THE IMMUNE SYSTEM-6.4

Gillian & Jorelle

http://youtube.com/v/zQGOcOUBi6s

OVERVIEW OF THE IMMUNE

SYSTEM. :)→ → →

IMMUNE SYSTEM-Enables an animal to avoid or limit infections

SOME VOCAB. YOU SHOULD KNOW ALREADY.. >:)

PATHOGENS- Things that cause disease

MICROBES- bacteria, archaebacteria, protists, some fungi

INNATE AND ADAPTIVE IMMUNITY INNATE IMMUNITY- A defense that is active immediately upon infection (NON-SPECIFIC RESPONSES TO PATHOGEN)● Thought of as a front line defense against pathogens.● Prevent exposure of pathogens.

○ External barriers, internal cellular/chemical defenses.● Available to ALL ANIMALS/PLANTS

ADAPTIVE IMMUNITY- A defense that is composed of specialized, systemic cells-in prevention of Pathogens (SPECIFIC RESPONSES TO PATHOGENS)● VERTEBRATES ONLY- produce arsenal of receptors each recognize a

feature. (specificity)● B cells and T cells.

ANALOGY OF THE IMMUNE SYSTEMThink of your body as a castle…

In a castle there is a certain system in keeping invaders out.

(3) lines of defense in a castle Wall/Moat

Guards

Spies

In our bodies we have (3) Lines of defenseThe first (2) lines of defense are NONSPECIFIC

INNATE DEFENSE MECHANISMS

The 3rd line of defense is ADAPTIVE IMMUNITY

ANALOGY OF THE IMMUNE SYSTEM1st Line of defense=CASTLE’S WALLS/MOAT

*NONSPECIFIC INNATE DEFENSE MECHANISM*

Acts like a barrier that help prevent pathogens from entering the body. (prevents infection)

Skin=Castle’s Walls

Mucous Membranes-release mucus contains antimicrobial substances. (includes Lysosomes) =Castle’s Moat → removal of microbes

Cilia-Respiratory System, takes out mucus with its trapped microbes

Stomach Acid- prevents the growth of bacteria because of low pH (as well as the skin)

-NONSPECIFIC- It does not target the specific invaders directly, it’s just there.

ANALOGY OF THE IMMUNE SYSTEM2nd Line of defense=THE GUARDS

*NONSPECIFIC INNATE DEFENSE MECHANISMS*

Microbes that get into the body encounter the second line of defense, which is to limit the spread of invaders in advance of specific immune responses.

Inflammatory response- EX) swelling, pain, etc.

Histamine-triggers vasodilation (enlargement of the blood vessels), which increases blood supply to the area, bringing more phagocytes. Secreted by basophils (a type of circulating white blood cell) and mast cells, found in the connective tissue. Responsible for for symptoms of the common cold.

Prostaglandins- further promotes blood flow to the area, helps deliver antimicrobial peptides

Chemokines- secreted by blood vessel endothelium and monocytes also attract phagocytes to the area

Pyrogens- released by certain leukocytes, increased body temper. to speed up the immune system and make it more difficult for microbes to function.

Inflammatory ResponseThe inflammatory response, such as pain and swelling, is brought

about by molecules released upon injury of infection

Mast cells release histamine, which triggers blood vessels to dilate and become more permeable

Activated macrophages and neutrophils release cytokines, signaling molecules that modulate the immune response and promote blood flow to the site of injury or infection

Enhanced blood flow to the site helps deliver antimicrobial peptides

This results in an accumulation of pus, a fluid rich in white blood cells, dead pathogens, and cell debris from damaged tissues

Inflammatory Response ContinuedInflammation can be either local or systemic (throughout the body)

Fever is a systemic inflammatory response triggered by substances released by macrophages

Septic shock is a life-threatening condition caused by an overwhelming inflammatory response

Chronic inflammation can also threaten human health

ANALOGY OF THE IMMUNE SYSTEM2nd Line of Defense=THE GUARDS (Continued)

●***Phagocytes- ingest invading fungal and bacterial microbes. (Phagocytosis)

●complement- A group of (30) proteins that lead to the lysis (bursting) of invading cells; activated by substances on microbial surfaces

● Interferons- block against cell-to-cell viral infections, helps activate macrophages

●Natural killer (NK) cells- they go around the body detecting abnormal cells, destroy virus-infected body cells by releasing chemicals (includes cancerous cells) they attack the cell membrane, causing it to lyse (burst open) and die.

