Microbes

o Previously against the germ theory - good to have them to grind

up tissue
o Exotoxins: secreted by bacteria - on surfaces etc, but if inside
your body they could
o Staphlococcus in un-refridgerated food = #1 cause of food
poisoning - by exotoxin
o Enterotoxin - damages intestinal mucousal cells
o Diphtheria - Diplococcus of oral cavity - produces a grey web in
esophagus
o Endotoxins: stays inside the bacteria, requires activation by
immune system
o Gram(-) bacteria, lipopolisaccarides (LPS) identified and
broken up into endotoxins
Endogenous (produced within body) pyrogen raising
body temperature to lethal levels
vasodilator (in general, would cause unconsciousness
due to BP collapse, *endotoxic shock)
lowers pulse pressure
o slow blood flow - thrombus formation and leads to
embolism - leading to infarction
Viruses
o interfere with cell function or kill the cell
o virus commits cell to producing viral proteins
o can alter DNA via reverse transcriptase
o 2 ways of cellular killing:
o replicates and offspring perforate the cell membrane when
escaping (HIV- affect helper t-cells(T4), Polio)
o some virus can put a marker on the cell surface to tag it for
infection, cytotoxic (T) lymphocytes find them and kill them
(delete)
eg. Hepatitis hepatocyte develop membrane
marker, attacked by cytotoxic t-cells
cell in scenerio 2 is still functioning but still need to
stop proliferation so you need to kill it off
Physical agents
Freezing/burning
o direct mechanical damage
o extreme vasoconstriction leading to ischemia/hypoxia
Changes in pressure
o diving, when coming up too fast gases that were submerged
come up and bubble up (released gas) in blood vessels block the
flow of blood = ischemia/hypoxia
Electrical Currents
o semi conductors, we are a resistor, heat produced with large
current passing through it

o interfere with tissues's conduction

o neurons and muscles need the electrical status of cells to
function
Intracellular accumulations
o Abnormal metabolism:
o eg. fatty liver, liver not designed to store fat - designed for
metabolism
Ratio change of in/out will cause storage
o Lack of enzyme: eg. lysosomal storage disease - improper
breakdown will cause buildup
o Indigestible materials: eg. carbon inhalation - no enzyme to
break down atoms, it just sits there and get's phagocytosed by
macrophages but goes nowhere - causes chronic inflammation class of diseases:
o Pneumoconioses
Necrosis enzymatic digestion of cellular debris
Liquefaction necrosis
o Watery break up by bacterial enzymes or body reaction
o Eg. Pimples
o Rate of dissolution of necrotic cells exceeds capacity of
body to produce replacement tissue. Seen in bacterial
infections
o Pyogenic (pus-forming) bacteria (such as staphylococci
[pimples], streptococci, and E. Coli) where bacteria feed on
& liquefy dead tissue. Heterolysis & autolysis occur.
Coagulation necrosis
o Protein denaturing, material is hardened, usually due to
lack of blood supply
o Denaturation of cellular proteins; usually occurs during
profound ischemia, e.g. myocardial infarction. Cytoplasm is
eosinophilic (red), nucleus is basophilic (blue)
Caseous necrosis
o Chronic infection, over lapping of continued damage and
healing
o Crumbly necrotic material, amorphous and resembling
cottage cheese
o Eg. Mycobacterium Tuberculosis, can also occur in lung
fungal infections, (histoplasmosis)
o Cheese-like deposits are formed, seen in tuberculosis and
fungal disease, not as rapid as liquefactive necrosis, debris
is enclosed within tubercular granulomas.
Gummatous Necrosis
o Similar to caseous, necrotic material is gummy
o Eg. Treponema palladium (Syphlillis) - produces a gummy
substance, it can be similar to TB

Fat necrosis
o Fat break down to fatty acids and mixed with calcium
o Saponification
o Found in ethanol abuse, alcoholic pancreatic
damage/pancreatitis
o Pancreatic acinar cells are damaged and release some of
their enzymes within the pancreas. Usually includes
rupture of the pancreas, which releases pancreatic
enzymes such as lipase, which digest fat. The adipose
tissue surrounding the area is then partially digested,
resulting in saponification (akin to soap formation) where
fatty acids form a complex with calcium. Islands of fat
necrosis occur.
Gangrene defined by the process by which it tissue dies
typically ischemia and bacterial infection and enzymatic activity
o Wet similar to liquefactive necrosis
liquefaction necrosis and bacteria plays large role
o Dry hard formation similar to coagulative necrosis
Diabetic wound ulcers, poor circulation
coagulative process (in Diabetes: toes and feet) &
little or no infection
coagulative necrosis, seen in diabetes, poor
circulation - starts in toes and moves up some of the
tissue needs to be removed, antiseptics, dilate blood
vessels, special shoes
o Gas anaerobic bacteria ferments tissue to make energy
without oxygen, creates gas (CO2), can have subcutaneous
crepitus
Clostridium bacteria flourishes with lack of O2, get
fermentation of tissue, which is CO2 forming. Hear a
crepitus sound in stethoscope. Treatment is to put in
high O2 chamber.
o Most often occurs in a limb that has suffered ischemic
damage and has been attacked by bacteria. The actual
mechanism of cell death is simply loss of blood.
o Cellulitis - also means a spreading bacteria in the skin
Dead or injured tissues often incorporate Ca into the healing
Dogs not = wolves
Complex lipid is a lipid combined with a protein or carbohydrate
o Lysosomal Storage Diseases:
as many as there are enzymes
Tay-Sach's Disease genetic autosomal recessive
disorder whereby there is an insufficient activity of
hexosaminidase A causing the lipids accumulate in
the brain and interfere with normal biological
processes.
it causes a progressive deterioration of nerve

