Immunology Chapter 43. Immune System A wide variety of pathogens (including parasites) think that animal hosts are excellent habitats and very tasty To.

Immunology

Chapter 43

Immune System

• A wide variety of pathogens (including parasites) think that animal hosts are excellent habitats and very tasty

• To stop from becoming a bacterial hotel, animals have ways to fight back

• Most critical component – know self from non-self cells and tissues

• Next, know how to kill the invaders without harming yourself

Two main components of vertebrate immune response:

Why is the innate immune response critical ?Time!

Innate Immunity - External

• Skin– Barrier, oil glands and sweat modify pH, salt level

• Mucous Membranes– Barrier, mucous traps and cilia removes particles

• Secretions– Stomach acid, lysozyme

Innate Immunity – Internal

• Phagocytic cells– Recognize non-self– Phagocytosis – engulf invader– Digest and display

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Figure 43.4 Phagocytosis

Microbes

MACROPHAGE

Vacuole Lysosomecontainingenzymes

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2

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6

Pseudopodiasurroundmicrobes.

Microbesare engulfedinto cell.

Vacuolecontainingmicrobesforms.

Vacuoleand lysosomefuse.

Toxiccompoundsand lysosomalenzymesdestroy microbes.

Microbialdebris isreleased byexocytosis.

Innate Immunity – Internal

• Phagocytic cells– Recognize non-self– Phagocytosis – engulf invader– Digest and display

• Antimicrobial proteins– Defensins, etc. - lysis of bacterial walls– Complement – lysis by cascade

The Defensins and cathelicidins

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Jan, 2001. The Defensins and cathelicidins [online]. Seacroft and St James's University Hospitals, UK. Available from http://www.cysticfibrosismedicine.comAnti microbial peptides called defensins and cathelicidins are innate immune factors present in airway surface liquid and make up part of the lung's natural defences (Bals et al, 1998; Bals et al, 1998; Singh et al, 1998). These peptides are produced by several different cell types including airway epithelial cells, macrophages and neutrophils. The defensins appear to be present in equivalent or higher concentrations in cystic fibrosis lungs as compared to controls. In cystic fibrosis their ability to kill bacteria may be impaired by the presence of abnormally high sodium concentrations within airway surface fluids (Bals et al, 1998; Bals et al, 1998, Goldman et al, 1998). Cathelicidin peptides also appear to have a wide range of antimicrobial activity although they may be under expressed in cystic fibrosis airways. The development of topically administered antimicrobial peptides may have a future role in the treatment of cystic fibrosis.

Innate Immunity – Internal

• Phagocytic cells– Recognize non-self– Phagocytosis – engulf invader– Digest and display

• Antimicrobial proteins– Defensins, etc. lysis of bacterial walls– Complement – lysis by cascade

• Inflammatory response– Injury causes release of signals (eg. Histamines) which increase

blood flow to site– Causes heat and swelling

Chemical signals released by mac’s and mast cells

Capillaries get leaky, agents move from blood to site

Chemokines released, attract more cells

Neutrophils and Mac’s eat em’ up

Innate Immunity – Internal

• Natural killer cells– Recognize and attack infected cells or cancer cells – Surface receptors recognize foreign antigens on self

cell– NK attach and kill target cell (apoptosis)

• Invertebrate Immunity– Only innate but still complex– Has recognition factors and antibacterials

Two main components of vertebrate immune response:

Acquired Immunity

• Lymphocyte– White blood cell that recognizes specific component

(usually protein) of an invader• Antigen

– Any foreign component that can elicit an immune response

• T cells– Develop in thymus, recognize antigens by specific

receptor (T cell receptor)• B cells

– Develop in bone marrow, recognize antigen by specific receptor (B cell receptor)

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Figure 43.7 Epitopes (antigenic determinants)

Antigen-binding sites

Antibody A

Antigen

Antibody BAntibody C

Epitopes(antigenicdeterminants)

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Figure 43.5 The human lymphatic system

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Interstitial fluid bathing the tissues, along with the white blood cells in it, continually enters lymphatic capillaries.

Fluid inside thelymphatic capillaries,called lymph, flowsthrough lymphaticvessels throughoutthe body.

Within lymph nodes,microbes and foreignparticles present in the circulating lymphencounter macro-phages, dendritic cells, and lymphocytes, which carry out various defensive actions.

Lymphatic vesselsreturn lymph to the blood via two large

ducts that drain into veins near the

shoulders.

Adenoid

Tonsil

Lymphnodes

Spleen

Peyer’s patches(small intestine)

Appendix

Lymphaticvessels

Lymphnode

Masses oflymphocytes andmacrophages

Tissuecells

Lymphaticvessel

Bloodcapillary

Lymphaticcapillary

Interstitialfluid

Specificity –what does he mean by that?

• Do T cells and B cells have specific receptors?

