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The IMMUNE SYSTEM
AP Bio Chapter 43
Antibody Immune System Response - Medical Animation
http://www.youtube.com/watch?v=iVMIZy-Y3f8
Organs of the Immune System
Fig. 43-7
Adenoid
Tonsil
Lymphnodes
Spleen
Peyer’s patches(small intestine)
Appendix
Lymphaticvessels Lymph
nodeMasses ofdefensive cells
Bloodcapillary
Lymphaticvessel
Tissuecells
Interstitial fluid
Lymphatic system
The Lymphatic System
• The lymphatic system aids the immune system in removing and destroying waste, debris, dead blood cells, pathogens, toxins, and cancer cells.
• The lymphatic system absorbs fats and fat-soluble vitamins from the digestive system and delivers these nutrients to the cells of the body where they are used by the cells.
• The lymphatic system also removes excess fluid, and waste products from the interstitial spaces between the cells.
What about the spleen?
• It acts as a filter for blood as part of the immune system. Old red blood cells are recycled in the spleen, and platelets and white blood cells are stored there.
The immune system recognizes foreign bodies and responds with the production of immune
cells and proteins
Two major kinds of defense have evolved:
• innate immunity and • acquired immunity
• Innate immunity is present before any exposure to pathogens and is effective from the time of birth
• It involves nonspecific rapid responses to pathogens
• Innate immunity consists of external barriers plus internal cellular and chemical defenses
• Acquired immunity, or adaptive immunity, develops after exposure to agents such as microbes, toxins, or other foreign substances
• It involves a very specific response to pathogens
Fig. 43-2
INNATE IMMUNITY
Recognition of traitsshared by broad rangesof pathogens, using asmall set of receptors
•
•Rapid response
•Recognition of traitsspecific to particularpathogens, using a vastarray of receptors
•Slower response
ACQUIRED IMMUNITY
Pathogens(microorganisms
and viruses)
Barrier defenses:SkinMucous membranesSecretions
Internal defenses:Phagocytic cellsAntimicrobial proteinsInflammatory responseNatural killer cells
Humoral response:Antibodies defend againstinfection in body fluids.
Cell-mediated response:Cytotoxic lymphocytes defendagainst infection in body cells.
Innate immunity of vertebrates
Physical
• Skin – low pH of skin secretions
• Mucous membranes lining digestive, respiratory, genitourinary tracts trap and remove microbes (with cilia in resp)
Chemical
• Lysozyme – enzymes that attack microbial walls, found in tears, saliva, and mucus
• Gastric juice – low pH
• Interferons – proteins produced by viral-infected cells to alert other cells to defend against viral reproduction also stimulates macrophages
• Complement – proteins in plasma that when activated by microbial contact may lyse cells, trigger inflammation, or assist acquired defensive immunity
Complement aiding the acquired immunity system
Cellular
• Macrophages – attack microbes in the spleen and interstitial fluid (known as monocytes in the blood)
• Neutrophils – most numerous phagocytizing cells, phagocytize bacteria
• Eosinophils – attack multicellular parasites
• Dendritic cells – in contact with environment, stimulate acquired immunity system
• Natural killer cells (NK cells) – recognize absence of self-markers on infected cells
macrophage
Neutrophils – first on the job
Eosinophils – attack multicellular parasites
A dendritic cell
http://www.rockefeller.edu/interactive/steinman/dendritic_cell_v5.swf
Dendritic cell
alerting the
acquired
immune
system
NK cell doing its job!
What are toll-like receptors?
• TLR’s are proteins that span membranes in leukocytes and other cells that recognize nonspecific microbes that breach physical barriers such as the skin or intestinal tract.
• They in turn activate the immune system.
• Originally identified in insects.
TLR’s spanning the membrane.
