Transcript Human Biology (BIOL 104)

Human Biology (BIOL 104)
Talk Seven:
Blood and the immune system
Chapters 8 and 9
Functions Of Blood
• Transportation –
– the blood transports dissolved gases, nutrients,
hormones and metabolic wastes.
• Protection –
– the blood restricts fluid losses through damaged vessels.
– Platelets in the blood and clotting proteins minimize
blood loss when a blood vessel is damaged.
• Regulation – Blood regulates the pH and electrolyte composition of
the interstitial fluids.
– Blood regulates body temperature.
Composition Of Blood
• Contains cellular and liquid components
• A specialized connective tissue
– Blood cells – formed elements
– Plasma – fluid portion and fibrinogen
• Blood volume
– Males: 5 – 6 liters
– Females: 4 – 5 liters
• The pH of blood is about 7.35-7.45
Composition Of Blood
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Composition of Whole Blood
Composition of Whole Blood
Composition of Whole Blood
The Blood, a quick look
A. Plasma
• Liquid portion of the blood.
•
•
•
•
•
•
•
Contains:
clotting factors,
Hormones
Antibodies
dissolved gases
Nutrients
waste
Copyright ©The McGraw-Hill Companies;
used with permission
Composition of Whole Blood
The Blood, a quick look
B. Erythrocytes - Red
Blood Cells
• Carry hemoglobin and
oxygen.
• Do not have a nucleus and
live only about 120 days.
• Can not repair themselves.
Copyright ©The McGraw-Hill Companies;
used with permission
Composition of Whole Blood
The Blood, a quick look
C. Leukocytes – White Blood
cells
• Fight infection and are formed
in the bone marrow
•
•
•
•
•
•
Five types –
neutrophil,
lymphocytes
eosinophils
basophils
monocytes.
Copyright ©The McGraw-Hill Companies;
used with permission
Composition of Whole Blood
The Blood, a quick look
•D. Thrombocytes –
Platelets.
•These are cell fragment that
are formed in the bone marrow
from magakaryocytes.
•Clot Blood by sticking together
– via protein fibers called fibrin.
Copyright ©The McGraw-Hill Companies;
used with permission
Blood Plasma
• Straw-colored, sticky fluid
portion of blood
• Approximately 90% water
• Contains:
– Ions – Na+ and Cl– Nutrients – sugars, amino
acids, lipids, cholesterol,
vitamins and trace elements
– Three main proteins Albumin (60%), globulin
(35%), fibrinogen (4%)
– Dissolved Gasses – including
O2 and CO2
– Waste Products – other
protein wastes such as urea
Erythrocytes – Red Blood
Cells (RBCs)
• Oxygen-transporting cells
– 7.5 µm in diameter (diameter of capillary 8 –
10µm)
• Most numerous of the formed elements
– Females: 4.3 – 5.2 million cells/cubic millimeter
– Males: 5.2 – 5.8 million cells/cubic millimeter
• Made in the red bone marrow in long bones,
cranial bones, ribs, sternum, and vertebrae
• Average lifespan 100 – 120 days
RBC Structure And Function
• Have no organelles or nuclei
• Hemoglobin – oxygen
carrying protein
– Each RBC has about 280
million hemoglobin
molecules
• Biconcave shape – 30%
more surface area
Red Blood Cells
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used with permission
Erythropoietin
• Produced in the kidney
• Low Oxygen in blood signals
production
• Athletes:
– Erythropoietin Injections
– Blood Doping
– Increase Viscosity Increase
Blood Pressure!
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RBC life span and circulation
• Replaced at a rate of about
3 million new blood cells entering
the circulation per second
• Damaged or dead RBCs are recycled
by phagocytes (in Spleen)
• Components of hemoglobin
individually recycled
– Heme stripped of iron and
converted to biliverdin, then
bilirubin
• Iron is recycled by being stored in
phagocytes, or transported
throughout the blood stream bound
to transferrin
Copyright ©The McGraw-Hill Companies;
used with permission
Leukocytes – White Blood
Cells (WBCs)
• Protect the body from infectious microorganisms
• 4,800 – 11,000/cubic millimeter
• Function outside the bloodstream in loose
connective tissue
• Diapedesis – circulating leukocytes leave the
capillaries
• WBCs have a nucleus and are larger than RBCs
• Most produced in bone marrow
• Lifespan of 12 hours to several years
• Granular Leukocytes
• Neutrophils: Most abundant. Have multi-lobed
nucleus.
