Chapter 43: The Immune System 1.What is the difference between non-specific & specific immunity….aka innate & acquired immunity? INNATE IMMUNITY Rapid

Chapter 43: The Immune System

1. What is the difference between non-specific & specific immunity….aka innate & acquired immunity?

INNATE IMMUNITY Rapid responses to a

broad range of microbes

ACQUIRED IMMUNITYSlower 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(cytotoxic lymphocytes)

Invadingmicrobes

(pathogens)

Phagocytic cells include:-Neutrophils-Monocytes/macrophages-Eosinophils-Dendritic cells

Figure 43.4 Phagocytosis

Microbes

MACROPHAGE

Vacuole Lysosomecontainingenzymes

1

2

3

4

5

6

Pseudopodiasurroundmicrobes.

Microbesare engulfedinto cell.

Vacuolecontainingmicrobesforms.

Vacuoleand lysosomefuse.

Toxiccompoundsand lysosomalenzymesdestroy microbes.

Microbialdebris isreleased byexocytosis.

Microbial debris can either be released or presented for immune system to “see.”






specific microbes


Skin

Mucous membranes

Secretions

Phagocytic cells






Invadingmicrobes

(pathogens)


Antimicrobial proteins include:- Lysozyme- Complement system- Interferons

Pathogen Pin

Macrophage

Chemical signals

CapillaryPhagocytic cells

Red blood cell

Bloodclottingelements

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 bloodto the injury site.

3 Neutrophils and macrophagesphagocytose pathogens and cell debris at the site, and the tissue heals.

4

Figure 43.6 Major events in the local inflammatory response

Chemicals released:- Histamine – causes dilation & increased permeability of capillaries- Prostaglandins – increase blood flow to deliver clotting elements

thrombin, fibrin, etc.






specific microbes


Skin

Mucous membranes

Secretions

Phagocytic cells






Invadingmicrobes

(pathogens)


Antimicrobial proteins include:- Lysozme- Complement system- Interferons




2. Where do these phagocytic cells reside?- Lymphatic system – most- Tissues & organs – macrophages

Figure 43.5 The human lymphatic system

1

2

3

4

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



2. Where do these phagocytic cells reside?- Lymphatic system – most- Tissues & organs – macrophages

3. How does the body mount a specific/acquired immune response?- B cells – humoral response- T cells – cell-mediated response- For both, the cells recognize specific shapes




specific microbes


Skin

Mucous membranes

Secretions

Phagocytic cells






Invadingmicrobes

(pathogens)

Figure 43.7 Epitopes (antigenic determinants)

Antigen-binding sites

Antibody A

Antigen

Antibody BAntibody C

Epitopes(antigenicdeterminants)

Antigen – any foreign molecule recognized by the body – antibody generatorEpitope – specific shape recognized by an immune cellsBoth B cells & T cells have receptors that must be complementary to the epitope

Info for you-Test Tuesday, 2/14-Labs – Thurs, Fri, Mon-Pre-labs – Thurs & Fri-Bring essays tomorrow -CC Registration Open House – Thurs, 2/9: 6:30 – 8:30



2. Where do these phagocytic cells reside?3. How does the body mount a specific/acquired immune response?4. How are the B cell & T cell receptors similar?

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

- Constant regions embedded in membrane- Variable regions that bind to epitopes (vary)- Quarternary proteins- B cells – 2 heavy & 2 light chains

- “Y”T cells – α and β chains

- “I”



2. Where do these phagocytic cells reside?3. How does the body mount a specific/acquired immune response?4. How are the B cell & T cell receptors similar?5. How do T cell receptors recognize antigens?

Figure 43.9 The interaction of T cells with MHC moleculesInfected cell

Antigenfragment

Class I MHCmolecule

T cellreceptor

Cytotoxic T cell(a)

MicrobeAntigen-presentingcell

Antigenfragment

Class II MHCmolecule

T cellreceptor

Helper T cell

(b)

11

22

The combination ofMHC molecule andantigen is recognizedby a T cell, alerting itto the infection.

A fragment offoreign protein(antigen) inside thecell associates withan MHC moleculeand is transportedto the cell surface.