Response
Toll-like receptors
Alert! Microbes entering!
http://www.youtube.com/watch?v=iVMIZy-Y3f8
Inflammatory response
• Redness, swelling, heat
• Damaged mast cells in connective tissue release histamine which triggers dilation and leakiness of blood vessels, activates macrophages, promotes blood flow to the area
• Fever – triggered by toxins or pyrogens released by macrophages, stimulates production of wbc’s, speeds tissue healing
• Septic shock – overwhelming systemic inflammatory response
Fig. 43-8-3
Pathogen Splinter
Macrophage
Mast cell
Chemicalsignals
Capillary
Phagocytic cellRed blood cells
Fluid
Phagocytosis
ACQUIRED IMMUNITY (adaptive immunity)
• Job of lymphocytes that circulate in the blood and lymph, conc in spleen and lymph nodes
• Develop from pluripotent stem cells in the bone marrow and liver of fetuses
• Become T cells after cells have migrated to the Thymus or
• B cells that develop in the Bone marrow
How do they work with the innate immune system?
Signaling molecules (cytokines) from macrophages and dendritic cells activate them.
What are antigens?
• Antigens – proteins or polysaccharides protruding from microbes or toxins floating around
• Epitope (antigenic determinants) – portion of the antigen recognized by immune cells
Fig. 43-10
Antigen-binding sites
Antigen-bindingsites
Epitopes(antigenicdeterminants)
Antigen
Antibody B
Antibody CAntibody A
CC
CV
V
V
V
C
There are millions of lymphocytes with their own types of antigen receptors. How
is the great diversity of B and T cells
produced?
• They are determined during early embryonic development by genetic recombination
• Receptors have constant regions and variable regions that are specific for antigens.
Fig. 43-9a
Antigen-bindingsite
Antigen-binding site
Disulfidebridge
Variableregions
Constantregions
Transmembraneregion
Plasmamembrane
Lightchain
Heavy chains
Cytoplasm of B cell
(a) B cell receptor
B cell
V
V
C C
V
V
C C
Fig. 43-9b
Antigen-bindingsite
Variableregions
Constantregions
Transmembraneregion
Plasmamembrane
T cell
chain chain
Disulfide bridge
Cytoplasm of T cell
(b) T cell receptor
C C
VV
What prevents B and T cells from reacting against the body’s own
molecules?
• Lymphocytes with receptors specific for body’s own molecules are either inactivated or destroyed by apoptosis. This is called self-tolerance.
How to distinguish self from nonself
• MHC molecules are so named because they are encoded by a family of genes called the Major Histocompatibility Complex
• They identify cells as belonging to you!
(histo = tissue)
• Class I MHC molecules are found on almost all nucleated cells of the body
• Class II MHC molecules are found on immune cells such as dendritic cells, macrophages, and B cells.
They digest antigens and display pieces of the antigen with their MHC complex and are called antigen-presenting cells (APC’s).
Class I – body cells Class II- immune cells
Once the cells engulf the antigens, they display them on their MHC complexes:“SELF-NONSELF”.
• Cytotoxic-T cells will bind to the MHC I complexes (recognize infected cells)
• Helper T- cells will bind to the MHC II complexes. MHC II cells are called APC’s (Antigen Presenting Cells).
Fig. 43-12
Infected cell
Antigenfragment
Class I MHCmolecule
T cellreceptor
(a)
Antigenassociateswith MHCmolecule
T cellrecognizescombination
Cytotoxic T cell (b) Helper T cell
T cellreceptor
Class II MHCmolecule
Antigenfragment
Antigen-presentingcell
Microbe
1
11
2
22
Immunological Memory
• When antigens react with the immune
cells, the cells that are specific for that antigen are activated to divide repeatedly and differentiate into clones:
• Effector cells – combative cells
• Memory cells – which carry receptors for that particular antigen
• This is called CLONAL SELECTION.
Fig. 43-14
B cells thatdiffer inantigen specificity
Antibodymolecules
Antigenreceptor
Antigen molecules
Clone of memory cells Clone of plasma cells
This one!