●Antimicrobial peptides (AMPs)- kill gram negative/positive bacteria, engulf viruses, fungi, etc.

CELLULAR INNATE DEFENSESOnce pathogens enter the body-PHAGOCYTOSIS

TOLL-LIKE RECEPTORS (TLRs)- helps the phagocytic cells recognize the group of pathogens. Then the TLR binds to fragments of molecules specific to the set of pathogens.

NEUTROPHILS- engulfs microbes and die within a few days MACROPHAGES- “giant eaters.” they engulf huge numbers of microbes over a long

period of time. In which, they digest the microbes with a combination of lysosome and (2) toxic forms of oxygen.

Both of which migrate to an infected site in response to local chemical attractants. (this response is called CHEMOTAXIS) ^^^^

DENDRITIC CELLS- antigen-presenting cells- development of adaptive immunity, contact with the environment.

EOSINOPHILS- (White blood cell) discharge destructive enzymes underneath mucous surface

EXAMPLES OF INNATE DEFENSE IN INVERTEBRATESex) Insects=exoskeletonLYSOZYME-Is responsible for the breaking down of bacterial walls which covers protection along with in ingest of food. (Digestive System)____________________________________________________________Hemocytes (red blood cells) circulate within hemolymph which carries out..

***PHAGOCYTOSIS-the ingestion/breakdown of foreign substances including bacteria → → →

also release antimicrobial peptides that alter the plasma membrane of fungi/bacteria

immune system recognizes bacteria/ fungi by structure on their cell walls.

EVASION OF INNATE IMMUNITY BY PATHOGENSAdaptations have evolved in some pathogens that enable them to be avoid destruction by phagocytic cellstuberculosis (TB) resists breakdown within lysosomes after being engulfed by a host cellMechanisms like this make certain fungi and bacteria substantial pathogenic threats

ANALOGY OF THE IMMUNE SYSTEM3rd Line of defense=SPIES

*ADAPTIVE IMMUNITY*

This defense system relies on the (2) types of LYMPHOCYTES- B-lymphocytes and T-lymphocytes (WHITE BLOOD CELLS)

Once matured, both types of cells circulate in the blood, lymph, and lymphatic tissue (spleen, lymph nodes, tonsils, etc.)

Both cells recognize different specific antigens.

***This defense system targets the individual pathogens/microbes directly.

VOCAB BEFORE WE GO INTO OUR LYMPHOCYTES. ANTIGEN- any substance that causes your immune system to produce antibodies against it

ANTIGEN RECEPTOR- an antibody protein that is not secreted but is anchored to the B-cell membrane

EPITOPE-the specific piece of the antigen that an antibody binds to

ADAPTIVE IMMUNE RESPONSE(3rd line of defense)ADAPTIVE IMMUNE RESPONSE- Is a specific response and involves (3) phases

RECOGNITION- Antigen receptors on B and T lymphocytes recognize specific antigens or epitopes by binding to them.

Antigens- any substance that elicits an immune response from B/T cells. In order to recognize an antigen-must be present to a B/T cell by antigen-presenting cell.

Epitopes- accessible piece of an antigen that elicits an immune response from B/T cells. Each B cells displays specificity for (1) epitope

ACTIVATION PHASE- The binding of an antigen receptor activates B/T cells causing them to undergo cell division. (cells form populations of effector cells and memory cells)

EFFECTOR PHASE- After being activated B cells produce a humoral response; they produce antibodies. T cells engage in a cell mediated response.

