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Blood & Immune System
Chapter 11 & 14
Physical characteristics of blood
 Fluid connective tissue
 matrix – “plasma” with dissolved proteins
 cells & cell fragments – “formed elements”
 temperature – 38o C
 5x more viscous than H2O
 pH – 7.35-7.45
Functions of Blood
 Transportation
 O2/CO2; nutrients/wastes; enzymes; hormones
 Regulation
 body temperature; pH & ion composition of interstitial
fluid; intracellular fluid volume
 Protection
 defense against pathogens; restriction of fluid loss at
injury sites
Composition of Blood
55% Plasma – liquid component of blood
45% Formed elements – cells/cellular fragments
Erythrocytes – red blood cells (RBCs)
Leukocytes – white blood cells (WBCs)
Platelets
Plasma
Formed Elements
granular
agranular
Hemopoiesis
Megakaryoblast
Erythrocytes (RBCs)
 Biconcave shape, flexible cells
around 5 million RBCs per mm3 blood
 average “life span” of 120 days
Cells contains cytosol, no nucleus/organelles; filled with
Hemoglobin (Hb)
Hemoglobin
Hemoglobin allows for
transport of O2 & CO2
 As RBCs get damaged/worn out, they must be
removed from circulation & replaced
 About 1% of the circulating RBCs are replaced
each day, at at rate of about 3 million RBCs per
second
 Worn out RBCs are removed by phagocytic cells
in the liver, spleen & bone marrow
Hemoglobin recycling
 “globin” proteins will be
broken down into amino acids
to be re-used by cells to make
new proteins
 Iron will be separated from
“heme” & can be stored in the
liver, & be re-used to make new
Hb
 the pigmented part of heme
will get converted to biliverden
& bilirubin (pigments), & most
will get excreted as part of bile
from the liver
Erythropoiesis
 The formation of RBCs
 Occurs in bone marrow
(myeloid tissue) due to
hypoxia detected in kidneys
Blood Typing
 There are many different surface antigens
(transmembrane proteins) within the plasma membrane of
your RBCs. These antigens (a.k.a. “agglutinogens”) are
genetically determined.
Your surface antigens are recognized by your immune
defense system as “self”.
 The presence or absence of 3 specific antigens (A, B &
Rh) determine your “blood type”
 Within your plasma, you may have specific antibodies
(a.k.a. “agglutinins”) against surface antigens that are not
yours.
 Plasma antibodies are responsible for “protecting” you
from an incompatible blood type
Blood Typing
If the Rh antigen is also present, the person is Rh+, if they
do not have the Rh antigen, they are Rh-
Blood Typing
When you combine the information from the AB & Rh
antigens, the possible blood types will be:
A+/AB+/BAB+/AB-
O+/OWhen considering whether a transfusion will be compatible,
it is most important to consider the donor’s surface antigens
& the recipient’s plasma antibodies
Blood Typing
 Unlike the AB grouping, people who are Rh- do not
genetically create antibodies against Rh in their plasma.
 Antibodies will only be formed after an initial exposure to Rh
 This could happen during an incompatible transfusion (i.e.
A+  A- ), or during pregnancy if an Rh- mom is carrying an
Rh+ baby.
 Rh antibody formation in a mom who is carrying an Rh+
baby will lead to “hemolytic disease of the newborn”
Leukocytes (WBCs)
 More like “typical” cells with single
nucleus, organelles
 5 types of WBCs characterized as
granular or agranular
 all function in defense
 average 6000-9000 WBCs/mm3 of
blood
 variable “life” span depending on
type of WBC- days (neutrophils) to
decades (lymphocytes); in sick person,
some WBCs live minutes to hours
Leukocytes (WBCs)
WBCs exhibit common characteristics:
 amoeboid movement
gliding movement of cell membrane/cytoplasm; allows WBCs to
move along blood vessel walls & throughout tissues
 diapedesis
can squeeze through epithelial cells of capillary walls to
migrate into tissues
 positive chemotaxis
WBCs are attracted to chemicals released by invading
pathogens & damaged tissues
 phagocytosis
neutrophils, monocytes, & eosinophils are phagocytic
Differential Count & Functions of WBCs
 “WBC differential count” – normal range (in
percentage) of WBCs in the peripheral circulation
 differential count will vary during specific types of
disorders, depending on which type of WBC responds
 WBC response based on functions of specific type
Differential Count & Functions of WBCs
 Neutrophils - 50-70%
function in acute bacterial infections; phagocytic
 Lymphocytes – 20-30%
function in “immunity” – specific resistance to disease
 Monocytes – 4-8%
