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Microbiology 1 > Lecture #8 - Innate Immunity > Flashcards

Lecture #8 - Innate Immunity Flashcards

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1
Q

The Immune System

A

• The immune system fights off foreign material that threatens the body
• Protects against disease
- think: police to patrol bad guys in a city with diff. departments & diff. neighbourhoods have diff. squads

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2
Q

Diff. immune system attributes depending on…

A

where in the body (b/c they offer diff. req’s that req. diff levels of protection

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3
Q

The Immune System

Consists of two branches:

A
  1. Innate
    • NON-specific
    - treats everything the same with only some differences that aren’t based on specificity but on broader similarity)
    - think: talking to worst enemy & grandma in same tone/engagement
  2. Adaptive
    • HIGHLY specific
    - tailoring response to SARS-COVI-2 delta, omricon etc. based on which variant you get, you’ll get a response which is why vaccinations against a variant won’t have same efficiency against another 1 b/c tailored
    - think: someone has brown hair for while & then changes it next day to red, you have to relearn them as red head
    - previous recognition of them is no longer effective, expect more work & decreased effectiveness initially
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4
Q

The Innate Immune System

A

• Protect humans from most infectious diseases

  • • Exists at birth and always present
  • doesn’t learn or grow

• Natural host resistance

  • • No memory
  • think: 50 1st dates - constantly relearning b/c you don’t remember anything from previous encounter
  • Can be specific for a particular tissue
  • Consists of:
  • Physical barriers
  • Chemical defenses
  • Cellular defenses
  • Molecular defenses
  • Physiological processes
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5
Q

The Innate Immune System

Infection site and tissue specificity

A

*what’s happening in the lung will have a diff. response & diff. things ignored then what might be happening elsewhere for ex

• Pathogens prefer a specific body site to initiate infection
- any organism that has the capacity to be able to tolerate it, must have an evolutionary measure in place - otherwise it cannot use stomach as mode of entry or place to grow
• Based on nutritional and metabolic needs
- better have what it req’s in the site where it lives or don’t work/thrive

• Mechanism of spread
• Aerosols vs blood/bodily fluids
- size, density, amount of time that material spends in atm will determine likelihood that it’s spread to someone else (if it settles out really quickly that means likelihood it’ll spread to another is less, esp. if there’s distancing. If it can linger in air for longer depending on transmission mode & form its in then it has opp. to cause more serious problems - persist for longer)

• Clostridium tetani can be INGESTED or can enter into DEEP WOUNDS
- cause tetanus - rigid paralysis from toxin

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6
Q

Clostridium tetani can be INGESTED or can enter into DEEP WOUNDS

B/t these 2 forms, do you req. the same amount of infectious material in both or amount that needs to enter will be same for all quartiles of entry?

A
  • causes tetanus - rigid paralysis from toxin
  • v. diff!
  • stomach - lose a lot of organism b/c of harsh conditions found there
  • deep wound - puts right where it needs to be in a v. hospitable, non-harsh envir., the quantity of infectious material is diff.
  • blood - pH is neutral, conditions fav. so organism can thrive under those conditions
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7
Q

The Innate Immune System

Natural host resistance

A

• Susceptibility to pathogens varies from one species to another

• Anthrax causes fatal blood infection in cattle and cutaneous infection in humans
- type of infection, severity of infection are all diff depending on organism

• HIV can infect human cells but not mice or guinea pigs

  • some ppl are resistant to diff forms while some are susceptible (COVID too)
  • b/c human immunodeficiency virus that req’s the CD4 receptor for the virus to get in under most conditions
  • can’t grow in lab ?
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8
Q

The Innate Immune System

Physical barriers to infection:

A
  1. Skin

2. Mucous membranes

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9
Q

The Innate Immune System
• Physical barriers to infection

  1. Skin
A

largest organ; covers all extremities

• Prevents invasion by microbes

  • b/c skin is forming TIGHT JUNCTIONS & MULTILAYERED
  • layers stacked on top of each other –> large amount of protection against infection

• Rich in tough protective protein
• KERATIN - lower [ ] creates more looseliness & flexibility
- finger nails are keratin protein - higher [ ]

• Slightly acidic ~pH 5
- provides protection against organisms that don’t like acid conditions

• High [NaCl]-periodic drying

  • creates a hypertonic condition that drags water out of the organism – organism doesn’t have opp. to do well, when it doesn’t have appropriate water content on the inside of the cell
  • maintain to fluorish

• Some fungal infections can grow right on the skin’s surface
- NOT penetrating
- doesn’t need to penetrate or have a puncture wound that’ll allow them to go any further in order to manifest & est. a successful infection - called tinia (fungal infection of a certain variety where you get pink patches right on the surface of skin that has higher moisture ex: from bra on skin)
- paler skin - pink patches
- darker skin - white patches
• Many require broken skin in order to PENETRATE and cause infection
- wound for ex

