Immunity Vocabulary: Pathogen, antigen,

antibody, artificial, natural, active, passive, specific, nonspecific, monoclonal, vaccination, phagocyte, macrophage, clotting, antibiotic, T-Cell, B-Cell, thrombin, prothrombin, fibrinogen, fibrin, platelets, innate, inflammation, fever, mucous, cell-mediated, humoral, effector cell, virus, bacteria

INNATE DEFENSES AGAINST INFECTION

Innate defenses against infection include the skin, mucous membranes, and phagocytic cells

• Innate immunity is the body’s first line of defense against all invaders– Skin provides tough barrier and

general chemical defenses– Mucous membranes– Stomach acid– Hairs, cilia

• Pathogens that get past the body's external defenses are met by innate defensive cells– Found in blood and interstitial fluid– Macrophages are large phagocytic

cells– Natural killer cells release

chemicals– Specific proteins attack microbes

or impede their reproduction• Interferons help cells resist

viruses• The complement system– Initiated by microbes, can lead to

lysis of invaders

Bacteria

Co

lori

zed

SE

M 3

,80

0

Virus Viral nucleic acid

New virusesInterferongenesturnedon

DNA

mRNA

Interferonmolecules

Host cell 1Makes interferon;is killed by virus

Host cell 2Protected against virusby interferon from cell 1

Interferon stimulatescell to turn on genesfor antiviral proteins

Antiviral proteins blockviral reproduction

The inflammatory response mobilizes nonspecific defense forces

• Tissue damage triggers the inflammatory response– Can disinfect tissues and limit further

infection• Steps of the inflammatory response

1. Tissue injury releases chemical signals such as histamine

2. Local blood vessels dilate and leakiness increases; phagocytes migrate to the area

3. Phagocytes consume bacteria and cell debris; tissue heals

• The inflammatory response may be widespread as well as localized– White blood cells may increase– Fever may stimulate

phagocytosis– Septic shock • Overwhelming systemic

inflammatory response• May cause death

Pin Skin surface

Bacteria

Chemicalsignals

White blood cell

Blood vessel

Tissue injury; release ofchemical signals such ashistamine

Dilation and increased leakinessof local blood vessels; migrationof phagocytes to the area

Phagocytes (macrophages andneutrophils) consume bacteriaand cell debris; tissue heals

Phagocytesand fluidmove into area

Swelling

Phagocytes

The lymphatic system is activated during infection• The lymphatic system is involved in both innate

and acquired immunity– Branching network of lymphatic vessels – Lymph nodes packed with macrophages and

white blood cells– Tonsils and adenoids– Appendix– Spleen– Bone marrow and thymus– Lymph, similar to interstitial fluid

• Main functions of the lymphatic system

– Return tissue fluid to circulatory system

• Lymphatic vessels take up fluid from tissue spaces

• Lymph reenters circulatory system through two large lymphatic vessels

– Fight infection

• Microbes picked up from infection sites travel in lymph through lymphatic organs packed with white blood cells

Adenoid

Tonsil

Lymph nodes

Right lymphaticduct, enteringvein

Thoracic duct,entering vein

Thymus

Thoracicduct

Appendix Spleen

Bonemarrow Lymphatic

vesselsLymphaticcapillary

Interstitial fluidTissue cells

Blood capillary

Lymphatic vesselValve

Masses oflymphocytes andmacrophages

Lymph node

ACQUIRED IMMUNITY*The immune response counters specific invaders

• The immune system recognizes and defends against invading microbes and cancer cells– Can distinguish one infectious agent from

another• Acquired immunity develops only after

exposure to a specific foreign substance (antigen)– System produces a specific type of antibody

that helps counter the antigen's effects– Primed system remembers the antigen and

reacts to it in the future

• Immunity is usually acquired by natural exposure to antigens but may be achieved by vaccination*

– Active immunity

• Person's own immune system actively produces antibodies

– Passive immunity

• Person receives premade antibodies, as a fetus does from its mother

• Immunity lasts only as long as the antibodies do

Natural v. Artificial*

Natural immunity is defined as that being acquired from having gotten the pathogen w/out being injected or inoculated.