1

2

- Class I MHC molecule of an infected cell- MHC usually empty but now filled - TC recognizes filled MHC & tries to form

complementary receptor

- Class II MHC of a phagocytic cell - Antigen-presenting cell (APC)



2. Where do these phagocytic cells reside?3. How does the body mount a specific/acquired immune response?4. How are the B cell & T cell receptors similar?5. How do T cell receptors recognize antigens?6. How does our body recognize “self” from “non-self?”

- MHC – Major Histocompatibility Complex - Cell markers that must be compatible for organ & tissue donations

7. How do B cells & T cells get their name?- Where they mature- B cells – bone- T cells – thymus

Figure 43.10 Overview of lymphocyte development

Bone marrow

Lymphoidstem cell

B cell

Thymus

T cell

Blood, lymph, and lymphoid tissues(lymph nodes, spleen, and others)



2. Where do these phagocytic cells reside?3. How does the body mount a specific/acquired immune response?4. How are the B cell & T cell receptors similar?5. How do T cell receptors recognize antigens?6. How does our body recognize “self” from “non-self?”7. How do B cells & T cells get their name?8. How is the variable region of a receptor formed?

- Gene rearrangement aka activation- NOT ALL CELLS IN OUR BODY HAVE THE SAME DNA

Figure 43.11 Immunoglobulin gene rearrangementDNA ofundifferentiatedB cell

DNA of differentiatedB cell

pre-mRNA

mRNA Cap

Transcription of resulting permanently rearranged,functional gene

RNA processing (removal of intron; addition of capand poly (A) tail)

B cell

B cell receptorLight-chain polypeptide

Intron

Intron

Intron

Variableregion

Constantregion

V1 V2 V3

V4–V39

V40 J1 J2 J3 J4 J5

V1 V2 V3 J5

V3 J5

V3 J5

V C

C

C

C

C

2

3

4 Translation

Poly (A)

Deletion of DNA between a V segmentand J segment and joining of the segments

1

- All variable regions do gene rearrangement – heavy & light (B), α and β (T)- Analogous to alternative mRNA splicing but DNA is completely deleted- Self-reactive receptors are eliminated



2. Where do these phagocytic cells reside?3. How does the body mount a specific/acquired immune response?4. How are the B cell & T cell receptors similar?5. How do T cell receptors recognize antigens?6. How does our body recognize “self” from “non-self?”7. How do B cells & T cells get their name?8. How is the variable region of a receptor formed?9. What happens after a receptor binds to an antigen?

- Clonal selection

Figure 43.12 Clonal selection of B cells

Antigen molecules

Antigenreceptor

B cells thatdiffer inantigenspecificity

Antibodymolecules

Clone of memory cells Clone of plasma cells

Some proliferating cellsdevelop into long-livedmemory cells that canrespond rapidly uponsubsequent exposureto the same antigen.

Antigen moleculesbind to the antigenreceptors of only oneof the three B cellsshown.

The selected B cellproliferates, forminga clone of identicalcells bearingreceptors for theselecting antigen.

Some proliferatingcells develop intoshort-lived plasmacells that secreteantibodies specificfor the antigen.

- T cells also go through clonal selection- T receptors not released like Ab from B cells- Note the ER in plasma/effector cells – secreting cell

Future infections Current infection



2. Where do these phagocytic cells reside?3. How does the body mount a specific/acquired immune response?4. How are the B cell & T cell receptors similar?5. How do T cell receptors recognize antigens?6. How does our body recognize “self” from “non-self?”7. How do B cells & T cells get their name?8. How is the variable region of a receptor formed?9. What happens after a receptor binds to an antigen?10. What is the difference between a primary & secondary immune response?

Figure 43.13 The specificity of immunological memory

Antibodiesto A

Antibodiesto B

Ant

ibod

y co

ncen

trat

ion

(arb

itrar

y un

its)

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

4



2. Where do these phagocytic cells reside?3. How does the body mount a specific/acquired immune response?4. How are the B cell & T cell receptors similar?5. How do T cell receptors recognize antigens?6. How does our body recognize “self” from “non-self?”7. How do B cells & T cells get their name?8. How is the variable region of a receptor formed?9. What happens after a receptor binds to an antigen?10. What is the difference between a primary & secondary immune response?11. Let’s consider the immune response….

