THE IMMUNE SYSTEM

We all get sick sometimes...but then we get better.

What happens when we get sick?

Why do we get better?

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ANATOMY OF THE IMMUNE SYSTEM

2 • The immune system is localized in several parts of the body – immune cells develop in the

primary organs

bone marrow and thymus (yellow) – immune responses occur in the

secondary organs

(blue)

ANATOMY OF THE IMMUNE SYSTEM

• Thymus 3 – glandular organ near the heart – where T cells learn their jobs • Bone marrow bones – – blood-producing tissue located inside certain blood stem cells give rise to all of the different types of blood cells • Spleen – serves as a filter for the blood – removes old and damaged red blood cells – removes infectious agents and uses them to activate cells called lymphocytes • Lymph nodes – small organs that filter out dead cells, antigens, and other “stuff” to present to lymphocytes • Lymphatic vessels – collect fluid (lymph) that has “leaked” out from the blood into the tissues and returns it to circulation

PASSIVE IMMUNITY

While your immune system was developing, you were protected by immune defenses called antibodies . These antibodies traveled across the placenta from the maternal blood to the fetal blood.

Antibodies (

Y

) are also found in breast milk. 4 The antibodies received through passive immunity last only several weeks.

INDUCTION OF AN IMMUNE RESPONSE

Foreign invaders - viruses, bacteria, allergens, toxins and parasites- constantly bombard our body. 5

YOUR ACTIVE IMMUNE DEFENSES Innate Immunity

- invariant (generalized) - early, limited specificity - the first line of defense

Adaptive Immunity

- variable (custom) - later, highly specific ‘‘remembers’’ infection

INNATE IMMUNITY

When you were born, you brought with you several mechanisms to prevent illness. This type of immunity is also called nonspecific immunity.

6 Innate immunity consists of: • Barriers • Cellular response – phagocytosis – inflammatory reaction – NK (natural killer) and mast cells • Soluble factors

• Physical

INNATE IMMUNITY

Barriers • Chemical

– skin – hair – mucous – sweat – tears – saliva – stomach acid – urine 7

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INNATE IMMUNITY

Cellular response

• nonspecific - the same response works against many pathogens • this type of response is the same no matter how often it is triggered • the types of cells involved are macrophages/ neutrophils , natural killer cells , and mast cells

Phagocytic cells include:

Macrophages engulf pathogens and dead cell remains Neutrophils release chemicals that kill nearby bacteria • pus = neutrophils, tissue cells and dead pathogens 9

Phagocyte migration

CELLS alive!

Neutrophils and macrophages recognize chemicals produced by bacteria in a cut or scratch and migrate "toward the smell". Here, neutrophils were placed in a gradient of a chemical that is produced by some bacteria. The cells charge out like a "posse" after the bad guys.

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Macrophages

• WBCs that ingest bacteria, viruses, dead cells, dust • most circulate in the blood, lymph and extracellular fluid • they are attracted to the site of infection by chemicals given off by dying cells • after ingesting a foreign invader, they “wear” pieces of it called antigens on their cell membrane receptors – this tells other types of immune system cells what to look for 11

Macrophage and

E. coli

12 ©Dennis Kunkel Microscopy, Inc., www.DennisKunkel.com

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Macrophage ingesting yeast

CELLS alive!

This human macrophage, like the neutrophil, is a professional "phagocyte" or eating cell (phago = "eating", cyte = "cell"). Here, it envelops cells of a yeast,

Candida albicans

. After ingestion, the white cell must kill the organisms by some means, such as the oxidative burst.

Neutrophils

• WBCs – are phagocytic, like macrophages • neutrophils also release toxic chemicals that destroy everything in the area, including the neutrophils themselves 14

Neutrophil phagocytosing

S. pyogenes,

the cause of strep throat

15 CELLS alive!

Human neutrophils are WBCs that arrive quickly at the site of a bacterial infection and whose primary function is to eat and kill bacteria. This neutrophil ingesting

Streptococcus pyogenes

was imaged in gray scale with phase contrast optics and colorized.

Neutrophil killing yeast

YEAST 

NEUTROPHIL

 CELLS alive!

One way that neutrophils kill is by producing an anti bacterial compound called “superoxide anion“, a process called oxidative burst. Here, an amoeboid human neutrophil senses, moves toward and ingests an ovoid yeast. In the next two panels, oxidation can be seen by using a dye, and is colorized here.

