Lecture 8: The Innate Immune system Flashcards
The Immune System
- 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
where in the body (b/c they offer diff. req’s that req. diff levels of protection
What are the 2 branches of the immune system?
- 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 - 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
The Innate Immune System
Protect humans from most infectious diseases
- • Exists at birth and always present
- doesn’t learn or grow
- always the same from birth to death; limitations b/c of this
• 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
Infection site and tissue specificity
*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
- ex- fecal oral mechanism of spread- things thare coming into stomach acidity of stomach (1-3) depending on how much food is present these will be very harsh conditions 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 (droplets) 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 (fecal oral) or can enter into DEEP WOUNDS
- cause tetanus - rigid paralysis from toxin
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?
- 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
Natural host resistance
• 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
Physical barriers to infection:
- Skin
2. Mucous membranes
- Skin
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
slightly acidic pH
• Rich in tough protective protein
• KERATIN - lower [ ] creates more looseliness & flexibility
- finger nails are keratin protein - higher [ ]
• 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
keratinocyte
type of cell that is distributed throughout skin and responsible for producing keratin
Where can some fungal infections grow?
• 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
What is the best treatment for a fungal infection?
- 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
Mucous membranes
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
traps microbes preventing infection
Contains ANTIMICROBIAL SECRETIONS
have enzymes & other defenins, that have opp. to kill off/limit growth of organisms coming in via this route
Explain how the mucous traps microbes?
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
What is the difference between Mucous membranes vs. Sereus membrane?
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)
The respiratory tract
• 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
epithelial cells
cells that line respiratory mucosa
cilia
attached to epithelial cells
- have hairs that allow motility so they can swish back and fourth to allow for movement of certain structures
Mucocilliary escalator
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
When sleeping at night with a cold:
- 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.)
Pertussis (whooping cough)
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)
The gastrointestinal tract
called an ALIMENTARY CANAL b/c we have an opening at top & bottom (mouth –> anus)
- 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
The stomach
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
- FEW microbes are able to SURVIVE in this environment
- b/c so acidic
- not a perfect fool proof antimicrobial defense
Few microbes are able to survive in this environment (stomach) b/c so acidic. Why is it not a perfect fool proof antimicrobial defense?
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
The small intestine
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
What is the overall function of the small intestine?
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
On the layer of the enterocites which line the SI, you also have ______, which are….
BRUSH BORDER ENZYMES
periferal proteins that behave as enzymes to digest maltose, sucrose, lactose, etc.
The large intestine (colon)
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
The large intestine (colon) overall function
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
Goal in LI is:
- 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
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
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
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
will kill the good ones
- lose competitive exclusion
- lose microbial antagonism
chose gram + infection b/c in reality gram - organisms live inside LI
The genitourinary tract
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
