T HE I MMUNE S YSTEM By Sarah Kellogg, Anna Smith, and Nicole Sinno.

THE IMMUNE SYSTEMBy Sarah Kellogg, Anna Smith, and Nicole Sinno

FUNCTION:To recognize and neutralize potentially harmful substances

Two types:Innate immunityAcquired/Adaptive immunity

Present before any exposure to pathogens

Effective from time of birth Nonspecific, responding to

broad range of microbes

Develops only after exposure to inducing agents such as microbes or toxins

Highly specific- distinguish one inducing agent from another

Innate Immunity Acquired/Adaptive

immunity

INNATE IMMUNITY: EXTERNAL DEFENSES

Skin is barrier that viruses and bacteria cannot normally penetrate

First Line of Defense

• However, tiny abrasions may allow them to get past

• Therefore… Mucous membranes lining digestive, respiratory, and genitourinary tracts prevents entry of microbes, and produce mucus to trap the microbes

• Secretions from skin and mucous membranes contain antimicrobial proteins that wash microbial colonization away (saliva and tears)

• • Lysozyme: an enzyme that digests cell walls of many bacteria

• Present in saliva, tears, and mucous secretions • Destroy bacteria as enter upper respiratory tract or openings

around eyes

•Mucous membranes provide hostile environment to microbes

•In humans, secretions from sweat glands give skin pH of 3 to 5

•Thus, skin too acidic for colonization of microbes

•Stomach too acidic for most microbes

•Hepatitis A virus can survive the acidic stomach

Phagocytosis: the ingestion of invading organisms by certain types of white blood cells

Phagocytes Defend against

microbes that have managed to enter the body

Attach to their prey via surface receptors and engulf them, forming vacuole that fuses with lysosome

Innate Immunity: Second Line of Defense: Internal Cellular and Chemical Defenses

WHITE BLOOD CELLS (LEUKOCYTES)• Attracted by chemical signals released by

damaged cells • 4 types of phagocytic white blood cells1. Neutrophils2. Macrophages3. Eosinophils4. Dendritic cells

1. Neutrophils: engulf microbes in infected tissue Self destruct in process of phagocytosis 60%-70% of all white blood cells

2. Macrophages more effective Develop from monocytes Most are permanent residents in organs and tissue Play role in acquired immunity

3. Eosinophils Defend against parasitic invaders by positioning

themselves near parasites wall and discharging hydrolytic enzymes

4. Dendritic cells Ingest microbes like macrophages do Main role: trigger acquired immunity

ANTIMICROBIAL PROTEINS

function in innate defense by attacking microbes directly or by impeding their reproduction

Complement system Include 30 serum proteins In absence of infection, these proteins are

inactiveo Substances on surfaces of microbes trigger steps

that activate this system and cause lysis of invading cells

Interferono Secreted by virus infected body cellso Induce neighboring cells to produce substances

that inhibit viral reproduction

INFLAMMATORY RESPONSE

INNATE DEFENSE

Histamine is release by mast cells When injured, mast cells release their histamine,

and trigger dilation and permeability of nearby capillaries

Helps deliver clotting agents to injured area Blood flow also brings large numbers of

phagocytes to the infected area Proteins called chemokines direct migration of

phagocytes Increased blood flow to injured site causes the

redness and typical of inflammation The blood filled capillaries leak fluid into

neighboring tissues causing the swelling

NATURAL KILLER CELL (NKC)INNATE DEFENSE

Patrol body and attack virus infected body and cancer cells

Once attached to virus infected cell (surface receptors) it releases chemicals that triggers apoptosis in cells they attack

Prevents cancer and viral infections

ACQUIRED IMMUNITY (BODY’S 2ND MAJOR KIND OF DEFENSE)

Lymphocytes provide the specificity and diversity of the immune system

Recognize particular microbes and foreign molecules (antigens) by means of antigen specific receptors in plasma membrane

Originate from pluripotent stem cells in bone marrow and later develop into either B or T cells

Vertebrates have two types of lymphocytes:1. B lymphocytes (B Cells)

Proliferate in bone marrow

2. T lymphocytes (T Cells) Migrate from bone marrow to mature in the thymus and develop

into T cells

NEW VOCABULARY

Antigens: any foreign molecule Antibodies: proteins secreted by B cells

during an immune response Antigen receptors: located on antigen and

allow B and T cells to recognize them

A lymphocyte actually recognizes and binds to just a small, accessible portion of the antigen called an epitope

