Chapter 21&22

Copyright © John Wiley & Sons, Inc. All rights reserved.

Chapter 21

Blood Vessels and

Hemodynamics


Blood Vessel Types

• Arteries – carry blood away from the heart

Large elastic arteries (>1 cm); medium

muscular arteries (0.1 – 10 mm); arterioles

(< 0.1 mm)

• Capillaries – site of nutrient and

gas exchange

• Veins – carry blood towards

the heart

Venules are small veins (< 0.1 mm)

Vessel Structure and Function


All blood and lymph vessels in the body share

components of 3 basic layers or “tunics”

which comprise the vessel wall:

• Tunica interna

(intima)

• Tunica media

• Tunica externa



Medium sized muscular (distributing)

arteries have more smooth muscle in their

tunica media.

• Muscular arteries help maintain the

proper vascular tone to ensure efficient

blood flow to the distal tissue beds.

• Examples include the brachial artery in

the arm and radial artery in the forearm.



Vessel Structure and Function An anastomosis is a union of vessels supplying

blood to the same body tissue. Should a blood

vessel become occluded, a vascular

anastomosis provides

collateral circulation (an alternative

route) for blood to reach a tissue.

• The shaded area in this graphic

shows overlapping blood

supply to the ascending colon.


Vessel Structure and Function Arterioles deliver blood to capillaries and

have the greatest collective influence on both

local blood flow and on overall blood pressure.

• They are the primary "adjustable nozzles”

across which the greatest drop

in pressure occurs.


Capillaries are the only sites in the entire

vasculature where gases, water and

other nutrients are

exchanged.

Venules and veins have

much thinner walls than

corresponding arterioles

and arteries of similar size.



Vessel Structure and Function The terminal end of an arteriole tapers toward

the capillary junction to form a single

metarteriole.

• At the metarteriole-capillary junction, the

distal most muscle cell forms the

precapillary sphincter

which monitors and

regulates blood flow

into the capillary bed.



The body contains

three types of

capillaries:

• Continuous

capillaries

• Fenestrated

capillaries

• Sinusoids



• Intravenous pressure

in venules (16 mmHg)

is less than half that

of arterioles (35

mmHg), and drops to

just 1-2 mmHg in

some larger veins.


Fluid Exchange - Starling Forces As blood flows to the tissues of the body,

hydrostatic and osmotic forces at the

capillaries determine how much fluid leaves the

arterial end of the capillary and how much is

then reabsorbed at the venous end. These are

called Starling Forces.

• Filtration is the movement of fluid through the

walls of the capillary into the interstitial fluid.

• Reabsorption is the movement of fluid from

the interstitial fluid back into the capillary.


Fluid Exchange - Starling Forces Two pressures promote filtration:

• Blood hydrostatic pressure (BHP) generated

by the pumping action of the heart -

decreases from 35 to 16 from the arterial to

the venous end of the capillary

• Interstitial fluid osmotic pressure (IFOP),

which is constant at about 1 mmHg


Fluid Exchange - Starling Forces Two pressures promote reabsorption:

• Blood colloid osmotic pressure (BCOP) is due

to the presence of plasma proteins too large

to cross the capillary - averages 36 mmHg on

both ends.

• Interstitial fluid hydrostatic pressure (IFHP) is

normally close to zero and becomes a

significant factor only in

states of edema.


Fluid Exchange - Starling Forces


Fluid Exchange - Starling Forces Normally there is nearly as much fluid

reabsorbed as there is filtered.

• At the arterial end, net pressure is outward at

10 mmHg and fluid leaves the capillary

(filtration).

• At the venous end, net pressure is inward at –

9 mmHg (reabsorption).

• On average, about 85% of fluid filtered is

reabsorbed.


Fluid Exchange - Starling Forces Fluid that is not reabsorbed (about 3L/ day for

the entire body) enters the lymphatic vessels

to be eventually returned to

the blood.


