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The Immune System (text p292-299)

The Lymphatic System

Modus Operandi Dock with receptors on target cell surface Insert viral DNA or RNA into host cell Use host cell machinery to replicate Lyse host cell and spread to nearby cells

Examples: smallpox, chickenpox, polio, influenza, HIV

Technically…viruses are not really alive.

Public Enemy #1 The Viruses

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Public Enemy #2 Bacteria

•  Modus operandi - Set up shop in tissues but remain

EXTERNAL to cells - Reproduce rapidly - Secrete exotoxins or contain

endotoxins as part of cell wall

•  Examples: Escherichia coli, Clostridium botulinum, Salmonella

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Public Enemy #3 Fungi

• Modus Operandi Similar to bacteria-

reproduce rapidly

Damage cells directly or indirectly by secreting enzymes

• Examples: Athlete’s Foot, Pneumocystis carinii (fungal pneumonia)

•  Herpes virus

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•  HIV infection

The Immune System is a Defence System: (fill-in-the-blank notes)

It protects the body from disease-causing invaders. It removes dead or damaged tissue and cells. It recognizes and removes abnormal cells.

The defences can be divided into three groups: A) First Line of Defence

- blocks entry of foreign agents into the body B) Second Line of Defence

- general or non-specific defenses against pathogens C) Third Line of Defence

- cell-mediated immunity (T cells) - cellular response - antibody-mediated immunity (B cells) - humoral response

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Humoral Cellular

Nonspecific

Humoral Cellular

Specific

macrophages, neutrophils

Histamines, interferon,

complement

T cells; other effector cells

B cells; antibodies

3rd Line 2nd Line

A) First Line of Defence - Physical and Chemical barriers (General defences) (text p293)

•  skin (largest barrier) - secretes oil that is acidic - kills bacteria - the surface is dry and pathogens are unable to enter

•  eyelashes •  tears & saliva secrete enzymes that breakdown bacterial walls

•  nose and respiratory tract - lined with cilia that sweep mucus and trapped particles into throat to be swallowed

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Food particle

Pyloric sphincter

STOMACH

Gastric juice

Interior surface of stomach

Gastric gland

Pits Gastric juice (mucus, HCI, and pepsinogen)

Epithelium

Chief cells

Pariental cells

Pepsinogen

1

2

3

HCI

Pepsin (active enzyme) Mucous

cells

•  stomach has acid pH that kills bacteria •  bacteria in the intestine prevent the development of

pathogens

B) Second Line of Defence - Non-Specific Defences

1. Chemical Barriers (Non-specific humoral response) i) Histamine and the Inflammatory Response

•  tissue damage triggers the inflammatory response (diagram)

•  non-phagocytic leucocytes release histamine

•  causes capillaries to dilate & become more permeable to fluid and leucocytes –  increases blood delivery to injured area

Pin Skin surface

Bacteria

Chemical signals

White blood cell

Swelling

Phagocytes and fluid move into area

Phagocytes

Tissue injury; release of chemical signals such as histamine

1 2 Dilation and increased leakiness of local blood vessels; migration of phagocytes to the area

3 Phagocytes consume bacteria and cell debris; tissue heals

Results in:

heat/fever - unfavorable to microorganisms

- mobilizes WBC - phagocytosis

- raises metabolic rate of surrounding cells

swelling/ redness - stimulates free nerve endings, pain

Tissue injury; release of chemical signals such as histamine

1 2 3 Dilation and increased leakiness of local blood vessels; migration of phagocytes to the area

Phagocytes consume bacteria and cell debris; tissue heals

Pin Skin surface

Bacteria

Chemical signals

White blood cell

Swelling

Phagocytes and fluid move into area

Phagocytes

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Animation showing interferon blocking viral replication.

ii) Anti-microbial chemicals

Interferons:

- “chemical scouts” alert other cells to the presence of invaders and interferes with viral replication

Interleukins:

-  causes fever high temp kills some infecting pathogens

iii) Complement Proteins:

- chemical defense system that kills bacteria - form pores in bacteria cell -  disrupts control of ion balance cells swell & burst -  cellular debris removed by phagocytes

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2. Cell-Mediated Immunity (Non-Specific Cellular Response) - Phagocytic WBC (text p293)

- neutrophils and monocytes, engulf bacteria and viruses

-  they “eat” any bacteria and virus-infected cells they encounter

-  Macrophages which develop from monocytes, also use phagocytosis - found in liver, spleen, brain and lungs and circulate in blood and interstitial fluid

