BLOOD

➢ Liquid connective tissue

➢ It has 3 general functions
1. Transportation: Gases, Nutrients, Hormones,
waste products
➢ like oxygen and carbon dioxide
➢ Oxygen carried by hemoglobin-can be found
in the blood
➢ Primary mode of transportation for hormones
are your blood stream
2. Regulation: pH, Body temperature, Osmotic
pressure
➢ Blood Ph is regulated through the kidney; if
the blood is detected to be too acidic or basic,
the body would release hormones as COMPONENTS OF BLOOD
response to reach or stabilize the ideal ph Blood Plasma - Water Liquid Extracellular Matrix
level • yellowish to white color
➢ Body temperature- through Vasoconstriction ➢ 91.5% water, 8.5 solutes (primarily proteins)
(aids in the retainment of heat) and ➢ Hepatocytes synthesize most plasma proteins
Vasodilation (aids in the release of heat). which are: Albumins, Globulins, Fibrinogen,
➢ Osmotic Pressure antibodies
• solute- solvent relationship; ➢ Other solutes include electrolytes, nutrients,
adjustment in blood volume through enzymes, hormones gases and waste
the regulation of water products
• Dehydration> body utilizes water Formed elements- cells and cell fragments
present at the blood stream ➢ Red blood cells (RBC)
• Too much water> body collects ➢ White Blood Cell (WBC)
excess water within the tissues and ➢ Platelets
excretes it
3. Protection: Clotting, White Blood Cells, proteins
➢ Clotting- response to open wounds restricting
the outflow of blood
➢ WBC- for immune response
➢ Dense, thick and sticky
➢ Temperature: 38C or 100.4F (1 degree
higher than rectal and oral temperature)
➢ pH: 7.35-7.45 (ave: 7.40)
• 7.37 (leans on the acidic side) 7.43 (leans
on the basic side)
➢ Color: Depends on Oxygen Saturation
• More oxygen: Ranges on the scarlet and
bright red tone
• Minimal to no oxygen content: dark red
➢ Normal Blood Volume: M-5-6L (1.5 gal) F-
4-5L (1.2 gal)
• Difference in blood volume is due to
difference in built between male and
Blood Plasma
female
➢ Nutrients- These include glucose, amino
• Hematocrit- percentage of red blood cells
acids, fats, cholesterol, phospholipids, vitamins
that is found within the blood (40-50% of
and minerals
the blood should be composed of RBC)
➢ Gases- some oxygen and carbon dioxide are
Regulated by hormones
transported by plasma: Plasma also contains a
• hormones associated with the kidney
substantial amount of dissolve nitrogen
mostly regulates the blood
➢ Electrolytes- most abundant: sodium ions
(blood’s osmolarity)
 • not only limited to action potentials
and muscle contractions; it is also
responsible for production and
activation of clotting factors
• abundance in sodium is significant in
osmosis
➢ Nitrogenous waste- byproducts of cellular
metabolism
• Usually cleared from the bloodstream and are
excreted by the kidneys at a rate that balances
their production
• expelled as urine through kidney
• expelled as feces through the intestines
➢ Amino acids
• These are formed from the break down of
tissue proteins or from the digestion of
digested proteins
• Basic structural building units of protein
• 20 different kinds of amino acids when
linked= form proteins
➢ Proteins
• The most abundant substance in plasma
by weight and play a part in a variety of
roles, including clotting, defense and
transport
• Three major categories of plasma protein:
• Albumin; Globulin; Fibrinogen
ALBUMINS
➢ The smallest and most abundant
➢ 60% of plasma protein; produced by liver
➢ Main contributor to osmotic pressure
• Reductions- result in a loss of fluid
from the blood and a gain of fluid in
the interstitial space
➢ Helps many substances dissolve in the plasma
by binding to them
➢ play an important role in plasma transport of
substances (drugs, hormone and fatty acids)
• Dissolves a lot of substances in the plasma
by binding into them
• In association with drugs, Albumin is able
to dissolve the coating or the drug itself;
thus, making the innate product available
for a specific organ.