Gas And Nutrient Exchange


The volume of blood returning through the

veins to the right atrium must be the same

amount of blood pumped into the arteries from

the

left ventricle – this is

called the venous return.

• Besides pressure, venous

return is aided by the

presence of venous valves,

a skeletal muscle pump,

and the action of breathing.

Venous Return


The skeletal muscle pump uses the action of

muscles to milk blood in 1 direction (due to

valves).

The respiratory pump uses the negative

pressures in the thoracic and abdominal

cavities generated during

inspiration to pull

venous blood towards

the heart.

Venous Return


Proximalvalve

Distalvalve

1

Proximalvalve

Distalvalve

1 2

Proximalvalve

Distalvalve

1 2 3


Although the venous circulation flows under

much lower pressures than the arterial side,

usually the small pressure differences

(venule 16 mmHg to

right atrium 0 mmHg),

plus the aid of muscle

and respiratory pumps

is sufficient.

Venous Return


Pressure, Flow, And Resistance Blood pressure is a measure of the force

(measured in mmHg) exerted in the lumen of

the blood vessels.

Blood flow is the amount of blood which is

actually reaching the end organs

(tissues of the body).

Resistance is the sum of

many factors which

oppose the flow of blood.


Pressure, Flow, And Resistance Cardiovascular homeostasis is mainly

dependent on blood flow… but blood flow is

hard to measure.

• Clinically, we check blood pressure

because it is easier to measure, and it is

related to blood flow.

• The relationship between blood flow, blood

pressure, and peripheral resistance follows a

simple formula called Ohms Law.BP = Flow x Resistance


Pressure, Flow, And Resistance In an effort to meet physiological demands, we

can increase blood flow by:

• Increasing BP

• Decreasing systemic vascular

resistance in the blood vessels

Usually our body will do both –

when we exercise, for example.

figure adapted from http://www.learnhemodynamics.com/hemo/ba

sics.htm


Pressure, Flow, And Resistance As we have already seen, peripheral resistance

is itself dependent on other factors like the

viscosity of blood, the length of all the blood

vessels in the body (body size), and the

diameter of a vessel.

The first two of these factors (viscosity and the

length of blood vessels) are unchangeable

from moment to moment.

• The diameter, however, is readily adjusted if

the body needs to change blood flow to a

certain capillary bed.


Pressure, Flow, And Resistance


Pressure, Flow, And Resistance Example: If the diameter of a blood vessel

decreases by one-half, its resistance to blood

flow increases 16 times!

• “Hardening of the arteries” (loss of elasticity)

seriously hampers the body’s

ability to increase

blood flow to meet

metabolic demands.


Autoregulation Homeostasis in the body

tissues requires the

cardiovascular system to adjust

pressure and resistance to

maintain adequate blood flow

to vital organs at all times – a

process called

autoregulation.

Autoregulation is controlled

through negative feedback

loops.


Autoregulation of blood pressure and blood

flow is a complex interplay between:

• The vascular system

• The nervous system

• The endocrine hormones and

organs like the adrenal gland

and the kidney

• The heart

Autoregulation


Autoregulation The vascular system senses alterations of BP

and blood flow and signals the cardiovascular

centers in the brain.

• The heart then appropriately

modifies its rate and force

of contraction.

• Arterioles and the precapillary

sphincters of the metarterioles

adjust resistance at specific

tissue beds.


Autoregulation Two of the most important control points are

the pressure receptors (called baroreceptors)

located in the arch of the aorta and the carotid

sinus. There are also baroreceptors in the kidney and

the walls of the heart.


Autoregulation Stimulation of the baroreceptors in the carotid sinus is called

the carotid sinus reflex , and it helps normalize blood

pressure in the brain.

Another type of sensory receptor important to the process of

autoregulation of BP are the chemoreceptors.


Autoregulation Chemoreceptors are found in the carotid

bodies (located close to baroreceptors of

carotid sinus) and aortic bodies (located in

the aortic arch).