cells and of mental and physical abilities

Gaucher Disease genetic disorder of result of a
buildup of certain fatty substances in certain organs,
particularly your spleen and liver, bone and marrow
due to defect in lysosomal glucocerebrosidase.
Neimann-Pick's Disease- autosomal recessive
disorder affecting sphingomyelinase causing
sphingomyelin accumulation and presentations of
affect in liver, spleen, CNS, brain stem, basal ganglia
Von gierke disease autosomal recessive disease
causing inability to break down glycogen for energy
due to lack of glucose-6-phosphatase, causing
glycogen build up and uncontrolled blood sugar
levels
Phenylketonuria autosomal recessive disorder
causing phenylalanine accumulation to toxic levels
due to lack of phenylalanine hydroxylase

Omega 3s - "slower rate of loss of brain mass" headline, but only in

elderly, 0.7 of 1%
1% incr in cholesterol levels with drinking decaf, statistically significant
but not clinically significant
Tissue Storage Disorders
o Water: Na pump doesn't work and causes Hydropic/Cloudy
Swelling
o Lipid:
Triglyerides 3 fatty acids combined with glycerol
back bone
Cholesterol
Complex - assoc with glucose or protein, in lysosomal
storage diseases
ex) Fatty Liver - fat sent to liver, changed then
secreted, but if amt of fat sent or secreted is
changed then the steady state needs to change
due to changes in amount in and out of the
liver
in the industrialized world with ethanol abuse
in third world usually due to starvation
Fat metabolism is predominantly done in the
liver
Starvation: forced to rely on stored fat for
energy, parts of body will send more to the
liver - good when trying to lose weight "fat
burners", if not deliberately dieting then it can
cause fatty liver - ex) in famine, Atkins
Diabetics, poorly regulated due to reliance of
fat use for energy

Impaired Phospholipid Synth:

o Fatty acids+Choline+Methionine -->
Phospholipid,
o Insufficient choline or methionine
reduces the phospholipid , pushes to the
Right: Fatty acids+Glycerol -->
Triglyceride
Fatty liver contd
o Kreb cycle = consumes glycerol,
o EtOH more available causes the Creb
cycle to slow down
o Increased glycerol adding up to drive
triglyceride reaction to the right
(increased tryglycerides)
o EtOH overconsumption is the leading
cause of Fatty Liver
Venous thrombi usually to lung pulmonary embolism
Arterial thrombi can be anywhere
Fat OUT
o Lack of apoprotein production - Liver usually emulsifies fat with
carrier apoproteins (oil and water don't mix) so it could form
globules that plug vessels (fat emboli), apoproteins allow
emulsification of fat in the blood
o Some conditions prevent apoproteins from being produced,
secreted, or coupled such as tetracycline or carbon
tetrachloride poisoning
o Hyperlipid fat globules ontop blood Grossly lipenic blood
o With apoprotein blocking toxins, liver will not release fat into
blood
o Lack of coupling - Some apoproteins have difficulty coupling
o Lack of lipid secretion - Cirrhosis can cause liver to be unable to
deliver apoprotein bound lipids
just lying around doing nothing will also cause the liver to get a bit
fatty
Liver Damage
o Weekend Binge = Chemical Hepatitis: inflamed liver, but
reversible
o Long term drinking will cause fatty liver
o Cirrhosis - some degree of irreversible damage permanent loss
of liver function
Liver Failure
o Fatty liver - Fatty Streaks - show up in blood vessels of
children/infants now, greyish lining as cholesterol deposition
o 80% liver failure for terminal

HDLs vs. LDLs

High density lipoproteins good carries cholesterol from cells to
liver for digestion (endocytose HDL) into bile and fecal matter and
lymphatic system.
Low density lipoproteins bad carries cholesterol to cells
o Atheroma - in 19-20s, bumps as endocytized blobs of
cholesterol, causes turbulence and localized increased in blood
pressure = region of endothelial nick/tear, heals with Ca and
turns to
o Atherosclerotic Bl Vessel Disease/Plaques - when you get older,
calcified deposits, hardened become less elastic and can't
absorb pulse and systemic hypertension
o Ratios are good indicator of lipid health
o Cholesterol engorged intima cells (foam cells) progress to grow
into a fibrous cap of fat engorged connective tissue atheroma
Framingham study
o People with high cholesterol had higher risk of cardiovascular
disease
o This cause lower cholesterol intake
7 country study?
o Dietary reccomendations (school lunches, etc.)
o Avoid dietary fat, cholesterols etc
Gene defects for overall health vs comparison of regular population
Decaffeinated coffee significant increase in cholesterol levels
o .05 = p-value or confidence interval
o indicated 95% confidentability that biological feed back vs fluke
o 2 point difference not clinically important!
precursor to cardiovascular disease
*Free Radicals exacerbate this process
Eggs, Shellfish, Organ Meats
o High in cholesterol, so they say, "don't eat it" - but you need it!
(to make phospholipid and steroid hormones)
o If you don't intake it, your body will make it via HMG-CoA
Reductase (liver enzyme to make cholesterol)
o Albumin in eggs can be allergenic
o 3-7/week, depending on biomass and diet, exercise, antioxidants
etc
o Saturated Fat (mostly from animal products, or cheaper
vegetable oils)
o Trans-Fatty acids occur naturally but not in high amounts so we
can't process them well
o consumption is more harmful to cholesterol levels, ex)
artificially hydrogenated oils
o Animal and plant sterols can block cholesterol reabsorption