Clonalselection
Monoclonal Antibody Production
Monoclonal Antibody Production
• The first exposure to a specific antigen represents the primary immune response
• During this time, effector B cells called plasma cells are generated, and T cells are activated to their effector forms
• In the secondary immune response, memory cells facilitate a faster, more efficient response
Fig. 43-15
Antibodiesto A
Antibodiesto B
Secondary immune response toantigen A produces antibodies to A;primary immune response to antigenB produces antibodies to B.
Primary immune responseto antigen A producesantibodies to A.
An
tib
od
y co
nce
ntr
atio
n(a
rbit
rary
un
its)
Exposureto antigen A
Exposure toantigens A and B
Time (days)
104
103
102
101
100
0 7 14 21 28 35 42 49 56
Remembering the antigen!
Vaccines stimulate a mild primary response so body can wage a secondary response to
recognize another attack.
Acquired Immunity: 2 types: Humoral and Cell-mediated
Humoral Immune Response (antibody-mediated response)
• involves B cells and
• production of antiBodies in response to free-floating antigens or those on surface of foreign cells
B cells mature into plasma cells that produce
antibodies.
Cell-mediated Response
• involves cytotoxic T cells that destroy target infected cells
The central role of Helper-T’s
• Immune cells (class II MHC) engulf antigens and display them on their MHC.
• Specific helper-T’s recognize the MHC-antigen complex.
Displaying the antigen
Binding to the helper-T
• A T-cell surface protein called CD4 binds the helper-T to the MHC-II.
• Activated helper-T’s release cytokines (interleukins)
- result in more specific help-T’s and memory cells being produced.
- stimulate both cell-mediated and humoral responses
Fig. 43-17
Antigen-presentingcell
Peptide antigen
Cell-mediatedimmunity (attack on
infected cells)
Class II MHC moleculeCD4
TCR (T cell receptor)
Helper T cell
Humoralimmunity
(secretion ofantibodies byplasma cells) Cytotoxic T cell
Cytokines
B cell
Bacterium
+
+ +
+
The central role of Helper-T’s
Binds
Animation: The Immune Response
Cell-mediated Response, how?
• When a nucleated regular cell becomes infected, pieces of antigens are combined with the MHC I and they bond to cytotoxic T cells with the help of CD8 surface proteins.
• The cytotoxic cell becomes a killer cell which releases perforin that punches holes in the infected cell.
• CD 8’s and CD 4’s are like bungy cords.
They holdthe MHCto the T orB cells
Cell Mediated ImmunityResponse of Cytotoxic T cells
Cytotoxic T-cell Activity Against Target Cells
Fig. 43-18-3
Cytotoxic T cell
Perforin
Granzymes
TCRCD8
Class I MHCmolecule
Targetcell
Peptideantigen
Pore
Released cytotoxic T cell
Dying target cell
Humoral Response, how?
• The B cell takes in a few foreign molecules and presents antigen fragments in its class II MHC to activated helper-T cells.
• The activated B cell then proliferates into a clone of plasma cells that will produce antibodies and a clone of memory B cells. (Some do not require T-cell binding or cytokines.)
Fig. 43-19
Antigen-presenting cell
Endoplasmicreticulum ofplasma cell
Secretedantibodymolecules
Bacterium
B cellPeptideantigen
Class II MHCmolecule
TCR CD4
Helper T cellActivatedhelper T cell
Cytokines
Clone of memoryB cells
Clone of plasma cells
2 µm
+
Humoral ImmunityT-Cell Dependent Antigens
Interaction of Antigen Presenting Cells and T-helper Cells
The cartoon illustrates how an antibacterial antigen-specific immune response is generated.
Microbes invade the body and are captured by dendritic cells (DCs, the ‘policemen’). The DC presents the antigen to the B and Th cells.
The B cells respond by “bombing” the microbes with antibodies.
