Chapter 43 Immune System Notes 1314 digestion of foreign substances Pathogen PHAGOCYTIC CELL Vacuole...
Transcript of Chapter 43 Immune System Notes 1314 digestion of foreign substances Pathogen PHAGOCYTIC CELL Vacuole...
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Essential knowledge 2.D.4: Plants and animals have a variety of chemical defenses against infections that affect dynamic homeostasis.
a. Plants, invertebrates and vertebrates have multiple, nonspecific immune responses.
Students should be able to demonstrate understanding of the above concept by using an illustrative example such as:
• Invertebrate immune systems have nonspecific response mechanisms, but they lack pathogen‐specific defense responses.
• Plant defenses against pathogens include molecular recognition systems with systemic responses; infection triggers chemical responses that destroy infected and adjacent cells, thus localizing the effects.
• Vertebrate immune systems have nonspecific and nonheritable defense mechanisms against pathogens.
b. Mammals use specific immune responses triggered by natural or artificial agents that disrupt dynamic homeostasis.
Evidence of student learning is a demonstrated understanding of each of the following:
1. The mammalian immune system includes two types of specific responses: cell mediated and humoral.
2. In the cell‐mediated response, cytotoxic T cells, a type of lymphocytic white blood cell, “target” intracellular pathogens when antigens are displayed on the outside of the cells.
3. In the humoral response, B cells, a type of lymphocytic white blood cell, produce antibodies against specific antigens.
4. Antigens are recognized by antibodies to the antigen.
5. Antibodies are proteins produced by B cells, and each antibody is specific to a particular antigen.
6. A second exposure to an antigen results in a more rapid and enhanced immune response.
✘Memorization of the structures of specific antibodies is beyond the scope of the course and the AP Exam.
Essential knowledge 3.D.2: Cells communicate with each other through direct contact with other cells or from a distance via chemical signaling.
a. Cells communicate by cell‐to‐cell contact.
To foster student understanding of this concept, instructors can choose an illustrative example such as:
• Immune cells interact by cell‐cell contact, antigen‐presenting cells (APCs), helper T‐cells and killer T‐cells. [See also 2.D.4]
• LO 2.29 The student can create representations and models to describe immune responses. [See SP 1.1, 1.2]
• LO 2.30 The student can create representations or models to describe nonspecific immune defenses in plants and animals.[See SP 1.1, 1.2]
Reinforcement:
• LO 3.34 The student is able to construct explanations of cell communication through cell‐to‐cell direct contact or through chemical signaling. [See SP 6.2]
• LO 3.35 The student is able to create representation(s) that depict how cell‐to‐cell communication occurs by direct contact or from a distance through chemical signaling. [See SP 1.1]
I. Pathogens, agents that cause disease, infect a wide range of animals, including humans
II. The immune system recognizes foreign bodies and responds with the production of immune cells and proteins
How does recognition occur?
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III. All animals have innate immunity, a defense active immediately upon infection
A. Present before any exposure to pathogens and is effective from the time of birth
B. Involves nonspecific responses to pathogens
IV. Vertebrates also have adaptive immunity (acquired immunity)
A. It involves a very specific response to pathogens
How do vertebrates develop adaptive immunity?
Pathogens(such as bacteria,fungi, and viruses)
INNATE IMMUNITY(all animals)
• Rapid response
Recognition of traits sharedby broad ranges ofpathogens, using a smallset of receptors
•
Recognition of traits specific to particularpathogens, using a vastarray of receptors
•
• Slower response
Barrier defenses:SkinMucous membranesSecretions
Internal defenses:Phagocytic cellsNatural killer cellsAntimicrobial proteinsInflammatory response
Humoral response:Antibodies defend againstinfection in body fluids.
Cell-mediated response:Cytotoxic cells defendagainst infection in body cells.
ADAPTIVE IMMUNITY(vertebrates only)
I. Innate Immunity of
Invertebrates
A. Exoskeleton made of chitin
B. Lysozyme, protects digestive system, breaks down bacterial cell walls
C. Hemocytes circulate and carry out phagocytosis, ingestion and digestion of foreign substances
Pathogen
PHAGOCYTICCELL
VacuoleLysosomecontainingenzymes
A. Innate defenses include:
1. barrier defenses
2. phagocytosis
3. antimicrobial peptides
4. natural killer cells
5. interferons
6. inflammatory response
Which of these are unique to vertebrates?