Figure 43.14 An overview of the acquired immune response - TH

Humoral immune response Cell-mediated immune response

First exposure to antigen

Antigens engulfed and displayed by dendritic cells

Activate

Gives rise to

HelperT cell

Active and memory helperT cells

(Clonal selection)

(Gene rearrangement)

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 binds to 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 dendritic cell 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

1

2 3

1

2 3

- CD4 on T cell keeps APC bound to T cell during gene rearrangement- Cytokines from APC stimulate TH to secrete its own cytokines- TH cytokines exert (+) feedback on TH & stimulate TC & B cells

Figure 43.14 An overview of the acquired immune response - TC



Antigens engulfed and displayed by dendritic cells

Antigens displayedby infected cells

Activate Activate

Gives rise to Gives rise to

HelperT cell

CytotoxicT cell


Memory cytotoxic

T cells

Active cytotoxic

T cells

Defend against infected cells, cancer cells, and transplanted tissues

Secretedcytokinesactivate

(Clonal selection)


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.

3

1

2

3

Figure 43.16 The killing action of cytotoxic T cells

- CD8 on T cell keeps infected cell bound to T cell during gene rearrangement- Granzymes released from TC digest a hole and allow perforins to create a pore- Infected cell commits suicide (apoptosis)

Fig. 43.14 An overview of the acquired immune response – B cells



Intact antigensAntigens engulfed and

displayed by dendritic cellsAntigens displayed

by infected cells

Activate Activate Activate

Gives rise to Gives rise to Gives rise to

B cell HelperT cell

CytotoxicT cell

Plasmacells

MemoryB cells


Memory cytotoxic

T cells

Active cytotoxic

T cells

Secrete antibodies that defend againstpathogens and toxins in extracellular fluid

Defend against infected cells, cancer cells, and transplanted tissues

Secretedcytokinesactivate

(Clonal selection)


Pathogens in fluid Infected cells

Figure 43.17 Humoral immune response

21

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



2. Where do these phagocytic cells reside?3. How does the body mount a specific/acquired immune response?4. How are the B cell & T cell receptors similar?5. How do T cell receptors recognize antigens?6. How does our body recognize “self” from “non-self?”7. How do B cells & T cells get their name?8. How is the variable region of a receptor formed?9. What happens after a receptor binds to an antigen?10. What is the difference between a primary & secondary immune response?11. Let’s consider the immune response….12. What are the 5 classes of antibodies?

- GAMED

Figure 43.18 The five classes of immunoglobulinsFirst Ig class produced after initial exposure to antigen; then its concentration in the blood declines

Promotes neutralization and agglutination of antigens; very effective in complement activation (see Figure 43.19)

Most abundant Ig class in blood; also present in tissue fluids

Only 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

Provides localized defense of mucous membranes byagglutination and neutralization of antigens (seeFigure 43.19)

Presence in breast milk confers passive immunity onnursing infant

Triggers release from mast cells and basophils of histamine and other chemicals that cause allergic reactions (see Figure 43.20)

Present primarily on surface of naive B cells that havenot been exposed to antigens

Acts as antigen receptor in antigen-stimulated proliferation and differentiation of B cells (clonal selection)

IgM(pentamer)

IgG(monomer)

IgA(dimer)

IgE(monomer)

J chain

Secretorycomponent

J chain

Transmembraneregion

IgD(monomer)



2. Where do these phagocytic cells reside?3. How does the body mount a specific/acquired immune response?4. How are the B cell & T cell receptors similar?5. How do T cell receptors recognize antigens?6. How does our body recognize “self” from “non-self?”7. How do B cells & T cells get their name?8. How is the variable region of a receptor formed?9. What happens after a receptor binds to an antigen?10. What is the difference between a primary & secondary immune response?11. Let’s consider the immune response….12. What are the 5 classes of antibodies?13. How are antigens removed?

