Birgit Woelker, PhD

The Lymphatic and Immune Systems

Chapter 13 INNATE IMMUNITY: First Line of Defense: Skin and Mucous Membranes

Innate defenses are nonspecific.

Skin as a physical barrier, pH of skin, enzymes in tears and saliva, microbial traps formed by earwax and mucus, hair in nostrils, cilia in trachea, pH of stomach acid, antimicrobial proteins, phagocytic cells

INNATE IMMUNITY: Second line of defense: White Blood Cells, Inflammation, Defensive Proteins and Fever

Phagocytes (Macrophages and Neutrophils) are white blood cells that attack and ingest invaders

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Bacteria

This specific defense system constists of millions of white blood cells called lymphocytes.

Our immune system –  Responds to foreign molecules called

antigens •  The immune system reacts to antigens

–  And “remembers” an invader

ACQUIRED IMMUNITY: Third Line of Defense

The inflammatory response turns on nonspecific defense forces

Pin Skin surface

Bacteria

Chemical signals

White blood cell

1 Tissue injury; release of chemical signals such as histamine

2 Dilation and increased leakiness of local blood vessels; migration of phagocytes to the area

3 Phagocytes (macrophages and neutrophils) consume bacteria and cell debris; tissue heals

Swelling

Phagocytes and fluid move into area

Phagocytes

Blood vessel

INNATE IMMUNITY:

New viruses

Host cell 1 Makes interferon; is killed by virus

4 Host cell 2

Protected against virus by interferon from cell 1

•  Interferons are proteins produced by virus-infected cells

–  That help other cells resist viruses

2 Interferon genes turned on

mRNA

3

Interferon molecules

DNA

1

Viral nucleic acid Antiviral proteins block viral reproduction

Interferon stimulates cell to turn on genes for antiviral proteins

5

INNATE IMMUNITY:

The lymphatic system becomes a crucial battleground during infection •  The lymphatic system

–  Is a network of lymphatic vessels and organs Adenoid

Tonsil

Lymph nodes

Right lymphatic duct, entering vein

Thymus

Appendix

Thoracic duct

Bone marrow

Lymphatic vessels

Spleen

Thoracic duct, entering vein

Lymph node

Masses of lymphocytes and macrophages

Valve

Lymphatic vessel

Blood capillary

Tissue cells

Interstitial fluid

Lymphatic capillary

b. Antibodies (IgG, IgA) are secreted into breast milk.

•  We can temporarily acquire passive immunity by receiving “premade” antibodies

ACQUIRED IMMUNITY:

a. Antibodies (IgG) cross the placenta.

Age (months)

Pneumococcal

2–18

2–18

2, 4, 6, 12–15 2, 4, 6–18 4–6

4–6

Suggested Immunization Schedule

Vaccine Age (years)

Hepatitis B Diphtheria, tetanus,

pertussis (DTP) Tetanus only

Haemophilus influenzae, type b Polio (IPV)

Measles, mumps, rubella (MMR)

Varicella (chicken pox)

Hepatitis A (in selected areas)

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

Birth, 1–2, 6– 18 2, 4, 6, 15– 18

11–12, 13– 18

2, 4, 6, 12–15

12– 15 4–6 , 11–12

12– 18

12– 18

11–12 –

•  Infection or vaccination triggers active immunity Two types of Lymphocytes are produced when an antigen is present

–  B cells secrete antibodies that attack antigens –  T cells attack cells infected with pathogens

Bone marrow Thymus

Stem cell

Immature lymphocyte

B cell Humoral immunity

Via blood

Antigen receptors

Via blood

T cell Cell-mediated immunity

Lymph nodes, spleen, and other lymphatic organs

Final maturation of B and T cells in lymphatic organ

Other parts of the lymphatic system

Antigens have specific regions where antibodies bind to them

•  Antigenic determinants

–  Are the specific regions on an antigen to which antibodies bind

Antibody A molecules

Antigen-binding sites

Antigen molecule

Antigenic determinants

Antibody B molecule

•  Millions of kinds of B cells and T cells, each with different membrane receptors

–  Wait in the lymphatic system, where they may respond to invaders

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Self Versus Nonself

Lymphocytes (B cells and T cells) are tested for potential self-reactivity. If their receptor binds to a self-testing cell, they will be destroyed.

Thus, there are no mature lymphocytes that react against self-proteins

Autoimmune diseases like Multiple Sclerosis or Type I diabetes occur when the self- testing fails.