GLOBULIN
➢ 36% of plasma proteins
➢ subdivided into three classes from smallest to
largest in molecular weight into:
1. Alpha Globulin (largest)
2. Beta Globulin
3. Gamma Globulin (smallest)
• Alpha and Beta binds into lipids and fat-
soluble vitamins to improve absorption; also,
with metal ions such as ferrous sulfate
• Gamma Globulin participates in immune
responses
The Globulins include:
1. High Density Lipoproteins (HDL), an alpha-
1 globulin
• Regarded as Good Cholesterol; prevents
the invasion and settlement of the
cholesterol on the walls of the arteries
2. Low Density Lipoproteins (LDL), a beta-1
globulin
• Bad cholesterol; urges the settlement of
cholesterol on the walls of the arteries; it
carries cholesterol and fats on tissues that
manufactures steroids in the body
• Utilized in cell membrane formation
FIBRINOGEN
➢ 4% of plasma proteins
➢ Produced by liver
➢ A soluble precursor of a sticky protein called
fibrin, which forms the framework of blood
clot
➢ Plays a key role in coagulation of blood
FORMED ELEMENTS OF THE BLOOD
1. White Blood Cells
2. Red Blood Cells
3. Platelets
FORMATION OF BLOOD CELLS
➢ Regulation:
• Negative Feedback System for RBC’S
and platelets
• WBC: based on response to invading
pathogens or foreign antigens
➢ Hemopoiesis or Hemotopoiesis*
• Red Bone Marrow primary site:
Pluripotent stem cells/
Hemocytoblasts
• Reproduce themselves
• Proliferate and differentiate
➢ Cells enter blood stream through sinuses
➢ Formed Elements do not divide once they
leave red bone marrow (Except:
Lymphocytes)
• Detection of low RBC’S and Platelets>
activates the production of RBC’S and
Platelets
• Detection of increase in RBC’S and
platelets> halts the production of it> looks for
the reason behind the increase and
normalizes the level by triggering apoptosis
• Red Bone Marrow primary site (from 3
months before birth and present)
• In an Embryo, Hematopoiesis occurs at the
embryonic yolk sac; later on, it would occur
liver, spleen, thymus and lymph nodes for the
 WBC (during Fetal life); after 3 months before ➢ Hemopoietic growth factors regulate
birth, Hematopoiesis occurs at the Red Bone differentiation and proliferation
marrow, located at the membranous bones • Erythropoietin- RBCs (produced by the
and trabecular bones (hip bones, vertebra, kidneys)
femur) • Plays a key role in the production
• Blood cells reproduce themselves (except of RBCs
platelets due to the absence of nuclei) • Thrombopoietin- Platelets (produced by
• lymphocytes still differentiate once they enter the liver)
the lymph node or tissue • Cytokines: Colony-stimulating factors
(CSFs) and Interleukins- WBCs
FORMATION OF BLOOD CELLS (produced by the bone marrow, dead
• Pluripotent stem cells produce: tissues, macrophages and other
1. Myeloid stem cells leukocytes)
• Give rise to red blood cells, platelets • Not all cytokines are capable of regulating
monocytes neutrophils, eosinophils and white blood
basophils and mast cells
• Progenitor cells RED BLOOD CELLS/ ERYTHROCYTES
2. Lymphoid stem cells give rise to: ➢ Biconcave discs; 7-8 μm diameter; due to its
• Lymphocytes and natural killer cells anucleated nature
• lymphoid and myeloid stem cells are ➢ Anucleated, no organelles
secondary stem cells; both originates from ➢ Life span: 100-120 days
hemocytoblast stem cells ➢ Production: Embryonic yolk sac
• Progenitor cells- differentiates into the • liver, spleen & lymph node
needed type of blood cell as per the body • third trimester up to 5 years old- bone
(regarded as “colony forming units”) marrow
• CFUe (Colony forming unit for erythrocytes; • Greater than 20 years old-
RBC) membranous bones
• CFUmeg (Colony forming unit ➢ Normal values
megakaryocytes; for platelets) • Female: 4.8 Million/mm3
• Male: 5.4 Million/mm3
➢ Function:
➢ Respiratory gas (oxygen and Carbon Dioxide)
transport
➢ Transports hemoglobin> carries oxygen from the
lungs to the tissues
➢ Contains large quantity carbonic anhydrase
which:
• Influences and somehow accelerates the transport
of your CO2 in the blood
• if its processed or through the occurrence of
enzymatic reaction, it produces water carbonic
acid and bicarbonate which can help the body to
regulate the ph level of the blood
• RBCs don’t resort with Mitochondria
• RBC contains strong plasma membrane; allowing
it to fold, penetrate and enter blood vessels
• stable demand of oxygen> production of RBC is
equal to its destruction
• If there is high demand for oxygen> increase in
production as compared to destruction
• The average produced and destroyed RBCs is
around 2 million
• Red Blood Cells contains High Glycolipids which
is responsible for Rh content and blood type
• Hemoglobin-oxygen carrying aspect of the RBC
• Hematocrit- percentage of RBCs within the blood; kailangan ng more hemoglobin para malagyan ng
around 40-50% oxygen for the tissue)
- Any condition that will decrease the qty. of 02
ERYTHROPOIESIS transported to the tissue → inc. rate of RBC
- Starts in the red bone marrow with production
proerythroblast - Anemia- low RBC
- Cell near the end of the development ejects
- Destruction of major portions of bone
nucleus and become a reticulocyte
marrow
- Develop into mature RBC within 1 to 2 days
- Negative feedback balances production with - High altitude- less oxygen, kala ng katawan
distraction mo mababa yung RBC so mag pproduce pa
- Controlled condition is amount of oxygen ng RBC para makapag transfer ng oxygen
delivery to tissues - Cardiac failure & lung diseases
- Hypoxia stimulates release of erythropoietin
- The genesis of red blood cell
ERYTHROPOIETIN
- From a stem cell magkakaron muna commited - One of the regulatory systems of the RBC
cell which is the colony forming unit - Principal factor that stimulates RBC
erythrocytes (CFUE) (dito mang gagaling so production
proerythroblast) - Areas formed:
- Kindey – 90%
PROERYTHROBLAST - Liver
- It will give rise to the basophil erythroblast - Non- renal sources - epinephrine,
norepinephrine & prostaglandins →
BASOPHIL ERYTHROBLAST stimulates kidneys
- Main effect:
- It is considered as a first-generation cell (dito o Stimulates the formation of
una nag kakaroon ng staining, staining which proerythroblast from its stem cell
could inidicate na nag kakaron na siya ng o Speed up the
hemoglobin) production/differentiation of new
cells
POLYCHROMATOPHIL ERYTHOBLAST
- Dito unang nakikita na may hemoglobin na. MATURATION OF RBC
Vitamin B12 and Folic acid
ORTHOCHROMATIC ERYTHOBLAST - Thymidine triphosphate >> DNA synthesis
- Tuloy lang yung pag produce ng hemoglobin - Deficiency: Mutation failure
(Kasabay ng pag taas ng hemoglobin concentration o Abnormal/ diminished DNA
nag sshrink din yung cell.) o Macrocyte production – type of RBC
(Yung nucleus nag sshrink at yung organelles, while which is very fragile , it is regular not
the endoplasmic reticulum is being absorb) by concave and it also very large so
mahirap mag travel sa blood vessel.
