the lymphatic system and immunity.ppt

8/23/2019 The Lymphatic System and Immunity.ppt

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The Lymphatic Systemand ImmunityDian Adiningsih, SKp., M.Kes., AIFO

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Overview

Introduction

Organization of the Lymphatic System Functions of the lymphatic system

Lymphatic vessels

Lymphocytes

Lymphoid nodules

Lymphoid organs Lymphatic system and body defenses

Nonspecific Defenses Physical barriers

Phagocytes

Immunological surveillance

Interferons Complement

Inflammation

Fever

Specific Defenses: The ImmuneResponse Forms of immunity

Properties of immunity

Overview of immune response

T cells and cell-mediated immunity

B cells and antibody-mediatedimmunity

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Introduction

Pathogens: microorganisms responsible for

human diseases

Bacteria

Viruses

Fungi

Parasites

Lymphatic system

Keeps us alive and healthy

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Organization of

Lymphatic System

3 components

Lymphatic vessels

Fluid (lymph)

Lymphoid organs

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Lymphatic System

Lymph

Lymphatic vessels

Lymphatic tissue Lymphatic nodules

Lymph nodes

Tonsils

Spleen

Thymus


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Functions of Lymphatic System

Production, maintenance, distribution oflymphocytes

Respond to presence of:

Invading pathogens

Abnormal body cells (virus-infected cells, cancer cells)

Foreign proteins (toxins released by bacteria)

Return of fluid and solutes from peripheral tissues toblood

Distribution of hormones, nutrients, and wasteproducts from tissues of origin to general circulation

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Lymphatic Vessels

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Lymphatic Vessels

Carry lymph away from tissues

Lymphatic capillaries

More permeable than blood capillaries

Epithelium functions as series of one-way valves


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Types of Lymphocytes

T cells (Thymus dependent)

80% of circulating lymphocytes

Cytotoxic T cells

Directly attack foreign cells or body cells infected by

viruses (cell-mediated immunity)

Helper T cells

Stimulate activities of both B and T cells Suppressor T cells

Inhibit both T and B cells

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Types of Lymphocytes

B cells (Bone-marrow derived)

10-15% circulating lymphocytes

Plasma cells

Responsible for production and secretion of antibodies

(immunoglobulins)

Responsible for antibody-mediated immunity

NK cells (Natural Killer)

5-10%

Attack foreign cells, normal cells infected with viruses, andcancer cells

Immunological surveillance

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Lymphocyte Development Lymphocytes arise from stem cells in the bone marrow

Newly formed lymphocytes are all alike

But they later develop into B cells or T cells, depending on where they

continue their maturation

Bone marrow

Lymphoid

stem cell

B cell

Blood, lymph, and lymphoid tissues

(lymph nodes, spleen, and others)

T cell

Thymus

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Lymphoid Nodules

Masses of lymphoid tissue w/o a capsule

Increase and decrease size depending on # lymphocytes

present

Found beneath epithelial lining of organs in: Respiratory system

Digestive system

Tonsils

Peyers patches

Urinary system

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Lymphoid Organs: Lymph Nodes

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Lymphatic Tissue and Nodules

Lymphatic tissue Consists mainly of

lymphocytes

Encapsulated or not

Lymphatic nodules

Numerous in loose

connective tissue of

digestive (Peyers

patches), respiratory,

urinary, reproductive

systems


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Lymph Nodes

Organized in cortex and medulla

Substances removed by phagocytosis or stimulatelymphocytes or both

Only structures to filter lymph

Afferent and efferent vessels


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Tonsils

Large groups of lymphatic

nodules in nasopharynx

and oral cavity

Provide protection againstbacteria and other

harmful material

Groups

Palatine Pharyngeal

Lingual


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Lymphoid Organs: Thymus

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Thymus

Located in superior mediastinum

Divisions: Cortex and medulla

Site of maturation of T cells


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Lymphoid Organs: Spleen

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Spleen

Located in left superior side of abdomen Can be ruptured in traumatic abdominal

injuries resulting in bleeding, shock, death

Blood flows through at 3 different rates Fast (most), slow, intermediate

Functions

Destroys defective RBCs Detects and responds to foreign substances

Limited reservoir for blood


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Spleen


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Body Defenses


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The Lymphatic System and Body Defenses