3RD LINE OF DEFENSE

T Lymphocytes-T cells-Form in the bone marrow and

mature in the thymus gland (A small organ in the thoracic cavity of vertebrates) Fight pathogens in cell-mediated immune response.

○ There main job is to fight pathogens in a cell-mediated response/immunity

ANTIGEN RECOGNITION BY T CELLS● Each receptor consists of (2) different

polypeptide chains (α and β)● Tips of the chain form a Variable (v) region; the

rest is a constant (C) region● V regions of the α and β chains together form an

antigen-binding site

ACTIVATION PROCESS OF T-CELLS○ the activation process begins when T cell antigen receptors

recognize and bind to antigens displayed on the surface of Antigen Presenting Cells (APCs) by a molecule- Major Histocompatibility Complex (MHC)- molecules are host proteins that display the antigen fragments on the cell surface

● A T cell can then bind both the antigen fragment and the MHC molecule

● This interaction is necessary for T cell to participate in adaptive immune response

○ Each t cell displays specificity for (1) epitope. Once activated, a t cell proliferates and forms a population of activated t clones. Some of the clones become effector cells-short lived defend the body-immune response, then the rest become memory cells-respond to any exposure to the same antigen years later.

MHC MOLECULES + APCs CLARIFICATIONMajor histocompatibility complex (MHC) molecules (also known as HLA-human leukocyte antigens)- collection of cell surfaces that identify the cells as self. (2) main classes of MHC markers

class I MHC molecules-found on the surfaces of every nucleated body cell

Class II MHC molecules-are found on specialized cells, including macrophages, B cells, dendritic cells, and activated T cells.

Antigen-Presenting Cells- they present an antigen/piece of antigen, an epitope, to the immune system. “HERE IS THE ENEMY!”

Process begins when APC- macrophage, dendritic cell, or B cell takes in an antigen. Either the APC becomes infected with the antigen or engulfs it. Once inside the host, enzymes break apart the antigen into fragments and attach them to an MHC molecules in the cytoplasm.

Then the MHC molecule- moves to the surface of the cell and displays it. (OTHER CELLS-T/B CELLS BECOME ACTIVATED IF THEY CAN PROPERLY BIND TO THE EXPOSED ANTIGEN.)

TYPES OF T CELLS2) main types of t cells●helper t cells (Th) → activated my

interaction with APC●cytotoxic t cells (Tc) → activated

by helper T cells

HELPER T CELLS● Activated by interaction with an APC-Antigen presenting cells● Once activated they announce to the immune system that foreign

antigens have entered to body● They trigger a humoral/cell-mediated response● In addition to activating other helper T cells, they activate cytotoxic

T cells that kill infected B cells that produce antibodies. They activate these other cells by releasing cytokines, interleukin-1 (I1-1), and interleukin-2 (I1-2). Because helper T cells have CD4 accessory proteins on their cell surface they are referred to as CD4 cells.

CYTOTOXIC T CELLSThey attack and kill body cells infected with pathogens as well as

cancerous cells. Also they recognize fragments of foreign proteins produced by infected cells/possess an accessory protein that binds to class I MHC molecules. They do it by a cell-mediated response.

An activated Cytotoxic T cells proliferates/differentiates into an effector cell and a memory cell. Also they secretes proteins that disrupt the membranes of target cells and trigger apoptosis.

Activated Cytotoxic cells attack and kill infected cells by releasing perforin (A protein that forms pores in the target cell’s membrane) and granzymes (Enzymes that break down proteins) that cause the cell to lyse and die.

Infecting microbes are released into the blood/tissue and disposed by circulating antibodies.