Antigen-binding sites

Antibody A

Antigen

Antibody BAntibody C

Epitopes(antigenicdeterminants)

Bind to specific, intact antigens

Bind to fragments of antigens displayed by other cells

B Cell Receptors T Cell Receptors

T CELL RECEPTORS AND MHC

While receptors on B cell receptors recognize intact antigens, the receptors on T cells recognize small fragments of antigens bound to normal cell surface proteins

These cell surface proteins are called MHC molecules (major histocompatibility complex)

Newly synthesized MHC molecules are transported toward the plasma membrane, bind with a peptide antigen within the cell, and bring it to the surface of the cell Antigen presentation

T CELL RECEPTORS AND MHC CONTINUED

Two ways a foreign antigen can end up inside cells of body, depending on source, antigens are handled by a different class of MHC molecule and recognized by specific T cell:

1. Class 1 MHC molecules All nucleated cells of body Bind peptides synthesized within the cell Any body cell infected or cancerous display antigens Recognized by subgroup cytotoxic T cells

2. Class II MHC molecules Cell types dendritic, macrophages, and B cells Bind peptides from foreign molecules internalized and

fragmented through phagocytosis or endocytosis Dendritic cells, macrophages, and B cells display antigens Helper T-cells recognize antigens

T CELL RECEPTORS AND MHC CONTINUED

Microbe Antigen-presentingcell

Antigenfragment

Class II MHCmolecule

T cellreceptor

Helper T cell

A fragment offoreign protein(antigen) inside thecell associates withan MHC moleculeand is transportedto the cell surface.

1

The combination ofMHC molecule andantigen is recognizedby a T cell, alerting itto the infection.

2

(b)

CLONAL SELECTION OF LYMPHOCYTES

Antigen binds to B or T cell Lymphocyte becomes activated and forms

two clones of cells1. Effector cells (combat pathogens)2. Memory cells (long lived and have receptors

for same antigen)

PRIMARY IMMUNE RESPONSE

o When body is first exposed to antigen: Antigen binds to to a mature lymphocyte Lymphocyte is activated (clonal selection) takes 10 to 17 days for effective response to an

antigen

SECONDARY IMMUNE RESPONSE

Upon second exposure to the antigen: Some of the B cells produced during clonal

selection differentiate into another kind of white blood cell called a memory cell

Memory cells can last a very long time—years, decades, or a whole lifetime

If particular pathogen happens to enter body again, memory cells trigger a second round of clonal selection called the secondary immune response

Faster response (2-7 days) and greater magnitude So effective that all the invaders are usually

destroyed before any symptoms appear

TYPES OF B AND T CELLS

B- Cells Plasma B-Cells- Secrete

antibody molecules, which prevent pathogens from working

Memory B-Cells-Long living cells that are created during the primary immune response, if they recognize the pathogen that triggered their creation, they start a secondary immune response.

T-Cells Cytotoxic T Cell- Destroys cells

infected with pathogens or that have turned cancerous.

Memory Cytotoxic T Cells-Long living cells that are created during the primary immune response, if they recognize the pathogen that triggered their creation, they start a secondary immune response.

Helper T Cells-Recognize pathogens and trigger a primary immune response and signal other lymphocytes to activate.

THE TWO BRANCHES OF ACQUIRED IMMUNITY

Humoral Immune Response-The activation of B cells, which results in the production of secreted antibodies that circulate in the blood.

Cell-Mediated Immune Response-The activation of cytotoxic T cells , which destroy cells that have been infected by viruses or other pathogens. They can also destroy cancer cells

HELPER T CELL RESPONSE

CYTOTOXIC T CELL RESPONSE

B CELL RESPONSE (T-DEPENDENT ANTIGENS)- ANTIGENS THAT INDUCE ANTIBODY PRODUCTION ONLY WITH ASSISTANCE FROM HELPER T CELLS

ANTIBODIES(IMMUNOGLOBULIN)

Bind to antigens to inactivate pathogens

Some antigens can evoke B cell response without helper T cells called T-independent antigens• Most antigens recognized by B cells contain multiple

epitopes• Exposure to single antigen stimulates variety of B cells

giving rise to thousands of plasma cells• Plasma cells in one clone secrete antibodies specific to

epitope that provoked production

ANTIBODIES

Secreted antibody has general Y-shaped structure as B cell receptor but lacks transmembrane region that would anchor it to plasma membrane

Antigen binding sites on antibody responsible for ability to identify antigen

Tail of Y shaped body responsible for distribution in body and mechanisms for removing antigens (constant (C) regions of heavy chains)

Five major types of heavy-chain constant regions Determine five major classes of antibodies Based on immunoglobulin (Ig)

ACTIVE AND PASSIVE IMMUNIZATION

Active Immunity-Immunity created by natural exposure to a pathogens. It can also be created by vaccination

Passive Immunity-Immunity that is conferred by the transfer of antibodies from an outside source into an organism.