Nonspecific Defenses

Do not distinguish one threat

from another

Physical barriers

Phagocytic cells Immunological surveillance

Interferons

Complement

Inflammation

Fever

Specific Defenses

Protect against particular

threats

Develop after birth

Dependent on activity oflymphocytes

B cells

T cells

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The Complement System

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Macrophage

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Specific Defense: The Immune Response

Respond to specific antigens

T cells

Cell-mediated immunity (cellular immunity)

Provide defense against abnormal cells and pathogens inliving cells

B cells

Antibody-mediated immunity (humoral immunity)

Provide a defense against antigens and pathogens in body

fluids

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Immune System

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Properties of Immunity

Specificity

Versatility

Memory

Tolerance

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Overview of Immune Response

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PERTAHANAN TUBUH MELAWAN BAKTERI DANVIRUS

PATOGEN


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PERTAHANAN TUBUH MELAWAN BAKTERI DAN VIRUS

PATOGEN


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PERTAHANAN TUBUH MELAWAN BAKTERI DANVIRUS

PATOGEN


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Forms of Immunity

Either innate or acquired

Innate

Genetically determined

Acquired Active or Passive

Active Immunity

Naturally acquired immunity

Induced active immunity

Passive Immunity

Induced passive immunity

Natural passive immunity

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Innate vs. acquired immunity

INNATE IMMUNITY

Rapid responses to a

broad range of microbes

ACQUIRED IMMUNITY

Slower responses to

specific microbes

External defenses Internal defenses

Skin

Mucous membranes

Secretions

Phagocytic cells

Antimicrobial proteins

Inflammatory response

Natural killer cells

Humoral response

(antibodies)

Cell-mediated response

(cytotoxiclymphocytes)

Invading

microbes

(pathogens)

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Innate I: External Defenses Physical barriers against the entry of microorganisms and viruses

Intact skin and mucous membranes

Mucus: a viscous fluid that traps microbesand other particles

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In the trachea, ciliated epithelial cells Sweep mucus and any entrapped microbes upward, preventing the

microbes from entering the lungs

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Innate I: External Defenses

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Secretions from the skin Give the skin a pH between 3 and 5, which is

acidic enough to prevent colonization of many

microbes Also include proteins such as lysozyme, an enzyme

that digests the cell walls of many bacteria

Innate I: External Defenses

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Innate II: Internal Defenses

Phagocytosis by phagocytes (cells) Phagocytes: Types of white blood cells

Ingest invading microorganisms

Initiate the inflammatory response

Fever, Pain .

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Phagocytic CellsPseudopodia

surroundmicrobes.

1

Microbes

are engulfed

into cell.

2

Vacuole

containing

microbesforms.

3

Vacuole

and lysosome

fuse.

4

Toxic

compounds

and lysosomal

enzymes

destroy microbes.

5

Microbial

debris is

released by

exocytosis.

6

Microbes

MACROPHAGE

Vacuole Lysosome

containing

enzymes

3 m

e.g. Macrophages, a specific type of

phagocytic cells


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I t II I t l D f


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Natural Killer Cells

Do not eat the pathogen itself but

Attack virus-infected body cells and cancer cells

Trigger apoptosis in the cells they attack


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Innate II Internal Defenses


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Adenoid

Tonsil

Lymphnodes

Spleen

Peyers patches

(small intestine)

Appendix

Lymphatic

vesselsMasses of

lymphocytes and

macrophages

Tissue

cells

Lymphatic

vessel

Bloodcapillary

Lymphatic

capillaryInterstitial

fluid

Lymph

node

The lymphatic systemInterstitial fluid bathing the

tissues, along with the white

blood cells in it, continuallyenters lymphatic capillaries.