RETICULOCYTE Because of its fragility hindi niya
- Kapag nawala na yung nucleus and maccarry yon kung saan needed
organelles, kapag na expel na and nag karon yung oxygen, masisira muna siya
na ng exocytosis sa nucleus it become a bago madala
reticulocyte
- Lalabas siya sa bone marrow papunta sa bone Vitamin B12 (Cyanocobalamin):
capillaries through the diapedesis or o Absorbed by ileum of small
squeezing out to the corner of the bone intestine
marrow o Pernicious Anemia
- Baby erythrocyte Folic Acid:
- Kapag nalabas na yung mga meron siya dun Sprue- small intestine absorption abnormality
lang si magiging fully mature erythrocyte after
1 to 2 days being outside of the bone marrow HEMOGLOBIN
Globin – 4 polypeptide chains
REGULATION OF RBC PRODUCTION - Heme in each of 4 chains
Tissue oxygenation – basic regulator of RBC - Iron ion can combine reversibly with one
production oxygen molecule (4 ions per hemoglobin)
Tissue hypoxia- mababa yung oxygen na - Also transports 23% of total carbon dioxide
narereceive ng tissue and it could cause or trigger it
would stimulate the production of more RBC (
 o Combines with the amino acids of
globin.
- Nitric oxide (NO) binds to hemoglobin
o Releases NO causing vasodilation
to improve blood flow and oxygen
delivery
SICKLE CELL ANEMIA
- Hemoglobin chain abnormality
- Amino acid valine is substitutes for glutamic
acid at one point in each of the two beta
chains
- RBC’s become rigid and sticky and are shaped
like sickles or crescent moons
- Nag kakaron ka ng red blood shape
cristalization instead of having a by concave
nagkakaron ng sickle RBC
- Exposure of affected RBC to low oxygen >>
formation of elongated crystals inside the cell
FORMATION OF HEMOGLOBIN
1) Succinyl- CoA binds with glycine to from a
pyrrole molecule.
2) In turn, four pyrroles combine to form
protoporphyrin IX
3) Which then combines with iron to form the
heme molecule
4) Finally, each heme molecule combines with a
globin, forming a subunit of hemoglobin
called hemoglobin chain (alpha, beta, gama
and delta chain)
1 Hemoglobin chain – made up of heme and globin
Heme – made up of protoporphyrin IX and iron
Globin – a polypeptide chain which synthesize by
ribosomes.
Most common type of hemoglobin is hemoglobin A
which compose of two alpha and 2 beta hemoglobin
chains.
ROLE OF HEMOGLOBIN
- Under normal conditions, oxygen is
carries to the tissue almost entirely by
hemoglobin
- 15 grams of hemoglobin in each 1000ml
of blood
- 1 grams of hemoglobin can bin d with a
maximum of 1.34 milliliters of oxygen
- Oxygen does not combine with the two
positive bonds of the iron in the
hemoglobin molecule but binds loosely
with one of the so-called coordination
bonds of the iron atom.
IRON METABOLISM
- N): 4-5g
- 65% found in hemoglobin
- 4% found in myoglobin
- 1% found in virous heat compound that
promotes intracellular oxidation later
- 15 to 13% is stored for it para magamit
- Absorbed by the small intestine
- 1 of the composition of the hemoglobin (so
kung walang iron hindi ka makakapag
produce ng hemoglobin)
- Blood Plasma: Combines with apotransferrin
>> transferrin or hemoglobilin
- Cell: combines with apoferritin >> ferritin
(storage iron. a protein that storage your iron
- Hemosiderin – insoluble form of iron
- Hypochromic Anemia- is when RBC contains
less hemoglobin than usual, which Is because
there is an adequet quantity of iron na
dumadaloy sa body
- Regulation: alteration on absorption – if the
body does not command more iron hindi siya
iaabsorb ng katawan ilalabas siya.
