12-chapt13 lecture anim - nassau community · pdf file• vessels merge before entering one...

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Chapter 13

Lecture and

Animation Outline

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13.1 The Lymphatic System

• The lymphatic system consists of:

– Lymphatic vessels

– Lymphoid organs

• Three functions contribute to homeostasis.

– Returning excess tissue fluid to the bloodstream

– Absorbing fats from the digestive tract and transporting them to the bloodstream

– Defending the body against disease

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Lymphatic Vessels

• Lymphatic vessels

– Form a one-way system that begins with lymphatic capillaries

• Lymphatic capillaries

– Found in most areas of the body

– Small, closed-ended vessels with thin walls

– Capillaries merge into larger vessels

• These larger vessels carry the lymph into the thoracic and lymphatic ducts

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Lymphatic Vessels

• Lymphatic capillaries

– Absorb excess tissue fluid

• Consists of water and solutes

– Nutrients, electrolytes, and oxygen derived from plasma

– Hormones, enzymes, and wastes products secreted by cells

– Return fluid inside, called lymph, to the bloodstream

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Lymphatic Vessels

• Lymphatic capillaries join to form lymphatic vessels.

• Vessels merge before entering one of two ducts.

– Thoracic duct

• Returns lymph collected from body below thorax, left arm,

left side of head, and neck into the left subclavian vein

– Right lymphatic duct

• Returns lymph from the right arm and right side of the

head and neck into the right subclavian vein

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spleen

tonsil

inguinal lymph nodes

right lymphatic duct

empties lymph into the

right subclavian vein


axillary lymph nodes

thoracic duct

left subclavian vein

red bone marrow

thymus

Figure 13.1

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13.1 Lymphatic System

• Larger lymphatic vessel structure similar to veins– One-way valves prevent lymph backflow

– Movement of lymph dependent on skeletal muscle contractions

• Edema– Localized swelling caused by accumulation of

fluids in the tissues

– Too much fluid made and/or not enough being drained

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tissue cell

lymph node

lymphaticvessel

valve

lymphatic capillary

blood capillary

tissuefluid

lymphaticcapillary

bloodcapillary

Figure 13.1

9


spleen

tonsil

inguinal lymph nodes tissue cell

lymph node

right lymphatic duct

empties lymph into the



axillary lymph nodes

thoracic duct

lymphatic

vessel

valve

lymphatic capillary

blood capillary

tissue

fluid

lymphatic

capillary

blood

capillary

left subclavian vein

red bone marrow

thymus

Figure 13.1

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Lymphoid Organs

• Lymphoid organs contain many lymphocytes

– White blood cells involved in adaptive immunity

– Two types of lymphoid organs:

• Primary lymphoid organs

• Secondary lymphoid organs

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Lymphoid Organs

• Primary lymphoid organs

– Where lymphocytes develop and mature

– Red bone marrow, thymus

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Lymphoid Organs

• Secondary lymphoid organs

– Where lymphocytes become activated

– Spleen, lymph nodes

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tonsil

lymphaticvessel


Figure 13.2

14

medulla

tonsil

a. Thymus

641 µm

lobule

cortex

lymphaticvessel

© The McGraw-Hill Companies, Inc./Dennis Strete, photographer


Figure 13.2a

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medulla monocyte

lymphocyte

tonsil

a. Thymus

641 µm

lobule

cortex

lymphatic

vesselb. Red bone ma rrow

310 µm

a: © The McGraw-Hill Companies, Inc./Dennis Strete, photographer; b: © R. Valentine/Visuals UnlimitedFigure 13.2b

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medulla monocyte

lymphocyte

tonsil

medulla

641 µm

c. Lymph node

capsule

cortex

a. Thymus

641 µm

lobule

cortex

lymphatic

vesselb. Red bone marrow

310 µm

a: © The McGraw-Hill Companies, Inc./Dennis Strete, photographer; b: © R. Valentine/Visuals Unlimited; c: © Fred E. Hossler/Visuals UnlimitedFigure 13.2c

