immunity vocabulary: pathogen, antigen, antibody, artificial, natural, active, passive, specific,...
TRANSCRIPT
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
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
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