LIFE SPAN OF RED BLOOD CELLS
- Live only about 120 days
- Cannot synthesize new components – no
nucleus
(+) cytoplasmic enzymes- maintains the friability
of the cell membrane (kahit patay na yung RBC
kaya niya pa din pumunta sa kaya niyang
puntahan)
- Yung iron mo na naka store sa hemoglobin
they keep it as a ferus form or inferic form
- Ferus form- if it is in ferus form it can easily be
converted to in another form of iron
- Inferic form – kailangan pa ng another
chemical reaction for to be converted
- Ruptured red blood cells removed from
circulation and destroyed by fixed
phagocytotic macrophages in spleen and liver
- Breakdown products recycled
o Globin’s amino acid recycles
o Iron reused
o Non-iron heme ends as yellow
pigments urobilin in urine or brown
pigment stercobilin in feces
RBC LIFE CYCLE
1. Red blood cell and phagocytosis – Once na
namatay na yung RBC it is divided into Globin
and Heme
2. Globin just becomes an amino acid and then
it is reused for protein synthesis
 3. Heme is further broken down, nagiging ferus
and nagiging biliverdin
4. Ferus it could combine it apotransferrin to
become transferrin or it could combine with
apoferritin which would make the iron or
ferus ferritin (meron siyang choice kung ano
gusto niya maging)
5. Si transferrin nasa blood plasma, pwede siya
mastore sa liver as ferritin
6. Pwede lang ulit siya makalabas to become
ferus of transferrin para makapag travel sa
blood plasma and go to the bone marrow to
be combine with vitamin B12, globin and be
stimulated by erythropoietin to become
globin.
7. Pwede din mag stay siya sa liver as ferritin
8. The noniron part is converted in to Biliverdin
which is a green pigment while the bilirubin
is a yellow orange pigment, and it is then
stored para matransport siya sa liver to
become bilirubin. found in the bile duct, nag
ttravel siya sa bile duct papunta sa
9. Bilirubin will pass through bile duct and small
intestine papunta sa large intestine getting
ready for it to be excreted
10. Meron siyang dalawang choice na mag
eexcrete ba siya sa kidney or sa intestine
11. Once it reaches your large intestine it
becomes, bilirubin becomes urobilinogen
12. Then the urobilinogen if it wishes to be
excreted to the kidneys pupunta siya sa
kidney then mag cconvert into urobilin, that is
a yellow pigment, eto yung nag bibigay kulay
sa urine
13. But if it wishes to stay large intestine and be
excreted into feces, the urobilinogen just
converts and stay in the large intestine and be
converted to stercobilin and be excreted to
feces. Stercobilin is a brownish pigment.
ANEMIA & POLYCYTHEMIA
• ANEMIA – an abnormality or a decrease in the
number of red blood cell
• POLYCYTHEMIA – excessive amount of red blood
cell
• Blood Loss Anemia
o excessive blood loss
o ex. Secondary hemorrhage – causes
anemia because it replenishes longer for
about 3-6 weeks
• Microcytic Hypochromic Anemia
o Smaller red blood cells with little amount
of hemoglobin
o Because of chronic blood loss, not
enough iron to produce or form
hemoglobin
o Less hemoglobin = smaller red blood
cells produced
• Aplastic anemia
o Caused by bone marrow dysfunction,
• Megaloblastic Anemia
o Large ugly shaped red blood cell because
of malabsorption of vitamin B12 or folic
acid, resulting to slow reproduction of
erythroblast and erythrocytes that
produces deformed red blood cells
• Pernicious anemia
o Mainly caused by lack of intrinsic factor
found at stomach mucosa resulting to
vitamin B12 deficiency = no hemoglobin
= smaller or deformed red blood cell
o Intrinsic factor – absorb vitamin B12
• Hemolytic Anemia
o abnormality that makes the RBC fragile/
easily ruptured
o Hereditary spherocytosis
▪ Spherical shaped, very small
▪ Not flexible enough that it will
easily rupture
o Sickle Cell Anemia
▪ RBC crystallization
▪ May damage adjacent vessels
leading to vessel hemorrhage &
further damage to tissues
• Polycythemia Vera (Erythremia)
o Aka primary polycythemia
o Excessive RBC
o Hematocrit reaches 60-75%
o Caused by genetic aberration into the
hemocytoblast cell – (which produces
stem cells), leading to genetic dysfunction
which affects the cells where the blood
cells came from
• Secondary Polycythemia
o Increase in red blood cell secondary to the
exposure to a hypoxic environment
o Automated response of the body to
produce higher numbers of red blood cell
whenever exposed in a hypoxic
environment
WHITE BLOOD CELLS / LEUKOCYTES
Normal: 7000 WBCs per microliter of blood
Range: 5000 – 10000 WBCs per microliter of blood
• Mobile units of the body’s protective system
• Types:
o Granular leukocytes: Neutrophils (62%),
eosinophils (2.3%), basophils (0.4%)
o Agranular leukocytes: lymphocytes (30%)
& monocytes (5.3%)
o Occasionally: produces plasma cells
• Produced in bone marrow: granulocytes &
monocytes and a few lymphocytes
• Lymph tissue: lymphocytes & plasma cells
• Transported into areas of serious infection &
inflammation

TYPES OF WHITE BLOOD CELLS

• Differentiation of granular and agranular is

because of the staining of leukocytes highlighting
the granules

GRANULAR LEUKOCYTES Genesis of Myelocytes

• Neutrophil – very small, evenly distributed, pale
lilac granules, has 3-5 nucleus
• Eosinophil – large uniform sized granule, stains
red-orange if exposed to acidic dyes
• Basophil – stained by blue & purple if exposed to
basic dyes, round variable granules
AGRANULAR LEUKOCYTES
• Lymphocyte - circular
• Monocyte – kidney shaped,
macrophage once needed
o fixed (tissue) macrophages –
particular tissue
o wandering macrophages –
tissue & gather at
infection/inflammation
LEUKOGENESIS
• stem cell >> then all came from the myeloblast >>
becomes promyelocyte >> gives off daughter
cells for the granular leukocytes & monocytes >>
also gives off megakaryocyte that produces
platelets
Genesis of Lymphocytes
• only produced by lymphogenous tissue: spleen,
lymph nodes, thymus, etc.
