The IMMUNE SYSTEM

AP Bio Chapter 43

Antibody Immune System Response - Medical Animation

http://www.youtube.com/watch?v=iVMIZy-Y3f8

Organs of the Immune System

Fig. 43-7

Adenoid

Tonsil

Lymphnodes

Spleen

Peyer’s patches(small intestine)

Appendix

Lymphaticvessels Lymph

nodeMasses ofdefensive cells

Bloodcapillary

Lymphaticvessel

Tissuecells

Interstitial fluid

Lymphatic system

The Lymphatic System

• The lymphatic system aids the immune system in removing and destroying waste, debris, dead blood cells, pathogens, toxins, and cancer cells.

• The lymphatic system absorbs fats and fat-soluble vitamins from the digestive system and delivers these nutrients to the cells of the body where they are used by the cells.

• The lymphatic system also removes excess fluid, and waste products from the interstitial spaces between the cells.

What about the spleen?

• It acts as a filter for blood as part of the immune system. Old red blood cells are recycled in the spleen, and platelets and white blood cells are stored there.

The immune system recognizes foreign bodies and responds with the production of immune

cells and proteins

Two major kinds of defense have evolved:

• innate immunity and • acquired immunity

• Innate immunity is present before any exposure to pathogens and is effective from the time of birth

• It involves nonspecific rapid responses to pathogens

• Innate immunity consists of external barriers plus internal cellular and chemical defenses

• Acquired immunity, or adaptive immunity, develops after exposure to agents such as microbes, toxins, or other foreign substances

• It involves a very specific response to pathogens

Fig. 43-2

INNATE IMMUNITY

Recognition of traitsshared by broad rangesof pathogens, using asmall set of receptors

•

•Rapid response

•Recognition of traitsspecific to particularpathogens, using a vastarray of receptors

•Slower response

ACQUIRED IMMUNITY

Pathogens(microorganisms

and viruses)

Barrier defenses:SkinMucous membranesSecretions

Internal defenses:Phagocytic cellsAntimicrobial proteinsInflammatory responseNatural killer cells

Humoral response:Antibodies defend againstinfection in body fluids.

Cell-mediated response:Cytotoxic lymphocytes defendagainst infection in body cells.

Innate immunity of vertebrates

Physical

• Skin – low pH of skin secretions

• Mucous membranes lining digestive, respiratory, genitourinary tracts trap and remove microbes (with cilia in resp)

Chemical

• Lysozyme – enzymes that attack microbial walls, found in tears, saliva, and mucus

• Gastric juice – low pH

• Interferons – proteins produced by viral-infected cells to alert other cells to defend against viral reproduction also stimulates macrophages

• Complement – proteins in plasma that when activated by microbial contact may lyse cells, trigger inflammation, or assist acquired defensive immunity

Complement aiding the acquired immunity system

Cellular

• Macrophages – attack microbes in the spleen and interstitial fluid (known as monocytes in the blood)

• Neutrophils – most numerous phagocytizing cells, phagocytize bacteria

• Eosinophils – attack multicellular parasites

• Dendritic cells – in contact with environment, stimulate acquired immunity system

• Natural killer cells (NK cells) – recognize absence of self-markers on infected cells

macrophage

Neutrophils – first on the job

Eosinophils – attack multicellular parasites

A dendritic cell

http://www.rockefeller.edu/interactive/steinman/dendritic_cell_v5.swf

Dendritic cell

alerting the

acquired

immune

system

NK cell doing its job!

What are toll-like receptors?

• TLR’s are proteins that span membranes in leukocytes and other cells that recognize nonspecific microbes that breach physical barriers such as the skin or intestinal tract.

• They in turn activate the immune system.

• Originally identified in insects.

http://upload.wikimedia.org/wikipedia/commons/0/06/TLR3_structure.png

TLR’s spanning the membrane.