  • best mode of treatment: TOPICAL (CREAM)
  • not swallowing an antieukartic drug that can do non-specific tissue damage, once loose through body
  • prefered b/c issues with selective toxicity - leaving own cells alone while harming bad cells
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10
Q

The Innate Immune System
• Physical barriers to infection:

  1. Mucous membranes
A

*have OPENINGS to outside of the body (get dirty/contaminated b/c of openings to external envir. so become infective more freq)
Line tracts (open) in the body
• Respiratory tract (for respir. path’s to enter), digestive tract (call it fecal oral spread - spread from mouth to other end & again), reproductive tract (for STI’s for ex), urinary tract (opp. to come up to bladder & eventually onto the kidney’s)
- rich in goblet cells

Mucous produced by GOBLET CELLS
- viscous glycoprotein
• (viscosity) Traps microbes preventing infection/opp. to penetrate deeper within the tract (stops them in their tracks)
- mucous prod. there, then gets expelled to the outside of body where its physically removing these contaminants, preventing serious infection

Contains ANTIMICROBIAL SECRETIONS
- have enzymes & other defenins, that have opp. to kill off/limit growth of organisms coming in via this route

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11
Q

Mucous membranes vs. Sereus membrane

A

Mucous membranes - have OPENINGS to outside of the body (get dirty/contaminated b/c of openings to external envir. so become infective more freq)

Sereus membrane - CLOSED OFF (sterile sites b/c no openings to outside of body, therefore consistently have protection against microbial contamination)
- ex: abdominal cavity (periteneum)

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12
Q

The Innate Immune System
• Physical barriers to infection:

  1. Mucous membranes
    • The respiratory tract
A

• Contains the MUCOCILLIARY ESCALATOR

  • Mucosal epithelial cells contain CILIA (can switch back & forth to allow for movement of certain structures)
  • Serve to filter incoming air
  • Sweeping action of cilia allows the removal of mucous and trapped microbes from the lungs
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13
Q

What are the cells called that line respiratory mucosa? What’s attached to the cells?

A
  • epithelial cells

- cilia is attached

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14
Q

Mucocilliary escalator

A

any bact. that come in this way, the goblet cells are gonna serve to create the viscosity & the cilia with their movements up & down & back & forth are gonna allow the mucous to physically exit the body

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15
Q

When sleeping at night with a cold:

A
  • theirs a large # of respiratory contaminants
  • result:
  • more mucous prod. b/c body understands need to trap these guys
  • cilia have moved against the force of gravity (easier when laying flat)
  • get urge to cough when awake b/c got an accumulation of mucous right there)
  • when cough can either: physically remove from body or swallow it (sending mucous (glycoprotein - nutrients), bact. (dead & alive - PL’s, nucleotides, AA’s, & sugars) & immune cells, dust/debris (dead skin cells) to get broken down by digestive tract so you get source of nutrient for building blocks or ATP prod.)
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16
Q

Pertussis (whooping cough)

A

caused by bordetella bacterium & the Pertussis toxin it produces destroys epithelial lining, so you lose that lining

result:

  • have infection
  • excellerated mucous prod.
  • got mucous that needs to be cleared from the airway
  • but get no help from ciliated cells
  • therefore, on you to cough to physically clear the lung which is far from the throat, so now its an exaggerated cough (whooping cough) & can die from exhaustion (just finding ability to breathe)
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17
Q

The Innate Immune System
• Physical barriers to infection:

  1. Mucous membranes
    The gastrointestinal tract
A

a. The stomach

b. The small intestine

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18
Q

The gastrointestinal tract

A

called an ALIMENTARY CANAL b/c we have an opening at top & bottom (mouth –> anus)

  • think: factory (jacket goes from location to location, becoming further assembled in the process)
  • when we take nutrients into the body, they move from location to location along length of eliminatory canal, being further digested at each station in order to change chemical comp. & simplify material along the way
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19
Q

The Innate Immune System
• Physical barriers to infection:

  1. Mucous membranes
    a. The stomach
A

1st location esophagus delivers food to is the stomach

• Strongly acidic: pH~2

  • pH 1-3
  • 1 = HCl acid which comes from gastric glands has a pH of 1 (SA that fully depros)
  • 3 = BUT add food to stomach (which isn’t strongly acidic - buffer scenario so its not acidic all the time b/c can be destructive)
  • also has PEPSIN - proteolytic enzyme, acid in stomach unraveals the protein you consumed, therefore proteins become denatured, exposing peptide bonds & then pepsin has a go at some of those in order to fragment & simplify the dietary protein or protein part of bact. cell or your own cells or enzymes from mouth for ex
  • outcome: later on during digestion, there’s less work to be done
  • Contains PROTEASES (enzymes that breakdown protein)
  • FEW microbes are able to SURVIVE in this environment
  • b/c so acidic
  • not a perfect fool proof antimicrobial defense
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20
Q

Few microbes are able to survive in this environment (stomach) b/c so acidic. Why is it not a perfect fool proof antimicrobial defense?