– They are the first to respond to infection,
and engulf pathogens during phagocytosis.
– Eosinophils: Have bi-lobed nucleus
• Known to increase in number in the event
of parasitic worm infection and during
allergic reaction.
– Basophils: U-shaped or lobed nucleus.
• In connective tissues release histamines
along with Mast Cells
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• Agranular Leukocyles
– Monocytes: Largest of the white blood
cells.
• Differentiate into even larger
Macrophages
• Phagocytize pathogens, old cells and
debris
• Stimulate production of other white
blood cells
– Lymphocytes: Two types:
• T-lymphocytes – Destroy any cell with
foreign antigens
• B-lymphocytes – Produce antibodies
that combine with antigens
– Target pathogens for destruction
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White Blood Cells
Type Of White Blood Cells
% By Volume Of WBC
Description
Function
Neutrophils
60 – 70 %
Nucleus has many
interconnected lobes; blue
granules
Phagocytize and destory
bacteria; most numerous WBC
Eosinophils
2–4%
Nucleus has bilobed nuclei; red
or yellow granules containing
digestive enzymes
Play a role in ending allergic
reactions
<1%
Bilobed nuclei hidden by large
purple granules full of chemical
mediators of inflammation
Function in inflammation
medication; similar in function to
mast cells
Dense, purple staining, round
nucleus; little cytoplasm
the most important cells of the
immune system; effective in
fighting infectious organisms;
act against a specific foreign
molecule (antigen)
Largest leukocyte; kidney
shaped nucleus
Transform into macrophages;
phagocytic cells
Basophils
Lymphocytes (B Cells and 20 – 25 %
T Cells)
Monocytes
4–8%
Summary of Formed Elements
Platelets
• Structure
– Small cellular fragments; originate in bone
marrow from giant cell megakaryocyte
– Contain several clotting factors – calcium ions,
ADP, serotonin
• Function
– Involved in stopping bleeding when a blood
vessel is damaged; Process is called hemostasis
Blood Cell Formation
•
Hematopoiesis – process by which blood
cells are formed
•
100 billion new blood cells formed each
day
•
Takes place in the red bone marrow of
the humerus, femur, sternum, ribs,
vertebra and pelvis
– Red marrow – actively generates new
blood cells
• Contains immature erythrocytes
• Remains in epiphyses, girdles, and
axial skeleton
– Yellow marrow – dormant
• Contains many fat cells
• Located in the long bones of adults
– Tissue framework for red marrow
• Reticular connective tissue
Cell Lines in Blood Cell Formation
• All blood cells originate
in bone marrow
• All originate from one
cell type
• Blood stem cell
(pluripotential
hematopoeitic stem cell)
– Lymphoid stem cells - give
rise to lymphocytes
– Myeloid stem cells - give
rise to all other blood cells
Human Blood Groups
• A, B, AB, and o
• First found during the Crimean war (1854 – 1856)
– British Army Surgeon kept records of successful blood
transfusions
• A to A and B to B worked
• A to B or B to A were always fatal
• Also found that o was the universal donor
– People with this type of blood can give it to anyone
• AB type people can receive blood from anyone
– Universal recipient.
Why does this happen?
Figure 7.4
Both type A and type B blood
have specific carbohydrates
which are on the surface of
the blood cells.
AB blood has both
carbohydrates
on the surface of the blood
cells
o blood has no carbohydrates
Carbohydrates are:
N-Acetylglucosamine,
galactose and fucose
Also known as antigens
Why does this happen?
http://learn.genetics.utah.edu/units/basics/blood/types.cfm
Why does
this
happen?
Figure 7.4
Antigen: Molecule that
stimulates an immune
response, especially the
production of antibodies by
plasma B cells. Antigens are
usually proteins or
polysaccharides.
A person who receives
incorrectly matched blood will
make antibodies against the
blood group antigens.
Blood cells clump together in
blood vessels with fatal
results.
Why does
this
happen?