o Cholest-off
o Margerine benecol, take control, fat with plant sterols
o Increased risk of atheroscleric plaque and cardiovascular
related issues
Artherosclerotic plaque increased turbulence and pressure can cause
endothelial microtears causing inflammatory response and Ca+
deposition and hardening called artheroscelortic blood vessel disease
o Increased inflammatory causes increased free radicals and
worsens artherosclerotic blood vessel disease
o Atheromas found in young men (in war cadavers)
o Fatty streak in infants can turn into atheromas in adults
o Atherosclerotic plaques in older adults can cause cardiovascular
death
o Vascular claudication muscle cramping
o Arterial clotting in brain can cause dementia
Soy and LDL cholesterol
o Studies disproved LDL lowering from 80-90s
Addisons disease the hand
Amyloidosis
Extra cellular deposition of light chains proteins into tissue
Myxedema mucopolysaccharide storage from hypothyroidism can
cause carpal tunnel syndrome

Mineral storage disorders

Iron hemochromatosis
o Transferrin elevations indication higher iron binding
Calcium calcification
o Aterial blood is more alkaline
o Venous blood is more acidic
o Arterial/metastatic calcification because pH
Elevated Ca+ levels
o Elevated Parathyroid hormone (PTH)
Increases Ca+ absorption and reabsorption
o Dystrophic calcification
Rheumatic fever heart valve calcification
Heart murmur
Antibodies of streptococcus antibodies after
infection subsided, antibodies attack body
(autoimmune) specifically epithelium of hearth
valves
o Stenosis
o Dental work can introduce oral bacteria
into blood stream and cause endocarditis
if there is cardiac valve stenosis Myoitis ossificans
Artherosclerotic plaque arterial calcification
Ghon lesion tuberculosis caused lymph node
calcification
Copper ceruloplasmin carries copper, copper deposition into
tissues
o Lentiforme nucleus fine motor skills, damage to same
would be uncoordinated non-functional movements
o Liver damage
o Hepatolenticular choreiform movements
Chorea/choreiform movements caused by:
Rheumatic fever
Wilsons disease
Huntingtons disease
Spleen red blood cell graveyard
Removes unhealthy, old RBCs out of circulation by cell lysis
Bilirubin metabolism
Jaundice hyperbilirubinemia
Bilirubin back up/block can be caused by:
o Gallstones
o Pancreatic tumor (Steve Jobs)
o over whelmed by excess RBC lysis (hemolytic anemia)
and release of bilirubin

Urate (uric acid) storage

Crystallization
hyperuricemia
damage to synovial fluid
crystalline arthitides
gouty arthritis
o could also be calcium crystals
o could be genetic
o diet
foods high in nucleic acids (DNA) purines
Homogentistic acid alkaptonuria
tyrosine metabolism
Addisons disease
Adrenal insufficiency
Decreased adrenocortical function
Less ACTH causes pituitary to make more ACTH which is similar
to MSH (melanocyte stimulating hormone)
o 60:1 ACTH:MSH to cause stimulation
Causes hyperpigmentation
Pneumoconiosis
Accumulation of non-degradable material in the lungs
Coal miners lung - anthrocosis
Mesothelioma
Abestosis
Aging and free radicals
Free radical theory unsupported for aging
Shortening of telomeres
Progeria
o Accelerated aging
o Werner syndrome
DNA unwinding and prevents proper cell division

Inflammation
Aspect of the immune system
Increased vascular permeability to allow WBC and Ab
mobilization
Increased vascular flow
Exudation
Rubor - redness
Calor - heat
Tumor - swelling
Dolor pain
Axial flow in the center of the capillary
White cells marginate/margination towards the outsides of the
capillaries/endothelium
WBC pavementing onto endothelium and can escape the when
the pores open up for emigration
o Margination then
o Pavementing
o Emigration (vs RBCs which do diapedesis)
Ameboid like movements of WBC
o Neutrophils first then monocytes
Rouleaux formation where RBCs stack onto each other
o ESR erythrocyte sedimentation rate general marker of
inflammation increased rate during inflammation
Chemotaxis
C5a protein released to stimulate WBC mobilization
o C5 C5a + C5b
Chemoattractants
Formation of antibody and antigen complexes with the use of
complement
Opsonization encapsulation of pathogen
for susceptibility for phagocytic attempt
C3 C3a + C3b
NK cells

Neurocalometer/nervoscope measures the DIFFERENCES of skin

temperature, with dual probe thermography
Acute increase in temperature
Chronic decrease in temperature
Neurological lesions/subluxations can affect
vasodilation/constriction thus temperature vs. traditional ohms
law
Inflammatory response
o Triple red response normal physiology response
Red streak
Red flare
Wheal palpable bump
Tool is not measuring baseline and is producing (evoked) red
response
o Can be used for differences in evoked responses
TyTron C-3000
o Electromagnetic sensors/night vision
o Assesses baseline more
Nervoscope reliable?
o Reliability = can tests be reproduced regardless of person
using/conducting test
o Kappa = statistical function for reliability
fair rating in only 4 segments, 5 vertebrae of
thoracic spine
Misleading to call reliable