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medulla monocyte

lymphocyte

tonsil

medulla

white pulp

381 µm

d. Spleen

641 µm

c. Lymph node

capsule

cortex

a. Thymus

641 µm

lobule

cortex

lymphatic

vessel

red pulp

capsule

b. Red bone ma rrow

310 µm

a: © The McGraw-Hill Companies, Inc./Dennis Strete, photographer; b: © R. Valentine/Visuals Unlimited; c: © Fred E. Hossler/Visuals Unlimited; d: © The McGraw Hill Companies, Inc./Al Telser, photographer

Figure 13.2d

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Primary Lymphoid Organs

• Red bone marrow

– Network of connective tissue fibers and stem cells

– Stem cells develop into various white blood cells

– Blood cells enter bloodstream at sinuses

– B cells remain and mature in the bone marrow

– T cells migrate from bone marrow and reach

thymus

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Primary Lymphoid Organs

• Thymus

– Soft, bilobed organ located between trachea and

the sternum

– Site of T cell maturation

– Site where T cells that are capable of reacting to the body’s own cells undergo apoptosis

• Must distinguish “self” from “non-self”

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Secondary Lymphatic Organs

• Lymphocytes migrate from the blood into secondary lymphoid organs.

• Lymphocytes may encounter foreign molecules or cells where they proliferate and become

activated.

• Activated lymphocytes reenter the blood, where

they search for sites of infection or inflammation.

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• Spleen is located in the upper left side of

abdominal cavity.

– Mostly red pulp, where macrophages remove old and defective blood cells

– Also contains white pulp, lymphatic tissue where lymphocytes can react to foreign invaders

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• Lymph nodes are small, ovoid structures located along lymphatic vessels, through which

lymph must pass.

• Connective tissue divides organ into nodules and sinuses.

– Each nodule is packed with B and T cells.

– Macrophages engulf pathogens as lymph moves

through.

– Viruses, bacteria and debris in lymph are removed.

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13.2 Innate Immunity

• The lymphatic system works with the immune system to protect the body from pathogens, toxins

and other invaders.

• Immunity is the body’s ability to remove or kill foreign substances, toxins, pathogens, and cancer cells.

• Innate immunity mechanisms function without

previous exposure to an unwanted substance.

• Adaptive immunity is dependent upon exposure to specific antigens.

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13.2 Innate Immunity

• Mechanisms of innate immunity are

divided into four types.

– Physical and chemical barriers

– Inflammation

– Phagocytes and natural killer cells

– Protective proteins

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Physical and Chemical Barriers

• Skin and mucous membranes lining the respiratory, digestive and urinary tracts serve as mechanical

barriers.

• The upper respiratory tract has cilia to remove trapped particles.

• Oil glands on skin secrete chemicals to weaken or kill some bacteria.

• Stomach is acidic.

• Normal bacteria in the intestines and other areas

outcompete potential pathogens.

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Inflammatory Response

• Inflammation response

– Series of events caused by physical or chemical trauma to tissue or pathogens

– Tends to wall off infections and increase access to

the immune system

– Four signs at inflamed area

• Redness, heat, swelling, and pain

• Caused by changes in the capillaries in damaged area

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Inflammatory Response

• Three cell types in the skin and connective

tissue promote inflammatory response.

– Mast cells release histamine which causes

capillaries to dilate.

– Macrophages and dendritic cells are

phagocytic and release cytokines.

• Cytokines are chemical messengers that influence

activities of other immune cells.

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mast cell

histamine

cytokines

Skin

Tissue

2. Macrophages and dendritic cellsphagocytize pathogens and release cytokines, which stimulate theinflammatory reaction.

injured tissue

pathogen

macrophage

neutrophil

monocyte

dendriticcell

4. Blood clotting walls offcapillary and preventsblood loss.

3. Neutrophils and monocytes (which becomemacrophages) squeeze through thecapillary wall and phagocytize pathogens.

blood clot

Capillary

1. Injured tissue cells and mast cellsrelease histamine which causes capillaries to dilate and increasesblood flow.

Figure 13.3

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Phagocytes and Natural Killer Cells

• Phagocytes are cells that migrate through the walls of dilated capillaries.