When they detect hypoxia (low O2),

hypercapnia (high CO2), or acidosis (high H+),

they signal the cardiovascular centers.

• They increase sympathetic stimulation

increasing heart rate and respiratory rate,

and vasoconstricting the vessels (arterioles

and veins) to increase BP.


Autoregulation The Renin-angiotensin-aldosterone (RAA)

system is an important endocrine component

of autoregulation.

• Renin is released by kidneys when blood

volume falls or blood flow decreases.

• It is subsequently converted into the active

hormone angiotensin II which raises BP

by vasoconstriction and by stimulating

secretion of aldosterone from the

adrenal glands.


Autoregulation Epinephrine and norepinephrine are also

released from the adrenal medulla as an

endocrine autoregulatory response to

sympathetic stimulation.

• They increase cardiac output by increasing

rate and force of heart contractions.

Antidiuretic hormone (ADH) is released from

the posterior pituitary gland in response to

dehydration or decreased blood volume.


Autoregulation Atrial Naturetic Peptide (ANP) is a natural

diuretic polypeptide hormone released by cells

of the cardiac atria.

• ANP participates in autoregulation by:

Lowering blood pressure (it causes a direct

vasodilation)

Reducing blood volume (by promoting loss

of salt and water as urine)


Circulation In an autoregulatory response, important

differences exist between the pulmonary and

systemic circulations:

• Systemic blood vessel walls dilate in

response to hypoxia (low O2) or acidosis to

increase blood flow.

• The walls of the pulmonary blood vessels

constrict to a hypoxic or acidosis stimulus

to ensure that most blood flow is diverted to

better ventilated areas of the lung.


Circulation A measure of peripheral circulation can be done

by checking the pulse. The pulse is a result of

the alternate expansion and recoil of elastic

arteries after each systole.

• It is strongest in arteries closest to the heart

and becomes weaker further out.

• Normally the pulse

is the same as

the heart rate.


Circulation Blood pressure is the pressure in arteries

generated by the left ventricle during systole

and the pressure remaining in the arteries

when the ventricle is in diastole.


Alterations Of Blood Pressure About 50 million Americans have hypertension

(HTN).

• It is the most common disorder

affecting the CV system

and is a major cause of

atherosclerotic vascular

disease (ASVD), heart

failure, kidney disease

and stroke.


Alterations Of Blood Pressure Hypertension is defined as an elevated

systolic blood

pressure (SBP), an elevated diastolic blood

pressure (DBP), or both. Depending on

severity, it is classified as pre-hypertension,

Stage 1 HTN, or stage 2 HTN.


Alterations Of Blood Pressure Hypotension is defined as any blood pressure

too low to allow sufficient blood flow (hypo-

perfusion) to meet the body's metabolic

demands (to maintain homeostasis).

Many persons, especially some thin, young

women, have very low BP, yet experience no

dizziness, fatigue, or other symptoms – they

are not hypotensive, and in fact are probably

very healthy (cardiovascular wise).

Hypotension leading to hypo-perfusion

(pressure and flow are related) of critical

organs results in shock


Shock And Homeostasis The 4 basic types of shock are:

• Hypovolemic shock, due to decreased

blood volume

• Cardiogenic shock, due to poor heart

function

• Obstructive shock, due to obstruction of

blood flow

• Vascular shock, due to excess vasodilation -

as seen in cases of a massive allergy

(anaphylaxis) or sepsis. In the U.S., septic

shock causes >100,000 deaths/yr. and is the

most common cause of death in hospital

critical care units.


Shock and Homeostasis

Heart rate & force increase Vasoconstriction or vasodilation

depending on type of shock ADH released conserve water Renin released Angiotensin II Aldosterone released

conserve Na+ ANP inhibited

The body responds via negative feedback to restore homeostasis


Shock And Homeostasis


Circulatory Routes Blood vessels are organized into circulatory

routes that carry blood to specific parts of the

body.

• The pulmonary circulation leaves the right

heart to allow blood to be re-oxygenated and

to off-load CO2.