Artificial immunity is defined as having being given through an injection or inoculation

Being exposed to Chicken Pox when young is “natural”, while getting the chicken pox vaccine is considered “artificial”.

Lymphocytes (WBC’s) mount a dual defense

• Lymphocytes originate from stem cells in the bone marrow

• Humoral immunity

– B cells secrete antibodies that circulate in blood and lymph to sites of infection

– Defends primarily against bacteria and viruses present in body fluids

• Cell-mediated immunity

– In the thymus, immature lymphocytes specialize into T cells

– T cells attack cells infected with pathogens, fungi and protozoans, cancer cells

– T cells also promote phagocytosis and production of antibodies

• Functioning of B and T cells

– Certain genes in the cell are turned on

– Cell synthesizes specific protein molecules, which are incorporated into the plasma membrane

– Antigen receptors sticking up from cell surface recognize specific antigens and mount a defense

• Millions of diverse B and T cells stand ready to recognize and bind virtually every possible antigen

Bone marrow

Stem cell

Immature lymphocyte

Viablood

Thymus

Antigenreceptors

B cell

Humoralimmunity

Viablood

T cell

Cell-mediatedimmunity

Final maturationof B and T cells inlymphatic organ

Lymph nodes, spleen, andother lymphatic organs

Other parts of thelymphatic system

Antigens have specific regions where antibodies bind to them

• Antigens are usually molecules on the surface of viruses or foreign cells

• Antigenic determinants are the specific regions on an antigen to which antibodies bind

– Antigens may have several different determinants

– Immune system may direct several distinct antibodies against one antigen

Antibody Amolecules

Antigen-bindingsites

Antigenmolecule

Antigenicdeterminants

Antibody Bmolecule

Clonal selection musters defensive forces against specific antigens*

• Primary immune response: lymphocytes exposed to antigen for the first time– Antigen activates a small subset of

lymphocytes (B cells) bearing complementary receptors

– The selected B cells multiply into clones of effector and memory cells

• Effector (plasma) cells* – Combat the antigen– Secrete antibody molecules that

circulate in blood and contribute to humoral immunity

– Last only 4 or 5 days• Memory cells – Remain in lymph nodes – May last for decades, sometimes

confer lifetime immunity

• Secondary immune response*– Memory cells exposed to same antigen a

second time– Second round of clonal selection ensues– Secondary response is faster and

stronger; produces very high levels of antibodies

Animation: Role of B Cells

Comparison of primary and secondary immune response Primary response

Takes several days to occur, during which the individual may become ill

Antibody level peaks in about two weeks, activated cells die out

Secondary response Occurs quickly Is of greater magnitude and lasts

longer

• Acquired immunity is specific: the body's response to a second antigen is not influenced by its response to the first one

Second exposureto antigen X,

first exposureto antigen Y

Secondary immuneresponse to

antigen X

Primary immuneresponse to

antigen X

Primary immuneresponse to

antigen Y

First exposureto antigen X

Antibodiesto X

Antibodiesto Y

An

tib

od

y c

on

ce

ntr

ati

on

0 7 14 21 28 35 42 49 56Time (days)

Antibodies are the weapons of humoral immunity

• Antibody molecules are secreted by plasma (effector) B cells

• Antibody molecule structure

– Y shaped, made of two identical "heavy" and two identical "light" polypeptide chains

– A C (constant) and a V (variable) region on each chain

– Antigen-binding sites specific to the antigenic determinants that elicited its secretion

• Antibody functions in humoral immunity

– Binds its antigen at the antigen-binding site

– Assists in elimination of the antigen, at the C region of the heavy chains

Antibodies mark antigens for elimination• Involves a specific recognition-and-attack

phase followed by a nonspecific destruction phase

• Antibodies mark invaders by forming antigen-antibody complexes

• Binding triggers ways to eliminate the invader– Neutralization – Agglutination of microbes– Precipitation of dissolved antigens – Activation of complement system

Binding of antibodies to antigensinactivates antigens by

Neutralization(blocks viral bindingsites; coats bacteria)

Agglutinationof microbes

Virus

Bacterium

Bacteria

Precipitation ofdissolved antigens

Antigenmolecules

Activation ofcomplement system

Complementmolecule

HoleForeign cell

Cell lysisPhagocytosis

Enhances

Macrophage

Leads to

Monoclonal antibodies are powerful tools in the lab and clinic

• Antibodies are used in clinical diagnosis, treatment, and research (pregnancy tests, cancer)

