Specific and Non Specific Immune Responses and Immune Disorders

Microbiology AssignmentPrepared by :

TARIQ JAVED GILL.

B. Sc. N Semester I Year 2012-2014

OBJECTIVES:At the end of session the audience will be able to:Define specific and non specific immune responses. Understand how the Immune System works. Explain about the common Immune Disorders.

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IMMUNE RESPONSE• The immune response is how your body recognizes and defends itself against bacteria,

viruses, and substances that appear foreign and harmful.

• The immune system protects the body from possibly harmful substances by recognizing and responding to antigens. Antigens are substances (usually proteins) on the surface of cells, viruses, fungi, or bacteria. Nonliving substances such as toxins, chemicals, drugs, and foreign particles (such as a splinter) can also be antigens. The immune system recognizes and destroys substances that contain antigens.

• Your own body's cells have proteins that are antigens. These include a group of antigens called HLA antigens. Your immune system learns to see these antigens as normal and usually does not react against them.

• We survive because our body’s immune system defends us against pathogens (disease-causing agents). The immune system consists of cells and tissues found throughout the body. The body uses both nonspecific and specific defense mechanisms to prevent infection and to detect and destroy pathogens.

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Non Specific Immune ResponseINNATE IMMUNITY OR NON SPECIFIC IMMUNITY

Innate, or nonspecific, immunity is the defense system with which you were born. It protects you against all antigens. Innate immunity involves barriers that keep harmful materials from entering your body. These barriers form the first line of defense in the immune response. Examples of innate immunity include:

Cough reflex

Enzymes in tears and skin oils

Mucus, which traps bacteria and small particles

Skin

Stomach acid

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First line of nonspecific defensesThe body’s surface defenses are nonspecific, meaning they do not target

specific pathogens.

SKIN is the first of our immune system’s nonspecific defenses against pathogens.

• Skin acts as a nearly impenetrable barrier to invading pathogens, keeping them outside the body.

• This barrier is reinforced with chemical weapons – oil and sweat!

• Oil and sweat make the skin’s surface acidic, inhibiting the growth of many pathogens and sweat contains

• the enzyme lysozyme which digests bacterial cell walls.

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CONTINUED

• Internal surfaces of the body through which pathogens can pass are covered by MUCOUS MEMBRANES.

• Mucous membranes are layers of epithelial tissue that produce sticky, viscous fluid called mucus.

• Mucous membranes line the digestive system, nasal passages, lungs, respiratory passages, and the reproductive tract.

• Skin and mucous membranes work to prevent any pathogens from entering the body; nevertheless, sometimes these defenses are penetrated.

• When invaders reach deeper tissue, a second line of nonspecific defenses takes over.

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Second line of nonspecific defensesWhen the body is invaded, four important non-specific

defenses take action:

1. The Inflammatory ResponseCaused by injury or local infection, like a cut or a scrape

Is a series of events that suppress infection and speed recovery

Imagine that a splinter has punctured your finger, creating an entrance for pathogens.

Infected or injured cells in your finger release chemicals, including histamine.

Histamine causes local blood vessels to dilate, increasing blood flow to the area.

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CONTINUEDIncreased blood flow brings white blood cells to the infection site,

where they can attack pathogens.

This also causes swelling and redness in the infected area.

The whitish liquid, or pus, associated with some infections contains white blood cells, dead cells and dead pathogens.

Inflammation aids the fight against infection by increasing blood flow to the site and raising temperature to retard bacterial growth.

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Continued

The events in a local inflammation. When an invading microbe has penetrated the skin, chemicals, such as histamine and prostaglandins, cause nearby blood vessels to dilate. Increased blood flow brings a wave of phagocytic cells, which attack and engulf invading bacteria.

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2. The Temperature Response

When the body begins its fight against pathogens, body temperature increases several degrees above the normal value of about 37°C (98.6°F).

This higher temperature is called a fever, and it is a common symptom of illness that shows the body is responding to an infection.

Fever is helpful because many pathogenic bacteria do not grow well at high temperatures.

But, very high fever is dangerous because extreme heat can destroy important cellular enzymes.

Temperatures greater than 39°C (102°F) are considered dangerous and those greater than 41°C(105°C) can be fatal.