Figure 7.4
Controlled by three alleles
Allele A – dominant
has info for making antigen A
Allele B – dominant
has info for making antigen B
Allele o – recessive
produces neither antigen
AA & Ao gives rise to A type blood
BB & Bo give rises to B type blood
AB is co-dominant - AB type blood
oo is recessive – o type blood
Rh Factor
• There are four blood groups but eight blood
types.
• The Rh-factor!!
•
•
•
•
85% Positive (US population)
15% Negative
Genetic factor
Can cause Hemolytic Disease and death of
infants.
The genetics of the Rh factor
• Another blood grouping system independent
of ABo – the Rh-factor
– Again, three genes (alleles): located very close
together on the same chromosome.
• First C & c, second D & d, third E & e
• Unlike the ABo system there is no codominance, c, d, and e are recessive to C, D,
and E.
• ccddee is known as Rh-negative. All others
Rh-positive.
How common is your blood type?
46.1%
38.8%
11.1%
3.9%
How common is your blood type?
34
Hemolytic disease
• If a child is Rh+, a Rh- Mother can begin to produce
antibodies Rh+ red blood cells
– Rh factor crosses placenta and mother makes
antibodies
• In subsequent pregnancies these antibodies can
cross the placenta and cause hemolysis of a Rh+
Childs red blood cells.
– Can lead to mental retardation or death
• Prevented by giving Rh- women a Rh immunoglobulin
injection no later than 72 hours after birth.
Attacks any of the babies Abs in mother before
her own antibodies are produced
Hemolytic
disease
Figure 7.5
(1)
Hemolytic
disease
Figure 7.5
(2)
Hemolytic
disease
Figure 7.5
(3)
•Prevented by giving Rh- women
a Rh immunoglobulin injection no
later than 72 hours after birth.
•Attacks any of the babies Abs
in mother before her own
antibodies are produced.
Malaria – an agent of natural Selection
• As any species evolves, biological differences
among its population arise largely through natural
selection.
• Diseases are among the selective forces that can
result in genetic differences among populations.
• In disease-ridden areas of the world, natural
selection acts to increase the frequency of alleles
that confer partial resistance to a disease while
decreasing the frequency of alleles that leave
people susceptible to a disease.
Malaria – an agent of natural Selection
• New traits are produced by mutation and are then
subject to natural selection.
• The traits that survive are adaptations.
• Malaria causes 110 million cases of illness each year
– Close to 2 million deaths each year.
• Rare before the invention of agriculture
– Did much to change the selective pressure on human
populations
Malaria – an agent of natural Selection
Figure 7.8 (1)
Malaria – an agent of natural Selection
Figure 7.8 (2)
Malaria – an agent of natural Selection
Figure 7.8 (3)
Malaria – an agent of natural Selection
Figure 7.8 (4)
Malaria – an agent of natural Selection
Figure 7.8 (5)
Malaria – an agent of natural Selection
Figure 7.8 (6)
Malaria – an agent of natural Selection
Figure 7.9
sickle-cell anaemia
• Hereditary blood disorder
• Characterized by an abnormality in
the oxygen-carrying hemoglobin
molecule in red blood cells that
leads to a propensity for the cells
to assume an abnormal, rigid,
sickle-like shape under certain
circumstances.
• Almost 300,000 children are born
with a form of sickle cell disease
every year, mostly in sub-Sarahan
Africa but also in other countries
such as the West Indies, South
Asia and in people of African origin
elsewhere in the world.
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A small change in a gene
can have many phenotypic
consequences.
Figure 7.10
Malaria – an agent of natural Selection
• Most victims of malaria are young children
• Where malaria occurrence is high, so is the HBs
allele
– Odd, as Sickle Cell Anemia is nearly always fatal
before reproductive age
– HBs allele confers resistance to malaria
• So in areas of high occurrence to malaria, the HBs
allele may cause a genetic disorder, but increases
the overall fitness of a population where malaria
occurs.
Malaria – an agent of natural Selection
The Immune System
• Immunity is the ability to react to
antigens so that the body remains free
of disease.
– Disease is a state of homeostatic
imbalance.
• Can be due to infection or failure of the immune
system.
