mbio 1220 the innate immune system, lecture 12

innate immunity

refers to defenses that are present at birth

• these are non-specific defenses: acting against most microbes in the same way

  • treat everyone the same

    • not good! address accordingly

  • one site fills all

  • can’t modify of give a tailored response

• there is no memory component: cannot recall previous contact with a foreign microbe

  • every time it sees E. coli it will treat it like its the first time it has been seen

  • first attacks

  • non-specific so while fighting away it affects you (why u feel yucky)

• always present

  • responds rapidly to an infection

  • it is active before an infection occurs

• the innate system includes

  • physical barriers - first line of defenses

  • chemical barriers - first line if defenses

  • cellular defenses: the second line of defense

  • inflammation

  • fever

  • molecule defenses

what are the first line defenses of the innate immune system?

• physical barriers

• chemical barriers

physical barriers

1. skin

2. mucous membranes

3. fluid flow

skin (biggest organ)

• the outer surface of the skin consists of dead cells and protective protein called keratin

  • constantly moving bacteria

  • multi-layer dead → no vascular layer

• the layers of the skin are frequently shed which removes microbes

• skin is very dry which inhibits microbial growth

  • skin infection are more common on moist areas of the skin or in moist environments

  • the outer layer of the skin is an excellent defenses and is rarely penetrated by microbes

  • most infections occur under the skin once the skin has been broken although fungi can sometimes grow on the skin’s surface: eating dead skin cells (don’t need to eat something, micro-abrasion)

  • some microbes are able to eat dead skin cells and oils that are secreted by the skin

  • if this happens body odor results

good job of keeping bad things out

have to defend our skin

dry (but not in all areas like armpit)

skin that’s moist will have more microbial growth

mucous membranes

• these membranes are involved in fluid exchange

• they offer less protection than the skin

• mucous membranes line ‘tracts’ such as the digestive, reproduction, and respiratory tracts (goblets full of mucous)

• they secrete mucous which is a glycoprotein that keeps the membrane from drying and cracking

  • the mucus traps microbes

  • cilia than moves the mucous containing microbes way

open outside of the body

100% contaminated

tract

fluid flow

• saliva, tears, urine, and vaginal secretions move microbes away/out of the body

• deportation

• alt. kill each (takes so much energy)

chemical barriers

1. acidity of body fluids and skin

2. lysozyme

3. the normal microflora

acidity of body fluids

• stomach: hydrochloric acid creates a pH of 2

  • this is low pH destroys many bacteria

• skin: fatty acids and lactic create a pH of 3-5

  • these conditions prevent the growth of many microbes

• when you eat your pH increases

• H. pylori causes ulcers

lysozyme

• an enzyme that degrades peptidoglycan

• lysosome is found in sweat, tears, saliva, and nasal secretions

• fragmented

• cults linear chains causes bugs to be sensitive to osmolarity

• cuts sections: NAM NAG NAM NAG

the normal microflora

• this is acquired shortly after birth

• it functions to prevent the growth of pathogens

  • competitive exclusion and microbial antagonism

• highly protective because taking up space

cellular defenses

the second line of defense

• virus got in

• consists of

  • leukocytes which are white blood cells (WBCs)

    • phagocytes: white blood cells that use phagocytosis to “eat” microbes

    • increase in number when infection

    • like a vccum and take the bad guy in → has to kill while inside

• there are tow types of leukocytes

  • granulocytes (BIG granules)

  • agranulocytes (small granules)

  • both have cytoplasm granules

granulocytes

• these have large granules in their cytoplasm and are visible under light microscope

• there are three sub-groups of granulocytes

basophils

• these are weak phagocytes

• they secrete chemo-attractants

• they release histamine which usually causes allergies and inflammation

  • HIS → antiphallic shock, vasodilator, bronchoconstrictor

  • need epi pen

  • open up granules → disaster

eosinophils

• these destroy large pathogens such as pathogenic worms

• they produce extracellular digestive enzymes to attack the parasite → extra-cellular digestion *find eukaryotic problems and spit on them to digest them

neutrophils

• these are strong phagocytes

• they can leave the blood and enter the infected tissue

• they destroy foreign microbes and particles by phagocytosis

• increase permeability to capillary to allow release of neutrophils

• lot of primary function to phagocytosis but don’t mind to do it. neutrophil primary function is phagocytosis

basophils

• these are weak phagocytes

• they secrete chemo-attractants

• they release histamine which usually causes allergies and inflammation

  • HIS → antiphallic shock, vasodilator, bronchoconstrictor

  • need epi pen

  • open up granules → disaster

MAST CELLS: exactly like basophil but are in tissues

eosinophils

• these destroy large pathogens such as pathogenic worms

• they produce extracellular digestive enzymes to attack the parasite → extra-cellular digestion *find eukaryotic problems and spit on them to digest them

neutrophils

• these are strong phagocytes

• they can leave the blood and enter the infected tissue

• they destroy foreign microbes and particles by phagocytosis

• increase permeability to capillary to allow release of neutrophils

• lot of primary function to phagocytosis but don’t mind to do it. neutrophil primary function is phagocytosis

agranulocytes

• these also have granules in their cytoplasm which are visible under a light microscope

