Inflammation Flashcards
Define inflammation
INFLAMMATION= an immune response of living tissue to injury, caused by harmful stimuli or insults
= the goal of inflammation is to eliminate cause, clear out necrotic cells + TISSUE REPAIR
what are the signs of acute inflammation
Signs of acute inflammation
◊ Redness (rubor)
◊ Heat (calor)
◊ Pain (dolor)
◊ Swelling (tumor)
(these combined can cause..) Loss of function (functio laesa)
define the following:
* Endocarditis
* Cystitis
* Dermatitis
* Pneumonitis (pneumonia)
Endocarditis= inflammation of endocardial wall
Cystitis= inflammation of the bladder
Dermatitis= inflammation of skin tissue
Pneumonitis (pneumonia)=inflammation of lung tissue
what immune cells are involved in acute inflammation? list some of their functions + know what they look like histologically
Neutrophils (polymorphs)(main guy)
* circulating immune cells and first cell to arrive in inflamed tissue.
* predominant immune cell type for first 6-24h.
* segmented nucleus, granular cytoplasm full of granules containing enzymes etc.
* most abundant polymorph.
Monocytes
* circulating immune cells that migrate into tissue following signal from inflammatory mediators and in tissue mature into macrophages
Macrophages
* derived from circulating monocytes in blood.
* predominate after 24h.
* attack pathogens and clear up debris
* Large w fluffy edges
Eosinophils
* Respond especially to allergies and helminth (parasitic worm) infections.
* Bilobed nucleus and abundance of red granules in cytoplasm.
Mast cells
* Tissue resident cell .
* Small nucleus, cytoplasm packed with blue granules.
* Releases granules containing inflammatory mediators , vasoactive amines (e.g. histamine, cytokines).
Natural Killer Lymphocytes
* Circulating immune cells.
* Directly lyse virally infected cells, tumour cells or antibody-coated cells.
*Release pro-inflammatory cytokines
Define chemotaxis and explain what a chemoattractant is
Chemotaxis= Directional movement of cells towards an extracellular chemoattractant molecules, against a concentration gradient.
Chemoattractants are small soluble molecules that bind to receptors on leukocytes causing their stimulation, polarization, and locomotion. common examples include:
○ Bacterial & fungal products (i.e. N-formylmethionyl-leucyl-phenylalanine [fMLF or fMLP])
○ Pro-inflammatory mediators
* Leukotrienes and prostaglandins
* Chemokines (group of cytokines)
* Complement components C5a & C3a (remember as ‘a’ stands for attract)
How does opsonisation enhance phagocytosis?
- Opsonisation is the enhancement of phagocytosis by opsonin molecules (*) (antibody and/or complement molecules) which coat antigens and ‘tag’/mark them for elimination by phagocytes (macrophages and neutrophils).
Opsonins= chems that bind to pathogen + ‘tag’ them so they’re easily recognised by phagocyte (phagocytes have receptors that bind to opsonins) e.g. IgG acts as opsonin, C3b acts as a opsonin {C3b bind covalently to the pathogen and thereby target it for destruction by phagocytes equipped with receptors for C3b}
N.B.
* C-reactive protein (produced by the liver) plays an important role in activation of complement and opsonisation of bacterial cells
* Recognition and attachment of antigens to neutrophils and macrophages for phagocytosis is facilitated by opsonisation
Summary acute inflammation: cascade of inflammatory mediators in response to tissue injury
STEP 1
Tissue damage causes release of vasoactive + chemotactic factors that can trigger a local increase in blood flow + capillary permeability
- more leucocytes drawn to inflamed area via increased blood flow & chemotaxis
** STEP 2**
Permeable capillaries allow an influx of fluid (exudate) + cells into tissue
- enhanced adhesion of leucocytes to blood vessel walls due to sticky integrins
STEP 3
Phagocytes migrate to site of inflammation (AKA CHEMOTAXIS)
Chemotaxis= Directional movement of cells towards an extracellular chemoattractant molecules, against a concentration gradient.
- better-facilitated entry of leucocytes into injured tissue via extravasation, due to leaky vessels and chemotaxis.
STEP 4
* Phagocytes + antibacterial exudate destroy bacteria
* Phagocytosis - the recognition, engulfment and digestion of material by phagocytic cells (phagocytes)
- faster clearance of pathogens & damaged cell contents & resolution thanks to inflammatory mediators
Describe the process of NETosis by neutrophils and its role in inflammation
Neutrophils release NETs via a multistep process called NETosis. To date, 2 mechanisms by which neutrophils release NETs in host defense are known as suicidal NETosis and vital NETosis.
just know that NETosis is neutrophil cellular suicide
n.b. The specific mechanisms that regulate these forms of cell death have not yet been completely clarified.