1

Fluid inside the

lymphatic capillaries,

called lymph, flowsthrough lymphatic

vessels throughout

the body.

2

Within lymph nodes,

microbes and foreign

particles present in

the circulating lymph

encounter macro-

phages, dendritic cells,

and lymphocytes,

which carry out

various defensive

actions.

3

Lymphatic vessels

return lymph to the

blood via two large

ducts that drain into

veins near theshoulders.

4


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Inflammation (set fire in Greek)Injured hand

First response to damage or infection:

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INFLAMATION Response Redness, Fever, Pain

Pathogen Pin

Macrophage

Chemical signals

Capillary

Phagocytic cells

Red blood cell

Blood

clotting

elements

Blood clot

Phagocytosis

Fluid, antimicrobial proteins,

and clotting elements move

from the blood to the site.

Clotting begins.

2Chemical signals released

by activated macrophages

and mast cells at the injury

site cause nearby capillaries

to widen and become more

permeable.

1 Chemokines released by various

kinds of cells attract more

phagocytic cells from the blood

to the injury site.

3 Neutrophils and macrophages

phagocytose pathogens and

cell debris at the site, and the

tissue heals.

4

Septic shock: systemic inflammation

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Acquired Immunity

Is the bodys second major kind of defense

Involves the activity oflymphocytes

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Self vs. Nonself

How immune system

consider pathogens asnon-self?

There are receptor for pathogens

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Antigen Recognition by Lymphocytes

Two main types of lymphocytes

1) B lymphocytes (B cells)

2) T lymphocytes (T cells)

Have about 100,000 antigen receptor that all recognize

the same epitope

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Antigen-

binding

sites

Antibody A

Antigen

Antibody B

Antibody C

Epitopes

(antigenic

determinants)

Antigen and Epitopes

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Figure 43.8 Antigen receptors on

lymphocytesAntigen-

binding

site

Antigen-

binding siteDisulfide

bridge

Light

chain

Antigen-

binding

site

Heavy chains

Cytoplasm of B cell

b chainDisulfide bridge

a chain

C C

V V

C C

T cell

A T cell receptor consists of one

a chain and one b chain linked by

a disulfide bridge.

(b)A B cell receptor consists of two identical heavy

chains and two identical light chains linked by

several disulfide bridges.

(a)

Variable

regions

Constant

regions

Transmembrane

region

Plasma

membrane

B cell Cytoplasm of T cell

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B C ll R t f A ti


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B Cell Receptors for Antigens

B cell receptors Consist of four peptides

Bind to specific, intact antigens Are often called membrane antibodies or membrane immunoglobulins

Antigen-

binding

site

Antigen-

binding site

Disulfide

bridgeLight

chain

Heavy chains

Cytoplasm of B cell

A B cell receptor consists of two identical heavy

chains and two identical light chains linked by

several disulfide bridges.

(a)

Variable

regions

Constant

regions

Transmembrane

region

Plasma

membrane

B cell

C C

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T Cell Receptors for Antigens


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Antigen-

Binding site

b chainDisulfide bridge

a chainT cell

A T cell receptor consists of one

a chain and one b chain linked by

a disulfide bridge.

(b)

Variable

regions

Constant

regions

Transmembrane

region

Plasma

membrane

Cytoplasm of T cell

T Cell Receptors for Antigens

T cell receptor

Consists of two different polypeptide chains

Detect antigen + MHC

V V

C C

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43.8 T Cell Receptors

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MHC molecules (produced by infected cells)

Present antigens in the infected cells

T cells recognize the MHC+ antigen complex

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T Cells and Cell-Mediated Immunity

T cells recognize antigens when bound tomembranes of other cells

Membrane receptors called major

histocompatibility complex (MHC) proteins Depending on their source

Peptide antigens are handled by different classesof MHC molecules

Class I and Class II

Present to different lyphocytes

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Class I MHC Proteins

Found on the surfaces of all of our cells

MHC proteins bind small peptide molecules

normally present on cell membrane

Normal peptides: T cell ignores

Abnormal, virus, or bacteria (nonself): T cell

activated

Destroys abnormal/infected cell

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Infected cell

Antigen

fragment

Class I MHC

molecule

T cellreceptor

Cytotoxic T cell

A fragment of

foreign protein

(antigen) inside the

cell associates withan MHC molecule

and is transported

to the cell surface.