– Engulf pathogens by forming an endocytic vesicle

– Vesicles fuse with lysosomes (digestive enzymes)

– Neutrophils

• First to arrive at inflamed area, accumulation forms pus

– Monocytes

• As inflammatory response continues monocytes migrate from blood

• When in tissues, these cells become macrophages

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Phagocytes and Natural Killer Cells

• Natural killer (NK) cells

– Large granular lymphocyte-like cells

– Kill some virus-infected and cancer cells by cell-to-cell contact

– Seek out and kill cells lacking a particular type of

“self” molecule on their surface

• MHC-I (major histocompatibility class I)

• Some cancer or virus-infected cells lack MHC

– Do not recognize specific antigens

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Protective Proteins

• The complement system consists of plasma proteins designated by the letter C and a

number (i.e C3)

• They complement certain immune actions

– Ex: Certain complement proteins bind to mast cells

and cause histamine release.

– Ex: Certain complement proteins attract phagocytes by binding to pathogen surfaces.

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Protective Proteins

• Complement System

– “Complement” certain immune responses

– Form membrane attack complexes

• Interferons

– Proteins produced by infected cells that “warn” non-infected cells


complement

proteins

membrane

attack complex

fluids

andsalts

Figure 13.4

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13.3 Adaptive Immunity

• Adaptive Immunity occurs when innate defense fails to prevent an infection.

– System recognizes, responds to and often eliminates antigens

• Antigen: any molecule that stimulates an adaptive immune response

– Immune system is able to distinguish “self” from “nonself”

– Usually takes 5-7 days to become fully activated

• May last for years

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Antigen Receptor Diversity and Clonal Selection

• Adaptive defenses depend on B and T cells.

– Both cells recognize antigens because they have

specific antigen receptors.

– Each lymphocyte has only one type of receptor.

– Diversity is needed for the many possible antigens.

– Specific B and/or T cells are produced for almost

any possible antigen.

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• The clonal selection theory states that only a few cells within a population of B and T cells

have antigen receptors for any specific antigen.

• “Selection” occurs when an antigen binds to

receptors of a particular lymphocyte.

– It divides repeatedly, forming clonal cells.

– Only cells that have a receptor specific to an

antigen divide in the process.

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• Various immune defenses do not ordinarily

react to our own normal cells.

– Our immune system can distinguish “self” from “nonself.”

– However, because generation of antigen

receptors is a random genetic process, some of these receptors can react with “self” antigens.

– Such lymphocytes are destroyed by apoptosis early in development.

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B Cells and Antibody-Mediated Immunity

• B cells activated in lymph nodes or spleen

when the BCRs bind specific antigens.

• Cytokines secreted from helper T cells

stimulate B cells to divide.

• Defense by B cells is called antibody-

mediated immunity.

– Also called humoral immunity because the

antibodies are found in blood and lymph.

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• Activated B cell clones

– Most become plasma cells

• Mass production of antibodies

– Some become memory cells

• Long-term immunity

– If same antigen returns, memory B cells divide and quickly give rise to more plasma cells

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B cell

antigens

B-cell

receptor(BCR)

Figure 13.5

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B cell

antigens

B-cellreceptor(BCR)

Activation cytokines from T cells

Clonal expansion

Memory B cellsFigure 13.5

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B cell

antigens

B-cellreceptor

(BCR)


Figure 13.5

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B cell Clonal Selection Theory

– An antigen binds to the antigen receptor of only one type of B cell or T cell, and then this B cell or T cell divides, forming clones of itself.

– Only the B cell with a BCR shape that fits the antigen undergoes clonal expansion.

– Most clones become plasma cells, but some become memory cells.


antibody

Plasma cells

B cell

antigens

B-cell

receptor

(BCR)


Clonal expansion

Memory B cells

Apoptosis

Apoptosis

Figure 13.5

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• Structure of an Antibody– Antibodies are also called immunoglobulins (Ig)

– Y-shaped

• Each arm has two chains.

– “Heavy” long chain

– “Light” short chain

• Each chain has two regions.

– Constant (C) regions – constant within same class of

antibody

– Variable (V) regions vary between antibodies

» Binds to antigen

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C C

C = constantV = variable

heavy

chain

light

chain

antigen binds

to binding site

antigen-binding

sites

shape of antigen fits

shape of binding site

antigen

Figure 13.6a

45


Courtesy Dr. Arthur J. Olson, Scripps Institute

Figure 13.6b

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C C

antigen

a.