Putting it all together…
http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter24/animation__the_immune_response.html
Fig. 43-16
Humoral (antibody-mediated) immune response
B cell
Plasma cells
Cell-mediated immune response
Key
Stimulates
Gives rise to
+
+
++
+
+
+Memory B cells
Antigen (1st exposure)
Engulfed by
Antigen-presenting cell
MemoryHelper T cells
Helper T cell Cytotoxic T cell
MemoryCytotoxic T cells
ActiveCytotoxic T cells
Antigen (2nd exposure)
Secretedantibodies
Defend against extracellular pathogens by binding to antigens,thereby neutralizing pathogens or making them better targetsfor phagocytes and complement proteins.
Defend against intracellular pathogensand cancer by binding to and lysing theinfected cells or cancer cells.
+
+ +
Types of Antibodies• Antibodies are proteins
that are made of light and heavy chains.
• There are 5 different antibodies: IgM, IgG, IgA, IgD, and IgE. IgG is the most abundant.
• IgE – antibodies involved in allergies
Respond toDifferentantigens
IgE Mediated Hypersensitivity
IgE Mediated Hypersensitivity
Antibodies label antigens for disposal by 1) Neutralization – blocking the ability of
a virus or bacterium to infect a host cell by binding to its surface
2) Opsonization – antibodies (opsonins) coat microbes for phagocytosis by macrophages
opsonization
3) Antigen-antibody complexes on microbes can activate the complement system and trigger a membrane attack complex (MAC).
Y’s and C’shaving a party!
Fig. 43-21
Viral neutralization
Virus
Opsonization
Bacterium
Macrophage
Activation of complement system and pore formation
Complement proteins
Formation ofmembraneattack complex
Flow of waterand ions
Pore
Foreigncell
Active and Passive immunity:
• Active – production of antibodies from exposure or from immunization
• Passive – temporary immunity by antibodies supplied from the placenta, mother’s milk, or antibody injection
Immune Rejection
• Blood Matching: Antibodies to blood group antigens can stimulate an immune response.
• A person will make antibodies to other blood antigens than its own.
You make antibodies against anyblood antigens you do not have.
• Transplanted tissue and organs are rejected due to foreign MHC molecules. The use of closely related donors and immune suppression drugs help to minimize rejection.
• In bone marrow transplants, the recipient’s bone marrow cells are destroyed by radiation, eliminating the recipient’s immune system.
• The lymphocytes in the bone marrow transplant may produce a graft versus host reaction to the host cells if the MHC
molecules are not
closely matched.
Immune System Disorders
• Allergies are hypersensitivities to certain environmental antigens, or allergens.
- IgE antibodies produced in an initial
exposure may bind to mast cells and cause a histamine response.
• Anaphylactic shock is a severe allergic response in which vasodilation leads to a life-threatening drop in blood pressure
Autoimmune disease – immune system turns against itself
• Ex - lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus, and multiple sclerosis.
rheumatoid arthritis
Lupus
Systemic lupus erythematosus (SLE) is a long-term autoimmune disorder that may affect the skin, joints, kidneys, brain, and other organs.
Multiple Sclerosis
• Multiple sclerosis (or MS) is a chronic, often disabling disease that attacks the central nervous system (CNS).
• Symptoms may be mild, such as numbness in the limbs, or severe, such as paralysis or loss of vision.
• The body’s own defense system attacks myelin, the fatty substance that surrounds and protects the nerve fibers in the central nervous system. The nerve fibers themselves can also be damaged.
• Immunodeficiency – may be developmental (genetic) or in response to a chemical, drugs, cancer, viruses (HIV).
• Severe combined immunodeficiency (SCID), is a genetic disorder in which both B cells and T cells) of the adaptive immune system are impaired due to a defect in one of several possible genes.
• Exercising to exhaustion and stress can impair the immune system.
How tricky are pathogens
• Antigenic variation – changing their surface epitopes to be unrecognizable
• Some viruses go into a latency period and “hide” from the immune cells
• AIDS does both of these.