Inflammation Flashcards
What is inflammation
Inflammation is the response of vascularized tissue that delivers leucocyte and molecules of host from circulation to the site of infection and cell damage in order to eliminate the offending agent
What are the 5 R of inflammation
Recognition
Recruitment
Removal
Regulation
Repair
What are cardinal signs of inflammation
Calor
Rubor
Dolar
Tumour
Functional loss
Describe vascular events of inflammation
Transient vasoconstriction
Vasodilation
Describe vascular events of inflammation
Transient vasoconstriction
Vasodilation
Causes of increased vascular permeability
Endothelial cell contraction
Endothelial injury
Increased transcytosis of protein
Leakage from new blood vessels (angiogenesis)
Describe cellular events of inflammation
Recruitment of WBC
Activation of WBC
Phagocytosis
Killing and degradation
Steps of leucocyte recruitment
Margination and rolling
Adhesion
Transmigration
Migration to interstitial tissue
Rolling is mediated by which adhesion molecules
Selectins
What are the 3 selectins
E selectin
P selectin
L selectin
What molecules mediate adhesion
Integrins join on ligand on cell endothelium
What is diapedesis
After being arrested on the endothelial
surface, leukocytes migrate through the vessel wall primarily by squeezing between cells at intercellular junctions.
This extravasation of leukocytes, called diapedesis,
What is chemotaxis
After extravasating from the blood, leukocytes move toward sites of infection or injury along a chemical gradient by a process called chemotax
What are chemotactic agents
Bacterial products, particularly peptides with N-formylmethionine termini
• Cytokines, especially those of the chemokine family
• Components of the complement system, particularly C5
• Products of the lipoxygenase pathway of arachidonic
acid (AA) metabolism, particularly leukotriene B4
(LTB4)
Why are neutrophils abundant in acute inflammation
- They are most numerous
- React rapidly to cytokines
- Attach firmly to adhesion molecules
- They short lived
Leucocyte activation enhances the following function
1.Phagocytosis
2.Intracellular destruction of phagocytosed microbes and dead
cells
3. Liberation of substances that destroy extracellular microbes
and dead tissues,
4.Production of mediators, including arachidonic acid metabolites and cytokines, that amplify the inflammatory reaction, by recruiting and activating moreleukocytes
What are steps of phagocytosis
(1) recognition and attachment of the particle to the ingesting
leukocyte;
(2) engulfment, with subsequent formation of a phagocytic vacuole; and
(3) killing and degradation of the ingested
material.
What is opsonisation
material.
Leukocytes bind and ingest most microorganisms and
dead cells by means of specific surface receptors. Some of
these receptors recognize components of the microbes and
dead cells and other receptors recognize host proteins,
called opsonins, that coat microbes and target them for
phagocytosis (the process called opsonization).
What happens during oxidative burst
Increased oxygen consumption
Glycogen catabolism
Glucose oxidation
Production of ROS
What are neutrophlic extra-cellular trap NEXT
These are fibrillar network produced by neutrophils
These traps provide high concentration of antimicrobial substance at site of infection and prevent spread of microbes by trapping them
Clinical examples of leucocyte induced injury
Acute respiratory distress
syndrome
Acute transplant rejection Lymphocytes; antibodies and
complement
Asthma Eosinophils; IgE antibodies
Glomerulonephritis Antibodies and complement;
neutrophils, monocytes
Septic shock Cytokines
Chronic
Rheumatoid arthritis Lymphocytes, macrophages;
antibodies?
Asthma Eosinophils; IgE antibodies
Atherosclerosis Macrophages; lymphocytes?
Chronic transplant rejection Lymphocytes, macrophag
What can be the defects in leucocyte functions
LEUCOCYTE ADHESION DEFECT: type 1 due to defective synthesis of the CD18 β
Type 2 : due to by a defect in fucose
metabolism resulting in the absence of sialyl–Lewis X,
the oligosaccharide on leukocytes that binds to selectins
on activated endothelium.