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3. Proteins that kill or inhibit pathogens

Certain proteins circulate in the blood and become active when they encounter certain pathogens.

Then they form a membrane attack complex (a ring-shaped structure that ruptures the cell membrane of pathogens).

Another nonspecific defense is interferon (a protein released by cells infected with viruses).

Causes nearby cells to produce an enzyme that prevents viruses from making proteins and RNA.

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4. White Blood Cells

The most important counterattacks in the second line of nonspecific defenses are carried out by three types of white blood cells: Neutrophils, Macrophages and Natural killer cells.

These cells patrol the bloodstream, wait within the tissues for pathogens, and then attack the pathogens.

Each kind of cell uses a different mechanism to kill pathogens:

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Neutrophils

Is a WBC that engulfs and destroys pathogens.

Most abundant type of WBC

Sacrifice themselves to defend the body

Engulf bacteria and then release chemicals that kill the bacteria and themselves

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Macrophages

Ingest and kill pathogens they encounter

Clear dead cells and other debris from the body

Most travel through the body in blood, lymph, and fluid between cells

Concentrated in particular organs, especially the spleen and lungs.

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Natural Killer CellsLarge WBC that attacks cells infected with pathogens

Destroy an infected cell by puncturing its cell membrane

Water then rushes into the infected cell, causing the cell to swell and burst

One of the body’s best defenses against cancer – can detect cancer cells before a tumor can develop

SPECIFIC IMMUNE RESPONSEThe Immune Response:The Third Line of Defense

What happens when pathogens occasionally overwhelm your body’s nonspecific defenses?

Pathogens that have survived the first and second lines of nonspecific defenses still face a third line of specific defenses the immune response.

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SPECIFIC IMMUNE RESPONSEFew of us pass through childhood without contracting some sort of infection. Chicken pox, for example, is an illness that many of us experience before we reach our teens. It is a disease of childhood, because most of us contract it as children and never catch it again. Once you have had the disease, you are usually immune to it. Specific immune defense mechanisms provide this immunity.

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DISCOVERY OF SPECIFIC IMMUNE SYSTEM

In 1796, an English country doctor named Edward Jenner carried out an experiment that marks the beginning of the study of immunology. Smallpox was a common and deadly disease in those days. Jenner observed, however, that milkmaids who had caught a much milder form of “the pox” called cowpox (presumably from cows) rarely caught smallpox. Jenner set out to test the idea that cowpox conferred protection against smallpox. He infected people with cowpox and as he had predicted, many of them became immune to smallpox. We now know that smallpox and cowpox are caused by two different viruses with similar surfaces. Jenner’s patients who were injected with the cowpox virus mounted a defense that was also effective against a later infection of the smallpox virus. Jenner’s procedure of injecting a harmless microbe in order to confer resistance to a dangerous one is called vaccination. Modern attempts to develop resistance to malaria, herpes, and other diseases often involve delivering antigens via a harmless vaccinia virus related to cowpox virus.

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Key Concepts of SpecificImmunity

Antigens are molecules, usually foreign, that provoke a specific immune attack. This immune attack may involve secreted proteins called antibodies, or it may invoke a cell-mediated attack.

A large antigen may have several parts, and each stimulate a different specific immune response. In this case, the different parts are known as antigenic determinant sites, and each serves as a different antigen. Particular lymphocytes have receptor proteins on their surfaces that recognize an antigen and direct a specific immune response against either the antigen or the cell that carries the antigen.

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CONTINUED Lymphocytes called B cells respond to antigens by producing

proteins called antibodies. Antibody proteins are secreted into the blood and other body fluids and thus provide humoral immunity. (The term humor here is used in its ancient sense, referring to a body fluid.)

Other lymphocytes called T cells do not secrete antibodies but instead directly attack the cells that carry the specific antigens. These cells are thus described as producing cell-mediated immunity.

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Third line of defense – Specific immune response

The immune response consists of an army of individual cells that rush throughout the body to combat specific invading pathogens.

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Cells Involved in the Immune ResponseWBC are produced in bone marrow and circulate in blood and lymph. Of

the 100 trillion cells in your body, about 2 trillion are WBC.

Four main kinds of WBC participate in the immune response: macrophages, cytotoxic T cells, B cells, and helper T cells.