Response

Toll-like receptors

Alert! Microbes entering!

http://www.youtube.com/watch?v=iVMIZy-Y3f8

Inflammatory response

• Redness, swelling, heat

• Damaged mast cells in connective tissue release histamine which triggers dilation and leakiness of blood vessels, activates macrophages, promotes blood flow to the area

• Fever – triggered by toxins or pyrogens released by macrophages, stimulates production of wbc’s, speeds tissue healing

• Septic shock – overwhelming systemic inflammatory response

Fig. 43-8-3

Pathogen Splinter

Macrophage

Mast cell

Chemicalsignals

Capillary

Phagocytic cellRed blood cells

Fluid

Phagocytosis

ACQUIRED IMMUNITY (adaptive immunity)

• Job of lymphocytes that circulate in the blood and lymph, conc in spleen and lymph nodes

• Develop from pluripotent stem cells in the bone marrow and liver of fetuses

• Become T cells after cells have migrated to the Thymus or

• B cells that develop in the Bone marrow

How do they work with the innate immune system?

Signaling molecules (cytokines) from macrophages and dendritic cells activate them.

What are antigens?

• Antigens – proteins or polysaccharides protruding from microbes or toxins floating around

• Epitope (antigenic determinants) – portion of the antigen recognized by immune cells

Fig. 43-10

Antigen-binding sites

Antigen-bindingsites

Epitopes(antigenicdeterminants)

Antigen

Antibody B

Antibody CAntibody A

CC

CV

V

V

V

C

There are millions of lymphocytes with their own types of antigen receptors. How

is the great diversity of B and T cells

produced?

• They are determined during early embryonic development by genetic recombination

• Receptors have constant regions and variable regions that are specific for antigens.

Fig. 43-9a

Antigen-bindingsite

Antigen-binding site

Disulfidebridge

Variableregions

Constantregions

Transmembraneregion

Plasmamembrane

Lightchain

Heavy chains

Cytoplasm of B cell

(a) B cell receptor

B cell

V

V

C C

V

V

C C

Fig. 43-9b

Antigen-bindingsite

Variableregions

Constantregions

Transmembraneregion

Plasmamembrane

T cell

chain chain

Disulfide bridge

Cytoplasm of T cell

(b) T cell receptor

C C

VV

What prevents B and T cells from reacting against the body’s own

molecules?

• Lymphocytes with receptors specific for body’s own molecules are either inactivated or destroyed by apoptosis. This is called self-tolerance.

How to distinguish self from nonself

• MHC molecules are so named because they are encoded by a family of genes called the Major Histocompatibility Complex

• They identify cells as belonging to you!

(histo = tissue)

• Class I MHC molecules are found on almost all nucleated cells of the body

• Class II MHC molecules are found on immune cells such as dendritic cells, macrophages, and B cells.

They digest antigens and display pieces of the antigen with their MHC complex and are called antigen-presenting cells (APC’s).

Class I – body cells Class II- immune cells

Once the cells engulf the antigens, they display them on their MHC complexes:“SELF-NONSELF”.

• Cytotoxic-T cells will bind to the MHC I complexes (recognize infected cells)

• Helper T- cells will bind to the MHC II complexes. MHC II cells are called APC’s (Antigen Presenting Cells).

Fig. 43-12

Infected cell

Antigenfragment

Class I MHCmolecule

T cellreceptor

(a)

Antigenassociateswith MHCmolecule

T cellrecognizescombination

Cytotoxic T cell (b) Helper T cell

T cellreceptor

Class II MHCmolecule

Antigenfragment

Antigen-presentingcell

Microbe

1

11

2

22

Immunological Memory

• When antigens react with the immune

cells, the cells that are specific for that antigen are activated to divide repeatedly and differentiate into clones:

• Effector cells – combative cells

• Memory cells – which carry receptors for that particular antigen

• This is called CLONAL SELECTION.

Fig. 43-14

B cells thatdiffer inantigen specificity

Antibodymolecules

Antigenreceptor

Antigen molecules

Clone of memory cells Clone of plasma cells

This one!