becomes LIFE SPAN OF WBC
• Granulocytes: 4-8 hours circulating in the blood
reside in a & another 4-5 days in tissues where they are
needed
roam the • Monocytes: 10-20 hours in the blood, before
sites of wandering through capillary membranes into
tissues
o Macrophages: months unless die
because of phagocytosis
• Lymphocytes – life spans of weeks or months
• Platelets in the blood are replaced about once
every 10 days
FUNCTIONS OF WBCs
• Leukocytosis – normal protective response to
invaders, strenuous exercise, anesthesia, &
surgery
• Leukopenia – WBC less than 5000 molecules per
microliter of blood, not good
• General function – combat invaders by
phagocytosis or immune responses
• Neutrophils & Macrophages: attack & destroy
invading bacteria, viruses, & other harmful agents
• Eosinophil: counter parasitic/bacterial activity,
lessen allergic activity
• Basophil: immediate allergic response, prevent
blood loss
NEUTROPHILS & MACROPHAGES
• Neutrophils & macrophages are active
phagocytes
 o Enter tissue spaces by diapedesis o Neutrophilia – sudden increase of
o Move through tissue spaces by ameboid neutrophils in affected regions
motion o Happens in 1st hour of inflammation
o Attracted by inflamed tissue areas o Triggered by TNF (tumor necrosis factor)
chemotaxis (stimulus) & IL-1 (interleukin-1)
• Neutrophils respond most quickly to tissue o Neutrophil extravasation – process of
damage by bacteria transfer of neutrophil from capillary to
o Uses lysozymes, strong oxidants, affected region
defensins – proteins that promote o Selectin holds integrin of neutrophil >>
antibacterial activity cells separate or loosens >> go to the
• Monocytes take longer to arrive but arrive in larger injured tissue attracted by chemical
numbers & destroy more microbes reactions
o Enlarge and differentiate into • Third line of defense: second macrophage
macrophages invasion
o Call many macrophages
PHAGOCYTOSIS o Monocytes are delayed because it is not
• Neutrophil: 1:3-20 (1 neutrophil could eat 3-20 matured macrophages yet that is why it is
microbes) 3rd line of defense
• Macrophage: 1:100 (1 macrophage could eat 100 • Fourth line of defense: increased production of
microbes) granulocytes and monocytes by bone marrow
o Reticuloendothelial system • Feedback control of responses:
▪ aka monocyte macrophage o Produces monocyte: GM-CSF
system (Granulocyte-macrophage colony-
▪ local tissue macrophages: stimulating factor), G-CSF (Granulocyte -
histiocyte – for the skin, alveolar colony stimulating factor); M-CSF
macrophage – for the lungs, (Macrophage colony-stimulating factor)
kupffer cells – for the liver o Main feedback mechanism: TNF (tumor
▪ combination of monocytes, necrosis factor), IL-1 (interleukin-1)
mobile macrophages, fixed tissue
macrophages, specialized EOSINOPHILS & BASOPHILS
macrophages that are ready
▪ generalized phagocytic system
for all tissues
• Means cellular ingestion of the offending agent:
o 3 selective procedures:
o If surface is smooth, the rougher the
surface = high chance of undergoing
phagocytosis
o Protective protein coat that is repellant to
phagocytosis
Eosinophils – leave capillaries and enter tissue
o Immune response if antibodies carried the
• Release histaminase – decrease histamine
pathogen to the phagocytic agent
activity (lessen the allergic reaction)
• Most important function of neutrophils &
• Phagocytize antigen-antibody complexes
macrophages
- very important for parasitic infection
• Opsonization: pathogen selected for
Basophils – leave capillaries
phagocytosis and destruction
• Similar function to mast cells
• Residues: consumed by lysosomes (proteolytic
-release Heparin
enzymes)
• Release Histamine, Bradykinin, and Serotonin
INFLAMMATION • Mediates inflammatory and immediate
allergic responses
• Entire complex of tissue changes d/t tissue injury
• First line of defense: local tissue macrophages LYMPHOCYTES
o Fixed macrophages activated by initial
• Major soldiers of the immune system
inflammatory response, undergo rapid
- Responsible for acquired immunity
enlargement >> phagocytosis
-B cells – Destroying bacteria and inactivating
• Second line of defense: neutrophil invasion
their toxins
(*Neutrophilia)