• The systemic circulation leaves the left

side of the heart to supply the coronary,

cerebral, renal, digestive and hepatic

circulations (among others). The bronchial

circulation provides oxygenated blood to the

lungs, not the pulmonary circulation, which

oxygenates blood!


Systemic Circulation - Arteries Aorta (one)

Brachiocephalic (one)

Common Carotid

External Carotid

Internal Carotid

Subclavian

Axillary

Brachial

Radial

Ulnar

Bronchial (usually

3)

Renal

Iliac (common,

internal, external)

Femoral

Popliteal


Systemic Circulation - Arteries


Systemic Circulation - Veins

Vena Cava

Brachiocephalic

(two)

External Jugular

Internal Jugular

Subclavian

Axillary

Brachial

Median Cubital

Iliac (common,

internal,

external)

Femoral

Popliteal

Saphenous

Hepatic portal


Systemic Circulation - Veins


Portal Circulation The hepatic portal system is designed to

take nutrient- rich venous blood from the

digestive tract capillaries, and transport it to

the sinusoidal capillaries of the liver.

• As it percolates through the liver sinusoids,

the hepatocytes of the liver, acting as the

chemical factories of the body, extract and

add what they wish to maintain homeostasis

(extracting sugars, fats, proteins when

appropriate and then dumping them back

into the circulation when necessary).


Portal Circulation


Fetal Circulation The fetus has special circulatory requirements

because their lungs, kidneys and GI tract are

non-functional.

The fetus derives its oxygen and

nutrients and eliminates wastes

through the maternal blood supply

by way of the placenta. Normally,

there is no maternal/fetal mixing;

the fetus is totally dependant on

capillary exchange.


Oxygenated blood leaves the placenta through

the umbilical vein. It then bypasses the liver

via the ductus venosus and dumps into the

inferior vena cava en route to the right heart.

This oxygen-rich blood then

bypasses the lungs by

traveling to the left heart

through the foramen ovale.

Fetal Circulation


Blood remaining in the right heart that

manages to flow through the right ventricle

meets with very high resistance from the

closed and soggy lungs.

This blood is diverted into the

left-sided circulation by passing

through the ductus

arteriosus before returning

to the placenta via the

umbilical arteries.

Fetal Circulation


Fetal circulation (before birth)


Neonatal Circulation After Birth At birth, the neonate’s lungs open and in just a

few seconds, there is a massive drop in

pulmonary vascular resistance.

• Blood now entering the right heart now sees

lower pressure looking into the lungs and has

no “incentive” to flow through the foremen

ovale or the ductus arteriosus.

Another change also occurs very rapidly - the

umbilical cord is severed.

• And so begins the adult pattern of blood flow.


Neonatal Circulation After Birth Within hours, days, or weeks after birth, the

umbilical vein atrophies to become the

ligamentum teres.

• The ductus venosus atrophies to become the

ligamentum venosum.

• The foramen ovale becomes the closed fossa

ovale.

• The ductus arteriosus atrophies to become

the ligamentum arteriosum.

• Umbilical arteries atrophy to become the

medial umbilical ligaments.


Neonatal Circulation After Birth


Chapter 22

The Lymphatic System and

Immunity


The Lymphatic System A system consisting of lymphatic vessels

through which a clear fluid (lymph) passes

The major functions of the lymphatic system

include:

• Draining interstitial fluid

• Transporting dietary lipids absorbed by the

gastrointestinal tract to the blood

• Facilitating the immune responses


The Lymphatic System Components of the lymphatic

system include:

• Lymphatic capillaries

• Lymphatic vessels

• Lymph nodes

• Lymphatic trunks

• Lymphatic ducts

• Primary lymphatic organs

• Secondary lymphatic organs

and tissues


Lymphatic Vessels and Fluid Lymph is a clear to milky fluid in the

extracellular fluid compartment. Extracellular

fluids include:

• Plasma – the liquid component of blood

• Interstitial fluid – the clear fluid filtered

through capillary walls when it enters the

“interstitium” (space between cells, also called

the intracellular space)

• Lymphatic fluid – the unaltered interstitial

fluid that enters the lymphatic vessels. In the

GI tract, lymphatic fluids also include absorbed

dietary lipids.