• Include skin and mucous membranes of the respiratory, urinary, and reproductive tracts
o Mucus traps and allows for the removal of microbes
o Body fluids including saliva, mucus, and tears
o Low pH of skin and the digestive system
• Phagocytic cells recognize pathogens by TLRs, Toll‐like receptors
o Uses lysosome to destroy the microbe
o Types of phagocytic cells:
1. Neutrophils
2. Macrophages Dendritic cells
3. Eosinophils
• Natural killer cells also involved
EXTRACELLULARFLUID
PHAGOCYTICCELL
VESICLE
Lipopolysaccharide
Helperprotein
TLR4Flagellin
TLR5
CpG DNA
ds RNA
TLR9
TLR3 Innate immuneresponses
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• Peptides and proteins function by attacking pathogens or impeding their reproduction
o Interferon interfere with viruses and help to activate macrophages
o About 30 proteins make up the complement system
causes lysis of invading cells
helps trigger inflammation
• Inflammatory response, such as pain and swelling, is brought about by molecules released upon injury of infection
o Mast cells release histamine
• Activated macrophages and neutrophils release cytokines
How do cytokines help the immune response?
Pathogen Splinter
Mastcell
Macro-phage
Capillary
Redblood cells
Neutrophil
Signalingmolecules
Movementof fluid
Phagocytosis
1. Which of the following defense mechanisms is incorrectly paired with its function?
a) gastric juice– kills bacteria in the stomach
b) fever– may stimulate phagocytosis
c) lysozyme– attacks the cell wall of viruses
d) histamine– causes blood vessels to dilate
2. Which of the following statements best describes an insect’s immune system?
a) Insects rely on the barrier defense of an exoskeleton.
b) Hemocytes can carry out phagocytosis of bacteria and foreign substances.
c) Lysozyme and a chitin‐lined intestine with a low pH protect an insect’s digestive system.
d) All of the above are part of an insect’s innate immunity.
• The adaptive response relies on two types of lymphocytes
o T cellsmature in the thymus
o B cells mature in bone marrow
How are pathogens recognized by lymphocytes?
• Antigens are substances that can elicit a response from a B or T cell
o B and T cells have antigen receptors
Bind to part of the receptor called an epitope
Antigen receptors
Mature B cell Mature T cell
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A. Each B cell antigen receptor is a Y‐shaped molecule with two identical heavy chains and two identical light chains
1. Constant regions of the chains vary little
2. Variable regions differ greatly providing antigen specificity
B. Binding of a B cell antigen receptor to an antigen is
1. an early step in B cell activation
2. gives rise to cells that secrete antibodies or immunoglobulins (Ig)
Cytoplasm of B cell
Antigen-binding site
B cellantigenreceptor
B cell
Lightchain
Disulfidebridge
Antigen-binding site
Variable regions
Constant regions
Transmembraneregion
Heavy chains
Plasmamembrane
C C
AntibodyAntigenreceptor
B cell
Antigen Epitope
Pathogen(a) B cell antigen receptors and antibodies
Antibody C
Antibody BAntibody A
Antigen
(b) Antigen receptor specificity
Cytoplasm of T cell
Plasmamembrane
chain chain
Disulfidebridge
Antigen-bindingsite
Variableregions
Constantregions
Transmembraneregion
V V
C C
A. T cell and B cell antigen receptors are functionally different
B. T cells bind to antigen fragments displayed/presented
1. antigen fragments are bound MHC molecules
T cellantigenreceptor
T cell
• MHC (major histocompatibility complex) molecules are host proteins that display the antigen fragments on the cell surface, a process called antigen presentation.
• A T cell can then bind both the antigen fragment and the MHC molecule.
This interaction is necessary for the T cell to participate in the adaptive immune response
A. The adaptive immune system has four major characteristics:
1. Diversity of lymphocytes and receptors
2. Self‐tolerance; lack of reactivity against an animal’s own molecules
3. B and T cells proliferate after activation, clonal selection
a. effector cells act immediately against the antigen
b. memory cells that can give rise to effector cells if the same antigen is encountered again
4. Immunological memory
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AntigenAntigenreceptor
Antibody
Plasma cellsMemory cells
B cells thatdiffer inantigenspecificity
Primary immune responseto antigen A producesantibodies to A.
Secondary immune response toantigen A produces antibodies to A;primary immune response to antigenB produces antibodies to B.
Exposureto antigen A
Exposure to antigens A and B
Time (days)
An
tib
od
y c
on
ce
ntr
ati
on
(arb
itra
ry u
nit
s)
104
103
102
101
100
0 7 14 21 28 35 42 49 56
Antibodiesto A
Antibodiesto B
3. Which of the following statements correctly describes the main difference between innate immunity and adaptive immunity?
a) Innate immunity responds only to free pathogens in a localized area; adaptive immunity responds only to pathogens that have entered body cells.
b) Innate immunity involves only leukocytes, whereas adaptive immunity involves only lymphocytes.
c) Complement proteins participate in adaptive immunity but not in innate immunity.
d) Innate immunity recognizes molecules common to a set of pathogens, whereas adaptive immunity reacts to specific microbes on the basis of their unique antigens.