Primary Lymphatic Organs
• Lymphatic organs
contain large numbers of
lymphocytes (White
Blood cells).
• Primary organs are:– Red Bone Marrow.
• Site of stem cells.
– Source of B lymphocytes.
– Thymus Gland.
Lymphocytes from bone
marrow pass through to
form T-lymphocytes
• Produces thymic hormones
(thymosin).
• Aids in T lymphocyte
maturation.
Secondary Lymphatic Organs
• Secondary lymphatic organs are places
where lymphocytes encounter and bind
with antigens.
–
–
–
–
Spleen.
Lymph nodes.
Tonsils.
Peyer’s patches.
Lymphatic Organs
Secondary Lymphatic Organs
• Spleen – upper left of
abdominal cavity behind
stomach. Sectioned off by
connective tissue- white
pulp & red pulp.
– White pulp – lymphocytes
– Red pulp – filters blood.
Blood entering the spleen
passes through red pulp
before it leaves (network
of sinuses)
– FRAGILE
Secondary Lymphatic Organs
• Lymph Nodes – occur along
lymphatic vessels. Formed
from connective tissue.
– Packed full of Blymphocytes
– As lymph courses through
sinuses it is filtered by
macrophages, which engulf
pathogens and debris.
– Also present- Tlymphocytes – fight
infection and attack
cancer cells
Secondary Lymphatic Organs
• Tonsils – patches of
lymphatic tissue.
• Perform the same
function as lymph nodes
– First line of defense
• Peyer’s Patches – on
the intestinal wall and
appendix. Attack
pathogens that ender
the body by way of the
intestinal tract.
Nonspecific Defenses
• Barriers to Entry.
– Mucous membranes
• Line respiratory, digestive, and urinary tract.
– Oil gland secretions.
• Chemicals that kill or weaken bacteria on
skin
– Ciliated cells.
• Sweep mucus & particles into throat
– Bacteria
• Both in stomach and vagina, prevent
pathogens from gaining a foot-hold.
– Acid
Innate Immunity
• One important function of the immune system is to
promote growth and repair after injury
– Either via physical damage or microorganisms
• The mobilization of innate immune cells to get rid
of damaged cells or microorganisms is called
inflammation
• Small molecules called cytokines are also involved
Innate Immunity
• Inflammatory Reaction.
– Tissue damage causes
– tissue cells and mast cells to release chemical
mediators.
Innate Immunity
• Inflammatory Reaction.
• Histamine and kinins.
– Capillaries dilate and become more permeable.
» Skin reddens and becomes warm.
– Proteins and fluids escape from tissue. Swelling
occurs
Innate Immunity
• Inflammatory Reaction.
– Proteins and fluids escape from tissue and cause
swelling.
» Swelling stimulates free nerve endings, causing
the sensation of pain.
Innate Immunity
– Neutrophils and
Monocytes migrate to
site of injury.
– Amoeboid – can change
shape – squeeze
through capillary walls
and enter tissue fluid.
– Neutrophils engulf
pathogens –destroyed
by hydrolytic enzymes
when fused to a
lysosome
Innate Immunity
• Macrophages:
Monocytes change into
these as they leave the
blood and enter the
tissues.
– These are phagocytic
cells
– Can eat many (100’s) of
pathogens and survive.
– Eat old blood cells and
bits of dead tissue
– Stimulate the immune
response.
• Increase production of
white blood cells in bone
marrow
Innate Immunity
• Macrophages:
Monocytes change into
these as they leave
the blood and enter
the tissues.
• Macrophages enter
lymph vessels carring
bacteria fragments to
lymph nodes
• This starts a specific
immune response
Protective protein system
• Known as Complement proteins
• Are activated when pathogens enter the body.
• Complement certain immune responses.
Protective protein system
• Attract phagocytes.
• Form holes in bacteria.
• Interferon binds to receptors of non-infected cells
causing them to prepare for possible attack
Specific immunity
• Antigen--shape on cell, allows recognition of
self and detection of foreign cells.
• Antibody--protein that recognizes and binds
antigens.
• Specific defenses respond to antigens.
– Lymphocytes recognize an antigen due to antigen
receptors whose shape allows them to combine
with a specific antigen.