A

viruses like HIV that come into baby’s body via infected breast milk

  • virus isn’t bothered by these conditions & have capacity to survive transit directly through
  • therefore, not all viruses will have problems with this so it’s not a perfect fool proof antimicrobial defense
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21
Q

The Innate Immune System
• Physical barriers to infection:

  1. Mucous membranes
    The gastrointestinal tract
    b. The small intestine
A

• PANCREATIC JUICE (has trypsin, chymotrypsin, carboxypeptidase & pancreatic lypase (respon. for most fat digestion that occurs from the digestive tract, pancreatic amylase & nuclease enzymes to digest DNA & RNA that might be present within the tract) buffers acidity of incoming contents from the stomach: pH ~7
- don’t want acidic conditions in intestine b/c can create ulcers & will also be inhospitable for the envir. that the enzymes req here (pH neutral)
- contains HCO3-; neutralizes the acidic material that’s coming from the stomach so you don’t have an acidic envir. here where it shouldn’t be - protection
• Contains PANCREATIC ENZYMES

• Contains BILE from the liver

  • serves to emulsify fat
  • stored in gall bladder
  • break fats into smaller, manageable pieces (hydrophobic fats want to stay together to min. contact with the water)
  • bile salts are amphipathic & have opp. to interact with fat droplets & water fav. – keeps them apart so pancreatic lipase can digest them more effectively in a more timely fashion
  • can also tear apart bact. mem

• Very DIFFICULT for microbes to MAINTAIN CELLULAR INTEGRITY in this harsh environment

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22
Q

The small intestine

A

receives chyme that still has a lot of nutrients that’ll req. increased help for digestion

*- really simplifying dietary nutrient source - making it into small molecules that are v. easy to digest & absorb into the blood to be sent off to various cells within your body

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23
Q

On the layer of the enterocites which line the SI, you also have ______, which are….

A

BRUSH BORDER ENZYMES

periferal proteins that behave as enzymes to digest maltose, sucrose, lactose, etc.

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24
Q

The Innate Immune System

  1. Mucous membranes
    The large intestine (colon)
A

Contains the normal microbiota

• Normal resident bacteria that live SYMBIOTICALLY inside of the colon

• Use ATTACHMENT sites to persist
- b/c if can’t stay - will be flushed out b/c of constant forward movement of this material

  • CONSUME UNDIGESTED nutrients
  • Competitive exclusion
  • PRODUCE ANTIMICROBIAL compounds
  • Microbial antagonism
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25
Q

The large intestine (colon)

A

not doing enzymatic digestion - not taking things apart (everything we needed to absorb from a nutrient standpoint has been absorbed)
- therefore, material entering LI is undigested content & waste products that are supposed to leave body

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26
Q

Goal in LI is:

A
  • take back water to keep a consistant texture for our stole
  • so its not diarrhea which will also dehydrate us
  • & take back a lot of salts which is an incentive for water to follow
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27
Q

The large intestine (colon)

Use attachment sites to persist

think:

A

put garbage out & someone sees & wants it

  • SI passes it to LI b/c it didn’t want it or didn’t have a mode to digest it
  • microflora that live in LI can eat it & digest it if they have the enzymes to do so
  • your trash is their benefit
  • when they digest it, some of that material can enter your blood b/c if its hydrophobic it can move directly across layer of LI through to blood supply on other side which means you took even more nutrients & cals from your food but also help each other provide a nutrient envir to feed off of
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28
Q

The large intestine (colon)

Consume undigested nutrients

A

Competitive exclusion

  • competing with each other
  • by consuming those undigested nutrients, should a bad bact be able to enter the body, it’s not gonna have opp. to persist b/c these good guys are there consuming nutrients & taking up space
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29
Q

The large intestine (colon)

Produce antimicrobial compounds

A

Microbial antagonism
- producing bad things - toxic, poisonous to organism, therefore means won’t be able to persist if there’s toxicity that kills off the cell

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30
Q

Imagine you take an antibiotic for UTI, & although it’s atypical say its gram + (using broad spectrum 1 that’s both gram +/-). What’s the prob in add. to benefit it does in killing threat to you?

A

will kill the good ones

  • lose competitive exclusion
  • lose microbial antagonism

chose gram + infection b/c in reality gram - organisms live inside LI

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31
Q

The Innate Immune System
2. Mucous membranes

The genitourinary tract

A

diff in males & females

• Genital and urinary tracts are SEPARATE in FEMALES (genital tract - vaginal –> cervix –> uterus –> FT’s –> ovary & then urethra –> bladder –> ureters –> kidneys) and JOINT in MALES (urethra serves as a port of passage for serum & urinary tract (similar to females)

  • Urinary tract contains urine
  • Includes many toxins that are intolerable by bacteria
  • The act of urination physically removes contaminating microbes
  • The female reproductive tract contains normal microbiota
  • Glycogen secreted by vaginal epithelial cells supplies nutrients for microbial growth (@ puberty)
  • Lactobacillus acidophilus
  • Ferments glucose to lactic acid (drops pH of vaginal lumen)
  • Local pH ~4.5 (antimicrobial defense against STI’s b/c slightly acidic - also reason why semen contains alkaline secretion b/c sperm will be comprised by this acidity as well - imp. opp. to protect them against acidity to make sure they can make it to the egg properly
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32
Q

Why are woman encouraged to urinate after sexual activity?