Figure 43.19 Antibody-mediated mechanisms of antigen disposalBinding of antibodies to antigens

inactivates antigens by

Viral neutralization(blocks binding to host)

and opsonization (increasesphagocytosis)

Agglutination ofantigen-bearing particles,

such as microbes

Precipitation ofsoluble antigens

Activation of complement systemand pore formation

Bacterium

Virus Bacteria

Solubleantigens Foreign cell

Complementproteins

MAC

Pore

Enhances

Phagocytosis

Leads to

Cell lysis

Macrophage

MAC – membrane attack complex

Chapter 43: The Immune System1. What is the difference between non-specific & specific immunity….aka

innate & acquired immunity?2. Where do these phagocytic cells reside?3. How does the body mount a specific/acquired immune response?4. How are the B cell & T cell receptors similar?5. How do T cell receptors recognize antigens?6. How does our body recognize “self” from “non-self?”7. How do B cells & T cells get their name?8. How is the variable region of a receptor formed?9. What happens after a receptor binds to an antigen?10. What is the difference between a primary & secondary immune response?11. Let’s consider the immune response….12. What are the 5 classes of antibodies?13. How are antigens removed?14. What is the difference between passive & active immunity?

- Passive – transfer of antibodies – breastfeeding, injection (rabies)- Active – body creates its own antibodies during an infection – vaccine

15. What needs to match for blood transfusions?- Type – A, B, AB or O- Rh factor- Pregnancy issues – Rh- mom with prior Rh+ fetus having another Rh+

Based on Glycoproteins on RBC surface

Table 43.1 Blood Groups That Can and Cannot Be Safely Combined in Transfusion

Type O- : Universal donorType AB+ : Universal recipient


innate & acquired immunity?2. Where do these phagocytic cells reside?3. How does the body mount a specific/acquired immune response?4. How are the B cell & T cell receptors similar?5. How do T cell receptors recognize antigens?6. How does our body recognize “self” from “non-self?”7. How do B cells & T cells get their name?8. How is the variable region of a receptor formed?9. What happens after a receptor binds to an antigen?10. What is the difference between a primary & secondary immune response?11. Let’s consider the immune response….12. What are the 5 classes of antibodies?13. How are antigens removed?14. What is the difference between passive & active immunity?15. What needs to match for blood transfusions?16. What needs to match for organ transplants?

- MHC17. What happens with an allergic response?

Figure 43.20 Mast cells, IgE, and the allergic response

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 allergysymptoms.

3

1

2

3

Allergen

IgE

Histamine

GranuleMast cell

- Allergies are hypersensitivities to allergens- Anaphylactic shock – widespread mast cell degranulation causes abrupt

dilation of peripheral capillaries & quick drop in BP


innate & acquired immunity?2. Where do these phagocytic cells reside?3. How does the body mount a specific/acquired immune response?4. How are the B cell & T cell receptors similar?5. How do T cell receptors recognize antigens?6. How does our body recognize “self” from “non-self?”7. How do B cells & T cells get their name?8. How is the variable region of a receptor formed?9. What happens after a receptor binds to an antigen?10. What is the difference between a primary & secondary immune response?11. Let’s consider the immune response….12. What are the 5 classes of antibodies?13. How are antigens removed?14. What is the difference between passive & active immunity?15. What needs to match for blood transfusions?16. What needs to match for organ transplants?17. What happens with an allergic response?18. What are some autoimmune diseases?

- Lupus- Rheumatoid arthritis

- Insulin-dependent diabetes- MS – multiple sclerosis


innate & acquired immunity?2. Where do these phagocytic cells reside?3. How does the body mount a specific/acquired immune response?4. How are the B cell & T cell receptors similar?5. How do T cell receptors recognize antigens?6. How does our body recognize “self” from “non-self?”7. How do B cells & T cells get their name?8. How is the variable region of a receptor formed?9. What happens after a receptor binds to an antigen?10. What is the difference between a primary & secondary immune response?11. Let’s consider the immune response….12. What are the 5 classes of antibodies?13. How are antigens removed?14. What is the difference between passive & active immunity?15. What needs to match for blood transfusions?16. What needs to match for organ transplants?17. What happens with an allergic response?18. What are some autoimmune diseases?19. What happens with AIDS?

- Acquired Immune Deficiency Syndrome

Documents

Chapter 43: The Immune System 1.What is the difference between non-specific & specific immunity….aka innate & acquired immunity? INNATE IMMUNITY Rapid