Lymphatic Vessels and Fluid The flow of lymph fluid is always from the

periphery towards the central vasculature.

• It starts as interstitial fluid.

• Then enters lymphatic

capillaries.

• It travels in lymphatic

vessels to the regional

lymph nodes…


Lymphatic Vessels and Fluid The flow of lymph fluid continued…

• Lymph ascends or descends to the thorax,

either to the Left or Right Lymphatic Duct.

• Lymph fluid’s final destination is the

bloodstream, as it enters through the

Subclavian veins.


Lymphatic Vessels and Fluid Lymphatic capillaries are slightly larger than

blood capillaries and have a unique one-way

structure.

• The ends of endothelial cells overlap and

permit interstitial fluid to flow in, but not out.

• Anchoring filaments pull openings wider when

interstitial fluid accumulates.

There are specialized lymphatic capillaries

called lacteals that take up dietary lipids in the

small intestine.

Chyle is the name of this “lymph with

lipids”.


Lymphatic Vessels and Fluid

Lymphatic capillaries showing blind ends and one way flow


Lymphatic capillaries unite to form larger

lymphatic vessels which resemble veins in

structure but have thinner walls and more

valves.

Lymphatic vessels pass

through lymph nodes –

encapsulated organs with

masses of B and T cells.

• Function as lymph filters



Lymphatic fluid is moved by pressure in the

interstitial space and the milking action of

skeletal muscle contractions and respiratory

movements.

• An obstruction or

malfunction of lymph

flow leads to edema

from fluid

accumulation in

interstitial spaces.



Lymphatic Organs The lymphatic system is

composed of a number of

primary and secondary

organs and tissues widely

distributed throughout

the body - all with the

purpose

of facilitating the immune

response.


Lymphatic Organs Primary lymph organs are the bone marrow

and thymus.

• Sites where stem cells divide and become

immunocompetent (capable of

mounting an immune response)

Secondary lymphatic organs are

sites where most immune responses

occur, including the spleen and

lymph nodes, and other lymphoid

tissues such as the tonsils.


Lymphatic Organs Thymus

• The outer cortex is composed of a large

number of immature T cells which migrate

from their birth-place in red bone marrow .

They proliferate and begin to mature with

the help of Dendritic cells (derived from

monocytes) and specialized epithelial cells

(help educate T cells through positive

selection) – only about 25% survive.

• The inner medulla is composed of more

mature T cells.


Lymphatic Organs The thymus slightly protrudes from the

mediastinum into the lower neck.

• It is a palpable 70g

in infants, atrophies

by puberty, and is

scarcely distinguishable

from surrounding fatty

tissue by old age.


Lymphatic Organs There are about 600 lymph nodes scattered

along lymphatic vessels (in superficial and deep

groups) that serve as filters to trap and

destroy

foreign objects in lymph fluid.

Important group of regional

lymph nodes include:

• Submandibular

• Cervical

• Axillary

• Mediastinal

• Inguinal


Lymph fluid enters the node through afferent

vessels and is directed towards the central

medullary sinuses.

Efferent vessels convey

lymph, antibodies and

activated T cells out of

the node at an indentation

called the hilum.

Lymphatic Organs


The spleen is the body’s largest mass of

lymphatic tissue.

The parenchyma of the organ consists of:

• White pulp - lymphatic tissue where

lymphocytes and macrophages carry out

immune function

• Red pulp – blood-filled venous sinuses where

platelets are stored and

old red cells

are destroyed

Lymphatic Organs


Lymphatic Organs


The Immune Response Our immune response includes innate and

adaptive responses:


Innate Immunity The innate immune response is present at

birth. It is non-specific and non-adaptive.