• Immunity is primarily the result of the action of B
lymphocytes and T lymphocytes.
Natural Killer Cells
• Natural killer cells kill
virus-infected cells
and tumor cells by
cell-to-cell contact.
– Large, granular
lymphocytes.
T Cells
• Provide cell-mediated immunity.
• Produced in bone marrow, mature in thymus.
• Antigen must be presented in groove of HLA
molecule.
• Cytotoxic T cells destroy non-self protein-bearing
cells.
• Helper T cells secrete cytokines that control the
immune response.
T cells attack foreign cells directly
• Killer cells (“cytotoxic”), or CD8+ is a main type
B Cells
• Provide antibody-mediated immunity against
bacteria.
• Produced and mature in bone marrow.
• Reside in spleen and lymph nodes.
– Circulate in blood and lymph.
• Directly recognize antigen and then undergo clonal
selection.
• Clonal expansion produces antibody-secreting
plasma cells and memory B cells.
• The antigen selects which
lymphocyte will undergo clonal
expansion and produce more
lymphocytes with the same
type of antigen receptor
– Some become memory
cells – long term immunity
to the same infection.
– B-cells become plasma
cells – fight infection
• Make Antibodies
– Apoptosis – when danger
of infection is over, all
plasma cells undergo
programmed cell death
Clonal selection
Theory
Specific Defenses
• Antibodies
• A large Y-shape protein produced
by plasma cells that is used by the
immune system to identify and
neutralize foreign objects such as
bacteria and viruses.
• The antibody recognizes a unique
part of the foreign target, called
an antigen
• Each tip of the "Y" of an antibody
contains a paratope that is
specific for one particular epitope
on an antigen
– allowing these two structures to bind
together with precision
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Specific Defenses
• Antibodies
• Using this binding mechanism, an
antibody can tag a microbe or an
infected cell for attack by other
parts of the immune system
• or can neutralize its target
directly (for example, by blocking a
part of a microbe that is essential
for its invasion and survival).
• The production of antibodies is the
main function of the human immune
system.
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Specific Defenses
• Antibodies
• Classes.
• IgG - Enhances phagocytosis
• IgM - Activates complement
proteins.
• IgA - Prevents attachment of
pathogens.
• IgD - Antigen receptors on virgin B
cells.
• IgE - Immediate allergic response.
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Induced Immunity
• Active Immunity.
– Immunization involves
use of vaccines.
– Contain an antigen to
which the immune
system responds.
– Primary
response.
Secondary
(booster)
response.
– Dependent upon the
presence of memory B
and T cells capable of
responding to lower
antigen doses.
Induced Immunity
• Passive immunity
• occurs when an
individual is given
prepared antibodies.
– Temporary.
• No memory cells.
• Primary and
secondary
injections
Issue - Allergies
• Occurs when your immune system reacts atypically
to some antigens to which the host does not need
protection.
• Pollen, dust mites, cats, a hard days work!
– Called Allergens
• The atypical response produces a special antibody
– IgE
• A form of innate immunity
Allergies
• IgE binds to mast cells.
•
When a person later
encounters the same
allergen, the allergen binds
to the IgE on the mast cell
• This triggers the explosive
release of histamine
• Capillaries dilate and
become more permeable.
• Skin reddens and becomes
warm. Proteins and fluids
escape from tissue.
Swelling occurs
–
Allergies
• The large amounts of
histamines released in an
allergic reaction cause
strong symptoms
• Runny eyes, sneezing, or
shortness of breath
• Depends upon the tissue in
which the mast cells were
triggered
Allergies
• As allergy symptoms are caused by histamines,
taking antihistamines stops the build up of
histamines in the cells of blood vessels.
• However, antihistamines do not stop the immune
response or the release of histamines in mast cells
• Other allergies are mediated by T-cells
– Latex, poison ivy, dyes or chemicals in cosmetics or
clothing
– Antihistamines do not help in these allergic reactions
Allergies
• As each allergy is an antigen-specific immune
response it shows memory and a greater response
on the next exposure
– This is why allergies get worse over time
• Thousands of different substances can produce
allergies in people – each triggered by a specific
antigen-specific response
– Why people are usually bothered by only a few
• Appears to be inherited