Clonal Selection in B- Cells

Primary immune response

B cells with different response

Cell activation: growth, division, and differentiation

Antibody molecules

Plasma (effector) cells secreting antibodies

Endoplasmic reticulum

Clone of memory cells

Antigen receptor (antibody on cell surface)

Antigen molecules

2

First exposure antigen

3

4

1

5

5

Antigen molecules

6 Second exposure to same antigen

Antibody molecules

Endoplasmic reticulum

Plasma (effector) cells secreting antibodies Clone of memory cells

Secondary immune response

Primary Response

Secondary Response

Primary vs. Secondary Immune Response •  The primary immune response is slower than the

secondary immune response

Time (days)

Second exposure to antigen X

First exposure to antigen X

Secondary immune response to

antigen X

Primary immune response to antigen X

Antibodies to X

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Primary vs. Secondary Immune Response •  The primary immune response is slower than the

secondary immune response

Time (days)

Second exposure to antigen X,

first exposure to antigen Y

First exposure to antigen X

Secondary immune response to antigen X

Primary immune response to

antigen Y

Primary immune response to

antigen X

Antibodies to X

Antibodies to Y

Ant

ibod

y co

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ion

56 49 42 35 28 21 14 7 0

Antibodies are the weapons of humoral immunity •  Antibody molecules

–  Are secreted by plasma (effector) B cells

Figure 24.8A

C C

C = constant V = variable

heavy chain

light chain

antigen binds to binding site

antigen-binding sites

shape of antigen fits shape of binding site

antigen

tic

Antibody Structure

Binding of antibodies to antigens inactivates antigens by

Neutralization (blocks viral binding sites;

coats bacteria) Agglutination of microbes

Precipitation of dissolved antigens

Activation of Complement system

Cell Iysis Phagocytosis

Virus

Bacterium

Bacteria

Antigen molecules

Complement molecule

Foreign cell Hole

Macrophage

Enhances Leads to

Antibodies mark antigens for elimination •  Antibodies promote antigen elimination

–  Through several mechanisms

Monoclonal antibodies are powerful tools in the lab and clinic

Antigen injected into mouse Tumor cells grown in culture

B cells (from spleen) Tumor cells

Cells fused to generate hybrid cells

Single hybrid cell grown in culture

Antibody

Hybrid cell culture, producing monoclonal antibodies

Monoclonal antibodies are produced by fusing B cells specific for a single antigenic determinant with easy to grow tumor cells

Helper T cells stimulate humoral and cell-mediated immunity

•  Helper T cells and cytotoxic T cells

–  Are the main effectors of cell-mediated immunity

•  Helper T cells

–  Also stimulate the humoral responses

•  The activation of a helper T cell and its roles in immunity

Microbe Macrophage

Antigen from microbe (nonself molecule)

1

Self protein

2 3

4

5 6

7

Antigen-presenting cell

Interleukin-1 stimulates helper T cell

Helper T cell

Interleukin-2 stimulates cell division

Interleukin-2 activates other B cells and T cells

Humoral Immunity (secretion of antibodies by plasma cells)

Cytotoxic T cell

Cell-mediated immunity (attack on infected cells)

Binding site for antigen

Binding site for self protein

B cell Self-nonself complex T cell

receptor

HIV destroys helper T cells, compromising the body’s defenses

•  The AIDS virus attacks helper T Cells

–  Opening the way for opportunistic infection

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•  HIV, the virus that causes AIDS, attacks T- helper cells and eventually destroys the body’s ability to fight infection

3 Infected cell is destroyed

1 Cytotoxic T cell binds to infected cell

2 Perforin makes holes in infected cell’s membrane and enzyme enters Self-nonself

complex

Infected cell

Cytotoxic T cell

Perforin molecule

Foreign antigen

Enzyme that can promote apoptosis

Hole forming

Cytotoxic T cells destroy infected body cells

•  Cytotoxic T cells

–  Bind to infected body cells and destroy them

Cytotoxic T cells may help prevent cancer

•  Cytotoxic T cells may attack cancer cells

–  Which have abnormal surface molecules

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The immune system depends on our molecular fingerprints

•  The immune system

–  Normally reacts only against nonself substances, not against self

–  May reject transplanted organs because these cells lack the unique “fingerprint” of the recipient’s self proteins

DISORDERS OF THE IMMUNE SYSTEM CONNECTION Malfunction or failure of the immune system causes disease

•  In autoimmune diseases

–  The system turns against the body’s own molecules

•  In immunodeficiency diseases

–  Immune components are lacking, and frequent infections recur

•  Physical and emotional stress

–  May weaken the immune system

Allergies are overreactions to certain environmental antigens

•  Allergies

–  Are abnormal sensitivities to antigens (allergens) in the surroundings

•  The two stages of an allergic reaction

B cell (plasma cell)

Antigenic determinant

1 Allergen (pollen grain) enters blood stream

2 B cells make antibodies

3 Antibodies attach to mast cell

Sensitization: Initial exposure to allergen

Mast cell

Histamine

4 Allergen binds to antibodies on mast cell

5 Histamine is released, causing allergy symptoms

Later exposure to same allergen

An Allergy is a immune response without a pathogen present

Movies

Stress hormones and immunity http://p2048-ezproxy.ncc.edu.ncc.idm.oclc.org/login?url=http://digital.films.com

Films on Demand: Seriously stressed: Stress hormones and the immune system