• It includes our first

line of external,

physical, and

chemical barriers

provided by the

skin and mucous

membranes.


Innate Immunity Our nonspecific innate

immune response also

includes various

internal defenses

such as antimicrobial

substances, natural

killer cells, phagocytes,

inflammation, and

fever.


Innate Immunity Internal defenses:

• Phagocytes

Wandering and

fixed macrophages

• Natural killer (NK) cells

• Endogenous antimicrobials

• Complement system

• Iron-binding proteins

• Interferon


Innate Immunity Phagocytosis is a non-specific process wherein

neutrophils and macrophages (from monocytes)

migrate to an infected area. There are 5 steps:

• Chemotaxis

• Adherence

• Ingestion

• Digestion

• Killing


Innate Immunity


Innate Immunity Fever is an abnormally high body temperature

due to resetting of the hypothalamic

thermostat.

• Non-specific response:

speeds up body reactions

increases the effects of endogenous

antimicrobials

sequesters nutrients from microbes


Innate Immunity Inflammation is defensive response of almost

all body tissues to damage of any kind

(infection, burns, cuts, etc.).

• The four characteristic signs and symptoms of

inflammation are redness, pain, heat, and

swelling.

• It is a non-specific attempt to dispose of

microbes and foreign materials, dilute toxins,

and prepare for healing.


Innate Immunity The inflammatory response has three basic

stages:

• Vasodilation and increased permeability

• Emigration (movement) of

phagocytes from the

blood into the

interstitial space

and then to site

of damage

• Tissue repair


Innate Immunity Vasodilation allows more blood to flow to the

damaged area which helps remove toxins and

debris.

• Increased permeability permits entrance of

defensive proteins (antibodies and clotting

factors) to site of injury

Other inflammatory mediators include

histamine, kinins, prostaglandins (PGs),

leukotrienes (LTs), and complement.


Innate Immunity Emigration of phagocytes depends on

chemotaxis

• Neutrophils predominate in early stages but

die off quickly.

• Monocytes transform into macrophages and

become more potent phagocytes than

neutrophils.

Pus is a mass of dead phagocytes and

damaged tissue.

Pus formation occurs in most inflammatory

responses and usually continues until the

infection subside.


Innate Immunity The inflammatory response is depicted in this

graphic:

• Edema results from

increased permeability

of blood vessels.

• Pain is a prime symptom

which results from

sensitization of nerve

endings by the

inflammatory chemicals.


Adaptive Immunity Substances recognized as foreign that provoke

an immune response are called antigens (Ag).

Adaptive immunity describes the ability of the

body to adapt defenses against the antigens of

specific bacteria,

viruses, foreign tissues…

even toxins (think of the

snake handler who

becomes immune to the

venom of snake bites).


Adaptive Immunity Two properties distinguish between adaptive

immunity and innate immunity:

1. Specificity for foreign molecules which act as

Ag

this involves distinguishing self-molecules

(normal, not antigenic) from nonself

molecules

2. Memory for previously

encountered Ag


Not all foreign substances are antigenic: We

don’t make antibodies to glass, for example.

Molecules, or parts of molecules tend to be

antigenic if they are:

• Foreign – not ourselves

• Organic

• Structurally complex (proteins are usually

complex and form many of the most potent

antigens)

• Large (high molecular weight)

Adaptive Immunity


Antigens can have multiple antigenic

determinants called epitopes.

• Each epitope is capable of producing

an immune response.

Entire microbes may act as an

antigen, but typically just

certain small parts (epitopes) of

a large antigen complex triggers

a response.

Antigens can have multiple antigenic determinants called epitopes. Each epitope is capable of producing an immune

response.

Adaptive Immunity


Adaptive Immunity The adaptive immune response cannot get

started without the aid of the nonspecific

phagocytosis that occurs in the innate immune

response.

• The phagocytic cells that initiate the process

are called antigen presenting cells.