DEFECT IN MICROBIAL ACTIVITY : eg chronic granulomatous disease
DEFECTS IN PHAGOLYSOSOME FORMATION
What are morphological patterns of acute inflammation
- SEROUS INFLAMMATION is characterized by the outpouring of a watery, relatively protein-poor fluid that, depending on the site of injury, derives either from the plasma or
from the secretions of mesothelial
cells lining the peritoneal, pleural, and pericardial cavities. - FIBRINOUS INFLAMMATION occurs as a consequence of
more severe injuries, resulting in greater vascular permeability that allows large molecules (such as fibrinogen) to
pass the endothelial barrier - SUPPURATIVE (PURULENT) INFLAMMATION and abscess
formation. These are manifested by the collection of
large amounts of purulent exudate (pus) consisting of
neutrophils, necrotic cells, and edema fluid.
4.• AN ULCER is a local defect, or excavation, of the surface
of an organ or tissue that is produced by necrosis of cells
and sloughing (shedding) of necrotic and inflammatory
tissue
What are performed , cell derived inflammatory mediators
Histamine
Serotonin
What are newly synthesized cell derived mediators
Prostaglandin
Leucotrines
Platelet activating factor
Reactive oxygen species
Nitric oxide
Cytokines
Neuropeptides
Systemic effects of acute inflammation
1.Fever
2.Leucocytosis
3. Acute phase reactants- to protect normal cells, these are
•certain cellular protection factors
•some coagulation proteins
• transport proteins
•immune agent
• stress protein
• antioxidants
4. Lymphangitis
5. Septic shock
Outcomes of acute inflammation
- resolution- complete return to normal tissue
- Fibrous healing - repair by fibrosis
- Suppuration - acute abscess
- Chronic inflammation
What is granulomatous inflammation
Granulomatous inflammation is a distinctive type of chronic inflammation characterized by aggregates of activated macrophages and scattered lymphocytes, forming a granulomatous pattern.
What is granulomatous inflammation
Granulomatous inflammation is a distinctive type of chronic inflammation characterized by aggregates of activated macrophages and scattered lymphocytes, forming a granulomatous pattern.
What is the purpose of granulomatous inflammation
Type 4 hypersensitivity, it is a protective reaction by host but eventually causes tissue destruction because of persistence of poorly digestible antigen
What are characteristics of chronic inflammation
- INFILTRATION with mononuclear including macrophages, lymphocytes, plasma cell
- TISSUE DESTRUCTION by inflammatory cells (hallmark)
- REPAIR- either by proliferation or fibrosis
In what cases proliferation occurs
And in what cases fibrosis occurs
If the cells have capacity to regenerate, it heals by proliferation otherwise fibrosis
Chronic inflammation occurs due to?
- PERSISTENT INFECTION, difficult to eradicate
Persistent infection causes activation of t lymphocytes mediated response - IMMUNE MEDIATED INFLAMMATORY DISEASE eg rheumatoid arthritis
- EXCESSIVE and INAPPROPRIATE activity of immune system eg rheumatoid heart disease
- ALLERGIC DISEASES eg bronchial asthama
- Disease NOT CONVENTIONALLY inflammatory
- Prolonged exposure to TOXIC agents like silica
Main cells of chronic inflammation
Macrophages
Lymphocytes
Precursor of macrophages
Monocytes get converted into macrophages
Why?
1. Size increase
2. Life time increase
Macrophages of diff organs
Liver - kupffers cell
Spleen - sinus histocytes
Lungs - alveolar macrophages
Cns - microglial cells
All these together mononuclear phagocytic system
What activates the macrophages
Il1 , il13
Microbial products
t Lymphocytes types
Type 1 helper T cells - activates macrophages
Type 2 helper T cells - activate eosinophils and macrophages also recruitment of macrophages
Type 17 helper T cell - activating and recruiting monocytes and neutrophils
Factors required for classical and non classical macrophages activation
For classical- interferon gamma
For non classical - il13
Il4
What are the proteins involved in allergic reaction
Major basic protein and cationic protein
These proteins are toxic to parasites and also cause epithelial cell necrosis
What is granulomatous inflammation
Distinctive type of chronic inflammation characterized by aggregate
Where do we see granulomatous inflammation
- Prolonged inflammation
- Immune mediated inflammatory response eg crohn’s disease
- Unknown etiology eg sarcoidosis
- Foreign body - suture or spinctor
Morphology of granulomatous inflammation
