micro unit 9 - resistance to infection: cellular defenses

what lines of defense fall under innate immunity?

first + second

what line of defense falls under adaptive immunity?

third

intact skin acts as a _______ + _______ barrier

physical + chemical

what are some examples of intact skin as a physical and chemical barrier?

sweating, sebum

the first line of defense includes what non-aggressive structures?

1) intact skin

2) mucous membranes

3) normal flora

4) gastrointestinal tract

5) blood brain barrier

6) oxygen tensions

7) iron levels

8) defecation + vomiting

9) fever

hair, ciliated cells, tears, saliva, and mucous are part of what non-aggressive type of defense?

mucous membranes

normal flora is…

microbes that can be found in + on the body; their location and concentration is important to prevent other microbes from occupying the same area (bacteriocin production)

bacteriocin production

chemicals that bacteria produce that can be toxic to other bacteria

gastrointestinal tract

stomach (low pH), digestive juices, bile

blood brain barrier

ependymal cells + astrocytes + phagocytes → they police the area and eliminate anything that crosses that barrier

oxygen tensions

aerobic (lungs) + anaerobic (intestines)

what is meant by aerobic oxygen tensions?

anaerobes cannot live or reproduce in the lungs as the lungs have an aerobic environment (i.e. clostridium)

what is meant by anaerobic oxygen tensions?

aerobes cannot live or reproduce in the intestinal tract as the intestines have an anaerobic environment (i.e. pseudomonas)

iron levels

microbes require Fe⁺⁺ → during an infection, iron levels drop slightly (hypoferremia) which can cause organisms to die

hypoferremia

iron levels dropping slightly (happens during an infection)

defecation + vomiting

rids the body of microbes (leads to dehydration)

fever

release of pyrogens (substances that send signals to the brain to raise temperature)

what are the benefits of a low-grade fever?

increase in immune mechanism, immune in phagocytes, increase in interferon, inhibits growth of certain microbes

lysozymes

attacks certain gram + bacteria; the enzyme is found in tears, saliva, perspiration, granules of neutrophils

what resists lysozymes?

microbes that have capsules, they are more virulent

sebum

contains fatty acids that are toxic to gram - microbes

the cydal agents are…

complement, interferon, leukins, plakins, lactoferrin, transferrin

complement (cydal agents)

a serum that consists of 30+ protein that exists in an “inactive” state that targets gram - microbes and viruses

how does complement work?

if 1 of the 30+ proteins are activated, a domino effect occurs until all 30+ proteins are turned on → it attaches to the microbe and destroys it

what are triggers that activate complement?

fever, viral infection that produce interferon, presence of bacterial antigens

the first line of defense includes what aggressive structures?

1) lysozymes (enzyme that attacks gram + bacteria)

2) sebum (toxic to gram - microbes)

3) cydal agents (complement, interferon, leukins, plakins, lactoferrin, transferrin)

interferon

anti-viral protein

how does interferon work?

interferon is produced in small quantities; protects uninfected cells from being infected by the virus by covering receptor sites

patients with what viruses are given large doses of interferon?

chronic HBV + HCV; these large doses can be produced through genetic engineering

leukins

produced by leukocytes (wbc)

plakins

produced by platelets

what two proteins are involved in regulating iron levels?

lactoferrin + transferrin

lactoferrin

regulates the absorption, transport, and metabolism of Fe⁺⁺; found in tears, granules of neutrophils, and breast milk

transferrin

a serum protein that regulates the absorption, transport, and metabolism of Fe⁺⁺

the second line of defense includes what structures?

1) phagocytes (neutrophils, eosinophils, basophils, monocytes)

2)

phagocytosis

cells that are capable of ingesting microbes, debris, or foreign matter, “cell eating”

what are the steps of phagocytosis?

1) chemotaxsis

2) adhereance (opsonin proteins)

3) ingestion

4) digestion (lysosomes)

5) release or discharge

chemotaxsis (chemical movement)

phagocytes have to move the infected area; attracted by chemicals (activated complement, inteferon, vasodialators)

opsonization

opsonin proteins are sticky and produced by phagocytes

ingestion

phagocytic vacuole or phagosome

digestions

lyososomes break down the captured microbe

release/discharge

cell releases broken up bits or pieces of the captured microbe

what step of phagocytosis are capsules MOST resistant to?

adherence

why are capsules resistant to adherence?

because capsules are made of a mucopolysaccharide coating which makes it difficult for opsonin proteins to stick to it and engulf the microbe

why is mycobacterium difficult for lysosomes to digest?