 -T cells – attack viruses, fungi, 2) Precipitation – molecular complex
transplanted/cancer cells, and some bacteria enlargement that it is rendered insoluble and
• Natural Killer (NK) cells – attack a wide precipitates
variety of infectious microbes and certain 3) Neutralization – in which the antibodies cover
tumor cells the toxic sites of the antigenic agent
4) Lysis – directly attacking membranes of
BASIC TYPES OF ACQUIRED IMMUNITY cellular agents and thereby cause rupture of
Humeral Immunity Cell-mediated the agent
Immunity II . BY ACTIVATION OF THE “COMPLEMENT
• B-cell immunity • T-cell SYSTEM”
• B lymphocytes immunity • Enhance (complement the actions of
produced the • Activated T antibodies and phagocytic cells
antibody lymphocytes > destroy pathogens
• Preprocessing • Preprocessed • System of about 20 proteins, many of
organ: first found in thymus which are enzyme precursors (inactive
in Bursa of • Involves the state) >> activated by classical pathway
Fabricious activation of • Classical pathway – initiated by an
• Midfetal: macrophages antigen-antibody reaction
Preprocessed in , natural killer - Antibody binds with an antigen>>
liver cells (NK), uncovering/activation of a specific
• Late fetal/post- antigen- reactive site >> binds directly into c1
birth: bone specific molecule >> triggers a cascade of
marrow cytotoxic T- reactions >> multiple end products are
• Humoral lymphocytes, formed
immunity=becaus and the END PRODUCTS OF THE “COMPLEMENT SYSTEM”
e it involves release of 1) Opsonization and Phagocytosis – C3b,
substances found various strongly activates phagocytosis by both
in the humours or cytokines in neutrophils and macrophages >> engulf the
body fluids response to bacteria to which the antigen-antibody
an antigen. complexes are attached.
2) Lysis. – Lytic complex (combination of
NATURE OF ANTIBODIES multiple complement factors and designated
• Antibodies are gamma globulins called C5b6789). This has a direct effect of rupturing
immunoglobulins (Ig) the cell membranes of bacteria or other
• 20% of all the plasma proteins invading organisms.
• Composed of combinations of light and heavy 3) Agglutination - change the surfaces of the
polypeptide chains (variable portion) and the invading organisms, causing them to adhere
remaining constant portion to one another, thus promoting agglutination
• Each antibody is specific for a particular 4) Neutralization of viruses. – The complement
antigen – d/t unique structural organization of enzymes and other complement products can
amino acids attack the structures of some viruses and
thereby render them non virulent.
CLASSES OF ANTIBODIES
5) Chemotaxis. – Fragment C5a initiates
IgG, bivalent antibody and constitutes about 75 per chemotaxis of neutrophils and macrophages
cent of the antibodies of the normal person >> migrate into the tissue area adjacent to the
antigenic agent.
IgE, which constitutes only a small percentage of the
6) Activation of mast cells and basophils. –
antibodies but is especially involve in allergy.
Fragments C3a, C4a, and C5a activate mast
IgM, increase production formed during the primary cells and basophils >> release histamine,
response are of this type, have 10 binding sites that heparin, and several other substances into the
make them exceedingly effective in protecting the local fluids. >> cause increased local blood
body against invaders flow, inc leakage of fluid and plasma protein
into the tissue, and other local tissue reactions
that help inactivate or immobilize the
MECHANISMS OF ACTION OF ANTIBODIES
antigenic agent.
I. BY DIRECT ATTACK ON THE INVADER
1) Agglutination – Clumping
7) Inflammatory effects – Several other
complement products contribute to local
inflammation.
HELPER T CELLS
• Most numerous of the T cells
• 75% of all T cells
• They help in the functions of the immune
system
- They serve as the major regulator of virtually
all immune functions
- Forms a series of protein mediators, called
lymphokines, that act on other cells of the
immune system as well as on bone marrow
cells
CYTOTOXIC T CELLS
• Killer cells
• A direct-attack cell that is capable of killing
micro-organisms and even some of the
body’s own cells.
