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Ch. 48The Immune System

Nonspecific Defenses

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• Robert Koch (1843-1910): first scientist to establish step-by-step procedure for identifying the particular pathogen responsible for a disease• Studying anthrax (disease of cattle that can spread to humans), he

observed cattle with anthrax had swarms of bacteria in their blood

• He hypothesized that these bacteria caused anthrax, and tested this

• Experiment consisted of:

1. He isolated bacteria from a cow infected and grew the bacteria in a lab culture

2. He inoculated a healthy cow with bacteria from the culture the cow developed anthrax and Koch found the same bacteria in its blood

• These steps he developed for determining the cause of a given disease: Koch’s postulates

Disease Transmission

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• Scientists use Koch’s postulates to identify thousands of pathogens

• Human disesases are caused by:• Bacteria (botulism, tetanus, tuberculosis)

• Viruses (HIV, polio, rabies)

• Protists (malaria)

• Fungi (athletes foot, jock itch)

• Invertebrates

• Each pathogen affects the body differently

• Pathogens can spread 5 different ways in humans:• Air

• Food

• Water

• Person-to-person

• Bits of animals

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• Nonspecific defenses protect the body against any pathogen, regardless of its identify

• Most pathogens must enter body to cause disease

• Skin-physical barrier as long as it remains intact (make of keratin)

• Excessive damage can be life threatening• Severe burn: vulnerable to infections

• Skin continuously release sweat, oils, waxes: contain chemicals toxic to many bacteria and fungi• Sweat: contains enzyme lysozyme: destroys cell walls of bacteria

• Mucous membranes: epithelial tissues that protect interior surfaces of body that may be exposed to pathogens• Line respiratory tract, digestive system, urethra, vagina

• Serve as barrier and secrete mucus: sticky fluid that traps pathogens

• Covered with beating cilia: constantly sweep mucus and pathogens up to the pharynx where they are swallowed and forced into stomach (killed by acid)

Skin and Mucous Membranes

• Any pathogen that penetrates skin or mucus membrane stimulates this nonspecific defense mechanism

The Inflammatory Response

Pus: thick whitish or yellowish fluid accumulates in wounds, containing death pathogens and white blood cells

White blood cells involved:1. Phagocytes: engulf pathogens through endocytosis Ex. Neutrophil Ex. Macrophage2. Natural Killer Cells:Attack the cells that have been infected by pathogens, NOT THE PATHOGENS THEMSELVES(effective at killing cancer cells)

• Interferon: protein that inhibits reproduction of viruses• Produced in small amounts by cells infected by a virus

• Stimulates neighboring cells to produce an enzyme that inhibits synthesis of viral proteins prevents viruses from reproducing within these cells

• Fever: elevation in body temperature above normal 37oC (99oF)• Sign that body is responding to infection

• Some pathogens trigger fevers

• Some chemical signals released by macrophages trigger fevers

• Research suggests that moderate fever stimulates body’s defense mechanism (think about this in regards to enzyme activity………)

• High fever = harmful WHY?

• Greater than 105oF are often fatal

Other Nonspecific Defenses

Specific Defenses: The Immune System

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• Fights off invading pathogens & prevents growth and spread of cancers

• Consists of several organs, white blood cells in these organs, and white blood cell in blood & lymph

• Organs include:• Bone marrow

• Thymus

• Lymph nodes

• Tonsils

• Adenoids

• Spleen

The Immune System

• BONE MARROW• Soft material found inside bones

• Manufactures billions of new white blood cells (WBCs)

• Some WBCs remain in bone marrow to mature and specialize, while others travel to the thymus

• THYMUS• Gland in upper part of chest above heart

• Location where some WBCs mature

• LYMPH NODES• Located throughout body along vessels of

lymphatic system

• Contain large numbers of WBCs

• Filter pathogens from lymph and expose them to WBCs (for destruction)

• SPLEEN• Fist-sized organ located just behind stomach

• Filters pathogens from blood

• Stocked with WBCs that respond to trapped pathogens

Immune System Organs

• WBCs of immune system = lymphocytes• Accumulate in the lymph and lymph nodes

• Also found in spleen and blood

• Two main types:

• B cells: produced in bone marrow and mature in bone marrow

• T cells: produced in bone marrow but mature in thymus

LYMPHOCYTES ARE THE BODIES SPECIFIC DEFENSES

• When body invaded by pathogen, lymphocytes launch attack known as IMMUNE RESPONSE to eliminate pathogen