A

The act of urination physically removes contaminating microbes

  • b/c any contaminants that may have been redistributed b/c of the urethra, vaginal & rectum openings you have opp. for material in trace amounts to move back & forth (otherwise can dev. a bladder infection)
  • make way up urethra (short) (if able to spread it can cause pyelonephritis (life threatening b/c a) immune activation in kidney can lead to scar tissue & b) if bact makes way into blood then outcome is you might end up with sepsis
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33
Q

The Innate Immune System

• The Lymphatic System:

A
  • Composed of organs and vessels that allow immune cells to contact foreign antigenic material
  • An antigen is foreign material that is able to activate cells of the immune system
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34
Q

Components of the lymphatic system include:

A

Lymphatic vessels

Lymphoid organs

35
Q

Lymphatic vessels

A
  • Carry lymph from the tissues to the lymph nodes
  • Unidirectional (always away from tissues)

• Lymph is RICH in leukocytes (white blood cells)
- fluid is clear
• Free/NO of erythrocytes (red blood cells)

36
Q

Lymphoid organs

A

Primary and secondary

37
Q

Explain Lympathic System

A
  1. Blood comes in at arterial end of capillary
    - net filtration pressure forces fluid out into ECF (idea is to deliver O2 & nutrients to tissue cells)
    - if we call valve of fluid that gets pushed out here 100%
  2. At venule end of capillary we take back 90% of that filtered fluid b/c net filtration pressure fav’s absorption into capillary bed
    - allows us to maintain BV - b/c if we left behind all this material we’d a) be swollen & b) can’t maintain BV & BP b/c
  3. 10% not yet collected goes into lymphatic capillaries (then to lymphatic vessels & lymph nodes (have an accumulation of WBC’s)
    - allows unidirection (away from tissue)
    - therefore, ultimately collected 100% of what got filtered
38
Q

Step on nail (foot)

A
  • inoculated self with bact (ex: costilium tetani)
  • when you take back 10% of that filtered fluid into lymphatic capillary - those bact go into these & fluid flows away (with bact) to lymph node
  • cells all get diff activation signals based on their engagement with the bact & then their result from signals is to proliferate (mitotic division)
  • then to restore BV, 10% of that filtered fluid will go back into veins in neck
  • therefore, do put it back anyway, but just go round about way, just to make sure you have opp. to test for anything that shouldn’t be found in tissue
39
Q

How does your lymph node feel for you when you got a lot of mitotic div. that’s taking place inside that lymph node?

A

larger - swollen b/c so many cells/activity & indicates something is ary

40
Q

The Lymphatic System:

Primary lymphoid organs:

A

Bone marrow
- have diff. signals that’ll force prod. of diff things
• Leukocytes are PRODUCED here

Thymus gland
• Some leukocytes MATURE here

41
Q

B lymphocytes MATURE in

A

Bone marrow

42
Q

T lymphocytes MATURE in

But made in…

A

Thymus gland

made in Bone marrow

43
Q

The Lymphatic System:

Secondary lymphoid organs

A
  • Lymph nodes
  • Spleen
  • Mucosa associated lymphatic tissue (MALT)
  • **All contain a high concentration of leukocytes
  • b/c as foreign material is encountered, you have opp. to go forward & mount a response
  • think: place where police can come in contact with a criminal (ex: prison, police station etc.)
    • Incoming lymph is filtered
  • as lymph is filtering through, if anythings in there, those WBC’s turn on & activate
44
Q

The Innate Immune System

• Mucosa Associated Lymphatic Tissue (MALT):

A

• Associated with all mucous membranes

  • v. dirty (constantly contaiminated)
  • therefore, need for immune responses here more, then if it was a sterile location that rarely have microbes introduced

Call it GALT in intestines:
• GALT: Gut Associated Lymphatic Tissue
• Leukocytes present here are constantly phagocytosing material in their surroundings in search of foreign content
- always active when things that are found there that shoudn’t be

45
Q

GALT: Gut Associated Lymphatic Tissue doesn’t always work in our favour:

A
  • HIV + women that breastfeed their baby for ex
  • virus comes through to GIT & when GALT gets a grip on it (T helper cells in GALT that HIV goes into & infects)
  • fact that HIV is an immunotropic virus & specifically looking for immune cells, this makes the baby HIV +
  • works 100% against the virus in terms of getting rid of it provides a portal for infection
  • therefore, GALT isn’t fool proof, ideal or avoidable at times when it is an immunotropic virus, otherwise 100% effective at preventing infection
46
Q