Clonalselection

Monoclonal Antibody Production

Monoclonal Antibody Production

• The first exposure to a specific antigen represents the primary immune response

• During this time, effector B cells called plasma cells are generated, and T cells are activated to their effector forms

• In the secondary immune response, memory cells facilitate a faster, more efficient response

Fig. 43-15

Antibodiesto A

Antibodiesto B

Secondary immune response toantigen A produces antibodies to A;primary immune response to antigenB produces antibodies to B.

Primary immune responseto antigen A producesantibodies to A.

An

tib

od

y co

nce

ntr

atio

n(a

rbit

rary

un

its)

Exposureto antigen A

Exposure toantigens A and B

Time (days)

104

103

102

101

100

0 7 14 21 28 35 42 49 56

Remembering the antigen!

Vaccines stimulate a mild primary response so body can wage a secondary response to

recognize another attack.

Acquired Immunity: 2 types: Humoral and Cell-mediated

Humoral Immune Response (antibody-mediated response)

• involves B cells and

• production of antiBodies in response to free-floating antigens or those on surface of foreign cells

B cells mature into plasma cells that produce

antibodies.

Cell-mediated Response

• involves cytotoxic T cells that destroy target infected cells

The central role of Helper-T’s

• Immune cells (class II MHC) engulf antigens and display them on their MHC.

• Specific helper-T’s recognize the MHC-antigen complex.

Displaying the antigen

Binding to the helper-T

• A T-cell surface protein called CD4 binds the helper-T to the MHC-II.

• Activated helper-T’s release cytokines (interleukins)

- result in more specific help-T’s and memory cells being produced.

- stimulate both cell-mediated and humoral responses

Fig. 43-17

Antigen-presentingcell

Peptide antigen

Cell-mediatedimmunity (attack on

infected cells)

Class II MHC moleculeCD4

TCR (T cell receptor)

Helper T cell

Humoralimmunity

(secretion ofantibodies byplasma cells) Cytotoxic T cell

Cytokines

B cell

Bacterium

+

+ +

+

The central role of Helper-T’s

Binds

Animation: The Immune Response

Cell-mediated Response, how?

• When a nucleated regular cell becomes infected, pieces of antigens are combined with the MHC I and they bond to cytotoxic T cells with the help of CD8 surface proteins.

• The cytotoxic cell becomes a killer cell which releases perforin that punches holes in the infected cell.

• CD 8’s and CD 4’s are like bungy cords.

They holdthe MHCto the T orB cells

Cell Mediated ImmunityResponse of Cytotoxic T cells

Cytotoxic T-cell Activity Against Target Cells

Fig. 43-18-3

Cytotoxic T cell

Perforin

Granzymes

TCRCD8

Class I MHCmolecule

Targetcell

Peptideantigen

Pore

Released cytotoxic T cell

Dying target cell

Humoral Response, how?

• The B cell takes in a few foreign molecules and presents antigen fragments in its class II MHC to activated helper-T cells.

• The activated B cell then proliferates into a clone of plasma cells that will produce antibodies and a clone of memory B cells. (Some do not require T-cell binding or cytokines.)

Fig. 43-19

Antigen-presenting cell

Endoplasmicreticulum ofplasma cell

Secretedantibodymolecules

Bacterium

B cellPeptideantigen

Class II MHCmolecule

TCR CD4

Helper T cellActivatedhelper T cell

Cytokines

Clone of memoryB cells

Clone of plasma cells

2 µm

+

Humoral ImmunityT-Cell Dependent Antigens

Interaction of Antigen Presenting Cells and T-helper Cells

The cartoon illustrates how an antibacterial antigen-specific immune response is generated.

Microbes invade the body and are captured by dendritic cells (DCs, the ‘policemen’). The DC presents the antigen to the B and Th cells.

The B cells respond by “bombing” the microbes with antibodies.