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INNATE IMMUNITY

Cellular response

Inflammatory response • chemical and cell response to injury or localized infection • eliminates the source of infection • promotes wound healing 17 Step 1.

Circulation to the site increases  red and swollen tissue warm, Step 2.

WBCs leak into tissues  phagocytes engulf and destroy bacteria

INNATE IMMUNITY

Cellular response

Inflammatory response (cont’d) The release of histamine and prostaglandin causes local vessel dilation resulting in: • more WBCs to site • increased blood flow  redness and warmth • increased capillary permeability • phagocytes move out of vessels into intracellular fluid (ICF) • edema (swelling) due to fluids seeping from capillaries 18

INNATE IMMUNITY

Cellular response

Inflammatory response (cont’d) Fevers have both positive and negative effects on infection and bodily functions

POSITIVE

• indicate a reaction to infection • stimulate phagocytosis • slow bacterial growth – increases body temperature beyond the tolerance of some bacteria – decreases blood iron levels

NEGATIVE

• extreme heat  denaturation and enzyme interruption of normal biochemical reactions > 39 ° C (103°F) is dangerous > 41 °C (105°F) could be fatal and requires medical attention 19

Natural killer cells (NK cells)

• instead of attacking the invaders, they attack the body’s own cells that have become infected by viruses • they also attack potential cancer cells, often before they form tumors • they bind to cells using an antibody “bridge”, then kill it by secreting a chemical (perforin) that makes holes in the cell membrane of the target cell. With enough holes, the cell will die, because water rushing inside the cell will induce osmotic swelling, and an influx of calcium may trigger apoptosis.

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Mast cells • are found in tissues like the skin, near blood vessels.

• are activated after antigen binds to a specific type of antibody called IgE that is attached to receptors on the mast cell.

• activated mast cells release substances that contribute to inflammation, such as histamine.

• mast cells are important in allergic responses but are also part of the innate immune response, helping to protect from infection.

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22 Apoptosis or cell death CELLS alive!

Human neutrophils released into the blood "commit suicide“ after only 1 day. A neutrophil (left) undergoes apoptosis, a series of changes including violent membrane blebbing and fragmentation of DNA. Apoptotic cells break into smaller pieces called apoptotic bodies that other body cells recognize and eat.

• Your mom’s antibodies were effective for just a short time at birth, but your innate immune system can be activated quickly. It is always your first line of defense during an infection, but it can’t always eliminate the germ. • When this happens, your body initiates a focused attack against the specific pathogen that is causing the infection. This attack may lead to long-term protection against that pathogen. • This type of immunity is called

adaptive/acquired immunity ,

the customized second line of defense. 23

INDUCTION OF AN IMMUNE RESPONSE

Foreign invaders - viruses, bacteria, allergens, toxins and parasites- constantly bombard our body. 24

YOUR ACTIVE IMMUNE DEFENSES Innate Immunity

- invariant (generalized) - early, limited specificity - the first line of defense 1. Barriers - skin, tears 2. Phagocytes - neutrophils, macrophages 3. NK cells and mast cells 4. Complement and other proteins

Acquire Immunity

- variable (custom) - later, highly specific ‘‘remembers’’ infection

INDUCTION OF AN IMMUNE RESPONSE

YOUR ACTIVE IMMUNE

parasites- constantly bombard our body. 25

DEFENSES

Innate Immunity

- invariant (generalized) - early, limited specificity - the first line of defense 1. Barriers - skin, tears 2. Phagocytes - neutrophils, macrophages 3. NK cells

Adaptive Immunity

- variable (custom) - later, highly specific ‘‘remembers’’ infection 1.

APCs present Ag to T cells 2. Activated T cells provide help to B cells and kill abnormal and infected cells 3. B cells - produce antibody specific for antigen

STARTING AN IMMUNE

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RESPONSE

Foreign invaders - viruses, bacteria, allergens, toxins and parasites - constantly bombard our body.

    The response to this assault is a carefully orchestrated and controlled interaction between immune cells with the ultimate goal to eliminate the invader by pathogen-specific mechanisms.

Antigen presentation

APC T helper cell

Antigen-presenting cells (APCs) may be macrophages or B cells T cells have special antigen recognizing molecules on their surfaces called T cell receptors (TCR). An APC that has ingested antigen “presents” pieces of the Ag to T cell by docking with its TCR. This, and a 2 nd signal, activates the T cell.