The Innate Immune System

• Cellular defenses:

A

LEUKOCYTES-white blood cells

  • CIRCULATE in the BLOOD and the LYMPHATIC SYSTEM
  • RESIDE in the TISSUES and the LYMPH NODES
  • wait in case anything is encountered there
  • think: officiers present at stations (blood), neighbourhood (tissue)
  • everywhere so constantly have protection against what shouldn’t be there

• Play a role in BOTH innate and adaptive immunity

47
Q

The Innate Immune System
• Cellular defenses:
• Leukocytes-white blood cells

Two broad categories:

A

BOTH have cytoplasmic granules - just differ in size

  1. Granulocytes
  2. Agranulocytes:
48
Q

Granulocytes:

A

• LARGE, VISIBLE granules in the cytoplasm

• Granules are REACTIVE
• Can KILL MICROBES
• Can serve as SIGNALING MOLECULES to RECRUIT and ACTIVATE OTHER COMPONENTS of the immune system
- b/c once granules get released can bind to other immune cells & recruit them to create a response
- think: police radio for backup & share info about what they found

49
Q

3 types of granulocytes

A

a. Neutrophils
b. Eosinophils
c. Basophils and Mast Cells

50
Q

Granulocytes:

a. Neutrophils

A
  • Cytoplasmic granules contain
  • Lysozyme
  • Defensins

• CIRCULATE in the BLOOD
*- BUT can do EXTROVASATION - able to escape blood cell under characteristics of inflammation
- when theirs an inflammatory response taking place, these cells are able to squeeze out (b/c gaps or fenestrations in capillary become larger under inflammatory signals) & able to migrate to the tissue so they have better opp. to fight off infection
- think: like police get called to neighbourhood according to where needs for them might be located
• Exit the capillaries during periods of infection

• STRONGLY PHAGOCYTIC
- an endocytic event that then follows through & destroys these bact that are isolated where they shouldn’t be

• Very IMPORTANT cells of the innate immune system
- b/c behave as vacuum CLEANERS for threats that need to be removed from insides of body

51
Q

What are lysozymes & defensins?

A

chemicals that’ll be destructive to microbes
- allow microbe to be destroyed v. readily by presence of these chemicals when they get released (ex: PD structure, poke holes (defensins) inside cell to make it no longer vitable etc.

52
Q
  1. Granulocytes:

b. Eosinophils

A

• NON-PHAGOCYTIC cells
- every cell has opp. to do endocytosis but from an immune standpoint, this isn’t what they’re profession is

• Cytoplasmic granules will STAIN with ACIDIC dyes

• Work to DESTROY LARGE PARASITIC CELLS
- think: want to swallow other person - limitation is that its SAME SIZE (both Euk cells)
- parasites are Euk, phagocytes are Euk
• Protozoa and parasitic worms
*• SECRETE EXTRA-CELLULAR ENZYMES (that digest protein, lipid or sugar) and REACTIVE OXYGEN SPECIES (all over the surface & slowly dismember parasitic cell so its not structurally intact any longer)
- result: in high [ ] on top of worm (parasite) for ex
- complete destruction
- organism will lose all its physical characteristics & it gets broken down
- think: spitting on cracker - salivary amylase & lingual lipase will have destructive effects on chem. comp. of cracker but happens outside of your body
• H2O2, OH., O.

• Can also EXIT the CAPILLARIES INTO INFECTED TISSUES
* - capacity to do EXTRA-VASATION (leaving to find where infectious material will be)

53
Q
  1. Granulocytes:

c. Basophils and Mast Cells

A
  • Cytoplasmic granules STAIN with BASIC dyes
  • NOT STRONGLY PHAGOCYTIC (CAN do it)
  • can pick up things that don’t belong, take them in & destroy them, but not their main role
  • think: no one asked prof to pick up garbage in lecture hall but have no problem to
  • BASOPHILS CIRCULATE in the BLOOD
  • MAST CELLS RESIDE in MUCOSAL TISSUE

• DEGRANULATE IN RESPONSE to appropriate STIMULI
- think: same way policeman might be told to make an arrest
- receive signals that they respond to that then result in a characteristic outcome
• RELEASE HISTAMINE

54
Q
  1. Granulocytes:
    c. Basophils and Mast Cells

Release histamine

A
  • Important part of the ALLERGIC RESPONSE
  • Causes VASODILATION LOCALLY (increases BF)
  • Causes life threatening VASODILATION and BRONCHIOLCONSTRICTION when released SYSTEMICALLY
  • causes drop in mean arterial BP which puts you in shock & conseq is multi organ failure
  • bronchiolconstriction makes breathing more diff.
  • when epipen (epinephrine) behaves as an antagonist causing vasocon to build BP back & bronchodil to open airways buying just enough time for short lived hormone until it breaks down in your body to go to doctor to get antihistamine that’ll mop up material that shouldn’t be found in body to negate response hist. is creating
55
Q