• Perforins, literally punch round holes in the
membrane of the attacked cell
• Releases cytotoxic substances directly into the
attacked cell
• Attacked cell becomes greatly swollen, and it
usually dissolves shortly
SUPPRESSOR T CELLS
• Capable of suppressing the functions of both
cytotoxic and helper T cells
• Serve the purpose of preventing the cytotoxic
cells from causing excessive immune
reactions that might be damaging to the
body’s own tissues
• Classified, along with the helper T cells, as
regulatory T cells. It is probable that the
suppressor T-cell system plays an important
role in limiting the ability of the immune
system to attack a person’s own body tissues,
called immune tolerance
PLATELETS/THROMBOCYTES
• Production stimulated by: Thrombopoietin
- Myeloid stem cells develop eventually into a
megakaryocyte colony-forming cell>>
megakaryoblasts >> megakaryocytes
-Megakaryocytes>> Splinters into 2000-3000
fragments
• Platelet: each fragment enclosed in a piece of
plasma membrane
-Disc-shaped with many vesicles but no
nucleus
-Normal: 150,000 and 450,000/µƖ.
• Help stop blood loss by forming platelet plug
- Granules contain blood clot-promoting
chemicals.
• No nuclei = (-) reproduction
• Cytoplasm contents:
✓ Actin, myosin, and thrombosthenin – platelet
contraction
ER and Golgi apparatus – enzyme synthesis
Mitochondria – for ADP and ATP
✓ Enzyme system – prostaglandin synthesis
Fibrin-stabilizing factor – blood coagulation
Growth factor – cellular growth
• Plasma membrane: Glycoprotein coat
Half-life:8-12days
HEMOSTASIS
- is a sequence of responses that stops
bleeding.
- When blood vessels are damaged or ruptured,
the hemostatic response must be quick,
localized to the region of damage, and
carefully controlled in order to be effective.
Three mechanisms reduce blood loss: (1) vascular
spasm, (2) platelet plug formation, (3) blood clotting
(coagulation), and (4) Eventual growth of Fibrous
Tissue. When successful, hemostasis prevents
Hemorrhage: loss of a large amount of blood from the
vessels.
VASCULAR SPASM
- Contraction of the smooth muscles on the
injured vessel wall.
- When arteries, arterioles or tissues are
damaged, the circularly arranged smooth
muscle in their wall’s contracts immediately, a
reaction called vascular spasm.
- This reduces blood loss from several minutes
to several hours.
Results from:
1. Local myogenic spasm
2. Local autacoid factors from the traumatized
tissues and blood platelets
3. Nervous reflexes (stimulated by pain receptors)
Smaller vessels= vasoconstriction caused by
thromboxane A (released by platelets)
PLATELET PLUG FORMATION
- Platelet come in contact with damaged circular
surface >>> Change in platelet characteristics
- Platelets begin to swell, assume irregular form
with pseudopods (protruding in all directions
of their surface).
- Becomes sticky >>> adheres to collagen and
to vWF (von Willebrand factor).
- Secretes ADP (Adenosine DiPhosphate) and
PAF (Platelet Activating Factor)
- Enzymes form Thromboxane A2
- Fibrin Threads

CLOTTING OR COAGULATION
-process of gel formation
- series of chemical reactions that culminates in
formation of fibrin threads.
- If blood clots too easily, the result can be
thrombosis—clotting in an undamaged blood
vessel.
- If the blood takes too long to clot, hemorrhage
can occur.
The gel is called a blood clot.
- It consists of a network of insoluble protein
fibers called fibrin in which the formed
elements of blood are trapped.
Clotting can be divided into three stages:
1. Formation of prothrombin activator (Result of
blood vessel damage)
2. Conversion of Prothrombin to Thrombin.
Prothrombinase converts prothrombin into the
enzyme thrombin. Use of sufficient ionic
calcium.
3. Polymerization of Fibrinogen into fibrin (by
thrombin enzyme) >>> fibrin enmeshes
platelets, blood cells, and plasma to form the
clot.
>vitamin k- for blood clotting, prothrombin activator.
>clot retraction- indicates amount of platelets
BLOOD CLOTTING: INITIATION OF
COAGULATION
- Stimulus of the clotting initiating process:
1. Trauma to the vascular wall and adjacent
tissues
2. Trauma to the blood
3. Contact of the blood with damaged
endothelial cells/ elements outside the
vessels.
- Response: formation of prothrombin activator
- Extrinsic pathway – begins with trauma to
the vascular wall and surrounding tissues.
- Intrinsic pathway – begins in the blood.
- Blood clotting factors
THE EXTRINSIC PATHWAY
- Activated by tissue trauma
- The extrinsic pathway of blood clotting has
fewer steps than the intrinsic pathway and
occurs rapidly—within a matter of seconds if
trauma is severe.
- It is so named because a tissue protein called
tissue factor (TF), also known as
thromboplastin, leaks into the blood from
cells outside (extrinsic to) blood vessels and
initiates the formation of prothrombinase.
- Tissue factor/lipoprotein complex is a
complex mixture of lipoproteins and
phospholipids released from the surfaces of
damaged cells.
- In the presence of Ca2+, TF begins a sequence
of reactions that ultimately activates clotting
factor X.
