MGY277H1 Lecture Notes - Lecture 10: Humoral Immunity, Thymus, Epitope

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Lecture 10 Immunity and Vaccines
First Line Defenses-How do we stay healthy?
Where are the microbes in a healthy body?
Bone + Blood +Muscle +BladderSterile
Mouth + Skin NOT sterile
StomachAlmost Sterile (high acidity, low [microbes])
Small Intestine 10^4 (almost sterile)
Large Intestine10^10-11 per ml (extreme high)
Compartmentalization
Microbes are tolerate or even encourages to grow at some sites
Those exact same microbes can be deadly if introduced to a different site in
the body that is meant to be kept sterile
Examples: If E.coli in the colon goes into the blood stream you will duffer
from Sepsis (life threatening condition)
Fundamental concept
Multiple distinct mechanisms
work together to control
microbial growth in our tissues
No single system is
sufficient to protect us from all microbes
First line DefensesBody Borders
1st line defense against invading microbes
Some “boarder” are though to be “inside” the body but they are in contact
with external environment
Digestive tractstarts at mouth, ends at anus
Respiratory tractCavity that allows gas exchange
Skin
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Difficult for microbes to penetrate
All exposed surface covered with epithelial cells
oTightly packed, rest on fibrous layer
1. Epidermis many layers of epithetical cells
a. Outermost cells are dead, flat, filled with
keratin
b. Repis water, maintains dry environment
c. Continually slough off along with any attached
microbes
2. Dermis tightly woven fibrous connective tissue
a. Separate by basal lamina membrane
b. Cells surrounded by collagen and other elastic
protein
c. Cow dermis is main component of leather
Mucous Membrane
Line digestive, respiratory, genitourinary tracts
Constantly bathed in secretion (mucous)wash
microbes away
Peristalsis of intestines, mucoiliary escalator of respiratory tract move
microbes to areas for eliminateon (i.e when you blink/pee, etc)
But they are frequency location of infection
Antimicrobials substanceprotect skin & mucous membrane
1. Saltfrom perspiration on skin
a. Salt-intolerant organisms most susceptible
2. Lysozymedegrade peptide
a. Tears, Saliva, Mucus, Phagocytic cells, Blood
3. Peroxidase enzymes breakdown hydrogen peroxide to make highly
reactive O2 species
a. Saliva, Milk, Body tissue, phagocytes
b. Catalase-negative organisms most susceptible
4. Defensinsform pores in microbial membranes
a. Small peptides produce by neutrophils and epithetical cells
b. Small intestine produce huge amountsterile
5. Acidicstomach, vagina and tears make life inhospitable for most microbes
a. Stomach kept at low pH, along with acid stabilizing enzyme (digest
food) stomach will degrade most microbe we inject
b. Microbe that cause gastric ulcer live beneath the mucous layer (NOT
in the stomach)
c. Vaginal low pH created by epithelial secrete glycol as a carbon source
to support growth of lacto bacillilactic acid
6. Bileproduced by the gall bladder and injected onto stomach content as
they pass into the small intestine is a potent antimicrobial compound
a. Potent antimibrobial compound similar to detergent
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b. Intestine bacteria are resist to itmodify to create secondary Bile
acidmore portent and prevent competing microbe from
establishing home
Nutritional Immunitymaintain nutrient in form that are not easily accessible by
microbial invader (Iron is required for ALL forms of life)
1. Tranferrintransport iron form stores in the liver to cells that require it
for graoth
a. Quickly binds free iron to make it unavailable to most microbes
2. Lactoferrinreleased at sites of infection to further deplete iron
a. Binds tighter than Transferrin
b. DOES NOT transport Iron
3. HaptoglobinBind free hemoglobin released from lysed RBC
4. Albumen & CalprotectinBind free zinc to make it
unavailable to microbes
Microbial Helpers
Commensal Microbiotarepresents a population
of microorganisms that grow on body surfaces of
healthy individuals
NOT part of immune system but provide
protection
Important for development of immune
system in distinguishing harmless microbe
from pathogens
Provide protection by:
1. Competitive exclusion of pathogenscover
binding sites, consume available nutrient
2. Produce toxic compounds
a. E.coli may synthesize colicins in
intestinal tract
b. Lactobacillus in vagina produce low pH
Innate Immune Responses
Innate Immune response
Rapid response (within minutes to hr) after 1st line barriers have been
breached
Include phagocytic cells like neutrons and macrophages
Include antimicrobial proteins in the blood (complement)
Involves the recognition of specific microbial molecules and/ot tissue
damage by receptors on immune cells
Fundamental ConceptSelf Vs. Non-Self Recognition
The immune system must constantly distinguish what is self Vs. non-self
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