innate immune reponses
- 2nd line of defense ; defense without specific recognition
- recognize general molecular property marking invader as foreign (pathogen-associated molecular patterns)
- “identity” often carbohydrates or lipids on cell surface
-many cases innate response is to contain and limit spread of infection while adaptive mounts a more specific response
toll-like receptors - innate immune response
- toll proteins on immune plasma membrane act as pattern-recognition receptors
- bind large numbers of pathogen-associated molecular patterns
- trigger cytokine secretion (cytokines : small proteins involved in cell signaling)
- generate an innate immune response
interferon - “interfere” with viral replication
-cells infected with viruses produce proteins (interferons)
type 1 interferon
- released from virus infected cells into extracellular fluid and bind non-infected cells
- non-infected cells start producing antiviral proteins that can prevent viral replication if become infected
- can target most cells in body (as long as have type 1 interferon receptor)
type 11 interferon : interferon-gamma
- potentiates (increases effect of) type 1
- releases cytokines : proliferation some immune cells, secretion cytotoxic chemicals
- targets macrophages and NK cells (giving “activated” versions)
phagocytosis
process where pathogens and cellular debris are engulfed and destroyed
phagocyte
any cell that can do phagocytosis
neutrophils and macrophages - best
- *neutrophils** - quick response
- *macrophages** - largest capacity
-migrate to damaged area as neutrophils and monocytes (convert to macrophages)
4 phases of phagocytosis
adherence/ ingestion/ digestion/ killing
AIDK
aido is dumb kunt
-contact can also cause release of cytokines
alternative complement pathway
- plasma proteins (at least 30) from liver, circulate inactive in blood
- C3 activation by contact with microbe surface leads to cascade of activations
- activated proteins “complement” or enhance immune reactions
- development of membrane attack complex (MAC) by proteins C5-9
- embeds itself in pathogen forming pore-like channels
- killed by inflow entering intracellular compartment
- C3b acts like an opsonin (marker) - phagocytosis enhancement
- see later: effect vasodilation, blood vessel permeability, chemotaxis during inflammation
inflammation
local responses to tissue damage
sources of inflammation
- pathogens
- abrasions
- chemical irritants
- cell distortion or disturbance
- extreme temperature
- inflammatory response is remarkably similar no matter triggering event
characteristic symptoms of inflammation
- redness
- pain
- heat
- swelling
- can also be loss of tissue function in area sometimes
inflammatory response
-often some resident immune cells (like fixed macrophages) at injury location but may not be enough to deal with damage
goals of inflammatory response
- isolate, destroy or inactivate invader
- remove debris
- prepare for wound healing and tissue repair
example : a wood splinter has introduced bacteria through the skin defenses
stage 1 inflammatory response
- vasodilation and increased permeability of blood vessels
- release of inflammatory mediators : histamine, kinins, prostaglandins, complement proteins, cytokines, etc.
local effects inflammatory response stage 1
- vasodilation microcirculation : increases blood flow; delivery of leukocytes, plasma proteins, nutrients, oxygen (outward signs: local redness, heat)
- increased permeability : endothelial cells contract, opening spaces between them (will lead to chemotaxis into tissues from blood)
non-local effects - inflammatory response stage 1
- inflammatory mediators in blood trigger proliferation new immune cells (bone marrow)
- mobilization of stored immune cells (spleen, lymph nodes)
stage 2 - inflammatory response
movement by phagocytes into injury site from blood (within 1 hour)
- neutrophils early, later monocytes (mature into wandering macrophages)
3 steps of stage 2
MDC My Dark Crayon
margination : phagocytes and local endothelium each form adhesion molecules for attachment to local area
diapedesis : phagocyte migration through blood vessels walls into interstitial fluid of tissue
chemotaxis : phagocyte migration to injury site guided by cytokines (chemoattraction)
- fluid follows; local distension (outward signs: some edema/swelling, pain)
- cytokine can come from a number of sources and attract other needed things (other cells, proteins)
stage 3 -tissue repair
final stage of inflammation
- worn out, damaged, or dead cells replaced
- fibroblasts (connective tissue cells) divide rapidly producing large amounts of collagen
- new network blood vessels forms (angiogenesis): helps remove debris and delivers needed nutrients and oxygen
- local growth factors released from different cells control process
- remodelling may continue after initial repair
- depending on the tissue
- repair may leave no sign
- in other cases a scar (scar tissue: denser collagen fibers, decreased elasticity, fewer blood vessels)