- Once factor X is activated, it combines with
factor V in the presence of Ca2+ to form the
active enzyme prothrombinase, completing
the extrinsic pathway.
Factor V- only activated by proteolytic enzymes of
thrombin (released once the clotting begins)
-only accelerates the formation of Prothrombin
THE INTRINSIC PATHWAY
- Activated by blood trauma
- more complex than the extrinsic pathway, and
it occurs more slowly, usually requiring several
minutes.
- The intrinsic pathway is so named because its
activators are either in direct contact with
blood or contained within (intrinsic to) the
blood; outside tissue damage is not needed.
- If endothelial cells become roughened or
damaged, blood can come in contact with
collagen fibers in the connective tissue around
the endothelium of the blood vessel.
- In addition, trauma to endothelial cells causes
damage to platelets, resulting in the release of
phospholipids by the platelets.
- Contact with collagen fibers activates clotting
factor XII, which begins a sequence of
reactions that eventually activates clotting
factor X.
- Platelet phospholipids and Ca2+ can also
participate in the activation of factor X.
- Once factor X is activated, it combines with
factor V to form the active enzyme
prothrombinase, completing the intrinsic
pathway.
CLOTTING AND BLEEDING DISORDERS
Hemophilia A
- Lack of factor VIII (antihemophilic factor)
- Incest (baby gets Hemophilia A). Common in
monarchies before.
- is an inherited deficiency of clotting in which
bleeding may occur spontaneously or after
only minor trauma.
Thrombocytopenia
- Platelet deficiency
- Even normal movements can cause bleeding
from small blood vessels that require platelets
for clotting
Thrombus
- A clot in an unbroken blood vessel
 - Can be deadly in areas like the heart
Embolus
- Dislodged Thrombus.
- A thrombus that breaks away and floats freely
in the bloodstream
- Can later clog vessels in critical areas such as
the brain, heart, lungs.
BLOOD GROUPS AND BLOOD TYPES
The surfaces of erythrocytes contain a genetically
determined assortment of antigens composed of
glycoproteins and glycolipids.
Agglutinogens= surface of RBCs contain genetically
determined assortment of antigens
These antigens, called agglutinogens, occur in
characteristic combinations. Based on the presence or
absence of various antigens, blood is categorized into
different blood groups. Within a given blood group,
there may be two or more different blood types.
There are at least 24 blood groups and more than 100
antigens that can be detected on the surface of red
blood cells.
BLOOD GROUPS AND BLOOD TYPES
- based on two glycolipid antigens called A and
B.
- type A blood: People whose RBCs display
only antigen A have.
- type B: Those who have only antigen B are.
- type AB: Individuals who have both A and B
antigens are
- type O: those who have neither antigen A nor
B.
Blood plasma usually contains antibodies called
agglutinins(antigen) that react with the A or B
antigens if the two are mixed. These are the anti-A
antibody, which reacts with antigen A, and the anti-B
antibody, which reacts with antigen B.
You do not have antibodies that react with the
antigens of your own RBCs, but you do have
antibodies for any antigens that your RBCs lack.
For example, if your blood type is B, you have B
antigens on your red blood cells, and you have anti-A
antibodies in your blood plasma.
Although agglutinins start to appear in the blood
within a few months after birth, the reason for their
presence is not clear. Perhaps they are formed in
response to bacteria that normally inhabit the
gastrointestinal tract. Because the antibodies are large
IgM-type antibodies that do not cross the placenta,
ABO incompatibility between a mother and her fetus
rarely causes problems.
TYPING AND CROSS-MATCHING BLOOD FOR
TRANSFUSION
In the procedure for ABO blood typing, single drops
of blood are mixed with different antisera, solutions
that contain antibodies.
✓ One drop of blood is mixed with anti-A serum,
which contains anti-A antibodies that will
agglutinate red blood cells that possess A
antigens.
✓ Another drop is mixed with anti-B serum, which
contains anti-B antibodies that will agglutinate red
blood cells that possess B antigens.
✓ If the red blood cells agglutinate only when mixed
with anti-A serum, the blood is type A.
✓ If the red blood cells agglutinate only when mixed
with anti-B serum, the blood is type B.
✓ The blood is type AB if both drops agglutinate; if
neither drop agglutinates, the blood is type O.
HEMOLYTIC DISEASE
- RH Blood Group
- People whose RBC’s have the Rh antigen are
Rh+
- People who lack the Rh antigen are Rh-
- Normally, blood plasma does not contain
anti-RH antibodies
- Hemolytic disease of the newborn (HDN)- if
blood from Rh+ fetus contacts Rh- mother
during birth, anti-Rh antibodies made
▪ Erythroblasts Fetalis
▪ Affect is on second Rh+ baby
▪
DETERMING RH FACTOR
✓ In the procedure for determining Rh factor, a drop
of blood is mixed with antiserum containing
antibodies that will agglutinate RBCs displaying
Rh antigens.
✓ If the blood agglutinates, it is Rh+
✓ no agglutination indicates Rh−.
✓ Once the patient’s blood type is known, donor
blood of the same ABO and Rh type is selected.