Because Cytotoxic cells have CD8 accessory protein on their surface-CD8 cells

3RD LINE OF DEFENSE

B Lymphocytes- B cellsB cells mature in bone

marrow, from which they get their name.● Each B cell antigen receptor is

a Y-shaped molecule with two identical heavy chains and two identical light chains○ The constant regions of the

chains vary little among B cells, whereas the variable regions differ greatly

○ Together, the variable regions of the heavy and light chains form an antigen-binding site

ANTIBODIES Antibodies, also called immunoglobulins, are a group of globular

proteins.

Each antibody molecule is a Y-shaped molecule consisting of four polypeptide chains, two identical heavy chains and two identical light chains joined by disulfide bridges

it is now accepted that the blueprints for antibodies are made early in life, prior to any exposure to antigens .

when you are exposed to an antigen, antibodies are chosen by clonal selection from a limitless variety as needed

because of ↑, the variety in antibodies in unlimited and there is no viral disease for which humans cannot produce antibodies

B cells ContinuedBinding of a B cell antigen receptor to an

antigen is an early step in B cell activation

This gives rise to cells that secrete a soluble form of the protein called an antibody or immunoglobulin (Ig)

Secreted antibodies are similar to B cell receptors but are not membrane bound

The antibodies, rather than B cells themselves, defend against pathogens

B cell’s Steps to Activation1.an APC (macrophage-a large phagocytic cell found in stationary

form in the tissues or as a mobile white blood cell or dendritic cell-messengers between the innate and the adaptive immune systems) presents an antigen or epitope on its cell surface using a class II MHC molecule

2.a helper T cell that recognizes this epitope-MHC molecule complex is activated with the aid of cytokines secreted from the APC

Once activated, the B cell undergoes multiple cell divisions, producing thousands of clones

B cell ClonesSome of the clones that the B cell produces become effector cells,

also known as plasma cells, that secrete antibodies

The remainder of the clones develop into long-term memory cells that can rapidly respond to any exposure to the same antigen many years later

these memory cells are responsible for immunological memory and are the reason that a person does not, for example, get measles a second time

GENERATION OF B AND T CELL DIVERSITYBy combining variable elements, the immune system assembles a

diverse variety of antigen receptors

The capacity to generate diversity is built into the structure of Ig genes. (immunoglobulin-gene that encodes the light chain of both secreted antibodies and membrane bound B cell antigen receptors.)

Many different chains can be produced from the same gene by rearrangement of DNA

Arranged DNA is transcribed and translated and the antigen receptor is formed

SELF-TOLERANCENormally the immune system exhibits self tolerance- it does not

attack body cells. However, sometimes immature lymphocytes develop that have antigen receptors specific for the body’s own cells. DUN. DUN. DUN.

If the cells were allowed to escape, these cells would attack the body’s cells, a situation characteristic of autoimmune disease.

to avoid this, lymphocytes are tested for self-reactivity as they mature in the bone marrow.

B and T cells that are identified as self-reactive are destroyed by Apoptosis-programed cell death.

Regulatory T cells called Treg inhibit the activation of the immune system in response to self-antigens. They secrete interleukin-10 (I1-10)

PROLIFERATION OF B CELLS AND T CELLSIn the body there is a small fraction of antigen receptors specific for a

given epitopeIn lymph nodes, an antigen is exposed to a steady stream of lymphocytes until a

match is madeThis binding of a mature lymphocyte to an antigen initiates events that activate the

lymphocyteOnce activated B/T cell undergoes multiple cell divisions to produce a clone of identical cells (clonal selection)-fundamental mechanism in the development of immunity. ---------(2) types of clones are produced

effector cells-short lived, begin their battle against the antigen immediatelymemory cells-long lived, that remain in the body for the rest of one’s life and

can rapidly respond to any future exposure to the same antigen, even many years later. Memory cells are responsible for Immunological memory- ex) you usually don’t get measles the 2nd time.