C = constant

V = variable

heavychain

lightchain

antigen bindsto binding site

antigen-bindingsites

shape of antigen fitsshape of binding site

b.b: Courtesy Dr. Arthur J. Olson, Scripps Institute

Figure 13.6

47

Types of Antibodies

48

T cells and Cell-Mediated Immunity

• T cell leaveing the thymus has a unique T-cell receptor (TCR)

• Unable to recognize antigen without help

– Must be presented to TCR by an MHC (major

histocompatibility complex) protein on surface of another cell

• Types of T cells

– Helper T (TH) cells

– Cytotoxic T (TC) cells

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T-cell receptor (TCR)

Tc cell

Figure 13.7

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MHC-Icytokines


Binding toMHC-I + antigen Dendritic

cell

Tc cell

viralantigen

Figure 13.7

51


MHC-Icytokines

Binding to

MHC-I + antigenDendritic

cell

viral

antigen

Cytotoxic

Tcell

virus-infected

cell

Death by

apoptosis

Activation and

clonal expansion

Tc cell


Figure 13.7

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• TH cells recognize only those antigens presented by

specialized antigen-presenting cells (APCs) with MHC class II molecules on

their surface.

• TC cells recognize only those antigens presented by various cell types with MHC

class I molecules on their surface.


Cytotoxic

Tcell

virus-infected

cell

Death by

apoptosis

Activation and

clonal expansion

Apoptosis

Memory

T cell

cytokines


Binding to

MHC-I + antigen Dendritic

cell

Tc cell

viral

antigen

MHC-I

Figure 13.7

53

13.2 Innate and Adaptive Immunity

• TC Cells

– TC cells provide immunity against virus-infected cells and cancer cells.

– TC cells have storage vacuoles.

• Perforins form pores in abnormal cell membrane

• Granzymes induce apoptosis

– Some T cells become memory T cells.

• May live many years

• Can quickly jump start immune response to previous antigen

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vesicle

perforin

granzyme

Perforinformshole

in target cell.Granzymesenter through the

hole and causetarget cell to

undergo apoptosis.

Cytotoxic T cell


Target cell

Figure 13.8a

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vesicle

perforin

granzyme

target cell

(virus-infected

or cancer cell)

Perforin

forms hole

in target cell.

Target cell

Granzymes

enter through the

hole and cause

target cell to

undergo apoptosis.

Cytotoxic T cell

cytotoxic T cell


Figure 13.8a

56

a.

vesicle

perforin

granzyme

target cell(virus-infected

or cancer cell)

Perforinforms hole

in target cell.

Target cell

Granzymesenter through the

hole and causetarget cell to

undergo apoptosis.

cytotoxicT cell

target cell

SEM 1, 250 ××××

Cytotoxic T cell

cytotoxic T cell

b .


b: © Steve Gschmeissner/Photo Researchers, Inc.

Figure 13.8

57

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13.4 Active Versus Passive Immunity

• Immunity occurs when the body is protected

from various threats.

• Two types of adaptive immune responses

exist.

– Active immunity

• Individual alone produces an immune response against antigen

– Passive immunity

• Individual is given prepared antibodies either naturally or artificially by injection

60

Active Immunity

• Active Immunity

– Develops naturally after a person is infected

with an antigen

– Can be induced artificially – immunization

• Vaccine – substances that contain an antigen to which the immune system responds (traditionally)

– Genetically engineered microbes mass-produce antigens

– Depends on presence of memory B cells and

memory T cells

• Respond quickly to antigen if encountered again

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61Figure 13.9a

Suggested Immunization Schedule

Age (years)

4–6

11–12, 13–18

4–6

4–6, 11–12

2–18

2–18

11–12

Vaccine Age (months)

Birth, 1–2, 6– 18

2, 4, 6, 15– 18

2, 4, 6, 12– 15

Diphtheria, tetanus,Pertussis (DTP)

Hepatitis B

Tetanus only

Haemophilus

influenzae, type b

Polio (IPV)

Pneumococcal

Measles, mumps,rubella (MMR)

Varicella(chicken pox)

Hepatitis A(in selected areas)

Human papilloma-virus, types 6, 11, 16, 18

2, 4, 6–18

2, 4, 6, 12–15

12–15

12–18

12–18

–

a.