• monocytes and lymphocytes

agranulocytes → monocytes

• these are initially not phagocytic (baby, no job in the blood, immature)

• they leave the blood, enter into tissues and become macrophages

• macrophages are mature monocytes and strong phagocytes (professional phagocyte)

• macrophages are often found in organs and filter out invading pathogens as blood passes through

• *takes destroyed pieces and put on forehead to tell others about it and tell to learn it and find them

• when neutrophil is done it vomits out the bad (but is recycled as organic material)

agranulocytes → lymphocytes

• there are three types

  1. natural killer cells (NK cells)

  2. T and B lymphocytes

lymphocytes → natural killer cells (NK cells)

• these are responsible for killing infected body cells and tumor cells (cancer)

• they attack any body cell that displays unusual proteins in the plasma membrane

• risk increases when stressed

• kill cells that have warning on them

• if destroys good things it can’t be fixed

lymphocytes → T and B

• these are part of the adaptive immunity

phagocytes

• during infection monocytes and granulocytes migrate to the infected area

• NEED TO HAVE STIMULUS

• process of eating

• vacuum and now needs to clean → lysosome released to attack bug

• four main phases

  1. chemotaxis

  2. adherence

  3. ingestion

  4. digestion

four main phases of phagocytes

1. chemotaxis

   • phagocytes are attracted to foreign particles, damaged cells etc.

2. adherence

   • phagocyte attacks to a foreign particle

3. ingestion

   • pseudopods extend and engulf the particle

   • the particle is trapped in the phagosome

4. digestion

   • digestion enzymes enter the phagosomes

   • takes 10-30 minuets to kill a bacterium

   • fever (heat) will lie closer to 10 mins

   • heat speeds up

inflammation

• signs and symptoms

  • pain

  • redness

  • heat

  • swelling

  • loss of function

• inflammation functions to destroy an injurious agent

• it also acts to prevent the spreading of an injurious agent

• it repairs and replaces damage tissues

its a procedure → stop spread of bad guy

eliminate spread → kill in end (keep it local and deal with it)

stages of inflammation

1. tissue damage

   • open your inside to bad bacteria

2. vasodilation → increases pathways

   • the blood vessels dilate: more blood reaches the affected area

   • this allows white blood cells to access the area

   • brings nutrients for faster healing

   • this causes reddening, swelling (edema), increased temperature, and pain

   • the pain is also due to tissue damage

   • this allows fibrinogen clot formation

     • this segregates the affected area

     • prevents the spread of infection

   • heat due to friction, appears more red

3. phagocytosis

   • phagocytes destroy invading microbes

   • increase cells that vacuum up and kill product

4. tissue repair

   • new cells are produced

fever

• an increase in body temperature

• fever is controlled by hypothalamus in the brain (prostaglandin)

• it is triggered by toxins, LPS, and chemicals produced by the immune system

  • all of these things reset the bodies thermostat

• bacteria have growth curb → have optimum temp.

fever results in

• muscle contractions (shivering)

• increased temperature: faster metabolism, promotes healing

• faster phagocytosis (due to increased temperature)

• slows the growth of heat limited microbes

  • ex. E. coli prefers to grow at 37°C, growth slows at 40°C

• up to a certain temperature, fever is a defense against disease

  • but a fever above 43°C can cause death

• lift heat to higher volume due to contracting

• bacteria has phospholipid bonds, H-bonds → destroyed by heat

• Tylenol interferes with prostaglandins

molecular defenses → the complement system

• composed of ~ 30 proteins that circulate in the blood

  • proteins help clear out threat

  • off if healthy

  • one to turn on, tags others to activate

• they work together as a cascade

  • the action of one protein triggers the action of the next

• complement can be triggered by surface molecules invading microbes

  • ex. Lipopolysaccharide (LPS)

the result of the complement cascade

1. opsonization

   • C proteins attached to microbes and act as a flag to attract phagocyte

     • this increases phagocytosis by 1000x

   • done something to itself to make itself more visible

2. enhanced inflammation

   • increases blood vessel permeability

   • attracts phagocytes to the infection site

   • better because of complimentary protein

3. cytolysis

   • formation of the membrane attack complex (MAC)

     • pore formation

   • this pokes holes in the bacterial cell membrane

   • all fluids woosh out

   • gets harder to control

molecular defenses → interferon (IFN)

• produced upon infection with a virus

• it interferes with viral replication

• it is released by infected cells to warn neighboring cells

  • allows neighboring cells time to produce anti-viral proteins

  • interferon does not help cells that are already infected with virus

  • interferon is effective only for short period of time

• makes woke

• tell cells to up anti-viral response

• side-effects include:

  • nausea

  • fatigue

  • headache

  • vomiting

  • fever

• interferon can be toxic to organs

molecular defenses → transferrins

• iron binding proteins in blood, milk, saliva, and tears

• binds and sequesters iron so that it cannot be used by bacteria

• slows bacterial growth

• innate immune system

• bacteria don’t have Hb, bacteria have Fe in their ETC

• body grows out a sponge that sucks up Fe so it is not available for bacteria to use