Antigen-presenting cells (APCs) are mostly

dendritic cells and macrophages, and they

link the innate immune system

and the adaptive immune system.

• Dendritic cells are usually found

in tissues in contact with the

external environment, and they

are the most potent of the

antigen-presenting cell types.

Dendritic cells grow branched projections called dendrites that give the cell its name. However, these do not have any special relation with neurons which possess similar appendages

Adaptive Immunity


Adaptive Immunity As an antigen-presenting cell engulfs and

destroys a foreign invader, it isolates

the antigens those cells

“display”.

The APC then presents the foreign

Ag to a specific T lymphocyte

called a helper T cell

(also known as a CD4 cell) .

Processed Agis presented


Adaptive Immunity Once stimulated by antigen

presentation, helper T cells

become activated.

Activated helper T cells are

capable of activating other

lymphocytes to become T

cytotoxic cells (CD8 cells)

which directly kill foreign

invaders and B cells (which

make antibodies that kill or

helps kill foreign invaders).


Adaptive Immunity Activated B and T cells form the two arms of the

adaptive immune response: Antibody-

mediated immunity and Cell-mediated

immunity.

Helper T cells aid

in both types, and

both types work

together to form

specific bodily

defenses. The Innate and Adaptive Immune systems are depicted


Adaptive Immunity Cell-mediated immunity involves the production

of cytotoxic T cells that directly attack

invading pathogens (foreign invaders with Ag

harmful to us – particularly intracellular

pathogens and some cancer cells).

• Suppressor and memory T cells are also

produced. Antibody-mediated immunity involves the

production of B cells that transform into

antibody making plasma cells.

• Antibodies (Ab) circulate in extracellular fluids.

• B memory cells are also produced.


Adaptive Immunity B-cells can be activated

by direct recognition of

antigen through B-cell

receptors or through T-

helper cell activation.

• Activated B-cells undergo

clonal selection to become

antibody producing plasma

cells.


Adaptive Immunity


MHC Molecules Our immune system has the remarkable ability,

and responsibility, of responding appropriately

to a wide variety of potential pathogens in our

environment.

• The proteins that are used as cell-markers to

“flag” self from non-self are called MHC

molecules, and are coded for by a group of

genes called the major histocompatibility

complex (MHC).

MHC genes are diverse, and vary greatly

from individual to individual.


MHC Molecules There are two general classes of MHC

molecules, and at least one or the other, or

both, are found on the surface of all nucleated

cells in the body.

• Class I molecules (MHC-I) are built into

almost all body cells and are used to present

non-self proteins (from bacteria or viruses, for

example) to cytotoxic T cells.

• Class II molecules (MHC-II) are only found

only on APCs.

Both classes are important for antigen

processing and presentation.


MHC Molecules When APCs come across foreign antigens, they are

broken down and loaded onto MHC-II molecules of

APCs.

The Class II MHC molecules on the APCs present the

fragments to helper T cells, which stimulate an

immune reaction from other cells.

• Clones of activated T cells (and the antibodies

from plasma cells) are now “competent” to

recognize similar antigenic fragments displayed

by infected cells throughout the body and respond

harshly.


MHC Molecules Infected body cells present antigens using

MHC-1 molecules


MHC Molecules Cytotoxic T cell

destruction of an

infected cell by release

of perforins that cause

cytolysis

Microbes are destroyed

by granulysin.


Clonal Selection Clonal selection is the process by which a

lymphocyte proliferates and differentiates in

response to a specific antigen.

• A clone is a population of identical cells, all

recognizing the same antigen as the original cell. Lymphocytes undergo clonal selection to produce:

• Effector cells (the active helper T cells, active

cytotoxic T cells, and plasma cells) that die after

the immune response.

• Memory cells that do not participate in the initial

immune response but are able to respond to a

subsequent exposure - proliferating and

differentiating into more effector and memory

cells.


Cytokines Cytokines are chemical signals from one cell

that influences another cell.