IMMUNOLOGICAL MEMORYPRIMARY IMMUNE RESPONSE-

during the time of first exposure to a specific antigen, selected B and T cells give rise to their effector forms

SECONDARY IMMUNE RESPONSE-B and T lymphocytes produce a humoral immune response and a cell-mediated immune

response (Note: In the secondary immune response, memory cells facilitate a faster, stronger, and longer response. Immunological memory can span many decades)

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HUMORAL IMMUNE RESPONSE-antibodies help neutralize or eliminate toxins and pathogens in the blood and lymphCELL-MEDIATED IMMUNE RESPONSE- specialized T cells destroy infected host cells

IMMUNE RESPONSE

TYPES OF IMMUNITY

Passive Immunity-● Temporary● Antibodies are transferred to an

individual from someone else.● Ex: maternal antibodies that pass

through the placenta to the developing fetus or through breast milk to the baby

● a person with a weak immune system often receives an injection of gamma globulin (IgG), which are antibodies from many people, to boost the weak immune system

Active Immunity-● Permanent● The individual makes his or her own

antibodies after being ill and recovering or after being given an immunization or vaccine.

● A vaccine contains dead or live viruses or enough of the outer coat of a virus to stimulate a full immune response and to impart lifelong immunity

AllergiesAllergies are exaggerated (hypersensitive) responses to antigens called

allergens

In localized allergies such as hay fever, plasma cells secrete antibodies specific for antigens on the surface of pollen grains

This triggers immune cells in connective tissue to release histamine and other inflammatory chemicals

Antihistamines block receptors for histamine and diminish allergy symptoms

Allergies continuedAn acute allergic response can lead to anaphylactic shock, a life-

threatening reaction

Substances that can trigger anaphylactic shock in allergic individuals include bee venom, penicillin, peanuts, and shellfish

People with these hypersensitivities often carry epinephrine to counteract the allergic response

Autoimmune DiseasesThe immune system targets certain molecules of the body in the

bodies of people with autoimmune diseases

Some examples of some autoimmune diseasessystemic lupus erythematosus

rheumatoid arthritis

insulin-dependent diabetes mellitus

multiple sclerosis

Immune System AvoidancePathogens have evolved mechanisms to stop immune responses

the pathogen does this by altering how the immune system sees it by changing the epitopes it expresses

Epitopes- are an accessible pieces of an antigen that elicits an immune response from b/t cell

The changes the pathogens make to their epitopes are called antigenic variation

These changes are seen in the parasite that causes sleeping sickness and in the influenza virus

HIV (human immunodeficiency virus)Acquired immunodeficiency syndrome (AIDS) is caused by HIV , which both attacks and escapes the immune system

Facts about AIDS/HIV:It infects helper T cells with high efficiency It escapes the immune system through its high mutation rate, which

reduces the ability of the immune system to eliminate the infectionIt can undergo latency (viruses avoid an immune response by

infecting cells and then entering an inactive state called latency)People with AIDS are highly susceptible to infections and cancers that

a healthy immune system would normally defeatHIV cannot be cured, but drugs have been developed to slow HIV

replication and progression to AIDS

Cancer and ImmunityThe frequency of certain cancers increases when adaptive immunity is

impaired

20% of all human cancers involve viruses

The immune system can act as a defense against viruses that cause cancer and against cancer cells that harbor viruses

In 2006, a vaccine was released that acts against human papillomavirus (HPV), a virus associated with cervical cancer

OVERVIEW OF THE IMMUNE SYSTEM1.SPECIFICITY- The entire system depends on the matching of

antigen to antigen receptors and the matching of antigens to antibodies

2.DIVERSITY- A wide variety of different cell types defend our bodies from pathogens

3.MEMORY- B and T memory cells circulate for a lifetime

4.CAPACITY TO DISTINGUISH SELF FROM NONSELF- Fortunately, most of the time, the immune system does not attack healthy body cells. Phenomenon known as self-tolerance.