• Monoclonal antibodies

– All cells producing the antibodies are descendants of a single cell

– Harvested from cell cultures rather than from animals

• Production of monoclonal antibodies*

– Animal injected with antigen that stimulates its B cells to make specific antibodies

– B cells fused with tumor cells

– Hybrid cells make antibodies specific for the desired antigenic determinant

• Can multiply indefinitely in culture

- Harvest antibodies

Antigen injectedinto mouse

B cells(from spleen)

Tumor cells grownin culture

Tumor cells

Cells fused togenerate hybridcells

Single hybrid cellgrown in culture

Antibody

Hybrid cell culture,producing monoclonal antibodies

Helper T cells stimulate humoral and cell-mediated immunity

• Cell-mediated immunity produced by T cells battles pathogens that have entered body cells

• T cells respond only to antigens present on the surface of the body's own cells– Cytotoxic T cells attack infected cells

– Helper T cells • Help activate T cells, B cells, and macrophages

• Interact with antigen-presenting cells

• Precise interaction of antigen-presenting cells and helper T cells – Antigen-presenting cell self protein binds antigen

nonself molecules and displays them on the cell surface

– Helper T cells recognize and bind to the self-nonself complex

• Depends on highly specific receptors in the T cell's plasma membrane

– Binding activates helper T cells

• Enhanced by other signals

• Activated helper T cells promote the immune response, particularly secretion of stimulatory proteins

– Make helper T cells grow and divide, producing memory cells and additional helper T cells

– Help activate B cells, stimulating humoral immunity

– Stimulate activity of cytotoxic T cells

Microbe Macrophage

Self-nonselfcomplex

Antigen from microbe(nonself molecule)

Self protein

Antigen-presentingcell

T cellreceptor

Interleukin-1stimulateshelper T cell

Bindingsite forantigen

Bindingsite forself protein

HelperT cell

Interleukin-2stimulatescell division

B cell

Interleukin-2activatesother B cellsand T cells

Cell-mediatedimmunity(attack oninfected cells)

CytotoxicT cell

Humoralimmunity(secretion ofantibodies byplasma cells)

Cytotoxic T cells destroy infected body cells

• Like helper T cells, cytotoxic T cells recognize and bind with self-nonself complexes on infected cells

• Mechanism of cytotoxic T cell action– Binding to infected cell stimulates cytotoxic T cell to

synthesize perforin

– Perforin makes holes in infected cell's membrane, and T cell enzymes enter

– Infected cell is destroyed

Cytotoxic T cell bindsto infected cell

Self-nonselfcomplex

Perforin molecule

CytotoxicT cell

Enzyme thatcan promoteapoptosis

Holeforming

Perforin makes holes ininfected cell’s membraneand enzyme enters

Foreignantigen

Infected cellis destroyed

Infected cell

Cytotoxic T cells may help prevent cancer

• Genetic changes leading to cancer can result in new proteins displayed on cell surfaces

• T cells identify these tumor antigens as foreign and destroy the affected cells

Allergies are overreactions to certain environmental antigens

• Allergies are abnormal sensitivities to antigens (allergens) in the surroundings

• Allergic reactions occur in two stages– Sensitization: initial exposure to allergen

• Allergen enters bloodstream

• B cells make antibodies

• Antibodies attach to mast cells that produce histamines and trigger the inflammatory response

– Later exposure to same allergen

• Allergen binds to antibodies on mast cell

• Histamine is released, causing allergy symptoms

• Anaphylactic shock is a severe allergic reaction

– Causes severe drop in blood pressure

– Potentially fatal

B cell(plasma cell)

Mastcell

Antigenicdeterminant

Allergen (pollengrain) enters bloodstream

B cells makeantibodies

HistamineAntibodiesattach tomast cell

Sensitization: Initial exposure to allergen

Allergen bindsto antibodieson mast cell

Histamine isreleased, causingallergy symptoms

Later exposure to same allergen

Blood Clotting Crazy

Blood Clotting Better

Blood Clotting Best*