• They are small protein hormones that control

cell growth and differentiation:

Interferon

Interleukins

Erythropoietin

Tumor necrosis factor


Antibodies Antibodies (also called immunoglobulins or Igs)

are produced by plasma cells through antibody-

mediated immunity.

• Antibodies are composed of 4 peptide chains:

Two heavy chains and two light chains

• Disulfide bonds link the chains together in a Y-

shaped arrangement.

• The variable region (antigen-binding region)

gives an antibody its specificity.

• The stem is similar for each class of antibody.


Antibodies Single-Unit antibody structure


Antibodies Some of the ways antibodies are effective

include:

• Neutralizing a bacterial or viral antibody, or a

toxin by covering the binding sites and causing

agglutination and precipitation (making what

was soluble, insoluble)

• Activating the classical

complement pathway

• Enhancing phagocytosis -

a process called

opsonization


Antibodies The complement system is a series of blood

proteins that often work in conjunction with

antibodies – it can be activated by multiple

pathways in a step-wise or cascading fashion. It

encourages vasodilation and inflammation,

antigen opsonization,

and antigen

destruction.

The main proteins

are C1-C9.


A membrane attack complex (MAC) forms as a

result of activation of

the complement

cascade.

• The MAC

results in

lysis of the cell.

Antibodies


Antibodies There are 5 classes of antibodies:

• IgG – a monomer with two antigen-binding sites

Comprises 80% of total antibody

Only class able to cross the placenta

Provides long-term immunity

• IgM – a pentamer with ten antigen-binding sites

It is a great activator of complement, but has a

short-lived response.

It is the first antibody to appear in an immune

response


Antibodies Classes of Antibodies

• IgA – a dimer with four antigen-binding sites

prevalent in body secretions like sweat,

tears, saliva, breast milk and gastrointestinal

fluids

• IgE – a monomer involved in allergic reactions

comprises less than 0.1% of total antibody in

the blood

• IgD – a monomer with a wide array of

functions, some of which have been a puzzle

since its discovery in 1964


Antibodies

Classes of Antibodies


Antibodies Thousands of memory cells exist after initial

encounter with an antigen - this is called

Immunological Memory.

• With the next appearance of the same

antigen, memory cells can proliferate and

differentiate within hours.

This graphic shows that

serum antibody titers

are much higher and

much faster on the

second response


Gaining Immunocompetence Within the framework of innate and adaptive

immunity we have discussed, there are a

number of designations for the ways we can

become immunocompetent:

• “Natural Immunity” is not gained through

the tools of modern medicine, whereas

”Artificial Immunity” is.

• Active Immunity refers to the body’s

response to make antibody after exposure to a

pathogen (antigen).

• In Passive Immunity, the body simply

receives antibodies that have been preformed. Active immunity is long-term; passive is

short-term.


Gaining Immunocompetence Examples

• Natural active – contracting hepatitis A and

production of anti-hepatitis A antibodies

• Natural passive - a baby receives antibodies

from its mother through the placenta and

breast milk.

• Artificial active - a person receives a vaccine

of an attenuated (changed/weakened)

pathogen that stimulates the body to form an

antibody.

• Artificial passive – an injection of prepared

antibody


Immunological Surveillance A current theory purports that the formation of

cancer cells is a common occurrence in all of us,

and that the immune system continually

recognizes and removes them.

• There are a number of well-recognized tumor

antigens which are displayed on certain

cancerous cells.

These cells are targeted for destruction by

cytotoxic T cells, macrophages and natural

killer cells.

• Most effective in eliminating tumor cells due to

cancer-causing viruses


The Immune System and Aging Atrophy of the thymus gland results in decreased

T-helper cell populations, and a diminished

mediation of the specific-immune response.

• There is a resulting decreased B-cell response

and decreased number of T-cytotoxic cells.

Compromised immune function with age

results in increased titers of autoantibodies and

an increased incidence of cancer (both

contribute to overall mortality rates.)

Chapter 21&22

Science

Transcript of Chapter 21&22