1

The combination of

MHC molecule andantigen is recognized

by a T cell, alerting it

to the infection.

2

1

2

Class I MHC on almost all nucleated cells of the body Display peptide antigens to cytotoxic T cells

Produced by the

cell

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Class II MHC Proteins

Found only on membranes of lymphocytes andphagocytic antigen-presenting cells (APCs) Such as monocyte-macrophage group, free and fixed

macrophages

Specialized for activating T cells against foreign cells andproteins

Phagocytic APCs engulf and break down foreignantigens or pathogens Fragments of foreign antigens displayed on phagocytic

cells membrane Bind to Class II MHC proteins

T cells come in contact and become activated, starting the immuneresponse

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Class II MHC on dendritic cells, macrophages, and B cells Display antigens to helper T cells

1

2

Figure 43.9b

Microbe Antigen-

presenting

cell

Antigenfragment

Class II MHC

molecule

T cellreceptor

Helper T cell

A fragment of

foreign protein

(antigen) inside thecell associates with

an MHC molecule

and is transported


1

The combination ofMHC molecule and

antigen is recognized


to the infection.

2

(b)

Phagocytic Ag

Acquired

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MHCII


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MHCIIMHC I

Cytotoxic T cell Helper T cell

Killing Helping

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T Cells

T cell activation for both occur when MHCprotein contains specific antigen T cellprogrammed to detect

Once activated, T cells divide and differentiate into cells with specific function in immune response

Cytotoxic T cells

Helper T cells

Memory T cells Suppressor T cells

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Cytotoxic T Cells

Responsible for cell-mediated immunity

Activated by exposure to antigens bound to

Class I MHC proteins

Activated cells under cell division that produce

active cytotoxic T cells and memory cells

Track down and attack bacteria, fungi,

protozoa, or foreign transplanted tissue

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Cytotoxic T Cells

Destruction occurs by:

Releasing perforin (destructive protein)

Ruptures antigenic cell membrane

Secreting lymphotoxin (poison) Kills target cell

Apoptosis

Genetically programmed cell death T cells activate the genes within the target cell

Also called Killer T cells

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Cytotoxic T Cells:


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Cytotoxic T Cells:

A Response to Infected Cells and Cancer Cells

Cytotoxic T cells make CD8 A surface protein that greatly enhances the interaction

between a target cell and a cytotoxic T cell

Cytotoxic T cells

Bind to infected cells, cancer cells, and transplanted tissues

Binding to a class I MHC complex on an infected body

cell

Activates a cytotoxic T cell and differentiates it into an activekiller

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Cytotoxic T cell

Perforin

Granzymes

CD8TCR

Class I MHCmolecule

Target

cell Peptide

antigen

Pore

Released

cytotoxic

T cell

Apoptotic

target cell

Cancer

cell

Cytotoxic

T cell

A specific cytotoxic T cell binds to a

class I MHCantigen complex on a

target cell via its TCR with the aid of

CD8. This interaction, along with

cytokines from helper T cells, leads to

the activation of the cytotoxic cell.

1 The activated T cell releases perforin

molecules, which form poresin thetarget cell membrane, and proteolytic

enzymes (granzymes), which enter thetarget cell by endocytosis.

2 The granzymes initiate apoptosis within the

target cells, leading to fragmentation of the

nucleus, release of small apoptotic bodies,

and eventual cell death. The released

cytotoxic T cell can attack other target cells.