Describe the stages of phagocytosis
1) CHEMOTAXIS= phagocyte attracted by chemoattractants
2) ADHERENCE= phagocyte adheres to target particle e.g. pathogen. This adherence is facilitated by opsonins (these tag pathogen so its easily recognised)
3) INGESTION= phagocyte extends pseudopods + encloses it in a phagosome (membrane-bound vesicle)
4) PHAGOSOME MATURATION= phagosome(vacuole containing pathogen) merges w lysosomes{contain digestive enzymes + toxic reactive oxygen species/ROS}= forms PHAGOLYSOSOME
5) DIGESTION= enzymes + ROS breakdown ingested particle in phagolysosome
6) EXOCYTOSIS= indigestible/residual material is expelled from phagocyte via exocytosis
n.b. may turn into APCs (antigen presenting cells) for T-helper cells to recognise + facilitate adaptive immune response)
What blood tests check for inflammation in body
- C-reactive protein (CRP) test= blood test that checks for inflammation in body. CRP is a protein made by liver which indicates inflammation
- blood eurythrocyte sedimentation rate (ESR)= indicative of inflammation if elevated ESR {time RBCs take to settle in a tube of blood}
- full blood count= WBCs high e.g. lots of neutrophils- neutrophilia indicates inflammation, however, in severe inflammation e.g. sepsis neutrophils can be reduced (neutrophilia)
What is the difference between acute + chronic inflammation
ACUTE inflammation= an immediate inflammatory response to injury (temporary) [hours-weeks]
causes; injured tissue, pathogens
cells involved; neutrophils,monocytes,mast cells
onset;immediate
outcomes; healing, abscess formation, chronic inflammation
CHRONIC inflammation= a prolonged period of inflammation, acute inflammation thats failed to resolve
causes; persistent acute inflammation, persistent exposure to toxic agents, immune mediated (hypersensitivity)
cells; macrophages, lymphocytes, plasma cells, fibroblasts
onset;delayed
outcomes; tissue destruction, fibrosis{overgrowth, hardening, and/or scarring of tissues}
what is histamine and it’s role in inflammation
Histamine is a potent inflammatory mediator, commonly associated with allergic reactions, promoting vascular and tissue changes and possessing high chemoattractant activity
- histamine makes blood vessels dilate causing localised heat + redness, the raised temperature prevents pathogens reproducing
*histamines make blood vessel walls more leaky so blood plasma is forced out= tissue fluid causes swelling (oedema) + pain
what cells/mediators are responsible for the following cardinal signs on inflammation;
*redness
*swelling
*heat
*pain
*loss of function
*redness =increased blood flow; vasodilation induced by histamine from mast cells, and cytokines (e.g. TNF alpha) from macrophages
*swelling =exudation of fluid + cells into tissue: as above + chemoattractants (i.e. C3a)
*heat= increased blood flow and exudation of fluid (e.g. prostraglandins, leukotrienes,NO)
*pain= exudates stretch pain receptors + nerves: bradykinin,in plasma, and prostaglandin E2 from epithelial + immune cells increase pain sensitivity
*loss of function =pain + disruption of tissue structure by exudate of fluid + cells into tissue
what immune cells are involved in **chronic **inflammation? list some of their functions + know what they look like histologically
B cells (lymphocytes) and plasma cells
* Antigen specific receptors for recognition of antigen in 3D conformation.
* B cells mature into plasma cells which produce and secrete antibodies (immunoglobulins).
*Immunoglobulins (Ig) tag pathogens, marking them for destruction.
T cells (lymphocytes)
* Antigen specific receptors for recognition of linear peptide.
->Cytotoxic T cells (e.g. CD8 T cells) activated if recognition of peptides derived from endogenous sources, typically virally infected or cancer cells, for direct killing.
->Helper T cells (e.g. CD4 T cells) activated if recognition of peptides derived from exogenous sources expressed on antigen presenting cells (APC), for cytokine production and release to activate other immune cells
Fibroblasts
*Proliferate in response to chemokines secreted by macrophages.
*Synthesise extracellular matrix and collagen.
Macrophages
Tissue residence cells that mature from monocytes.
Activation via cytokines (IFN-γ) or through pattern recognition receptors (PRRs) by
Damage associated molecular patterns (DAMPS)
Pattern associated molecular patterns (PAMPS).
functions of macrophages:
-digestion/ killing of bacteria
-digestion of extracellular matrix
-stimulation of angiogenesis (blood vessel formation in wound healing)
-recruitment of other inflammatory cells
what is Granulomatous inflammation
Granulomatous inflammation
= chronic inflammatory reaction characterised by formation of GRANULOMAS [a collection of activated (epithelioid) macrophages] composed of:
○ Multinucleate giant cells (macrophages which have fused together surrounded by lymphocytes)
○ A fibrous rim
○ Sometimes w central necrosis (i.e. in tuberculosis)
Archetypal granulomatous disease: tuberculosis – one of few granulomatous diseases where granuloma has area of central necrosis
Other causes of granulomatous disease
* Bacteria (leprosy, syphilis, cat-scratch disease), parasites (schistosomiasis) or fungi (cryptococcosis)
* Inorganic material: silicosis, foreign-body
Unknown: sarcoidosis, Crohn’s disease