(top): © The McGraw-Hill Companies, Inc. Jill Braaten, photographer

62

• Follow immune response using antibody titer

– 1st exposure – titer rises slowly

– 2nd exposure – titer rises rapidly and to a higher

level


0 30 60 90 120 150 180

high

low

secondary responseprimary response

Pla

sm

a A

nti

bo

dy

Co

ncen

tra

tio

n

first exposureto vaccine

Time (days)

second exposureto vaccine

Figure 13.9b

63Figure 13.9 b.

Suggested Immunization Schedule

Age (years)

4–6

11–12, 13–18

4–6

4–6, 11–12

2–18

2–18

11–12

Vaccine Age (months)

Birth, 1–2, 6– 18

2, 4, 6, 15– 18

2, 4, 6, 12– 15

Diphtheria, tetanus,

Pertussis (DTP)

Hepatitis B

Tetanus only

Haemophilus

influenzae, type b

Polio (IPV)

Pneumococcal

Measles, mumps,

rubella (MMR)

Varicella

(chicken pox)

Hepatitis A

(in selected areas)

Human papilloma-

virus, types 6, 11, 16, 18

2, 4, 6–18

2, 4, 6, 12–15

12–15

12–18

12–18

–

a.

high

18015060 12030 900

Time (days)

primary response secondary response

second exposure

to vaccine

Pla

sm

a A

nti

bo

dy

Co

nce

ntr

ati

on

low

first exposure

to vaccine


a (top): © The McGraw-Hill Companies, Inc. Jill Braaten, photographer

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64

Passive Immunity

• Passive Immunity

– Received from another person’s antibodies or immune cells

– Common natural process

• Cross placenta but last only a few months

• Found in breast milk which prolongs immunity

– Temporary because there are no memory cells

• Used to prevent illness in an exposed individual

65b: © Digital Vision/Getty RF; c: © Aaron Haupt/Photo Researchers, Inc.

a. Antibodies (IgG) cross the placenta.

b. Antibodies (IgG, IgA) aresecreted into breast milk.

c. Antibodies can be injected by aphysician.


Figure 13.10

66

Immune TherapiesCytokines and Immunity

• Cytokines are signaling molecules that regulate white blood cell formation or function.

– Medical uses of cytokines

• Stimulation of blood cell production in cancer patients whose treatment reduces normal function of bone marrow

• Treatment of cancer by stimulating the immune response

– Interferons used to directly inhibit cancer growth or inhibit viruses that may cause cancer

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Monoclonal Antibodies

• Monoclonal antibodies are group of plasma cells from the same B cell.

– All produce antibodies against the same antigen.

– Hybridomas are made in the lab by fusing antibody-producing cells with myeloma cells.

– Monoclonal antibodies have many uses.

• Diagnostic tests

– Ex: pregnancy tests

• Vehicles for drug delivery

• Identification of infections

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myeloma cellsantigen

fusion into

hybridoma

b. Culture of surviving

hybridomas

c. Selection of antibody

producing clones

e. Purified monoclonal antibodies

a.

d. Clonal expansion of

antibody-producing cells

mouse spleen cells

Producing antibody

69

13.5 Adverse Effects of Immune Responses

• Sometimes the immune system responds

to harmless antigens in a manner that damages the body.

– allergic reaction

– incompatible blood type

– tissue rejection

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Allergies

• Allergies are hypersensitivities to substances such as pollen, food or animal hair.

– Such substances do not normally harm the body.

– The antigens that provoke such a response in these substances are called allergens.

71

Allergies• Immediate allergic response

– Can occur within seconds of contact with antigen

– IgE antibodies are attached to receptors on the plasma membrane of mast cells in the tissues and also to eosinophils and basophils in the blood

– Allergen attaches to IgE, causing mast cells to release histamine

– Histamine is responsible for allergy symptoms

– Examples – hay fever, asthma, food allergies

72

Allergies

• Anaphylactic shock is an immediate allergic response due to allergen entering the blood stream.

– Examples - bee stings, penicillin shots

– Response is characterized by a sudden, life-threatening drop in blood pressure due to the effects of histamine on capillaries.

– Epinephrine can counteract this reaction.

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Allergies

• Delayed allergic response– Initiated by memory T cells at the site of allergen

contact in the body

– Classic example is skin test for tuberculosis (TB)• Positive test result is skin becomes red and hardened

• Indicates previous exposure to TB

Figure 13.12

74

Blood-Type Reactions

• Several blood typing systems are currently in use.