function in chronic bacterial infections; migrate into
tissues to become “wandering macrophages”
 Eosinophils – 2-4%
active against parasites & elevated in allergic reactions;
destroy antibody-coated antigens by phagocytosis
 Basophils - <1%
release chemicals (histamine, heparin) during tissue
inflammation
Platelets (Thrombocytes)
 Cellular fragments (cell membrane “packet” filled with
cytoplasm) from large Megakaryocytes found within bone
marrow
 around 350,000 platelets/mm3
 platelets circulate for 9-12 days before being removed
from circulation
 platelets function in “hemostasis” – the processes that
stop bleeding from damaged blood vessels
Hemostasis
There are three overlapping processes of hemostasis:
1. Vascular spasm – damage to BV wall causes the smooth
muscle within the wall to spasm vasoconstriction &
decreased blood loss through vessel; begins within a few
seconds of injury, lasts about 30 minutes
2. Platelet plug formation – damaged BV endothelium gets
sticky & circulating platelets stick to the endothelium & each
other, creating a platelet plug; begins within 15 seconds of
BV damage; may be enough to stop bleeding completely
within a small BV (i.e. capillary)
3. Coagulation – blood clotting; complex series of steps
resulting in the conversion of fibrinogen  fibrin
Overview of Coagulation
• initiated by both
“extrinsic” (tissue) &
“intrinsic” (platelet) factors
• both pathways result in
activation of Factor X (10)
• activation of Factor X
begins the “common
pathway”
• all 3 pathways require
the presence of Ca2+ &
vitamin K
Coagulation
 Extrinsic pathway –
 begins with damage to surrounding tissues & BV
endothelium which cause the release of “tissue factors”
 eventually results in the formation of an enzyme (“Factor X
activator”) capable of activating Factor X
 shorter, quicker pathway for initiation of coagulation
 Intrinsic pathway –
 begins with the release of “platelet factors”
 eventually results in the formation of “Factor X activator”
 more complicated, slower pathway of coagulation
Coagulation
 Common pathway –
 begins with the activation of Factor X, by the production
of Factor X activator from either the extrinsic or intrinsic
pathway
 the activation of Factor X results in the formation of the
enzyme Prothrombinase
 Prothrombinase converts Prothrombin (a clotting protein)
 Thrombin (an enzyme)
 Thrombin converts Fibrinogen (soluble protein)  Fibrin
(insoluble protein strands that create the actual clot)
Clot Retraction, Repair & Removal
 Once the clot has begun to form, the fibrin threads &
trapped platelets cause the edges of the damaged vessel to
pull together causing “clot retraction”
 Repair to the damage vessel & surrounding tissues occur
as fibroblasts invade the area & endothelial cells regenerate
 Eventually the clot gets removed by the enzyme “plasmin”
in a process known as “fibrinolysis”
 A clot which remains present in an intact vessel is known as
a “thrombus”. Thrombi can block blood flow & pieces can
dislodge creating an “embolism”
Immunity
( Chap 14, p. 464-471)
Humans have two major types of defense mechanisms:
Non-specific defenses & Specific defenses
 Non-specific defenses
 do not distinguish between one threat and
another
 are present at birth
 include: physical barriers (e.g. skin), phagocytic
cells, inflammation, fevers, etc.
 Specific defenses
 protect against specifically identified threats
(i.e. may defend against one particular bacterial
infection but not a different one)
 many specific defenses develop after birth upon
exposure to an antigen (Ag); an antigen can be a
pathogen (disease-causing organism), foreign
protein (e.g. toxin), abnormal or infected body
cell, foreign tissue transplant
 specific defenses produce a state of long-term
protection known as “Immunity”
Immunity
( Chap 14, p. 464-471)
Immunity = specific resistance to disease
 depends on coordinated activity of T & B
lymphocytes
 T cells- involved in “cell-mediated (aka cellular)
immunity”; defense against abnormal cells &
intracellular pathogens
 B cells- involved in “antibody-mediated (aka
humoral) immunity”; defense against pathogens
(Ag’s) in body fluids (blood/lymph)
Overview of Immunity
Fig. 14-11)
Immunity is either “innate” or “acquired”
Innate Immunity
 present at birth
 independent of previous
exposure to Ag
 genetically determined
 species dependent
Acquired Immunity
 arises throughout life by active or passive means
Active immunity – development of resistance (i.e.