Attachment

Phagocytosis of Bacteria

Ingestion

Fusion with lysosome

Digestion

Release of digestion products from the cell

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Bacteria Viruses

SPECIFIC

Mucous membranes

Physical barriers

Cilia NON-SPECIFIC Cytokines Antimicrobial secretions (complement, interferon) Macrophages

Macrophages present antigens Cellular response

T cells Cytokines

Cytotoxic T cells

Humoral response

B cells Memory B cells

Plasma cells

Antibodies

–  Lymph nodes are packed with WBC

Masses of lymphocytes and macrophages

Lymphocytes

Macrophages

Outer capsule of lymph node

The lymphatic system becomes a crucial battleground during infection

Basophil

Neutrophil

Monocyte

Eosinophil

Lymphocyte Lymphocyte: Immunity

Monocytes: Become macrophages

Neutrophils: phagocytic cells

Eosinophils: Reduce inflammation

Basophils: Release histamine and increase inflammatory response

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Granulocytes- have irregular shaped nuclei with several lobes and their cytoplasm is filled with granules containing enzymes and antimicrobial chemicals

They include the following:

1.  Neutrophils - phagocytic; granules contain various agents for killing microbes

2. Eosinophils - granules contain toxic proteins for killing infectious organisms/parasites

3.  Basophils - granules contain inflammatory chemicals such as histamine

Mast cells are capable of inducing an inflammatory cascade in allergic rxns

Agranulocytes - have compact nuclei and have no visible cytoplasmic granules

1.  Monocytes - phagocytes; differentiate into macrophages

They include the following:

2. Lymphocytes -  involved with acquired immunity -  two types: B and T Lymphocytes -  B cells can further differentiate after antigen-activation to plasma cells that produce antibodies

C) Third Line of Defence - Specific Defenses (text p293-295)

•  invoked when the first and second line of defense fail •  response time is in days (slower but more specific) •  protection against specific antigens using antibodies •  uses B and T lymphocytes

Target cell

T-cells

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Antigens •  foreign molecules recognized by the immune system •  usually protein fragments or carbohydrates

(glycoproteins). •  Often part of a bacterial cell wall, viral coat or foreign cell

membrane

Fibers of the extracellular matrix

Glycoprotein Carbohydrate (of glycoprotein)

Microfilaments of the cytoskeleton

Phospholipid Cholesterol

Proteins CYTOPLASM

Glycolipid

Antibodies •  antibodies are proteins that bind to antigens •  antigens cause antibody production (antibody generators) •  antibodies are produced by B lymphocytes (B cells)

Antibody A molecules

Antigen

Antibody B molecule

Antigenic determinants

Antigen- binding sites

Antigens have specific regions where antibodies bind to them

Antigen-Antibody Reaction (Ag-Ab rxn)

1. T cells (Cellular Immunity)

Pathogen

Macrophage (will become APC)

Antigen from microbe (nonself molecule)

Self protein

Self protein displaying antigen T cell receptor

Helper T cell

Binding site for antigen APC

1

2

3 4

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T lymphocytes (T cells) •  develop in the bone marrow •  differentiate into mature

T cells in the Thymus gland •  circulate in the blood &

lymph

Activation of T cells •  T cells have receptors •  macrophages present antigen to T cells

•  the T cell divides and differentiates into a “cellular army”

•  helper T cells - recruit and activate B cells to make antibodies -  produce chemicals (cytokines) that speed the division of B-

lymphocytes •  suppressor T cells

-  inhibit immune reaction after the antigen has been destroyed •  memory T cells

- remember the antigen of the invader so it can mobilize the immune response quickly in the event of a second exposure

•  killer T cells (cytotoxic T cells) - secrete chemicals that destroy

infected body cells (puncture holes in their cell membrane)

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Cytotoxic T cells •  target and destroy infected body cells (specific antigen-bearing cells such as virus infected or cancer cells) •  contain perforin molecules •  form a pore in the membrane of the infected cell •  allows water and salts to enter cell swells and bursts

2. B cells (Antibody-Mediated Immunity)

B lymphocytes (B cells)

•  develop in the bone marrow •  differentiate into mature B cells in

the Bone marrow •  have antigen specific receptors

on their surface

•  produces specific antibodies

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Activation of B cells

•  helper T cell presents B cell with the antigen

•  antigen binds with receptors on B cell, this stimulates the B cell to divide and differentiate into:

Self protein displaying an antigen T cell

receptor lymphokines stimulates cell division

Killer T cell

lymphokines activates other T cells and B cells

B cell

Helper T cell

Macrophage (APC)

Chemical messenger Activates helper T cell

Cell-mediated Immunity (attack on infected cells)

Antibody-mediated Immunity (secretion of antibodies by plasma cells) - humoral immunity

•  Plasma cells: mass produce antibodies (2000 per second), which are released into the blood stream •  Memory cells: responsible for long-term immunity (hold the instructions of how to make the antibodies if needed again)

Antigen molecules

Variety of B cells in a lymph node

Cell growth division, and differentiation

Clone of many plasma cells secreting antibodies

Antibody molecules

Antigen receptor (antibody on cell surface)

•  antibodies circulate, find antigens, bind to them, inactivate them and mark them for later destruction by macrophages

Binding of antibodies to antigens inactivates antigens by

Neutralization (blocks viral binding sites;

coats bacterial toxins) Agglutination of microbes

Precipitation of dissolved antigens

Activation of complement

Virus

Bacterium

Bacteria

Antigen molecules

Complement molecule

Foreign cell Hole

Enhances

Phagocytosis

Macrophage

Cell lysis

Leads to

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Bacteria Viruses

SPECIFIC

Mucous membranes

Physical barriers

Cilia NON-SPECIFIC Cytokines Antimicrobial secretions (complement, interferon) Macrophages

Macrophages present antigens Cellular response

T cells Cytokines

Cytotoxic T cells

Humoral response

B cells Memory B cells

Plasma cells

Antibodies

Animation showing antibodies blocking viral absorption.

Primary immune response: reacting to first exposure to antigen Secondary immune response: reacting to a second exposure to the same antigen using memory B and T cells; more massive & faster response

Unstimulated lymphocyte

First exposure to antigen

FIRST CLONE

Memory cells

Effector cells Second exposure to antigen

SECOND CLONE

More memory cells New effector cells

Immunocompetence: the degree to which an antigen is identified, destroyed & disposed of by the immune system processes

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The secondary response provides active immunity (resistance) to certain diseases after having had them once.

Passive immunity is the acquisition of resistance through the use of vaccinations

•  Vaccines are made from killed pathogens or weakened strains that stimulate antibody production and formation of memory cells without causing the disease

•  Vaccination is a term derived from the Latin vacca (vacca = cow, after the cowpox material used by Jenner in the first vaccination)

•  the secondary response is the basis for vaccination

Edward Jenner Discovery of small pox vaccine

Milkmaids who had contracted cowpox (a mild disease) were subsequently immune to smallpox (a disfiguring and often fatal disease). Jenner introduced fluid from a cowpox pustule into people.

Smallpox is a serious, contagious, and sometimes fatal infectious disease. There is no specific treatment for smallpox, and the only prevention is vaccination.

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The vaccine does NOT contain the smallpox VIRUS and CANNOT give

you smallpox.

The smallpox vaccine helps the body develop immunity to smallpox. The vaccine is made from a virus called vaccinia which is a “pox”-type virus related to smallpox. The smallpox vaccine contains the “live” vaccinia virus—not dead virus like many other vaccines. For that reason, the vaccination site must be cared for carefully to prevent the virus from spreading.

Smallpox-Variola major Cowpox-Vaccinia virus

The smallpox vaccine is not given with a hypodermic needle. The vaccine is given using a bifurcated (two-pronged) needle that is dipped into the vaccine solution. When removed, the needle retains a droplet of the vaccine. The needle is used to prick the skin a number of times in a few seconds. The pricking is not deep, but it will cause a sore spot and one or two droplets of blood to form. The vaccine usually is given in the upper arm.

If the vaccination is successful, a red and itchy bump develops at the vaccine site in three or four days.

In the first week, the bump becomes a large blister, fills with pus, and begins to drain. During the second week, the blister begins to dry up and a scab forms. The scab falls off in the third week, leaving a small scar.

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Smallpox outbreaks have occurred from time to time for thousands of years, but the disease is now eradicated after a successful worldwide vaccination program.

The last case of smallpox in the United States was in 1949. The last naturally occurring case in the world was in Somalia in 1977.

After the disease was eliminated from the world, routine vaccination against smallpox among the general public was stopped because it was no longer necessary for prevention. Ali Maali--The last reported

naturally occurring case of smallpox.