3

1

2

3

Figure 43.16

The activated cytotoxic T cell

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Apoptosis and Macrophages

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Helper T Cells

Activated by exposure to antigens bound toClass II MHC proteins

Activated divide to produce

Active Helper T cells and memory cells Release variety of cytokines that:

Coordinate specific and nonspecific defenses

Stimulate cell mediated and antibody-mediated

immunity

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Helper T Cells: A Response to Nearly


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Helper T Cells: A Response to Nearly

All Antigens

Helper T cells produce CD4, a surface protein

Bind to class II MHC moleculeantigencomplexes on antigen-presenting cells

Activation of the helper T cell then occurs

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T helper cell (TH) activation


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TCR + CD4 binding to MHC+Ag

Proliferation of the T cell, stimulated

by cytokines from both the dendritic

cell and the T cell itself, gives rise to

a clone of activated helper T cells

(not shown), all with receptors for the

same MHCantigen complex.

The cells in this clone

secrete other cytokinesthat help activate B cells

and cytotoxic T cells.

Cell-mediated

immunity

(attack on

infected cells)

Humoral

immunity

(secretion of

antibodies by

plasma cells)

Dendritic

cell

Dendritic

cell

Bacterium

Peptide antigen

Class II MHC

molecule

TCR

CD4

Helper T cell

Cytokines

Cytotoxic T cell

B cell

1

2 3

1

2 3

MHC I +Ag

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Memory T Cells

During cell division for both cytotoxic andhelper T cells, some develop into memorycells

Remain in reserve If same antigen attacks 2nd time, memory T

cells immediately differentiate into cytotoxic Tcells and helper T cells

Allows for more rapid and effective immuneresponse

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Clonal selection of B cells


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Clonal selection of B cells

Generates a clone of short-lived activated effector cells

and a clone of long-lived memory cells

Antigen molecules

Antigen

receptor

B cells that

differ in

antigen

specificity

Memory cells

Plasma cells (effector cells)

Antigen molecules

bind to the antigen

receptors of only one

of the three B cells

shown.

The selected B cell

proliferates, forming

a clone of identical

cells bearing

receptors for the

selecting antigen.

Some proliferating

cells develop into

short-lived plasma

cells that secrete

antibodies specific

for the antigen.

Some proliferating cells

develop into long-lived

memory cells that can

respond rapidly upon

subsequent exposure

to the same antigen.

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In the secondary immune response


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Memory cells facilitate a faster, more efficientresponse

Antibodyconcentration

(arbitraryunits)

104

103

102

101

100

0 7 14 21 28 35 42 49 56

Time (days)

Antibodies

to A

Antibodies

to B

Primary

response to

antigen A

produces anti-

bodies to A

2Day 1: First

exposure to

antigen A

1 Day 28:

Second exposure

to antigen A; first

exposure to

antigen B

3 Secondary response to anti-

gen A produces antibodies

to A; primary response to anti-

gen B produces antibodies to B

4

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Suppressor T Cells

When activated, depress responses of other T

and B cells

Does not occur immediately

Takes much longer for these cells to become

activated

Act after initial immune response

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Humoral and cell-mediated immunity


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Humoral and cell mediated immunity

against different types of threats

Acquired immunityThe humoral immune response

the activation and clonal selection of B cells,

resulting in the production ofsecreted antibodiesThe cell-mediated immune response

involves the activation and clonal selection of

cytotoxic T cells

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Humoral immune response Cell-mediated immune response


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First exposure to antigen

Intact antigens Antigens engulfed anddisplayed by dendritic cells

Antigens displayedby infected cells

Activate Activate (by MHCII) Activate (MHC I)

Gives rise to Gives rise to Gives rise to

B cellHelper

T cell

Cytotoxic

T cell

Plasma

cells

MemoryB cells

Active andmemory

helper

T cells

Memorycytotoxic

T cells

Activecytotoxic

T cells

Secrete antibodies that defend against

pathogens and toxins in extracellular fluid

Defend against infected cells, cancer

cells, and transplanted tissues

Secreted

cytokines

activate

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B Cells and Antibody-Mediated Immunity:


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B Cells and Antibody Mediated Immunity:

B Cell Activation

Each B cell carries its antibody molecules in itscell membrane

If ISF contains antigens that can bind toantibodies, B cells become sensitized

Antigens enter B cell and become displayed on Class IIMHC proteins on surface of B cell