Each kind of cell has a different function:

Macrophages – consume pathogens and infected cells

Cytotoxic T cells – attack and kill infected cells

B cells – activate both cytotoxic T cells and B cells

Helper T cells – activate both cytotoxic T cells and B cells

These four kinds of WBC interact to remove pathogens from the body.

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Recognizing InvadersImagine that you have just come down with the flu. You have inhaled the

influenza viruses, but they were not trapped by mucus in the respiratory tract. The viruses have begun to infect and kill your cells.

At this point, macrophages begin to engulf and destroy the viruses.

An infected body cell will display antigens of an invader on its surface.

An antigen is a substance that triggers an immune response.

Antigens typically include proteins and other components of viruses or pathogen cells present on the cell surface.

WBCs of the immune system are covered with receptor proteins that respond to infection by binding to specific antigens on the surfaces of the infecting microbes.

These receptors recognize and bind to antigens that match their particular shape.

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Recognizing Invaders

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Immune response has two main parts

Two distinct processes work together in an immune response.

B cell response - a passive defense that aids the removal of pathogens from the body.

T cell response – an active, cell-mediated defense that involves the destruction of pathogens by cytotoxic T cells.

Both the T cell response and B cell response are regulated by helper T cells.

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Continued : Immune response has two main parts

Step 1 : When a virus infects body cells, the infected cells display the viral antigen on their surface.

Step 2 : Macrophages engulf the virus and display the viral antigen on their surface.

Step 3 :Receptor proteins on helper T cells bind to the viral antigen displayed by the macrophages. The macrophages release a protein called interleukin-1.

Step 4 : Interleukin-1 activates helper T cells, but helper T cells do not attack pathogens directly. Instead, helper T-cells activate cytotoxic T cells and

B cells. Stimulation by interleukin-1 causes helper T cells to release interleukin-2. Interleukin-2 stimulates further division of helper T cells

and cytotoxic T cells, amplifying the body’s response to the infection.

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Continued : Immune response has two main partsStep 5: Interleukin-2 released by helper T cells also activates B cells.

When activated by interleukin-2, B cells divide and develop into plasma cells. Plasma cells are cells that release special defensive proteins into the blood. These specialized proteins are called antibodies. An antibody is a Y shaped molecule that is produced by plasma cells upon exposure to a specific antigen and that can bind to that antigen.

Step 6: Plasma cells divide repeatedly and make large amounts of antibodies. Plasma cells either release antibodies into the bloodstream or attach them directly to the virus. Antibodies bind to the viral antigen on the virus and on infected cells. Antibodies mark the virus and infected cells for destruction.

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Continued : Immune response has two main parts

Step 7: When a plasma cell encounters a virus with an antigen that matches its antibodies, it binds to the virus. This causes other

viruses to stick together, forming a clump that can be easily identified and destroyed by macrophages.

Step 8: With the help of antibodies and plasma cells, cytotoxic T cells destroy infected cells by puncturing the cell membrane of the

infected cells. How do cytotoxic T cells recognize antigens? Your body makes millions of different T cells, each with receptor proteins that bind to a specific antigen. Receptor proteins on cytotoxic T cells bind to the viral antigen displayed by infected cells. For example, any of your body’s cells that bear traces of an influenza virus will be destroyed by cytotoxic T cells with receptor proteins that bind to the antigen of that virus.

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Continued

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Immune System Disorders.

Immune System Disorders

Hypersensitivity (Allergy): An abnormal response to antigens.

Four Types of Hypersensitivity Reactions:

• Type I (Anaphylactic) Reactions

• Type II (Cytotoxic) Reactions

• Type III (Immune Complex) Reactions

• Type IV (Cell-Mediated) Reactions

Type I (Anaphylactic) Reactions• Occur within minutes of exposure to antigen• Antigens combine with IgE antibodies• IgE binds to mast cells and basophils, causing them to undergo degranulation and release several mediators:• Histamine: Dilates and increases permeability of blood vessels (swelling

and redness), increases mucus secretion (runny nose), smooth muscle contraction (bronchi). • Prostaglandins: Contraction of smooth muscle of respiratory system and

increased mucus secretion.• Leukotrienes: Bronchial spasms.

• Anaphylactic shock: Massive drop in blood pressure. Can be fatal in minutes.