The Innate Immune System
• Cellular defenses

  1. Agranulocytes:
A

Contain cytoplasmic granules that are much smaller and more difficult to view than granulocytes

56
Q

The Innate Immune System
• Cellular defenses

  1. Agranulocytes:

Include:

A

a. Monocytes:
i. Macrophages:
ii. Dendritic Cells (DCs)

b. Lymphocytes:
i. B lymphocytes
ii. T lymphocytes
iii. Natural Killer Cells (NK cells)

57
Q

Agranulocytes:

a. Monocytes

A

think: baby - immature, live at home & have no job –> monocytes - no job, called monocyte, live in blood matures into macrophage (or DC) (adult) - get job - strong phagocytic ability (like neutrophile in granulocyte category) & leave blood (migrate into tissue), gonna be present in lung, skin, liver & serve as APCs

• CIRCULATE in the BLOOD

• MIGRATE INTO TISSUES and MATURE INTO either MACROPHAGES or DENDRITIC CELLS
• Once IN the TISSUES they are VERY STRONGLY PHAGOCYTIC
• PRESENT FOREIGN ANTIGEN to other cells of the immune system
- called antigen presenting cells (APCs)

58
Q
  1. Agranulocytes:

a. Monocytes:
i. Macrophages:

A

monocytes are immature, no job, & remain in blood
- BUT once they reach maturity, they escape from blood into the tissues & dev a job which is specialized phagocytosis

Located IN the TISSUES
• Lungs, connective tissue, spleen, liver
- any infectious material that comes in, they can initiate phagocytosis & removal of

Contain SPECIAL SURFACE RECEPTORS that allow them to recognize many pathogens with one receptor
- ways to identify what shouldn’t be there
• TOLL-LIKE RECEPTORS (TLRs) - inside cell mem.
- Recognize things like LPS, peptidoglycan,
elements of the fungal cell wall (can get Euk. infection with fungus)
• BINDING of the toll-like receptor to antigen INDUCES PHAGOCYTOSIS
- so organism can be taken into the cell where it’ll undergo subsequent destruction

59
Q
  1. Agranulocytes:
    a. Monocytes:
    ii. Dendritic Cells (DCs):
A
  • Found IN TISSUES that are often SITES OF ENTRY for INFECTIOUS MATERIALS
  • In the SKIN they’re called LANGERHAN’S CELLS
  • look like a star
  • can stick arms out into fluid that’ll be present at that tissue location so they can reach & grab materials that aren’t supposed to be present there
    • always have opp. to be able to find things of the skin surface, bring them in to the nearest lymph node & initiate response against them so it doesn’t have opp. to get into body when there’s a cut & cause a more serious infection – a PROACTIVE IMMUNE RESPONSE - anticipate over time, something serious will happen here

• Also FOUND IN the MUCOUS MEMBANES of the nose, the lungs and the intestines
- dirty b/c open to outside (constantly having contamination - req. an elevated defense so they don’t become infected more often than they already do)

• Regularly SAMPLE the SURROUNDINGS and PHAGOCYTOSE ANTIGENS
- then gets taken into interior & trafficked so other cells can see, activate & locate against that so you get a specific immune response in a ~memory format that’ll be protective at a later period of time
- Phagocytosed antigen is carried to lymphoid organs
- Presented to other cells of the immune system
(T/B lymphocytes)
- Activate the adaptive immune response (*get memory - benefit from it if gets into body b/c of an introgen)

60
Q
  1. Agranulocytes:

b. Lymphocytes:

A

• Leukocytes the are involved in the *ADAPTIVE immune response
- macrophages & DC are associated with innate immune response

• CIRCULATE through the BLOOD and REMAIN IN the LYMPHOID ORGANS
- high [ ]’s of lymphocytic cells

61
Q
  1. Agranulocytes:
    b. Lymphocytes:

i. B lymphocytes

A

made & matured in bone marrow

• Also called B CELLS or PLASMA CELLS
- name when they’re producing & secreting large amounts of antibody

• ANTIBODY PRODUCING/SECRETING CELLS
- imp in fending of infection

• Form the main component of HUMORAL IMMUNITY
- help with binding to material that shouldn’t be found inside body

62
Q
  1. Agranulocytes:
    b. Lymphocytes:

ii. T lymphocytes

A

made in thymus gland

• Also called T CELLS

• Different types (with diff role)
- T helper lymphocytes, cytotoxic T lymphocytes, regulatory T lymphocytes

• Form the main component of CELL MEDIATED IMMUNITY

63
Q

Humoral & cell mediated immunity are both elements of…

A

adaptive immunity

64
Q
  1. Agranulocytes:
    b. Lymphocytes:

iii. Natural Killer Cells (NK cells):

A

• DESTROY ABNORMAL CELLS in the body (cancer cells, infected cells)

*are innate immunity

65
Q

Bone marrow stem cell

A

based on diff chem envir’s or nodges into a certain direction, you have opp to turn this into either a myeloid or lymphoid precursor

