Immune System

first line of defense in innate system

surface barriers = skin and mucus membranes

second line of defense in innate system

internal defenses

• phagocytes

• natural killer cells

• inflammation

• antimicrobial proteins

• fever

chemicals of skin and mucus membrane

• acid (acid mantle)

• enzymes (lysozyme of saliva, mucus, and lacrimal)

• defensins (antimicrobial peptides inhibit microbial growth)

• mucin (sticky mucus of digestive/resp tract)

• other chemicals (lipids in sebum and dermicidin in sweat)

phagocytes

white blood cells that ingest and digest (eat) foreign invaders

Neutrophils

most abundant phagocytes, but die fighting; become phagocytic on exposure to infectious material

Macrophages

develop from monocytes and are chief phagocytic cells; most robust phagocytic cell

free (wander, alveolar macrophages)

fixed (permanent to organs, stellate macrophages in liver and microglia in brain)

step 1 of phagocytosis

• phagocyte recognizes and adheres to pathogen’s carbohydrate “signature”

• some organisms have capsules that hide them from phagocytosis

• opsonization

Opsonization

immune system uses antibodies or complement proteins as opsonins that coat pathogens

• HANDLES for phagocytes to grab onto to

step 2 of phagocytosis

Cytoplasmic extensions (pseudopods) bind to and engulf particle in vesicle called phagosome

step 3 of phagocytosis

Phagosome fuses with lysosome, forming phagolysosome

step 4 of phagocytosis

Phagolysosome is acidified, and lysosomal enzymes digest particles

step 5 of phagocytosis

Indigestible and residual waste is exocytosed from phagocyte

Helper T cells

• trigger macrophage to produce respiratory burst

Respiratory burst

• Releasing cell-killing free radicals

• Producing oxidizing chemicals (e.g., H2O2)

• Increasing pH and osmolarity of phagolysosome

Natural killer cells

• Nonphagocytic, large granular lymphocytes that

police blood and lymph

• Attacks foreign cells b/c no recognizable surface receptors

• Kill by apoptosis

• Secrete chemicals —> inc inflammatory response

4 benefits of inflammation

– Prevents spread of damaging agents

– Disposes of cell debris and pathogens

– Alerts adaptive immune system

– Sets the stage for repair

4 signs of inflammation

1. Redness

2. Heat

3. Swelling

4. Pain

stages of inflammation

– Inflammatory chemical release

– Vasodilation and increased vascular

permeability

– Phagocyte mobilization

inflammatory chemical release

• chemicals released in ECF by injured tissues, immune cells, blood proteins

• Histamine, kinins, prostaglandins, complement, cytokines

Vasodilation and increased vascular permeability

• causes hyperemia

• causes exudate

exudate

fluid containing clotting factors and antibodies

what does exudate result in

Results in local swelling (edema)

Swelling also pushes on nerve endings, resulting in pain

benefits of edema

• Surge of fluid in tissue sweeps foreign material into

lymphatic vessels for processing in lymph nodes

• Delivers clotting proteins and complement to area

• Clotting factors —> fibrin mesh —> scaffold for repair

step 1 of phagocyte mobilization

Leukocytosis.

Neutrophils enter blood from bone marrow

step 2 of phagocyte mobilization

Margination.

Neutrophils cling to capillary wall

Grabbed by CAMs that make neutrophils slow down

step 3 of phagocyte mobilization

Diapedesis: neutrophils flatten and squeeze between endothelial cells, moving into interstitial spaces

step 4 of phagocyte mobilization

Chemotaxis: inflammatory chemicals act as
chemotactic agents that promote positive
chemotaxis of neutrophils toward injured area

• monocytes —> macrophages arrive later for cleanup

pus

creamy yellow mixture of dead neutrophils, tissue/cells, and living/dead pathogens

abscess

collagen fibers are laid down, walling off sac of pus; may need to be surgically drained

antimicrobial proteins

interferons = attack

complement = hinder

interferons

Cells infected with viruses can secrete IFNs that “warn” healthy neighboring cells

Complement

• 20 diff blood proteins

• C1-C9

• Factors B, D, and P

• destroy bactera

• enhances inflammation

classical pathway of complement

antibodies bind to invading organisms and trigger activation cascade

lectin pathway of complement

• lectins are produced by innate system to recognize foreign invaders

• lectin binds to sugars on invaders —> activate complement

lectin pathway of complement

Complement cascade is activated spontaneously when certain complement factors bind directly to foreign invader

3 diff end results on complement pathways

• opsonization = coating of pathogen surface (tagging) to enhance phagocytosis

• MAC = poke hole in membrane to cause cell lysis (pop)

• enhances inflammation

benefits of fever

• Causes liver and spleen to sequester iron and zinc

(needed by microorganisms)

• Increases metabolic rate, which increases rate

of repair