Mast Cells and the Allergic Response

Mast Cells and the Allergic Response

Type II (Cytotoxic) Reactions• Involve activation of complement by IgG or IgM binding to an

antigenic cell.• Antigenic cell is lysed.• Transfusion reactions:• ABO Blood group system: Type O is universal donor.

Incompatible donor cells are lysed as they enter bloodstream.• Rh Blood Group System: 85% of population is Rh positive.

Those who are Rh negative can be sensitized to destroy Rh positive blood cells.•Hemolytic disease of newborn: Fetal cells are destroyed by maternal anti-Rh antibodies that cross the placenta.

Type III (Immune Complex) Reactions• Involve reactions against soluble antigens circulating in serum.• Usually involve IgA antibodies.• Antibody-Antigen immune complexes are deposited in organs,

activate complement, and cause inflammatory damage.• Glomerulonephritis: Inflammatory kidney damage.

• Occurs when slightly high antigen-antibody ratio is present.

Immune Complex Mediated Hypersensitivity

Type IV (Cell-Mediated) Reactions• Involve reactions by TD memory cells.• First contact sensitizes person.• Subsequent contacts elicit a reaction.

• Reactions are delayed by one or more days (delayed type hypersensitivity).• Delay is due to migration of macrophages and T cells to site of foreign

antigens.• Reactions are frequently displayed on the skin: itching, redness, swelling,

pain.• Tuberculosis skin test• Poison ivy•Metals• Latex in gloves and condoms (3% of health care workers)

• Anaphylactic shock may occur.

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Some Diseases of Immune System

• Allergic Contact Dermatitis Response to Poison Ivy Hapten

• Grave’s Disease:

• Myasthenia gravis:

• Systemic Lupus Erythematosus:

• Rheumatoid Arthritis:

• Insulin-dependent (Type I or Juvenile) Diabetes Mellitus:

• Acquired Immunodeficiency Syndrome (AIDS)

SUMMARY

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SUMMARY Type of Cell Function Location in the Body

Macrophage Ingests and kills pathogens Spleen, lungs, blood,

lymph, interstitial fluids

Neutrophil Engulfs and destroys pathogens Bloodstream, infection

sites

Natural Killer Cell Punctures infected cells Infected cells

Helper T Cell Activates cytotoxic T and B cells Bloodstream, infection

sites

Cytotoxic T Cell Punctures infected cells Infection sites

B Cell Labels invaders for destruction

By Macrophages Infection sites

Plasma Cell Releases antibodies Bloodstream

Memory Cell Protects against defeated

pathogens Bloodstream

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Summary Many of the body’s most effective defenses are nonspecific.

•Nonspecific defenses include physical barriers such as the skin, phagocytic cells, killer cells, and the complement proteins.•Inflammatory response aids the mobilization of defensive cells at infected sites.

Specific immune defenses require the recognition of antigens.

•Lymphocytes called B cells secrete antibodies and produce the humoral response; lymphocytes called T cells are responsible for cell-mediated immunity.

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Summary

T cells organize attacks against invading microbes.

• T cells only respond to antigens presented to them by macrophages or other antigen-presenting cells together with MHC proteins.• Cytotoxic T cells kill cells that have foreign antigens presented together with proteins.

B cells label specific cells for destruction. 1. The antibody molecules consist of two heavy and two light polypeptide regions arranged like a “Y”; the ends of the two arms bind to antigens.2. An individual can produce a tremendous variety of different antibodies

because the genes which produce those antibodies recombine extensively.

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Summary 3. Active immunity occurs when an individual gains immunity by prior exposure to a pathogen; passive immunity is produced by the transfer of antibodies from one individual to another.

All animals exhibit nonspecific immune response but specific ones evolved in vertebrates.

•The immune system evolved in animals from a strictly nonspecific immune response in invertebrates to the two-part immune defense found in mammals.

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SUMMARY The immune system can be defeated.

Flu viruses, trypanosomes, and the protozoan that causes malaria are able to evade the immune system by mutating the genes that produce their surface antigens. In autoimmune diseases, the immune system targets the body’s own antigens.

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REFERENCES:

www.mhhe.com/raven6e

www.biocourse.com

Source: The Immune System . Johnson, Raven. 2001. Biology: Principles and Explorations. Holt, Rinehart and Winston. Pages 931 - 937

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