Helper T cell activated by same antigen attaches to MHCprotein-antigen complex and secretes cytokines that:

Promote B cell activation Stimulate B cell division

Accelerate plasma cell production

Enhance antibody production

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B C ll A ti ti


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B Cell Activation

Activated B cells divide several times

Produce daughter cells that differentiate into:

Plasma cells

Synthesize and secrete large numbers of antibodies on surfaceof sensitized B cells

Memory cells

Similar to memory T cells

If exposed to same antigen, will differentiate into plasma cells

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A tib d St t


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Antibody Structure

Consist of short and heavy chains of polypeptides Each chain has constant and variable segments

Constant heavy chains form base of antibody molecule B cells produce only 5 types of constant segments

Specificity depends on variable segments of light and

heavy chains Free tips contain antigen binding sites (very specific for each type

of antigen)

Antigen-antibody complex Forms when antibody binds to proper antigen

Binds to sites and leads to B cell sensitization and animmune response

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Antibody ClassesFirst Ig class produced after initial exposure toantigen; then its concentration in the blood declines

IgM

(pentamer)


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y

Most abundant Ig class in blood; also present in

tissue fluidsOnly Ig class that crosses placenta, thus conferring

passive immunity on fetus

Promotes opsonization, neutralization, and agglutination

of antigens; less effective in complement activation

Than IgM (see Figure 43.19)

Present in secretions such as tears, saliva, mucus,

and breast milk

Triggers release from mast cells and basophils of

histamine and other chemicals that cause allergicreactions (see Figure 43.20)

Present primarily on surface of naive B cells that have

not been exposed to antigens

IgG

(monomer)

IgA

(dimer)

IgE

(monomer)

J chain

Secretory

component

J chain

Transmembrane

region

IgD

(monomer)

Promotes neutralization and agglutination of

antigens; very effective in complement activation

(see Figure 43.19)

Provides localized defense of mucous membranes by

agglutination and neutralization of antigens (see

Figure 43.19)

Presence in breast milk confers passive immunity on

nursing infant

Acts as antigen receptor in antigen-stimulated

proliferation and differentiation of B cells

(clonal selection)

From lymphocytes :

Ig M, Complement

Ig G, Major in bloodIg E, allergic

Ig D, Clonal selection

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A tib d M di t d Di l f A ti


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Antibody-Mediated Disposal of Antigens

The binding of antibodies to antigens Is also the basis of several antigen disposal

mechanisms

Leads to elimination of microbes by phagocytosis

and complement-mediated lysis

1) Neutralization

2) Agglutination

3) Precipitation

4) Complement reaction

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Antibody-mediated mechanisms of antigen disposal


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Binding of antibodies to antigens

inactivates antigens by

Viral neutralization

(blocks binding to host)

and opsonization (increases

phagocytosis)

Agglutination of

antigen-bearing particles,

such as microbes

Precipitation of

soluble antigens

Activation of complement system

and pore formation

Bacterium

Virus Bacteria

Soluble

antigens Foreign cell

Complement

proteinsMAC

Pore

Enhances

Phagocytosis

Leads to

Cell lysis

MacrophageFigure 43.19

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Classes of Antibodies (Immunoglobins Igs)


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Classes of Antibodies (Immunoglobins Igs)

IgG Largest and most diverse

Resist many viruses, bacteria, bacterial toxins

Can cross placenta What type of immunity is that?

IgM

Circulate; attack bacteria IgA

Found in exocrine secretions Ex?

Attack pathogens before they enter the body

IgE When bound to antigen, stimulates basophils and mast cells to release

chemicals to stimulate inflammation

IgD Attached to B cell and involved in their activation

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Antibody Function


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Antibody Function

Neutralization

Agglutination and Precipitation

Activation of a complement

Attraction of phagocytes

Enhancement of phagocytosis

Stimulation of inflammation

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Primary and Secondary Responses to


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Antigen Exposure

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Antibody for a specific antigen

is newly made or already exist?