it has wax in its cell wall; lysosomes don’t have the tools to properly digest the wax, so it makes it difficult for the body to fight against mycobacterium

granulocytes

granules that stain different colors

what are examples of granulocytes?

neutrophils, eosinophils, basophils

what color do neutrophils stain?

pale lilac

what color do eosinophils stain?

orange/red

what color do basophils stain?

blue/purple

what are examples of agranulocytes?

monocytes, lymphocytes

are lymphocytes phagocytic?

no, they are involved in making antibodies (humoral defenses)

what are agranulocytes?

do not contain granuoles in the cytoplasm

neutrophils

most abudant wbc in the body; make up 60-70% of our wbc; 12 microns in diameter; 1st wbc at infection site, last to leave ; (very phagocytic); scavenger cells that clean up debris

how can you distinguish neutrophils under the microscope?

look for granuoles that are light purple and how the nucleus has been segmented; these granuoles contain lysozyme and lactoferrin

leukocytosis is expected in what scenarios?

found in acute infections + neutrophilia

leukopenia

drop in wbc

leukocytosis

elevation in wbcs

neutropenia

elevation in neutrophils

neutropenia

drop in neutrophils

what wbc is most abundant, the first to arrive at the infection site and the last to leave, and is most phagocytic?

neutrophils

eosinophils

make up 2-4% of total wbc; 13 microns in diameter; some phagocytic activity; role in allergic reactions (hypersensitivity)

how can you distinguish eosinophils under the microscope?

stained red/orange; histamine found in the granules (1/3 of histamine is found here

vasodialation

opening of the blood vessels

eosinophilia

allergies + parasitic infections

what wbc plays a role in allergic reactions, stains red/orange, and contains 1/3 of the blood supply’s histamines?

eosinophils

basophils

make up 0.5-1% of wbc (least abundant wbc); some phagocytic activity; important role in graft rejection + viral immunity

how do you distinguish a basophil under the microscope?

granules stain dark purple; heparin, serotonin, and histamine (1/2 blood supply found here) are found in the granules

what wbc is the least abundant, plays a role in graft rejection + viral immunity, stains dark purple, and contains heparin, serotonin, and histamine?

basophils

monocyte

agranulocytic; makes up 3-8% of total wbc, largest wbc (16-20 microns); not phagocytic in the bloodstream until they enter tissue (macrophage); certain bacterial infections can cause monocytosis (elevation in monocytes)

what infections cause an elevation in monocytes?

tuberculosis, rickettsial infections, protozoan + fungal infections

what wbc is agranulocytic, the largest, and only phagocytic in tissue?

monocytes

which cells are phagocytic?

1) “wandering” or “free” phagocytes (neutrophils, eosinophils, basophils, monocytes)

2) “fixed” phagocytes or histiocytes (alveolar macrophages, kupffer cells, lymphocytic macrophages, microglial cells, osteoblasts)

what phagocytes are fixed?

alveolar macrophages, kupffer cells, lymphocytic macrophages, microglial cells, osteoclasts

where are kupffer cells found?

liver

where are microglial cells found?

brain + cns

inflammatory response

sum of reactions in the body incited by injury

what are the steps of inflammatory response?

1) vasodilation (blood vessels open up)

2) hemostatic plug (clotting)

3) pus formation

4) chemotaxsis (phagocytes signaled to site of infection)

5) margination (phagocytes go to margins of blood vessels)

6) diapedesis (phagocytes squeeze into tissue)

7) neutrophils (within hours, 4-5 fold increase), monocytes (12 hours, become macrophage in tissues), eosinophils + basophils show in this order

8) antibody formation

9) tissue repair (fibrinolysis + fibroblasts)

vasodilation

increase in diameter of blood vessels; increase in vascular permeability, increase in blood flow from capillaries to damaged tissues, edema (swelling), redness, warmth

what chemicals are involved in vasodilation?

bradykin, kinin, histamine (eosinophils + basophils), serotonin (platelets + basophils)

hemostatic plug

fibrin clot (wall off)

pus formation

dead cells and body fluids

margination

wbc cling to the inside lining of the blood vessels after phagocytes arrive at the site (chemotaxsis)

diapedisis

phagocytic wbc move from blood into the tissue, fever causes this process (takes only 2 minutes)

fibrinolysis

plasminogen converted into plasmin which breaks down the fibrin clot

fibroblasts

formation of scar tissue