antibody (Ab) production) to specific disease
secondary to exposure to specific Ag (pathogen)
 naturally acquired active immunity – natural exposure
results in immune response & development of long term
immunity
 induced (artificial) active immunity – deliberate “artificial”
exposure to Ag (i.e. vaccine/immunization)
Passive immunity – development of immunity due to
transfer of “pre-made” antibodies
 naturally acquired passive immunity – Ab’s transferred from
mom  baby across placenta or in breast-milk
 induced (artificial) passive immunity – administration of Ab’s
to fight disease after exposure to pathogen
Properties of Immunity
Immunity has four general properties:
 Specificity
 Versatility
 Memory
 Tolerance
Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings
Properties of Immunity
 Specificity – T & B cells have specific receptors that will
allow them to only recognize & target a specific Ag; this
process is known as “antigen recognition”
 Versatility – millions of different lymphocyte populations,
each with specific Ag recognizing receptors; allows for
“anticipation” of potential Ag’s
 Memory – after initial exposure, long term acquired
immunity occurs through the production of memory cells;
secondary exposure results in stronger faster response to
previously recognized Ag
 Tolerance – immune cells recognize self-antigens &
“tolerate” (ignore) them, only going after foreign (non-self)
Ag’s
Overview of the immune response
 The
purpose of the immune response is to inactivate or
destroy pathogens, abnormal cells & foreign molecules (such
as toxins)
 In order for the response to occur, lymphocytes must be
“activated” by the process of antigen recognition
 T cells are usually activated first, & then B cells. T cells mainly
rely on activation by phagocytic cells collectively known as
“antigen presenting cells (APC’s)”
 Once activated, T cells both attack the invader, & stimulate
the activation of B cells
 Activated B cells mature into “plasma cells” which produce
specific antibodies designed to inactivate the harmful antigen.
Cell Mediated (a.k.a. Cellular) Immunity
 In order for T cells to respond, they must first be activated by
exposure to an antigen which is bound to membrane receptors of
phagocytic antigen presenting cells (APC’s) (“antigen recognition”)
 These membrane receptors on cells are called “MHC proteins”
(major histocompatibility complex proteins), & are genetically
determined (i.e. differ among individuals)
 Antigens bound to MHC proteins “tell” the T lymphocyte what the
specific foreign invader is (i.e. a specific bacteria) so that the
lymphocytes can mount a cellular defense
Cell Mediated (a.k.a. Cellular) Immunity
Once a T cell is activated by the presentation of the combined
MHC/Ag, it will clone (by mitosis) & differentiate into:
 cytotoxic T cells – seek out the specific
pathogen/infected cell that contains the targeted Ag &
destroys it by secreting various chemicals
 helper T cells – necessary for coordination of both
specific & non-specific defenses, as well as for stimulating
both cell-mediated & antibody-mediated immunity.
In cell-mediated immunity they release chemicals
(cytokines) that strengthen the activity of cytotoxic T
cells.
 In antibody-mediated immunity they release
cytokines that stimulate activated B cell division &
differentiation into plasma cells
Cell Mediated (a.k.a. Cellular) Immunity
 memory T cells – remain “in reserve” so if same Ag
appears, these cells can immediately differentiate into
cytotoxic & helper T cells, causing a swift secondary
response to the invasion
 suppressor T cells – activated more slowly than the other T
cells; inhibit the response of the immune cells to prevent
potential “autoimmune” response
Direct physical &
chemical attack
Activated T cells clone &
differentiate into:
 Cytotoxic T cells
 Helper T cells
 Memory T cells
 Suppressor T cells
Antigens
CELL MEDIATED IMMUNITY
bacteria
ANTIGENS
viruses
bacteria
viruses
SPECIFIC
DEFENSES
(Immune
response)
APC’s phagocytize Ag & activate T
cells
Antibody Mediated (Humoral) Immunity
 B cells must also be activated before they can respond to
an invading Ag
 The body has millions of different B cell populations, each B
cell has its own particular antibody (Ab) molecule within its
cell membrane
 When the corresponding Ag invades the interstitial fluid
surrounding the B cell, the Ag binds to the Ab & is taken into
the cell, eventually being displayed on the B cell’s MHC
protein. The B cell is now “sensitized”
Helper T cells (that had been previously activated to the
same Ag) then attach to the sensitized B cells & activate them
by secreting chemicals (cytokines)
 Cytokine secretion results in B cell cloning & differentiation
into plasma cells & memory cells
Antibody Mediated (Humoral) Immunity
 Plasma cells produce millions of copies of antibodies
which are released into the blood & lymph
 Antibodies seek out & bind to the Ag forming an “Ab-Ag
complex”, eventually leading to the elimination of the antigen
by various means
 Memory cells remain in reserve to respond to any
subsequent exposure by the same Ag. Upon secondary
exposure, memory B cells quickly differentiate into Ab
producing plasma cells
Antibody Mediated (Humoral) Immunity
Antibody Mediated (Humoral) Immunity
Review of Immune Response