***In order to respond to a pathogen, lymphocytes must be able to recognize it as a foreign invader and distinguish it from normal cells of the body***

• Any substance immune system recognizes as potential pathogen and provokes an immune response = antigen• Examples of antigens: pathogens, parts of pathogens, bacterial

toxins, insect venom, pollen

• Every lymphocyte has receptor proteins scattered over the surface of its cell membrane• They recognize and bind to antigens that match their particular

3-D shape

• Surface of bacterial cell is covered with many different molecules (proteins, polysaccharides, etc.) each can function as an antigen and cause lymphocytes to react

• All the receptors on one individual lymphocyte ARE THE SAME, thus bind to the same antigen

• The immune system makes millions of DIFFERENT KINDS of lymphocytes, each carrying a UNIQUELY shaped receptor

Recognizing Pathogens

Pathogen with several different antigens on the surface

Three different lymphocytes, each with a different 3-D shaped receptor located on its surface. The antigen shown

will only fit into one of the three lymphocytes

• This is a 2 part assault on the pathogen, controlled by helper T cells:1. Cell-mediated response: involves T cell

2. Humoral response: involves mainly B cells

• First step in an immune response occurs when:• Macrophage engulfs and destroys a pathogen

• Macrophage then displays fragments of pathogen’s antigens on the surface of its own cell membrane

• When helper T cell with a receptor matching this antigen encounters the macrophage, the macrophage releases a cytokine called interleukin-1: this triggers the helper T cell to release a second cytokine called interleukin-2

Immune Response

• Interleukin-2 stimulates helper T cells and two other types of T cells-- cytotoxic T cells and suppressor T cells—to rapidly divide. • Cytotoxic T cells: combat pathogen by destroying any of body’s cells that have

been infected by the pathogen

• Cells invaded by pathogen are recognizable because they usually have some of pathogen’s antigens on their surface

• Attach to these antigens, and like Natural killer cells, they kill by puncturing cell membrane of their target

• Can also kill cancer cells and attack parasites and foreign tissues (such as those received from an organ transplant

• Suppressor T cells: help to shut down immune response after pathogen has been cleared from body

Cell-Mediated Immune Response

Summary of Cell-mediated immune response:

• Involves following WBC: macrophages, helper T cells, cytotoxic T cells, suppressor T cells

1. Macrophage releases interleukin-1 stimulates helper T cell

2. Helper T cell releases interleukin-2 causes cytotoxic T cells and suppressor T cells to begin dividing

3. Suppressor T cells divide slowly ultimately shut down immune response

4. Cytotoxic T cells destroy infected cells by puncturing their cell membranes

• Interleukin-2 and antigen presentation by a macrophage or T cell stimulate B cells to divide an differentiate into plasma cells• Plasma cells: highly specialized cells that produce

defensive proteins and secrete them into the blood—antibodies: identical to the plasma cell’s antigen receptors

• Y-shaped molecules

• The two arms of each Y are identical, and they recognize and attach to the same antigen

• One plasma cell can make up to 30,000 antibody molecules per second!

• They bind to specific pathogens but do not destroy them directly

• They either inactivate the pathogen or trigger its destruction by the nonspecific defenses

• Ex. by attaching to surface proteins of a virus, antibodies prevent the virus from entering a cell, thereby blocking its reproduction

• They also cause pathogens to clump together, facilitating phagocytosis by macrophages

Humoral Immune Response

• After infection has been overcome, immune response shut down and most of participating cell die• Some B cells and T cells remain, often throughout individuals lifetime as memory cells

• Memory cells: body’s long-term protection against reinfection by specific pathogen

• First time body encounters an antigen, immune response is called: Primary immune response

• Response of memory cells to subsequent infection by the same pathogen: Secondary immune response• Must faster and more powerful

• Produces many more antibodies

Primary and Secondary Immune Responses

• Person resistant to specific pathogen is said to have immunity to it

• Ways to acquire immunity:• Be infected by the pathogen and survive

• Vaccination

• Contain pathogens or toxins that have been modified so they can no longer cause disease

• Contain antigens that stimulate immune response, resulting in production of memory cells

