Acute Inflammation 2: Vascular Changes Flashcards
Why does ice stop the swelling associated with acute inflammation
Why does it work better when applied sooner rather than later?
What general process causes swelling after bee sting?
Decreases blood flow to the area
If fluid has already moved into the tissue, ice isn’t going to reverse it
Histamine: ⬆ BLood vessel permeability so fluid moves info the tissue
4
What are the Vascular changes that occur in acute inflammation?
Blood stasis- vasoconstriction
Vasodilation (⬆blood flow….rubor, calor)
Endothelial damage: ⬆ vascular permeability, ⬆interstitial fluid, ⬆interstitial proteins
Cellular response: leukocyte extravasation
Slide 3
What is the primary objective of the cellular response to inflammation?
The types of cells vary depending on?
Primary objective is to deliver leukocytes from the blood to the site of infection or injury.
The types of cells vary depending on:
-progression of inflammation (acute or chronic)
-nature of causative agent (trauma, infection. Viral, bacterial)
-initiated by changes in vascular permeability
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What are the different types of leukocytes in peripheral blood?
1) granulocytes
A) neutrophils (polymorphonuclear leukocytes)
B) eosinophils (large dull red granules- bilobed nucleus)
C) basophil and mast cells -very basophilic granules-kidney shaped nucleus)
These last 2 are both less common
- Mononuclear cells
A) lymphocytes -rim of deep blue cytoplasm
B) large lymphoid cells
C) monocytes and macrophages (pale blue abundant cytoplasm- clear vacuoles may be present - largest
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Leukocyte development
Produced in bone marrow- hemopoetic tissue can produce any type of cell
They come from 2 lineages:
Myeloid lineage- gives rise to most of the cells just talked about
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What are the cells of the cellular response
-The cell types involved depend on the nature of the stimulus
-each cell type is highly specialised to combat the initiating stimulus
Granulocytes (PMNL)
-neutrophils (bacteria)
-eosinophils (parasite and allergic stimuli)
-basophils (allergic responses)
Mononuclear cells
- monocytes (blood) and macrophages (bacteria, fungi, Protozoa)
- giant cells
- lymphocytes (virus, bacteria, parasites, allergens)
Platelets (vascular injury and coagulation)
Endothelial cells (chemical mediators)
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Granulocytes: Neutrophils
-respond rapidly to bacterial infections
-recruited by chemotactic factors (chemokines, complement (C5a), toxins, ECM degradation
Activated by phagocytic stimuli
-chemokines, cytokines, complement, Fc receptors
-degranulate: release bacteriocidal enzymes and free radicals
-digest microbes and tissue debris
-degrade bacterial cell walls
-activate inflammatory cells
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Granulocytes: Eosinophils
-parasitic and allergic responses
-release mediators from granules
-degranulation release
-enzymes (peroxidases, collagenases, histamines)
-toxic proteins (major basic protein, eosinophil, cationic protein, toxic to parasites
-Cytokines (INter leakin-3, IL-5, GM-CSF
-chemokines (IL-8)
-Leukotrienes: PAF
Motile with some minor phagocytic activity
13
Granulocytes: Mast cells
Located in connective tissue around blood vessels
-epithelial sub mucosa (GI, RT) & dermis
Sensitised by IgE binding to cell surface
-allergic responses, insect bite
-anaphylaxis
Degranulate readily when antigen bonds to cell surface IgE molecules
Granules release vasoactive substances:
-heparin: prevents thrombosis and blood stasis
-histamine: ⬆ vascular permeability, chemo attractant: neutrophils and eosinophils
-Leukotrienes: ⬆ vascular permeability and s.m contraction
14
Mononuclear cells: Macrophages
Derived from blood monocytes
-differentiate in tissue (histiocytes)
The major tissue phagocytic cell (“big eaters”)
-cells, bacteria, fungi, protozoa, tissue debris, particles…
Produce pro-inflammatory cytokines (cell signallers)
- Interleukin-1, TNF-a, IL-12 -amplifys response
- also IL-10 (anti-inflammatory) -downgrades the response
Aid some pathogens to escape destruction ‘Trojan horse’
Eg mycobacterium, Bruce.la
May fuse to form multinucleated giant cells in chronic conditions
Eg Langhans: typically with tuberculosis
-foreign body: typically with foreign material present in tissue
-touton: assosiated with disorders of the metabolism
15
Mononuclear cells: Lymphocytes
-large nuclei and little cytoplasm
-circulate through blood and lymph
-antibody and cell mediated immunity
-B cells and plasma cells (bone marrow)
-T cells (thymus)
-circulate in an inactive state
-must be activated by antigen via specific receptors:
-for T cells: presented by macrophages or dentritic cells
-for B cells: soluble or cell surface antigen
-can proliferate and adapt to changing antigens
-long lived cells that provide immunological “memory”
-basis for vaccines
T cells (cell-mediated immunity)
-Th1 cells- anti-viral
-Th2 cells- allergy, parasites
-T cytotoxic (CD8+) cells-kill virally infected cells
B cells (antibody-mediated or humoral immunity)
- produce antibodies specific to antigen
- combat extra cellular pathogens (bacteria, parasites) and neutralise viruses
Plasma cells
-mature B cells that produce mono-specific antibodies
-often seen in chronic inflammation
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Cellular processes: phagocytosis
- Recognition and attachment
- Engulfment
- Killing or degradation
- Recognition and attachment
- mannose receptors
- scavenger receptors
- opsonins= IgG, C3b, plasma lectins (MLB) - Engulfment
- dependant on polymerization of actin filaments - Killing or degradation
-oxygen-dependant mechanisms
-oxygen- independent mechanisms
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Slide 19 shows an image of phagocytosis occurring
Macrophage projects its cell membrane around the RBC and engluphes it. They can fill up their cytoplasm with lots of RBC
Cellular processes: Chemotaxis
What are the 2 types of chemoattractants and give some examples
At the site of injury, leukocytes undergo directional migration by a process termed chemotaxis.
Chemotaxis is movement of an organism in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. Wikipedia
- Exogenous chemoattractants
- bacterial products (peptides, lipids) - Endogenous chemoattractants
-C5a
-LTB4
-cytokines (IL-8)
-chemokines
-ATP
20
What are the functional responses induced on leukocyte activation
- Production of arachidonic acid metabolites
- Degranulation and secretion of lysosomal enzymes; activation of oxidative bursts
- Secretion of cytokines
- Modulation of leukocyte molecules
- Induction of cell division (lymphocytes)
Slide 22
Don’t worry too much about this slide just know that the lymphocytes have to be activated