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Figure 43.8 Antigen receptors on lymphocytes

Antigen-bindingsite

Antigen-binding siteDisulfide

bridge

Lightchain

Antigen-bindingsite

Heavy chains

Cytoplasm of B cell

chain

Disulfide bridge chain

V

VC

C CC

VV

V V

C C

T cell

A T cell receptor consists of one chain and one 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)

Variableregions

Constantregions

Transmembraneregion

Plasmamembrane

B cell Cytoplasm of T cell

Specificity –what does he mean by that?

• Do T cells and B cells have specific receptors?– They have different types of receptors– Each cell’s receptors recognize only one

antigen– Your lymphocytes can recognize thousands of

antigens, only one antigen/clone• There are many of each clone in your bloodstream

or lymph nodes

Humoral Immunity

• Antigen presenting cell contacts and activates helper T cells

• Cytokines (protein signals) released– Eg. interleukins

• B and T cells activated

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Figure 43.15 The central role of helper T cells in humoral and cell-mediated immune responses

After a dendritic cell engulfs and degrades a bacterium, it displays bacterial antigen fragments (peptides) complexed with a class II MHC molecule on the cell surface. A specific helper T cell bindsto the displayed complex via its TCR with the aid of CD4. This interaction promotes secretion of cytokines by the dendritic cell.

Proliferation of the T cell, stimulatedby cytokines from both the dendriticcell and the T cell itself, gives rise toa clone of activated helper T cells(not shown), all with receptors for thesame MHC–antigen complex.

The cells in this clonesecrete other cytokines that help activate B cellsand cytotoxic T cells.

Cell-mediatedimmunity(attack on

infected cells)

Humoralimmunity

(secretion ofantibodies byplasma cells)

Dendriticcell

Dendriticcell

Bacterium

Peptide antigenClass II MHC

molecule

TCR

CD4

Helper T cell

Cytokines

Cytotoxic T cell

B cell

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2 3

1

2 3

Humoral Immunity

• Antigen presenting cells contacts and activates helper T cells

• Cytokines (protein signals) released• B and T cells activated

– Cell binding produces greater response

Humoral Immunity

• Antigen presenting cells contacts and activates helper T cells

• Cytokines (protein signals) released• B and T cells activated

– Cell binding produces greater response• B cells divide (clones)• B-cells release antibody (Plasma cells)• Memory cells saved for later

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3

B cell

Bacterium

Peptide antigen

Class II MHCmolecule

TCR

Helper T cell

CD4

Activated helper T cell Clone of memory

B cells

Cytokines

Clone of plasma cellsSecreted antibodymolecules

Endoplasmicreticulum of plasma cell

Macrophage

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Figure 43.13 The specificity of immunological memory

Antibodiesto A

Antibodiesto B

Ant

ibod

y co

ncen

trat

ion

(arb

itrar

y u

nits

)

104

103

102

101

100

0 7 14 21 28 35 42 49 56Time (days)

Day 1: First exposure toantigen A

1

Primaryresponse toantigen Aproduces anti-bodies to A

2 Day 28: Second exposureto antigen A; firstexposure to antigen B

3

Secondary response to anti-gen A produces antibodiesto A; primary response to anti-gen B produces antibodies to B

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Cell-mediated Immunity

• Cytotoxic T cells recognize infected self cells

• Bind to cell and initiate apoptosis (process of cell self-destruction)

Cytotoxic T cell

Perforin

Granzymes

CD8TCRClass I MHCmolecule

Targetcell Peptide

antigen

Pore

ReleasedcytotoxicT cell

Apoptotictarget cell

Cancercell

CytotoxicT cell

A specific cytotoxic T cell binds to a class I MHC–antigen 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 pores in the target cell membrane, and proteolytic enzymes (granzymes), which enter the target cell by endocytosis.

2 The granzymes initiate apoptosis within the target cells, leading to fragmentation of thenucleus, release of small apoptotic bodies, and eventual cell death. The released cytotoxic T cell can attack other target cells.

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2

3

Antibodies

• Soluble proteins that recognize antigens on invaders

• Found in blood, mucus, and mother’s milk

• Antibody binding neutralizes invaders or activates immune response

Immunity

• Active Immunity– Produced by contact with an infectious agent– Can be natural (poked with a stick) or artificial

(stuck with a needle - vaccination)– See Jenner, milkmaids, and cowpox

• Passive Immunity– Transfer of serum from survivor to you– Eg. Mother’s milk, snake anti-venom

Acquired Immunodeficiency Syndrome (AIDS)

• Human immunodeficiency virus (HIV) infects and kills helper T cells

Acquired Immunodeficiency Syndrome (AIDS)

• Human immunodeficiency virus (HIV) infects and kills helper T cells

• HIV is an RNA virus, it mutates rapidly

• Once in your cells it incorporates into your DNA

• Transmission requires someone’s body fluid getting into you

Herpes virus – fast growth, bursts cell quickly

AIDS Virus – Slow growth, maximum virus production