BLOOD GROUPS

Type A red blood cells have A antigen molecules on their surface Thus, the A antigen may be recognized as foreign if

placed in the body of another person. Individuals with the A antigen do not produce antibodies against the A antigen, because they are self-tolerant, but they have antibodies against the B antigen, even if not exposed to foreign blood.

IgM antibodies Type B antigen found on type B red blood cells Both A and B antigens found on type AB red blood

cells Neither antigen found on type O

TISSUE AND ORGAN TRANSPLANTATION

MHC molecules responsible for stimulating immune response that leads to rejection of tissue and organ transplants and grafts

At least some MHC molecules on donated tissue are foreign to recipient

No danger of rejection if donor and recipient are identical twins or if tissue is grafted from one part of the body and inserted on another part

To minimize rejection: In bone marrow transplant,

ALLERGIES Hypersensitive responses to antigens (allergens)

which could include foods, animals, or plants Most common allergens involve antibodies of IgE class Example: hay fever occurs when plasma cells secrete

IgE antibodies specific for antigens on surface of pollen grains These antibodies attach to mast cells in connective tissues When pollen grains re-enter body, they attach to antigen-

binding sites of mast cell associated IgE antibody molecules inducing the mast cell to release histamine and other inflammatory agents Leads to allergy symptoms- difficulty breathing, sneezing, runny

nose, etc, or Anaphylactic shock from dilation of peripheral blood vessels that

leads to a drop of blood pressure and potential death

AUTOIMMUNE DISEASE

oImmune system looses tolerance for itself and turns against certain molecules in the body

oExample: systemic lupus erythematosuso Immune system generates antibodies against wide range

of self molecules including histones and DNA released by normal breakdown of body cells

o Symptoms: skin rashes, fever, arthritis, kidney dysfunction

IMMUNODEFICIENCY DISEASESInborn (Primary) Immunodeficiencies

• Result from defects in development of various immune system cells or defects in production of specific proteins, such as IgA antibodies or complement components

• Innate defense, acquired defense, or both may be impaired

• Severe combined immunodeficiency (SCID)• Both humoral and cell-mediated

branches of acquired immunity fail to function

• Bone marrow transplant necessary to supply functional lymphocytes

IMMUNODEFICIENCY DISEASESAcquired (Secondary) Immunodeficiencies

Stress and the Immune System

• Healthy immune system depends on endocrine and nervous system

• People suffering from depression more likely to develop cancer

• Physical and emotional stress can harm immunity• Hormones secreted by adrenal glands during stress

affected number of white blood cells a may suppress immune system

• Neurotransmitters secreted when relaxed and happy may enhance immunity

ACQUIRED IMMUNODEFICIENCY SYNDROMEAIDS

AIDS is caused by the loss of helper T cells Crippling both the humoral and cell-mediated

immune responses The loss of T Cells is caused by human

immunodeficiency virus (HIV), a retro virus that targets T Cells

Cannot be cured Some drugs slow the progress of the disease Frequent mutations limit the efficiency the

drugs Contracted by transfer of bodily fluids Estimated in 2003 that 40 million people were

infected

  1. Phagocytosis is best defined as _____.

a.The process by which a white blood cell engulfs and destroys a bacterium

b.The process by which a cell engulfs and takes up liquid

c.the fusion of an intracellular vesicle with the plasma membrane of a cell

d.the process of activating memory T cells

2. Which of the following is not part of the body’s innate nonspecific defense system?

a.Natural killer cellsb.Inflamationc.Phagocytosis by neutrophilsd.Phagocytosis by macrophagese.antibodies

3. An epitope associates with which part of an antibody?

a. The antibody binding siteb. The heavy chain constant region onlyc. The variable regions of a heavy chain

and light chain combinedd. The light chain constant regions onlye. The antibody tail

4. A macromolecule produced in the body, which recognizes another molecule as "foreign" to the body, is a(n) _____.

a. Antigenb. Antibodyc. Lymphocyted. macrophage

5. The first line of defense against infection is _____.

a. The skin and mucous membranesb. The inflammatory responsec. The immune systemd. Antibiotics