Mediators of inflammation
Histamine

Released by mast cells vasodilation

Endothelial contraction (causes
opening in spaces for
permeability)
serotonin
Works in cats?
Neurotransmitter
Lysergic acid LSD
Similar to serotonin, not degraded
rapidly
bradykinin
Primary involvement in pain
Factor XII Hageman factor in
blood clotting, through conversion
and cascades to produce kinin
C3a
primary
C3b
Primarily opsonization
C5a
Chemotactic agent mobilizes
WBCs
prostaglandins
Arachadonic acid cascade
pathways
Cyclooxygenase pathway
o Inhibited by ASA,
indomethicin
Power proinflammatory chemicals
leukotrienes
Arachadonic acid cascade
pathways
Lipoxygenase pathway
o Inhibited by singulair
(corticosteroids)
Power proinflammatory chemicals
Arachadonic acid pathway phospholipase is inhibited by
corticosteroids
NSAIDs inhibits COX-I (mucous producing stimulation) could cause GI
issues, gastritis, ulcers, death
Selective COX-II inhibitors Vioxx, celebrex stop pain without
effecting mucous production
Vioxx increases risk of heart attack by 2.3 times HIGH! Because
amount of people that suffer/die from cardiovascular issues (1 in
5)
28,000 CV events to 55,000 deaths

look for +++s

Histamine increased permeability (swelling and edema, tumor)
Bradykinin pain (dolor)
C3b opsonization
C5a chemotactic agent (in order to mobilize, also increases
permeability)
Prostaglandin vasodilation (rubor) and chemotaxis
Leukotrienes increased permeability (tumor) and chemotaxis
Acute inflammation
Chronic inflammation

Ongoing Tissue damage and

healing
Lacks cardinal signs?
Eg. Coal miners Pnuemoconosis ongoing
damage and healing
Eg. Chronic bladder
infections pylonephritis if
travels up vesicoureteral
valve prevents back flow
could have congenital
issues/scarring healing and
damage
Eg. Drinking
healing/damaging, chemical
hepatitis, fatty liver,
cirrhosis
Eg. Rheumatoid arthritis
autoimmune, flare up then
remission, causing
healing/damaging
Eg. TB, mycobacterium

healing and damaging

DHC damaged healing
compromise

Non-granuloma inflammation
Hepatitis due to ETOH
Pancreatitis
Epitheliod granuloma
Caseous necrosis and Infectious - Chronic infection and langhans
giant cells surrounded by fibroblast and plasma/lymphocytes
causes an inner caseous necrosis, tuberculosis
Non infectious/Non-caseous granuloma eg. Crohns disease.
Autoimmune disease, immune system attacks epithelium of GI
tract, scar tissue formation
o 50% small and large intestine involved
o 25% just large
o 25% just small
o Skip lesions patchiness
o Ulcerative cololitis only colon, throughout colon (not
patchy)
Noncaseating/Non-infectious non infection foreign body type
giant cell from inorganic non-degrading agent pneumoconiosis
(coal miners lung)
Cat scratch fever
o Stellate granuloma
o Rickettsia bacteria parasitic bacteria
o Draining into lymph nodes causing lymphadenopathy
Can become scarred over
Syphilis
o Very caseating!
Sarcoidosis symptoms and tests like TB, kabine test, no
infectious agent, idiopathic

Regeneration vs. Repair

Regeneration restoration to original form
Good mitotic ability (labile)
Repair includes scarring
No mitotic ability (permanent)
Regeneration
Restoration to original
form
Good, mitotic ability
labile
stable
Skin, internal and
Parenchymal tissue,
external
smooth muscle

regenerati
on

Repair
Includes scarring
No mitotic ability
Permanent
Eg. Lens cells (of eye),
neurons, striated
muscle

Tissue healing
Granulation tissue more cellular tissue
Hallmarks
o Mononuclear infiltration
o Proliferation of fibroblasts and small blood vessels
o Tissue fibrosis
o Tissue destruction
Fibers laid out by fibroblasts in granulation (new) tissue:
o Elastin
o Fibrulin
o Reticulin
o Collagen
Wavy bundles in regular tendon
Disarrayed in scar tissue
Macrophage phagocytosis to degrade necrotic tissue
Myofibroblast actin and myosin equipped fibroblast capable to
contract
Pale anmorphic scar smaller, final scar
Production of cicatrix
Inflammatory phase
Migration phase
Granulation tissue
Endothelial bud formation of new blood vessels
Contact inhibition
When contact, place of mitotic division
Proliferative phase
non-avoidable permability due to poorly developed blood
vessels
Maturation phase
Healing by first and 2nd intention
First intention well approximation of wound edges
o Minimal scarring
Second intention edges not closely approximation
o Requires more granulation tissue
o More scarring
Bone best connective tissue capable of regeneration
Wallerian degeneration
Neuron degeneration
Axon damage causes distal damage to the site of the injury
Mitosis of neurons first discovered in the hippocampus
o Seen in frontal cortex
Cell body of neuron perikaryon
Complete tearing is avulsion, can be partial

Formation of blood clot/inflammatory response

Tendons wavy bundle of regular connective tissue
o Damage (like whip lash injury) causes histological changes
in collagen formation and causes weakness, loss of
elasticity, instability and coupled with muscle atrophy.
Consistent flexion causes imbibition on open portion of disc
and expression on closed portion of disc.
o Imbibition increase blood flow, etc.
o Expression decreased blood flow, etc.