4. What accounts for the huge diversity of antigens to which B cells can respond?a) The antibody genes have millions of alleles.b) The recombination of a light and a heavy chain gene during development
results in millions of possible antigen receptors.c) B cells have thousands of copies of antibodies bound to their plasma
membrane.d) The antigen‐binding sites at the arms of the molecule can assume a huge
diversity of shapes in response to the specific antigen encountered.
• Acquired immunity has two branches:
o Humoral immune response
o Cell‐mediated immune response
How do the two types of responses differ?
• In the humoral immune response antibodies help neutralize or eliminate toxins and pathogens in the blood and lymph
• In the cell‐mediated immune response specialized T cells destroy affected host cells
A. Helper T cells triggers both the humoral and cell‐mediated immune responses
B. To activate adaptive immunity:
1. a foreign antigen must be present
2. the foreign antigen must be displayed on an antigen‐presenting cell using the class II MHC molecule
3. cytokines are released from both the antigen‐presenting cell and helper T cell
a. the helper T cell is activated and proliferates
b. cloned helper T cells activate:
i. B cells (humoral immunity)
ii. Cytotoxic T cells (cell‐mediated immunity)
Antigen-presentingcell
Pathogen
Antigen fragment
Class II MHC moleculeAccessory proteinAntigen receptor
Helper T cell
Cytokines
Humoralimmunity
Cell-mediatedimmunity
B cellCytotoxic T cell
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2
1
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A. Cytotoxic T cells are the effector cells
1. recognize fragments of foreign proteins produced by infected cells
2. possess an accessory protein that binds to class I MHC molecules
3. activated cytotoxic T cell secretes proteins that
a. disrupt the membranes of target cells
b. trigger apoptosis
Cytotoxic T cell
31 2
Accessoryprotein
Class I MHCmolecule
Infectedcell
Antigenreceptor
Antigenfragment
Perforin
Pore
Gran-zymes
ReleasedcytotoxicT cell
Dyinginfected cell
A. The humoral response is characterized by secretion of antibodies by B cells
B. In response to cytokines from helper T cells and an antigen
1. B cells proliferate
a. differentiates into memory B cells
b. antibody secreting effector cells, plasma cells
Pathogen
31 2
Antigen-presentingcell Antigen
fragment
Class IIMHC
molecule
Antigenreceptor
Accessoryprotein
Helper T cell
B cell
Cytokines
Activatedhelper T cell
Memory B cells
Plasma cellsSecreted
antibodies
• Antibodies do not kill pathogens; they mark them for destruction
So what do antibodies do?!?
1. Neutralization ‐ antibodies bind to viruses/toxins preventing infection of a host cell
2. Opsonization ‐ antibodies bind to antigens on bacteria creating a target for macrophages/neutrophils, triggering phagocytosis
3. Activation of complement system ‐ antigen‐antibody complexes may bind to a complement protein triggers a membrane attack leading to lysis of the foreign cell
OpsonizationNeutralization
Antibody
VirusBacterium
Macrophage
Activation of complement system and poreformation
Complement proteins
Formation of membraneattack complex
Flow of waterand ions
Pore
AntigenForeigncell
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Humoral (antibody-mediated) immune response Cell-mediated immune response
Antigen (1st exposure)
Engulfed by
Antigen-presenting cell
Helper T cell
Memoryhelper T cells
Antigen (2nd exposure)
B cell
Plasma cells
Secretedantibodies
Defend against extracellularpathogens
Memory B cellsMemory
cytotoxic T cellsActive
cytotoxic T cells
Defend against intracellularpathogens and cancer
Cytotoxic T cell
Key
Stimulates
Gives rise to
A. Active immunity develops naturally and can also develop following immunization, called vaccination
B. Passive immunity provides immediate, short‐term protection. It is conferred when:
1. IgG crosses the placenta from mother to fetus
2. IgA passes from mother to infant in breast milk
3. artificially by injecting antibodies
• Monoclonal antibodies – used in medical diagnosis and treatment
• Immune rejection – antibodies are important part of blood, tissue and organ transplants
• Allergies – exaggerated response of the immune system
• Autoimmune disease – loss of self tolerance
• Immunodeficiency disease – lack of response by the immune system
• Cancer – can result when adaptive immunity is inactivated
5. Clonal selection is responsible for the a) proliferation of effector cells and memory cells specific for an
encountered antigen. b) rearrangement of antibody genes for the light and heavy
chains.c) formation of cell cultures in the commercial production of
monoclonal antibodies.d) recognition of class I MHC molecules by cytotoxic T cells.
6. A transfusion of type B blood in a person who has type A blood would result in
a) the introduced blood cells being destroyed by innate defense mechanisms.
b) no reaction; B is a universal donor blood type.c) the recipient's anti‐B antibodies reacting with the donated red
blood cells.d) the recipient's B antigens reacting with the donated anti‐B
antibodies.