66
Q

DC, Macrophage, Neutrophil, & Mast cell functions:

A

phagocytosis & antigen presentation; allergy (mast cell) (allergen distruction)

67
Q

T cell function

A

cell-mediated immunity

68
Q

Plasma cell function

A

antibody production

69
Q

T cell & plasma cell are respon. in

A

adaptive immunity

  • allow opp to mount a more specific immune response
  • need that for adaptive immune system as a whole
70
Q

Each of these cell types will be produced according to…

A

need from bone marrow & have them made according to the schematic here in order to facilitate both branches of the immune system

71
Q

The Innate Immune System

• Molecular defenses:

A

are specific molecules

• SECRETED AT MUCOSAL SITES

• LYSOZYME:
• CUTS b-1,4 glycosidic bonds (b/t NAG & NAM) in peptidoglycan
- allow PD to be destroyed & bact doesn’t get protection against things like cell wall structure which protects against osmotic balance etc.
- therefore, organism doesn’t have an intact cell wall & suffers consequences of that as a result

  • DEFENSINS:
  • ANTIMICROBIAL PEPTIDES that POKE HOLES in bacterial cell membranes

organism loses structural integrity b/c all the contents from inside & outside will leak
- organism is ~dead

72
Q

The Innate Immune System

• Phagocytosis

A

• DESTROYS PATHOGENS that may have NEVER before been ENCOUNTERED in the body
- mounting a response against something that shouldn’t be there, in efforts to remove or eliminate it from the insides of the body

• INVOLVES LEUKOCYTES CAPABLE OF PHAGOCYTOSIS
*• Neutrophils (granulocyte) and macrophages (agranulocyte)
- are professional phagocytes
• RECOGNIZE (material that shouldn’t belong by) pathogen associated molecular patterns (PAMPS):
- think: can recognize ppl by eyes, hair etc.
- not specifically recognizing Tom Jones but recognizing fact that theirs hair so it must be a person
• LIPOPOLYSACCHARIDE (LPS on all Gram -, with PAMP, if phagocyte can recognize that, any gram - can be destroyed), lipoteichoic acid (in cell wall of gram +’s - if you can recognize lipoteicholic acid, gram +’s will be destroyed), flagellin (if you recognize this on a motile organism, the organism is gonna be subject to destruction)

• PAMPs are RECOGNIZED BY TLRs located on the surface of phagocytic cells (in phagocytic PM)
• TLRs are also called pattern recognition receptors (PRRs)
- & followed by a numerical designation
- TLR-1
- TLR-2

*• Interaction of PAMP with a TLR triggers phagocytosis

73
Q

Binding by ______ activates phagocyte to kill pathogen

A

phagocyte PRR

74
Q

The Innate Immune System

• Phagocytes engulf and destroy invading microbes

A
  • Cell membrane INVAGINATES around a foreign particle
  • ENGULFS it into a phagosome

• Phagosome FUSES with a LYSOSOME to form a PHAGOLYSOSOME
- digestive enzymes are unleashed on organism & then organism is fragmented & destroyed
• Filled with:
• Lysozyme and defensins
• Proteases (degrade proteins)
• Lipases (degrade phospholipids)
• Nuclease (degrade nucleicacids)

All these types of killing that happen b/c of the chemicals & enzymes are collectively referred to as:
• OXYGEN INdependent KILLING
- b/c it doesn’t make use of a reactive O2 species in order to complete the killing activity
- O2 doesn’t need to be avail.
- don’t need any radical like superoxide for ex
- & organism will naturally be subject to destruction b/c of the organic material that bug is made of & the enzymes & chemicals that destroy organic material

• OXYGEN DEpendent KILLING

75
Q

Phagosome fuses with a lysosome to form a phagolysosome

• Filled with:

A

• LYSOZYME and DEFENSINS
- respon. for destroying cell wall PD & poking holes in mem. of organism to subject it to death

• PROTEASES (degrade proteins)
- cut peptide bonds found within protein to breakdown & simplify structure

• LIPASES (degrade phospholipids)
- degrade glycerol attached to FA’s & head group

• NUCLEASE (degrade nucleicacids)
- present within phagolysozyme which specifically help with destruction of nucleic acid

76
Q

Phagocytosis 3 steps

A
  1. Bacterium binds to the surface of phagocytic cell (where PRR & PAMP come together)
  2. Invagination of phagocytic membrane traps the organism within a phagosome
  3. A lysosome fuses & deposits enzymes into the phagosome. Enzymes cleave macromolecules & generate reactive oxygen species, destroying the organism
77
Q

Phagocytosis continued:

Oxygen dependent killing:

A
  • Activated phagocytes produce reactive oxygen compounds:
  • H2O2 (hydrogen peroxide), O2• (superoxide), OH• (hydroxyl radical), HOCl, NO (nitric oxide)

• Kill ingested microbes by oxidizing cell components
- highly reactive molecules will go to town on this phagocytosis microorganism & cause widespread destruction to its mem, proteins, nucleic acid such that the organism won’t have capacity to survive

78
Q

Phagocytosis continued:

Once invaders have been killed:

A
  • NEUTROPHILS PERFORM EXOCYTOSIS
  • Fragments are expelled from the cell (vomiting material digested on inside (recycled nutrient, AA’s, carbs, etc.)