Immune system
Adaptive(required) vs. Innate immune system
Adaptive
Memory
o Develops memory based on pathogens that body has
been exposed to already
o Shortened latency period
o Improves with exposure
Specificity
o Use of antibodies specific for certain antigens (create
antibody-antigen complexes)
Amplification
Humoral vs. Cell mediated
B-lymphocytes T-lymphocytes
Originate in bone marrow (most Originate in thymus (primary
likely, maybe bursa) (primary lymphoid tissue)
lymphoid tissue)
IgM

Humoral mediated Cell mediated

IgG
IgA
IgE
T4
Helper T
CD4 (cluster
determinant
4+)

Plasma cells secreting antibodies - Promote Bcells to produce

antibodies
- HIV/AIDS
affects this cell
and prevents
the use of
acquired
immune system
Active
Produced by own body

T8
Cytotoxic cells
CD8 (cluster
determinant
8+)
Killer T cells
- Kill infected
cells
- Prevent future
infection

Passive
Produced outside of own
body

Natural
Artificial

Droplet infection
Vaccination

Nursing (breast milk)

Ab inoculation

NK cells natural killer cells completely different than Killer T cells

Clonal deletion theory of immuno-self-tolerance
Removal of future possibility of cells from that which was killed
Recognizes self cells

Innate
Born with and needed
Innate immunity
Physical barriers
Cellular
Chemical barriers
Skin, mucous
Monocytes(within blood pH, lipids, enzymes,
membranes
stream)
lysozymes (only
macrophages(microglial works in low pH, like
in CNS, kupfer in liver,
acidic environment of
langerhans cells in skin stomach, skin)
eosinophils
granulocytes
(polymorphic
neutrophils(PMN), mast
cells..)
cytokines
Cytokines
Cytokines
^stimulates/aids cellular^
Antibodies - opsonization
Lymphokines helps activity of
another WBC from a WBC
MIF migration inhibiting
factor
MAF macrophage
activating factor
o A proper adjustment
caused respiratory
burst physiological
response
b-lymphocytes
t-lymphocytes
humoral
Cellular
^Acquired immunity^
Vacca- cow milk maids were not getting small pox, infected by cow
pox due to cross reactive antibodies
Colostrum
Antibody rich serum from mammary glands

Only used in GI tract

Lipopolysaccarides can stimulate lymphocytes directly; lipoproteins

must be presented by macrophages (APC)
Macrophage antigen presenting cell APC
Not all

antigens are immunogens

 Immunogen produce a immune response

in the body
o Epitope certain sequences and shapes of
aminoacids
Hapten - a small molecule that can elicit an immune response only
when attached to a large carrier such as a protein;
the carrier may be one that also does not elicit an
immune response by itself.
large with same epitope simple, repetitive not
usually immunogenic like glycogen, polyvinylchloride
large, complex, foreign usually immunologic
response

Protein losing enteropathy protein loss due to conditions of gluten

allergy due to immune response
In Crohns, protein loss will steal from albumin, muscles, etc.
Loss of albumin edema due to loss of ability to maintain
osmotic pressures

IgD for antibody differentiation

IgM
IgG
Pentamer
Crosses the
forms ring
placental border
shape
life approx. 3
weeks
most abundant
in blood serum
binds to
monocytes,
enables
opsonization
longest half-life
(important for
fetus)

IgA
Usually dimers
Most abundant in
the body (75%)
Found in the GI
tract, secretory
organs
Allows alternate
Compliment
pathway (C3bBb)
Crohns elevated
IgA

IgE
Plays role in
allergic
response
(type I
hypersensitivi
ty)
Mast cell
interaction
Least
concentration
Aids IgA
Mast cell
contains ECFA
eiosinophil
chemotactic
factor of
anaphylaxis,
histamine

S = secretory
protein (made by
mucous membrane
in intestine) also
known as t protein
less hinging
capability
practical
valence of 5
theoretical
valence of 10

J joining protein
Valence 4
Antigen binding fragments (Fab) are bonded to Fragment crystallizable
(Fc) via disulphide bonds (which can hinge)

Paratopes on the Fab binds antigens determines specificity reacts

to specific/different epitopes
Fc determines where/how antibody works

Valence amount of sites that antibody can interact with

Vaccine vs. natural theory is vaccine is less taxing to system in
producing antibodies because less exposure at once

Certain degree/amount in order to

produce an immune producing
response
Toxoids of

of

Tetanus weakened form of toxin so that

body produces antibody has a cross
ability, not a perfect complex but
partial attachment
Closer to vaccine better the
immunity, higher the risk of
effects in body
Cow pox and small pox
Polio Sock vaccine exposure
weakened form of living virus, so it cannot
give you polio (some got polio via
reverse mutation back to wild type) Polio saven vaccine protein
of virus no nucleic material,
just protein, less risk of polio,
but not as good as sock
vaccine
Molecules involve =
preciptiation
Cellular (microbes,
cells) = agglutination
M= macrophage will
phagocytize after
opsonization. (C3b
compliment proteins
or antibodies)
Neutralization = alter
virus, alter virus
ability to transfer
DNA/RNA material,
etc.
NK cells Natural
Killer cells involved
in tissue rejection,
perforates (using
perforase) (ADCC
antibody dependent
cell-mediated
cytotoxicity) non
specific
Membrane attack
compliment
compliment proteins
that aid into cell
destruction