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Activated T helper cells induce effector and memory T H cells

T cell activation

Presentation of antigen to a T cell triggers its activation into a helper T (T H ) cell. Activated T H cells produce a cytokine called interleukin-2 (IL-2). IL-2 causes the T cells to divide. Some of the new T cells go into battle (T H effector cells) and some become memory cells.

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B cell activation and differentiation

Activated T helper cell

Antibodies Activated T cells interact with B cells through the action of cytokines. The B cells become activated and differentiate into plasma cells. Plasma cells secrete antibodies, which help to inactivate the antigen.

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CELLS alive!

How lymphocytes produce antibody

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Production of cytotoxic T cells

Activated T helper cell Cytotoxic T cell (T c )

T cells may be activated by IL-2 from T helper cells. Some will become cytotoxic T cells (T c ) that kill abnormal and infected cells. Others will become memory cytotoxic T cells.

Memory T c Effector T c

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PUTTING IT ALL TOGETHER…

APC T helper cell Activated T helper cell Cytotoxic T cell (T c )

Antibodies

Memory T c Effector T c

Lysis 32

IMMUNE RESPONSE

There are two phases in the generation of an immune response: • primary response – when the Ag is first encountered – the response is slow with the Ag because, at first, there are only a few B cells that react – the weak response allows the invader enough time to cause illness – a type of antibody (IgM) and memory B cells are produced • secondary response – the next time the antigen is encountered – the response is quicker and stronger each time – memory B cells recognize antigen and they all begin to divide quickly – lots of plasma cells are produced which make lots of a different type of antibody called IgG 33

The course of a typical antibody response

34 The first encounter with an antigen produces a primary response . Antibody against antigen A (blue) appears; its concentration rises to a plateau, and then declines. When antigen A and a new antigen, B, are encountered later, a very rapid and intense secondary response to A occurs due to immunologic memory. This is the main reason for giving booster injections after an initial vaccination. A primary response occurs to antigen B.

How does an immune response end?

• The immune response will end when the antigen that caused the response is no longer present – this is what happens when antibiotics are used to treat a bacterial infection. Once the bacteria are killed and cleared from the body, the production of a specific immune response to the bacteria will stop, including the activation of T cells and the production of specific antibodies. Suppressor T cells may help in this process.

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What makes us sick?

• “enemies” in the environment in the form of microbes and chemicals are constantly attacking our bodies, disrupting homeostasis • sometimes immune system homeostasis is disrupted on its own 36 it may over-react to antigens such as with allergies  it may under-react as with human immunodeficiency virus infection (HIV) it may react to self proteins as with autoimmune disease

Why does the immune system attack the body that it’s supposed to protect?

• failure to recognize some cells as “self” – in rheumatic fever, the streptococcus antigen is very similar to a protein in heart tissue, so the body mistakenly identifies heart tissues as foreign 37 • cells seen as foreign are attacked and destroyed – may be only a few select cells or organs ( organ-specific ) – e.g., multiple sclerosis, juvenile diabetes, rheumatic fever – may be systemic arthritis - e.g., systemic lupus erythematosus, rheumatoid

Acquired immunodeficiency

• caused by the human immunodeficiency virus (HIV) and is spread by contact with body fluids • infects CD4+ (helper) T cells, which decrease in number • decreased numbers of CD4+ T cells lead to increased susceptibility to opportunistic infections.

• treatments include drugs that inhibit the activity of HIV proteins, thereby preventing production of the virus 38 Worldwide HIV infection, 1999 HIV virus particle

THE IMMUNE SYSTEM IN HEALTH AND DISEASE

39 How does your everyday life affect your immune system?

Exercise and stress

• exercise has been shown to boost the immune response – moderate exercise increases the immune response in all age groups – intensive exercise can stress the immune system • lack of sleep and exhaustion decrease immune function • psychological stress has also been found to decrease immune function 40

Diet

• a well-balanced diet is essential for good immune system health – fats are very important in the production of WBCs, cytokines and natural killer cells – selenium, zinc, and copper are required in small amounts, which you get if you eat a balanced diet – vitamin E has been shown to boost antibody production in the elderly – vitamin B 6 aids in antibody synthesis • but mega-dosing can be harmful, too!

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Environment

Exposure to certain things in their environment may activate the immune systems of some people • Viruses • Chemicals – dioxin – pesticides – solvents • Sunlight • Bacteria • Food • Medication 42