• MACROPHAGES and DENDRITIC CELLS BECOME ANTIGEN (something your immune system responds to) PRESENTING CELLS
- rather than vomit out material, they instead take material & put it on the surface (call it antigen presenting)
- APC’s are respon. for priming other elements of the immune system by antigen presenting
• FRAGMENTS (used to show other immune system cells what’s going on - present it to them b/c they think they should take responses a lil further) OF the INTRUDER are PRESENTED ON the CELL SURFACE TO TRIGGER an ADAPTIVE immune response

79
Q

Inflammation:

A

• Occurs NON-SPECIFICALLY in response to tissue

damage, toxins, and infectious material (has been localized present on inside of body)

80
Q

Five cardinal signs of inflammation are:

A
  1. Redness (erythema)
    - increase BF, increase colourization
  2. warmth
    - warm to the touch
  3. pain
    - pain receptors alerting
  4. swelling (edema) and
    - b/c fluid is leaking out of BV in response to this inflammatory activity
  5. loss of function
    - b/c so much swelling, pain etc. that make it impossible for it to not be painful & function normally
81
Q

In response to infection injured tissue and leukocytes release…

A

PRO-INFLAMMATORY CYTOKINES (amp up immune response (trying to protect body & eliminate bad guys)
- draw other immune cells to this location (recruite them) & to get them to do things that are helpful
• Blood vessels DILATE
- increase diameter, increase flow, increase delivery of WBC’s & other helpful things to fend off infection as its occurring
• Allows MORE LEUKOCYTES to ACCESS the AREA

• Vessel WALLS become MORE PERMEABLE (opens up)
- gaps become wide enough for WBC’s to squeeze through them so they can get into ECF of tissue where infectious material is so they can mount response against - in order to initiate the distruction of what it is that shouldn’t be found there
• LEUKOCYTES CAN SQUEEZE INTO TISSUES
• EXTRAVASATION
• ATTACK INVADING PATHOGENS

• TEMPERATURE INCREASE may SLOW the GROWTH OF PATHOGENS
- b/c temp restricted (if not optimal temp, they’re not gonna do a great job in terms of replication rate)
• Also PROMOTES FASTER HEALING OF DAMAGED TISSUES

• BLOOD LEAKING INTO TISSUE SPACES CAN CLOT
• PREVENTS MOVEMENT (to other locations) of pathogens
*- b/c don’t want infectious material to become systemic or to deseminate to other parts of body that you’re trying to keep protective or coverted
- localization makes the job of immune system much easier - much less work to be done under these circumstances

82
Q

Fever:

A

An INCREASE in body TEMPERATURE
• CONTROLLED BY the HYPOTHALAMUS of the brain
• It is TRIGGERED BY TOXINS, LPS, and CHEMICALS (located where they shouldn’t be) produced by the immune
system
• All of these things RESET the bodies THERMOSTAT (setpoint temp - will be reset with interest to put things back to normal so you don’t end up with overgrowth or more serious infection (& end up with faster healing)

83
Q

Fever:

Results in:

A

• Muscle contraction-SHIVERING

  • muscles associated with hair follicles (erectopili muscles) contract as part of this response
  • heat will be a waste/byproduct
  • therefore, get increased temp, faster metabolism & faster healing
  • Increased temperature-FASTER METABOLISM and PROMOTED HEALING
  • FASTER PHAGOCYTOSIS (under influence of increased temp)

• SLOWER GROWTH of MICROBES
• E. coli prefers to grow at 37oC
• (will see a slower growth rate or slower rate of binary fission) Growth slows at 40oC
- situation now where organism with slow growth will replicate less, fewer organisms that need to be cleaned up by immune system & then that inturn means immune system can get job done faster (doesn’t have to go as far as to clean up infection)
- bact is more sensitive to temp b/c made of enzymes, PL’s etc.
- if you don’t have control over your temp, your own enzymes, PL’s, DNA are all gonna be destroyed by increased temp
- outcome: gonna be damaging/destructive to you, such that it can be lethal if not controlled & prevent it from getting to high

  • Up to a certain temperature FEVER is a DEFENSE against disease
  • Fever above 43oC can cause death
84
Q

What is the reason that a fever persisting for certain amount of time req’s doctor?

A

is b/c everything that drug (Tylenol - interfers with prostaglandin syn. so you can’t get a fever), breaks down in your system, if fever keeps coming back, that’s an indication that the infectious material is still there to trip this response
- so need to have that dealt with to get rid of it b/c immune system isn’t helping you if infection still persists, even after all that

Microbiology 1 (15 decks)

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