MAC membrane attack complex lysis the antigens

Compliment 3 into a and b fragments caused by Ag-Ab complex
(antibody dependent)
C3a histamine releases for inflammation (tumor)
C3b
opsonization
Ag-Ab complex sticks to endothelium
Causes Compliment 5 to break into C5a and C5b
o C5a chemotactic agent
o C5b activates MAC for antigen lysis
Antibody independent
o C3bBb Further breaks down compliment 3 into a and b
o Amplification (positive feedback)
Vertebrates evolved to produce classic pathway for complement
fixation

Human leukocyte antigen region (HLA region)

Found on chromosome 6
MHC major histocompatibility complex (all mammals)
o Tissue typing
o Human leukocyte antigen region (HLA region) homologous
to murine complex in mice
A, B, C, DQ, DR, DP MHC regions
All 6 (out of 12) must be found in the infant to confirm
fatherhood
eg.
Risk
If 1 of

spondylitis -

DR4 (fourth gene of DR

allele)
factor = number times more
1000, 3 times = 3 of 1000
1/5 for ankylosing
gotten later in life,
inflammatory arthritis,
fuses spine
also risk factor for psoriatic
arthritis
know DR4 and B27 rheumatoid
vs ankylosing
reiters urtheritis, conjunctivitis,
arthritis classic triad from
untreated STIs

Light chain synthesis

Light chain and heavy chains.
28000 genes in human genome

Light chain (v) genes

~200
Joining genes ~5
205 genes
1000 possibilities of light
chains

14,400 heavy chains =

(423 genes)

Heavy chains (v) ~200

Diversity genes ~12
Joining Genes ~6
218 genes
~14,400 possibilities of
heavy chains

1000 light chains x

14,400,000 antibodies

antigen production from genes that are chosen, excised, etc. from 423
genes comes 14,400,000 antibodies
in order to become immunogenic must be large (eg. Protein) and
complex (more than one epitopes)
Plan A) Accessory cell (like a macrophage) digests protein with more
than one epitope to breakdown and produce for antigen presentation
to resting CD4 (t-lymphocyte) for activation with correct affinity
Specific T-lymphocytes will divide and release:
Cytokine substance secreted by cells to WBC
o Lymphokine
Interleukin molecule released by WBC to other WBC
Stimulates b-cell to divide, differentiate and iG synthesis
Stimulates cytotoxic t-cell (killer t-cell, CD8) to lyse cells with
perforin
Plan B) Infected cell (virus or rickettsia) could present to CD8 to
stimulate proliferation, differentiation and cause cell lysis to perforin
MIF migration inhibiting factor
MAF macrophage activating factor
** real adjustment enhances

Plan A
Accessory cell (macrophage)
presents antigen
Activation of resting T cell (helper,
CD4)
Causes growth, proliferation and
release of interleukins (IL-2, INF,
TNF)
Activates macrophage, B-cells and
helper, CD8 tcells
CD8 perforin
b-cells Ig production
macrophage phagocytosis (with
aid of opsonization from Ig
production of b-cells)

Plan B
Infected cells present antigens to
cytotoxic (killer, CD8) t-cells
Perforin release

Brutons agammaglobulinemia Inability to produce Ig-G

Only males affected and skips generation
Sex-linked on x chromosome
Affects b-cells due to inablitiy to produce antibodies
DiGeorge syndrome thymus hypoplasia thymus maturation for bcell maturation and production infants embryological origination
Failure of cell-mediated system T-cells
Inherited defect
Combined b and T cell failure SCID, severed combined
immunodeficiency
Cured with gene surgery
1st disease to be cured
fetal tissue and defective gene is repaired with retrovirus
Primary vs Secondary immunodeficiency
Primary congenital/embryological
Secondary acquired immunodeficiency
Phagocyte deficiencies
Chronic granulomatous disease (CGD) sex-linked disorder
Phagocytic cell can phagocytose
Unable to produce hydrogen peroxide to destroy
Prone to infectious diseases
Granulomas
o Epitheliod granuloma
o Caseous necrosis and Infectious - Chronic infection and
langhans giant cells surrounded by fibroblast and
plasma/lymphocytes causes an inner caseous necrosis,
tuberculosis
o Non infectious/Non-caseous granuloma eg. Crohns
disease. Autoimmune disease, immune system attacks
epithelium of GI tract, scar tissue formation
50% small and large intestine involved
25% just large
25% just small
Skip lesions patchiness
Ulcerative cololitis only colon, throughout colon
(not patchy)
o Noncaseating/Non-infectious non infection foreign body
type giant cell from inorganic non-degrading agent
pneumoconiosis (coal miners lung)
o Cat scratch fever
Stellate granuloma
Rickettsia bacteria parasitic bacteria
Draining into lymph nodes causing
lymphadenopathy