Smallpox eradication, 1967–1978: a window of opportunity

•  Some fungi produce antibiotics – Penicillin was the first antibiotic to be discovered – discovered by Fleming in 1929 and turned into a

useful treatment by Florey and Chain (1940s) Staphylococcus aureus Penicillium

Zone of inhibited growth

•  prevents the formation of the bacterial cell wall others affect protein synthesis

Other antibiotics: Streptomycin Tetracycline

Antibiotics:

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Disorders of the Immune system (text p 298-299)

•  Allergic Reaction – abnormal sensitivities and an exaggerated

response by the immune system to a foreign substance

- weak antigens are called allergens - pollen, dust mites, mold, cat dander, food, medicines

Problem relates to Immune response memory - Antibodies are made and bind to mast cells. - Mast cell release histamine

- inflammation, runny eyes and nose, rashes

Allergen (pollen grain)

B cells make antibodies

Antigenic determinant

SENSITIZATION: Initial exposure to allergen

Antibodies attach to mast cell

B cell (plasma cell)

Histamine

Mast cell

Allergen binds to antibodies on mast cell

Histamine is released, causing allergy symptoms

LATER EXPOSURE TO SAME ALLERGEN

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Anaphylaxis  A severe allergic reaction  A life-threatening emergency

Asthma is a disease in which inflammation of the airways causes airflow into and out of the lungs to be restricted. When an asthma attack occurs, mucus production is increased, muscles of the bronchial tree become tight, and the lining of the air passages swells, reducing airflow (causing wheezing).

Autoimmune diseases – The immune system turns against the body’s

own cells and molecules

Eg:Rheumatoidarthritis

Membraneofthejointcavity

Attackingwhitebloodcells

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A chronic inflammatory autoimmune disorder in which B cells make antibodies against many sorts of molecules and may affect many organ systems including the skin, joints and internal organs.

LUPUS: systemic lupus erythematosus

Autoimmune disorder Symptoms

Target of Antibodies

Glomerulonephritis Lower back pain Kidney cell antigen that resembles Streptococcus antigen

Graves disease Restlessness, weight loss, irritability, increased heart rate and blood pressure

Thyroid gland antigen

Multiple Sclerosis Muscle weakness, NS damage Motor neurons

Pernicious anemia Fatigue and weakness Binding site for vitamin B on cells lining stomach

Rheumatoid arthritis Joint pain and deformity Cells lining joints

Systemic lupus Red rash on face, fever, weakness and kidney damage

DNA, neurons, blood cells

Type I diabetes Thirst, hunger, weakness, emaciation

Pancreatic beta cells

Ulcerative colitis Lower abdominal pain Colon cells

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“boy in the bubble”-David – died at age 12, lacked of a thymus gland

Immunodeficiency diseases

SCID - severe combined immunodeficiency

•  impaired immune response: both antibody-mediated and cell-mediated immune responses are non-functional

•  die at a young age from a minor bacterial threat

•  mutations in genes encoding proteins used in immunity result in impaired immune response

•  some SCID cases are due to ADA deficiency (adenosine deaminase)

•  target disease for gene therapy

•  collection of disorders that develop as a result of infection with HIV

•  HIV, human immunodeficiency virus (RNA-retrovirus)

•  14,000 people are infected with the AIDS virus every day (HIV is transmitted mainly in blood and semen)

AIDS: Acquired Immunodeficiency Syndrome

Former L.A. Laker Magic Johnson Structure of HIV

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•  The AIDS virus attacks helper T Cells – This cripples both cell-mediated & humoral immunity

•  HIV attacks the immune system –  It eventually destroys the body’s ability to fight

infection

AIDS leaves the body defenseless

Practicing safer sex could save many lives

•  So far, AIDS is incurable – Drugs and vaccines offer hope for the future

Stress & Immune Functioning Physical and emotional stress may weaken the

immune system

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Human Blood Types: (text p296)

Human Blood Types:

Human Blood Types:

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Human Blood Types:

Human Blood Types:

agglutination

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Bacteria Viruses

SPECIFIC

Mucous membranes

Physical barriers

Cilia NON-SPECIFIC Cytokines Antimicrobial secretions (complement, interferon) Macrophages

Macrophages present antigens Cellular response

T cells Cytokines

Cytotoxic T cells

Humoral response

B cells Memory B cells

Plasma cells

Antibodies