• The ABO system is the most clinically important.

• Information about one’s ABO type should be easily accessible in case an accident requires the need for blood.

75

ABO system

– Presence or absence of type A and type B antigens on red blood cells determines a persons blood type

– Four types of blood – A, B, AB, and O

– Plasma contains antibodies to antigens NOT present on the red blood cells

– Two antibodies• Anti-A

• Anti-B

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ABO system


AA Anti-B

BB Anti-A

A, BAB None

NoneO Anti-A and anti-B

Antibody in

Plasma

Antigen on

Red Blood CellsBlood Type

77

ABO System

• Transfusions

– Must consider recipient’s antibodies and donor’s antigens to prevent agglutination (clumping) and transfusion reaction

– Type O is universal donor

• Neither anti-A nor anti-B antibodies

– Type AB is universal recipient

• Neither A nor B antigens

78

+

no binding

+

binding

500 ××××

type A blood

of donor

anti-B antibody of

type A recipient

type A blood

of donor

anti-A antibody of

type B recipient

a. No agglutination

b. Agglutination

500 ××××


(both): © J. C. Revy/Phototake

Figure 13.13

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79

Rh System

• Rh factor is another important antigen in blood matching.

– Rh-positive

• Rh antigen is present on red blood cells

• 85% of US population

– Rh-negative

• Rh antigen is absent on red blood cells

• 15% of US population

• Normally do not have antibodies to the Rh factor, but they may make them when exposed to the Rh factor

80

Rh System

• Significant in Pregnancy if an Rh-negative mother is pregnant with an Rh-positive baby

– If baby’s cells leak into mother’s bloodstream, she forms anti-Rh antibodies.

– In a subsequent Rh-positive pregnancy, those antibodies attack baby’s RBCs, causing hemolytic disease of newborn.

– This can be prevented by giving the Rh-negative mother anti-Rh immunoglobulins by injection.

• The injection must be given before the mother becomes sensitized to produce her own antibodies.

81

Rh-negativered

blood cell of mother

Rh-positive

red blood cellof fetus

Fetal Rh-positive red blood cells leak across placenta into

mother’s bloodstream.

blood of mother


Figure 13.14a

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82

Mother forms anti-Rh antibodies that cross the placentaand attack fetal Rh-positive red blood cells.

blood of mother

anti-Rhantibody


Figure 13.14b

83

Hemolytic Disease of the NewbornCopyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Rh-negativered

blood cell of mother

Rh-positive

red blood cell

of fetus

a. Fetal Rh-positive red blood cells leak across placenta into

mother’s bloodstream.

b. Mother forms anti-Rh antibodies that cross the placenta

and attack fetal Rh-positive red blood cells.

blood of mother blood of mother

anti-Rh

antibody

Figure 13.14

84

Tissue Rejection

• Organs such as kidney and heart would be relatively easy to transplant from one person to

another if it were not for the rejection process.

• MHC proteins serve as antigens when organs of a different MHC type are transplanted into a recipient.

• It is difficult to find exact MHC matches between recipient and donor.

• Rejection is diminished by immunosuppressivedrugs.

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85

Tissue Rejection

• Xenotransplantation

– Use of animal instead of human organs

– Genetic engineering to make pigs less antigenic by removing MHC antigens

– Ultimate goal - make pig organs as widely accepted as type O blood

86

13.6 Disorders of the Immune System

• Autoimmune Disease

– Cytotoxic T cells or antibodies attack a person’s own cells.

• Myasthenia gravis - muscle weakness due to attack of neuromuscular junctions

• Multiple sclerosis - neuromuscular disorder due to attack on nerve fibers’ myelin sheaths

• Systemic lupus erythematosus – kidney damage due to deposition of antigen-antibody complexes

• Rheumatoid arthritis – joints affected

87

13.6 Disorders of the Immune System

• Immunodeficiency disease

– Immune system is unable to protect the body from disease.

• Acquired immune deficiency syndrome (AIDS)

• Primary (or congenital) immunodeficiency

– Child inherits missing or impaired immune system

– Severe combined immunodeficiency syndrome (SCID)

» Both antibody- and cell-mediated immunity are lacking or inadequate

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