Pathogens (Epitopes) are

manyHow to detect all of

them?

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Custom-tailored Ready-made


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Custom tailored y

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Complexity
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How can make a lot of

antibodies up to 1015 ?

Antigen diversity : 1015

Human gene number: ~35000

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Light chain diversity


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DNA of

undifferentiatedB cell

DNA of differentiated

B cell

pre-mRNA

mRNA Cap

B cell

B cell receptorLight-chain polypeptide

Intron

Intron

Intron

Variable

region

Constant

region

V1 V2 V3

V4V39

V40 J1 J2 J3 J4 J5

V1 V2 V3 J5

V3 J5

V3 J5

V C

C

C

C

C

Poly (A)

Deletion of DNA between a Vsegment

andJ segment and joining of the segments

1

Transcription of resulting permanently rearranged,functional gene

2

RNA processing (removal of intron; addition of cap

and poly (A) tail)

3

4 Translation

40 V X 5J

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Heady chain diversity


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50 V X 20 D x 6 J x 9 C

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B cell receptor diversity


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200 X 3600 = 720,000

Light chain Heavy chain

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Do you think

The complexity of antigen receptor

is enough to detect all of pathogen

in the world??

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Somatic mutations


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Some mutants binds to Ag better

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Diversity of immune receptors


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MHC diversity depend

on the number of

alleles

By Gene

rearrangement

By Gene

rearrangement


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How to resolve this problem?

Some antibody binds to self

proteins.

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Testing and Removal of Self-Reactive Lymphocytes


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B and T cells are maturing in the bone and thymus Their antigen receptors are tested for possible self-

reactivity

Self-reacting lymphocytes bearing receptorsfor antigens already present in the body are destroyed

by apoptosis or rendered nonfunctional

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Active and Passive Immunization


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Active and Passive ImmunizationActive immunity

Develops naturally in response to an infection

Can also develop following immunization, also called

vaccination

In immunization

A nonpathogenic form of a microbe or

part of a microbe elicits an immune response toan immunological memory for that microbe

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Passive immunity:

Is conferred naturally when IgG crosses theplacenta from Mother to Fetus

or when IgA passes from mother toinfant in breast milk

Can be conferred artificially by injectingantibodies into a nonimmune person


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The immune systems to

distinguish self from nonself limitstissue transplantation

Detected as enemies

-Pathogens

-Transplanted tissues

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Blood Groups and Transfusions


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Blood Groups and Transfusions Certain antigens on red blood cells

Determine whether a person has type A, B, AB, or Oblood

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Another red blood cell antigen the Rh factor


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Another red blood cell antigen, the Rh factor

During deliveryDuring pregnant

Babys blood exposed to

maternal immune system

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Tissue and Organ Transplants


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Skin [email protected]

Tissue and Organ Transplants MHC (Major Histocompatibility complex)


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MHC (Major Histocompatibility complex)

Tissue

Major Role: activating T-cells via interaction with peptide

antigen and T-cell [email protected]

MHC major role in tissue rejection


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MHCmajor role in tissue rejection

What is the role ofMHC normally?

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MHC for Antigen presentation


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MHC for Antigen presentation T cells recognize the MHC+ antigen complex

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Class I MHC l ll l d ll f h b d


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Infected cell

Antigen

fragment

Class I MHC

molecule

T cell

receptor

(a) Cytotoxic T cell

A fragment of

foreign protein


cell associates with

an MHC molecule

and is transported


1

The combination of

MHC molecule and

antigen is recognized


to the infection.

2

1

2

Class I MHC on almost all nucleated cells of the body Display peptide antigens to cytotoxic T cells

Produced by the

cell

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Class II MHC on dendritic cells macrophages and B cells


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Class II MHC on dendritic cells, macrophages, and B cells Display antigens to helper T cells

1

2

Figure 43.9b

Microbe Antigen-

presenting

cell

Antigen

fragment

Class II MHC

molecule

T cell

receptor

Helper T cell

A fragment of

foreign protein


cell associates with

an MHC molecule

and is transported


1

The combination of

MHC molecule andantigen is recognized


to the infection.