Can become scarred over

Down syndrome at risk reduced immune functionKaposis sarcoma

HIV positive people at risk* otherwise rare
Opportunistic
Secondary immunodeficiency
RNA virus
HIV Infects helper-t(4) cells CD4
o Unable to activate CD8 and b-cells
o Does/can remain dormant
Hepatitis B kills more people in America
Secondary immunodeficiency
can be medically produced for tissue acceptance such as
prednisone
Leukemia abnormal bone marrow, can produce non-effective
WBC, accompanied with anemia
lymphoma
Stress
Diabetes
Radiation and chemotherapy (kills rapid dividing bone marrow
cells)


Accellerate the deposition of cholesterol more than increasing
cholesterol
HDLs - JKS
- Is the study relevant to your chiropractic patients?
- Genetic disease that raises their HDL levels, so there are other factors
that might be at play
- Normal people with high HDL with less risk of cardio disease would be
relevant but these people are weirdos so its not as applicable to your
population
Mummies with Plaques
- looked back at mummies, all who were paleo and had same amount
of plaque as today's people
- Maybe they go along with aging, not diet
Animal and Plant Sterols
- stanins or stanols when incorporated into food get the label "heart
healthy" - have included them even in hydrogenated oils
-- if you want plant cholesterol just take the herb, don't take it with fat
because it will contradict the effects
- plant cholesterol reduces your cholesterol from animal sources,
reabsorb less in bile
- If you want to lower cholesterol - consume plant sterols - "cholest-off"
Soy and LDL
- soy, lower risk of cholesterol - back in '99 was claimed but now
disproven
- might be valuable because it would substitute other things that might
be harmful but no direct effect
*Mediterranean Diet - cardio disease, looking at diet alone less risk in
Europe than NA (except Britain)
- More olive oil, more fish consumption (omega 3s), red wine pigments would be free radical
scavengers
Amyloidosis (number of different conditions - depending on the
protein)
- condition where proteins accum in soft tissues - resulting in path and
impaired function
- AL: lymphocytes make huge amount of light chains that don't get
incorporated in antibodies
-- light chain accumulation in the body because it can't be incorporated
into the antibody
production
-- purplish blue in fingers and bruised on the skin - Purpura - cm sized
lesions, internal bleeding
Glycogen/Carbohydrate
- Von Gierke Disorder (see later in week 8)
Myxedema - in hypothyroidism, carpal tunnel syndrome due to
pressure increase -- mucopolysaccaride
Pigments
Biliruben Metabolism

-- Hemolysis in spleen - squeezes the RBCs, if they are old they get
lysed
-- Recycle the materials from the RBCs, Heme: iron and biliruben biliruben attaches to the glucouronic acid
in the liver --> bile secreted, emulsifies the dietary fat and become
digested
Too much hemolysis:
- internal bleeding, traumatized, genetic disease
- liver is overwhelmed with biliruben, can't make bile quickly enough so
biliruben is secreated into blood
and turns the skin a different colour depending on skin colour Jaundice
Bile duct blocked ex) gall stones, or tumour at the head of the
pancreas:
- fats are not able to be emulsified, biliruben backs up into the liver
and also pigments the blood
Addison's Disease
- browned areas in the wrinkles of the fingers
- pathology of the adrenal cortex - atrophy and loss of aldosterone,
cortisol and sex hormones
- Pituitary (master gland) will increase ACTH production (close to MSH melanocyte stim hormone) - acts
on melanocytes "by accident" and the skin gets darker = "bronzing"
(bronzing also referred to in iron
overload)
Occupational Lung Disease
- pneumoconiosis: inhaling non-digestable substances, left with chronic
inflammation
- Carbon, poor air quality, sandblasters, working in quarries, nickel
dust, asbestos, sandstorms
Minerals
Calcium
- levels can raise via: metastatic and dystrophic calcification
- metastatic - bl lvls raise above zone, 0.9-0.11%, Ca salts are not v
soluble in water, tends to form crystals
and can plaque out in certain places, ex) in a joint - takes away
lubrication takes away cartilage
-- Crystalline Arthritis - can be caused from Ca, urate, homogenticic
acid crystals
- alkaline areas are most affected - (not dissolved) - more likely in
arteries, less acidic metabolic
byproducts, or the stomach walls - secretion of HCl causes an alkaline
envir in the walls
- Parathyroid gland - regulates blood levels of Ca, makes parathyroid
hormone (parathormone), stim
osteoclasts to release ca, more reabsorption in sm intestine, kidney to
reabsorb -- sometime it freaks out
and reabsorbs too much or a tumour -- incr in activity = incr bl calcium
and metastatic ca
Copper
- Wilson's disease: genetic disease, abnormal ceruloplasmin - carrier