• Diseases controlled by vaccines:• Polio

• Measles

• Mumps

• Tetanus

• Diptheria

• Smallpox

• Booster shots are necessary because vaccines wear off over time

Immunity and Vaccination

• Sometimes immune system reacts to otherwise harmless antigens in ways that can be harmful

• Inappropriate reaction to a harmless substance: allergy• Antigens that can trigger allergic reactions:

• Pollen

• Animal dander

• Dust mites

• Food

• Fungal spores

• Allergic reactions include:• Watery eyes

• Wheezing

• Sneezing

• Symptoms of allergy result from release of histamine by cells exposed to antigen• Antihistamines help counteract effects of histamine and relieve symptoms of

allergies

Allergies

• Lymphocytes that recognize and react to the body’s own cells are usually eliminated during development, before they become functional• This prevents attack directed at the body’s own tissues

• Rare cases the immune system does respond to the body’s own cells, attacking them as if they were pathogens autoimmune disease

• Ex. Multiple sclerosis, affects nervous system

• T cells attack and slowly destroy the insulating material that covers nerves

Autoimmune Diseases

AIDS

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• AIDS (acquired immune deficiency syndrome)-a disease in which the immune system loses its ability to fight off pathogens and cancers• Caused by HIV (human immunodeficiency virus)-a type of

retrovirus

• HIV’s main target to invade = helper T cells

• Enters helper T cell by binding to a receptor called CD4

HIV and AIDS

• HIV begins to reproduce inside helper T cells within the body shortly after infection

• The presence of large numbers of viruses stimulates immune system to launch vigorous attack this causes the individual to experience short “flu-like” illness (fever, fatigue, body aches, swollen lymph nodes)• This occurs within a month or so of being infected

• This first battle is the beginning of a long-term struggle between HIV and the immune system

• HIV continues to replicate rapidly, but the immune system keep the virus in check infected person feels well and appears healthy• This lasts from 2-10 years

• For reasons not well understood, HIV eventually gets the upper hand in its battle with the immune system• The number of helper T cells in body begins to decline gradually

Course of the Disease

• The reduction in helper T cells is disastrous from infected person• Remember, helper T cells play crucial role as “commanders” of immune response,

activating BOTH cytotoxic T cells and B cells

• Immune system becomes weaker with declining number of helper T cells

• This makes infected individual vulnerable to variety of cancers and diseases that would NORMALLY be defeated = opportunistic infections: usually only strike people with weakened immune systems

• When number of helper T cells in blood falls below 200/mL, the individual is said to have AIDS

• normal = 600/mL

• AIDS is the last stages of HIV infection

• Few individuals live more than 2 years after being diagnosed with AIDS

• HIV transmitted by transfer of body fluids containing HIV viruses or HIV-infected cells

• Most commonly is sexual intercourse with an infected person• HIV-infected cells found in semen & vaginal secretions

• Infection can occur through vaginal, oral, or anal intercourse

• Use of condoms greatly reduces likelihood of transmission but DOES NOT ELIMINATE IT

• People infected with HIV or AIDS can transmit the virus

• Second most common means of infection= use of syringes and hypodermic needles that have been contaminated with blood containing HIV• People who inject intravenous drugs (heroin), and who share syringes or

hypoderminc needles with others are at HIGH RISK of infection

Transmission

• During early years of AIDS epidemic, many individuals were infected by receiving HIV-contaminated blood transfusions• Donated blood is now tested for presence of antibodies to HIV, and people that

may have been exposed to the virus are discouraged from donating

• Likelihood of being infected through a transfusion is very low

• You cannot be infected with HIV through casual contact (shaking hands, handling an object used by infected person)• HIV is not transmitted through air, water, or toilet seats

• No evidence it can be spread through bites of insects or fleas/ticks

• Early cases of AIDS were diagnosed in the US and Western Europe, but now is a worldwide problem

• Scientists trying to create vaccines for HIV must contend with its VERY RAPID EVOLUTION• Genes that code for the virus’s surface proteins mutate frequently

• This leads to new variants of the virus with slightly different surface proteins

• To produce an effective immunity, a vaccine against HIV must stimulate the immune system to respond to many variants of the virus• None have yet proven effective

• HIV’s rapid evolution complicates the task of developing treatments for HIV infection and AIDS.• The virus quickly becomes resistant to drugs used against it

• Scientists treat patients with three antiviral drugs (it is unlikely the virus will evolve resistance to all three drugs)

Treatments and Vaccines