2

(b)

Phagocytic Ag

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Tissue and Organ Transplants MHC (Major Histocompatibility complex)


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MHC (Major Histocompatibility complex)

Each has many types of [email protected]

MHC alleles are polymorphic


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MHC is polymorphic and

expression is co- 303 known HLA-


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p

dominantA alleles in

humans

(previous slide)but a maximum

of 2 per person

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The chances of successful transplantation are

i d


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increased

If the donor and recipient MHC tissue types are wellmatched (higher between relatives)

If the recipient is given immunosuppressive drugs

Pig without some antigens

Why xenograft difficult?

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GVHR Lymphocytes in bone marrow transplants


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y p y p

May cause a graft versus host reaction in recipients

Donor blood cells attack host

tissues

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Immune-Related

Diseases


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Immune-related diseases

Autoimmune diseases : reaction to self tissues

Immunodeficiency : no reaction to others

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Allergies


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Allergies are exaggerated (hypersensitive)

responses To certain antigens called allergens

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In localized allergies such as hay fever


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IgE antibodies produced after first exposure to an allergen attach to

receptors on mast cells

The next time the allergen binds to IgE and the mast cell secreteshistamines

Histamines

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The allergic response
http://upload.wikimedia.org/wikipedia/commons/6/6c/Histamine.png


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g p

IgE antibodies produced in

response to initial exposure

to an allergen bind to

receptors or mast cells.

1 On subsequent exposure to the

same allergen, IgE molecules

attached to a mast cell recog-

nize and bind the allergen.

2 Degranulation of the cell,

triggered by cross-linking of

adjacent IgE molecules,

releases histamine and other

chemicals, leading to allergy

symptoms.

3

1

2

3

Allergen

IgE

Histamine

Granule

Mast cell

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An acute allergic response sometimes leads to

h l i h k


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anaphylactic shock

A whole-body, life-threatening reaction that can occur withinseconds of exposure to an allergen

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MEKANISME RESPON ANAFILAKSIS


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Autoimmune diseases - Why?


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The immune system loses tolerance

for self and turns against certain

molecules of the body

Rheumatoid arthritisan autoimmune disease that leads to

damage and painful inflammation of

the cartilage and bone of joints

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Other examples of autoimmune diseases


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Other examples of autoimmune diseases

include

Systemic lupus erythematosus

Multiple sclerosis

Insulin-dependent diabetes

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Immunodeficiency Diseases


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An inborn or primary immunodeficiency

Results from hereditary or congenital defects thatprevent proper functioning of innate, humoral,

and/or cell-mediated defenses

An acquired or secondary immunodeficiency

Results from exposure to various chemical and

biological agents

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Inborn (Primary) Immunodeficiencies

Severe combined immunodeficiency (SCID)


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Severe combined immunodeficiency (SCID)

Both the humoral and cell-mediated branches of

acquired immunity fail to function

How to cure him?

A gene mutation results in

absence or nonfunctional blood

cell

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How to cure SCID?

1) Bone marrow


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Ashanti De Silva, the firsthuman to receive gene therapy (1990)

1) Bone marrow

transplantation

2) Gene-therapy

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Acquired (Secondary) Immunodeficiencies


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Acquired immunodeficiencies

Range from temporary states to chronic diseases

1m

AIDS kills the helper T-cells

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Cell-mediated

immunity

(attack on

infected cells)

Humoral

immunity

(secretion of

antibodies by

plasma cells)

Dendritic

cell

Dendritic

cell

Bacterium

CD4

Helper T cell

Cytokines

Cytotoxic T cell

B cell

1

2 3

1

2 3

AIDS attack TH [email protected]

Stress and the Immune System

Growing evidence shows


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Growing evidence shows

That physical and emotional stress can harmimmunity

Stress test:

If you see two identical dolphins,you are stress-free

the lymphatic system and immunity.ppt

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