for Cu, 3 kinds, and if one is

abnormal you improperly carry Cu and can get Cu-toxicity diseases due
to deposition in lentiform nucleus
(regulating small movements - choreaform movements) of brain and
the liver
*hepatolenticular degeneration
Iron
- Hemochromatosis/Hematochromatosis, similar to Wilson's - but Fe not
Cu, Fe overload due to abnormal
Transferrin, liver especially effected
Metastatic Calcification - arteriole side is more alkaline
Vitamin D binge + Ca can be problematic - because fat-soluble
Dystropic Calcification
- myeositis ossificans: when Ca deposit forms in a bone, due to genetic
modification or a blunt trauma
- enthesophathy: Calcification of soft tissues (tendons and ligaments)
at junctions to bone
-- rheumatoid arthritis - Calcaneal heel spur or alkalizing spondylysis
- athersclerosis: hardening of the arteries
- Ghon lesion: TB, calcified hylar lymph nodes (near apex)
- Rheumatic fever: in valves of the heart, autoimmune disease, initial
streptococcus infection as young
person, but after strep is gone the lagged Abs come out, cross reactive
with your own tissues widespread - but endothelium that covers heart valves is especially
attacked, will eventually heal but
roughen with Ca incorporated into healing, causes: stenosis - hard time
opening, or regurgitant - hard
time closing and results in a murmur, common during dental work to
introduce bacteria during dental work
but if you have a previous rheumatic fever (showing up as a murmur)
you can get subactute bacterial
endocarditis
Lipofuscin
Addison's Disease - overproduction of ACTH stimulates melanocytes
and can cause darkened skin
Urate
- Gout: result of uric acid concentration increases and forms crystals,
biol issue with processing , eating lots
of DNA also causes - from Adonine and Guanine - epithelial tissues are
rich in DNA, "rich foods" ex)
organ meats (liver, spleen, kidney, brains...) dairy, shellfish -- issues in
weight bearing joints
Txt: medications
Homogentisic Acid and Alkapton Protein
- Alkaptoneuria - can't process phenylalanine and tyrosine, autosomal
recessive, crystal that can
accumulate and be excreted in blood, and cause damage to cartilage,
heart valves and kidney stones
Aging and Free Radicals
- Free Radicals - if we age, its an irreversible cumulative effect of free

radicals, therefore antioxidant

scavengers will help delay aging
- But...has also been shown it doesn't have the evidence
- More recently - reason is that it became necessary to protect
ourselves from visible light that causes DNA
mutations, therefore protections from cancer cause death
Progeria
- disease of accelerating aging, child is 11!?, we have not discovered
the causative agent but likely a repair
enzyme, not able to have as many rounds of cell division
Werner's
- helicase enzyme has been implicated, has to do with winding of DNA
during cell division,
Chapter 6 - Inflammation
Inflammation: Good, Bad, Ugly
Protects you from microbial infections and toxins
Has cardinal signs and causes pain (dolour) - can be severe and
requires treatment Can lead to thrombus formation
Rheumatoid Arthritis - autoimmune that attacks your synovial
membrane, more ugly
Chronic - later process
Acute - co-incides with injury in the first few days
First line of immune defence is the skin (internal and external)
Interstitial spaces - don't have immune cells present
Blood vessels are somewhat leaky, but not for cells - Blood has WBCs
Acute inflammation starts the increase of permeability of blood vessels
to exit the blood and get to
interstitial spaces
Cardinal Signs of Actue Inflammation:
- Rubour (Redness)
- Calour (Heat)
- Tumour (Swelling)
- Dolour (Pain)
Phases of Acute Inflammation
1. Increased Vascular Flow
2. Increased Permeability - vasodilatation
3. Exudation of Transudate - serum without macromolecules/proteins or
cells
1. Hydrostatic: pushing of the heart ** increases
Oncotic: sucking due to solutes, drawing back into the bloodstream
--> Net surplus that pushes fluid out of the bloodstream
Expelling transudate increases viscosity of the blood - causes forward
pressure (on arteriole side)
30 mins into inflamm response, the backpressure increases with
increased viscosity (on the venule side)
2. Endothelial cells contract and pull away from each other, causes
gaps, energy is required to drag
phagocytic cells through the holes,
Neutrophils are predominant 1st (60% of WBCs) then monocytes 3-5%
predominant within 4 hours

3. Exudation - Exudate does contain proteins and cells, when the pores
are big enough to get cells and
Abs through
[Very short-lived vasoconstricion is not relevant, dilation is the most
important part]
Microcirculatory changes in Inflammation
- vessels have axial flow (down middle due to least resistance),
polynucleated WBC - neutrophil in middle
- dilation of blood vessel, neutrophil moves to margin of the blood
vessel *margination*, then adheres to the
vessel *pavementing*, can escape through tiny hole *emigration*
because it can change it's shape requires time (30m) and energy, once escaped they find bacteria to
endocytose
- Some RBCs escape by accident
- Rouleaux formation is the RBCs stacking into chains, could prevent
RBCs from escaping? - we do know it
increases possibility of blood clots leading to embolisms and
myocardial infarctions, have a higher sed
rate
- ESR - erythrocyte sedimentation rate - measure settling in solution, if
heavy it has an elevated sed rate
Macrophage-Monocyte System
- Macrophages of Blood Serum: monocytes
- CNS: Microglia
- Liver: Kupfer Cells
- Skin: Langerhan Cells
Leukocyte Emigration - (Diapedesis)
- some confusion on using for WBC emigration or accidental RBC
emigration
Chemotaxis
- when WBC escapes from a bl vessel it is attracted by chemotaxins to
the site of injury
- C5a: complement blood proteins, tend to react with each other and
broken down into fragments
- C5a forms at an injury site and attracts WBCs
Opsonization
- If target has been opsonized it becomes easier to phagocytose specific or immune-phase phagocytosis
- Like covering in a sticky material, increases the affinity of phagocytic
cell to the target
- C3b / CR1 R
- Epitope - IgG / Fc R