Putting it all together…

http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter24/animation__the_immune_response.html

Fig. 43-16

Humoral (antibody-mediated) immune response

B cell

Plasma cells

Cell-mediated immune response

Key

Stimulates

Gives rise to

+

+

++

+

+

+Memory B cells

Antigen (1st exposure)

Engulfed by

Antigen-presenting cell

MemoryHelper T cells

Helper T cell Cytotoxic T cell

MemoryCytotoxic T cells

ActiveCytotoxic T cells

Antigen (2nd exposure)

Secretedantibodies

Defend against extracellular pathogens by binding to antigens,thereby neutralizing pathogens or making them better targetsfor phagocytes and complement proteins.

Defend against intracellular pathogensand cancer by binding to and lysing theinfected cells or cancer cells.

+

+ +

Types of Antibodies• Antibodies are proteins

that are made of light and heavy chains.

• There are 5 different antibodies: IgM, IgG, IgA, IgD, and IgE. IgG is the most abundant.

• IgE – antibodies involved in allergies

Respond toDifferentantigens

IgE Mediated Hypersensitivity

IgE Mediated Hypersensitivity

Antibodies label antigens for disposal by 1) Neutralization – blocking the ability of

a virus or bacterium to infect a host cell by binding to its surface

2) Opsonization – antibodies (opsonins) coat microbes for phagocytosis by macrophages

opsonization

3) Antigen-antibody complexes on microbes can activate the complement system and trigger a membrane attack complex (MAC).

Y’s and C’shaving a party!

Fig. 43-21

Viral neutralization

Virus

Opsonization

Bacterium

Macrophage

Activation of complement system and pore formation

Complement proteins

Formation ofmembraneattack complex

Flow of waterand ions

Pore

Foreigncell

Active and Passive immunity:

• Active – production of antibodies from exposure or from immunization

• Passive – temporary immunity by antibodies supplied from the placenta, mother’s milk, or antibody injection

Immune Rejection

• Blood Matching: Antibodies to blood group antigens can stimulate an immune response.

• A person will make antibodies to other blood antigens than its own.

You make antibodies against anyblood antigens you do not have.

• Transplanted tissue and organs are rejected due to foreign MHC molecules. The use of closely related donors and immune suppression drugs help to minimize rejection.

• In bone marrow transplants, the recipient’s bone marrow cells are destroyed by radiation, eliminating the recipient’s immune system.

• The lymphocytes in the bone marrow transplant may produce a graft versus host reaction to the host cells if the MHC

molecules are not

closely matched.

Immune System Disorders

• Allergies are hypersensitivities to certain environmental antigens, or allergens.

- IgE antibodies produced in an initial

exposure may bind to mast cells and cause a histamine response.

• Anaphylactic shock is a severe allergic response in which vasodilation leads to a life-threatening drop in blood pressure

Autoimmune disease – immune system turns against itself

• Ex - lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus, and multiple sclerosis.

rheumatoid arthritis

Lupus

Systemic lupus erythematosus (SLE) is a long-term autoimmune disorder that may affect the skin, joints, kidneys, brain, and other organs.

Multiple Sclerosis

• Multiple sclerosis (or MS) is a chronic, often disabling disease that attacks the central nervous system (CNS).

• Symptoms may be mild, such as numbness in the limbs, or severe, such as paralysis or loss of vision.

• The body’s own defense system attacks myelin, the fatty substance that surrounds and protects the nerve fibers in the central nervous system. The nerve fibers themselves can also be damaged.

• Immunodeficiency – may be developmental (genetic) or in response to a chemical, drugs, cancer, viruses (HIV).

• Severe combined immunodeficiency (SCID), is a genetic disorder in which both B cells and T cells) of the adaptive immune system are impaired due to a defect in one of several possible genes.

• Exercising to exhaustion and stress can impair the immune system.

How tricky are pathogens

• Antigenic variation – changing their surface epitopes to be unrecognizable

• Some viruses go into a latency period and “hide” from the immune cells

• AIDS does both of these.