection or damage. Pathogen-associated molecular patterns
(PAMPs), essential for pathogen survival, are primarily detected by Alarmins and
also recognized by the innate immune system. Innate immune system lacks the ability to identify the different strains of pathogen than the adaptive system (Ashley
et al. 2012). Other receptors which identify damage signals are Toll-like receptors
(TLRs) and intracellular nucleotide-binding domain and NOD-like receptors or
NLRs (Medzhitov 2008). Once the ligands recognition occurs, NF-κB becomes
activated to TLR. NF-κB is released from IκB during transduction of signal and
translocated to the nucleus, where transcription is upregulated through binding to
target genes (Ashley et al. 2012). New protein synthesis is not required for NF-κB
elicitation and permits a rapid response. After transcription and translation, expression of interleukin-1-beta (IL- 1β), IL-6, tumour necrosis factor-alpha (TNF-α), the
major pro-inflammatory cytokines, occurs. Then these molecules recruit monocytes
and neutrophils at the site of infection. Rapid release of chemicals by neutrophils
occurs and this process requires the consumption of both glucose and oxygen,
known as the respiratory burst (Ashley et al. 2012) (Fig. 9.1).
C.S. Sharanya and M. Haridas
9.1
Introduction
The most general and fundamental indicator of all pathological conditions initiates
with inflammation, a general form of resistance broadly defined as a non-specific
response to tissue malfunction, and it is employed by immune systems to combat
pathogenic invaders (Ashley 2012).The Roman encyclopaedist Aulus Cornelius
Celsus described four principal effects of inflammation which were rubor, tumor,
calor and dolor and finally loss of function which was added by Virchow.
Inflammation is initiated by the presence of physical agents, chemicals, microorganisms, inappropriate immunological responses and tissue death. An important
stimulus of inflammation is caused by the endotoxins of bacteria and viruses.
Viruses mediate inflammation by entering and destroying the cells of the body. Loss
of blood flow causes tissue death due to lack of oxygen or nutrients, which also
results in inflammation. Inflammation is a major problem associated with diseases
like rheumatoid arthritis, cancer, obesity, neurodegenerative diseases, type 2 diabetes, cardiovascular diseases and ageing.
Inflammatory processes are generally of two kinds, acute and chronic. Acute
inflammatory response will rapidly set in and last briefly. It may be accompanied by
systemic reaction known as acute-phase response. It will be characterized by a rapid
change in several plasma proteins levels. Chronic inflammation develops when an
antigen persists for a long time and is characterized by macrophage accumulation.
Chronically activated macrophages release cytokines which stimulate fibroblast
proliferation and collagen production.
9.1.1 Mechanism of Inflammation
Cytokines which regulate inflammation also regulate a series of immunological,
physiological and behavioural processes. Initial step of inflammatory cascade is the
identification of infection or damage. Pathogen-associated molecular patterns
(PAMPs), essential for pathogen survival, are primarily detected by Alarmins and
also recognized by the innate immune system. Innate immune system lacks the ability to identify the different strains of pathogen than the adaptive system (Ashley
et al. 2012). Other receptors which identify damage signals are Toll-like receptors
(TLRs) and intracellular nucleotide-binding domain and NOD-like receptors or
NLRs (Medzhitov 2008). Once the ligands recognition occurs, NF-κB becomes
activated to TLR. NF-κB is released from IκB during transduction of signal and
translocated to the nucleus, where transcription is upregulated through binding to
target genes (Ashley et al. 2012). New protein synthesis is not required for NF-κB
elicitation and permits a rapid response. After transcription and translation, expression of interleukin-1-beta (IL- 1β), IL-6, tumour necrosis factor-alpha (TNF-α), the
major pro-inflammatory cytokines, occurs. Then these molecules recruit monocytes
and neutrophils at the site of infection. Rapid release of chemicals by neutrophils
occurs and this process requires the consumption of both glucose and oxygen,
known as the respiratory burst (Ashley et al. 2012) (Fig. 9.1).
C.S. Sharanya and M. Haridas