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Surface barriers • Skin • Mucous membranes. Innate defenses. Internal defenses • Phagocytes • NK cells • Inflammation • Antimicrobial proteins • Fever. Humoral immunity • B cells. Adaptive defenses. Cellular immunity • T cells. Figure 21.1. Inflammatory Response. - PowerPoint PPT Presentation
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Copyright © 2010 Pearson Education, Inc. Figure 21.1
Innatedefenses
Surface barriers• Skin• Mucous membranes
Internal defenses• Phagocytes• NK cells• Inflammation• Antimicrobial proteins• Fever
Humoral immunity• B cells
Cellular immunity• T cells
Adaptivedefenses
Copyright © 2010 Pearson Education, Inc.
Inflammatory Response
• Macrophages and epithelial cells of boundary tissues bear Toll-like receptors (TLRs)
• TLRs recognize specific classes of infecting microbes
• Activated TLRs trigger the release of cytokines that promote inflammation
Copyright © 2010 Pearson Education, Inc.
Phagocyte Mobilization
• Steps for phagocyte mobilization
1. Leukocytosis: release of neutrophils from bone marrow in response to leukocytosis-inducing factors from injured cells
2. Margination: neutrophils cling to the walls of capillaries in the inflamed area
3. Diapedesis of neutrophils
4. Chemotaxis: inflammatory chemicals (chemotactic agent) promote positive chemotaxis of neutrophils
Copyright © 2010 Pearson Education, Inc. Figure 21.3
Tissue injury
Release of chemical mediators(histamine, complement,kinins, prostaglandins, etc.)
Vasodilationof arterioles
Increased capillarypermeability
Local hyperemia(increased blood
flow to area)
Locally increasedtemperature increasesmetabolic rate of cells
Leaked protein-richfluid in tissue spaces
Leaked clottingproteins form interstitialclots that wall off area
to prevent injury tosurrounding tissue
Temporary fibrinpatch forms
scaffolding for repair
Healing
Capillariesleak fluid
(exudate formation)
Attract neutrophils,monocytes, andlymphocytes to
area (chemotaxis)
Release of leukocytosis-inducing factor
Leukocytosis (increased numbers of whiteblood cells in bloodstream)
Leukocytes migrate toinjured area
Margination (leukocytes cling to
capillary walls)
Diapedesis (leukocytes pass through
capillary walls)
Phagocytosis of pathogensand dead tissue cells
(by neutrophils, short-term;by macrophages, long-term)
Area cleared of debris
Pus may form
Signs of inflammation
Initial stimulusPhysiological response
Result
Innate defenses Internal defenses
Possible temporarylimitation of
joint movement
Heat Redness Pain Swelling
Copyright © 2010 Pearson Education, Inc.
Phagocyte Mobilization
• Steps for phagocyte mobilization
1. Leukocytosis: release of neutrophils from bone marrow in response to leukocytosis-inducing factors from injured cells
2. Margination: neutrophils cling to the walls of capillaries in the inflamed area
3. Diapedesis of neutrophils
4. Chemotaxis: inflammatory chemicals (chemotactic agent) promote positive chemotaxis of neutrophils
Copyright © 2010 Pearson Education, Inc. Figure 21.4, step 1
Innatedefenses
Internaldefenses
Leukocytosis.Neutrophils enter bloodfrom bone marrow.
Capillary wallBasementmembraneEndothelium
Inflammatorychemicalsdiffusingfrom theinflamed siteact as chemotacticagents.
1
Copyright © 2010 Pearson Education, Inc. Figure 21.4, step 2
Innatedefenses
Internaldefenses
Leukocytosis.Neutrophils enter bloodfrom bone marrow.
Margination.Neutrophils clingto capillary wall.
Capillary wallBasementmembraneEndothelium
Inflammatorychemicalsdiffusingfrom theinflamed siteact as chemotacticagents.
1 2
Copyright © 2010 Pearson Education, Inc. Figure 21.4, step 3
Innatedefenses
Internaldefenses
Leukocytosis.Neutrophils enter bloodfrom bone marrow.
Margination.Neutrophils clingto capillary wall.
Diapedesis.Neutrophils flatten andsqueeze out of capillaries.
Capillary wallBasementmembraneEndothelium
Inflammatorychemicalsdiffusingfrom theinflamed siteact as chemotacticagents.
1 2 3
Copyright © 2010 Pearson Education, Inc. Figure 21.4, step 4
Innatedefenses
Internaldefenses
Leukocytosis.Neutrophils enter bloodfrom bone marrow.
Margination.Neutrophils clingto capillary wall.
Diapedesis.Neutrophils flatten andsqueeze out of capillaries.
Chemotaxis.Neutrophilsfollow chemicaltrail.Capillary wallBasementmembraneEndothelium
Inflammatorychemicalsdiffusingfrom theinflamed siteact as chemotacticagents.
1 2 3
4
Copyright © 2010 Pearson Education, Inc.
Adaptive Defenses
• Adaptive immune response• Is specific
• Is systemic
• Has memory
• Two separate overlapping arms
1. Humoral (antibody-mediated) immunity
2. Cellular (cell-mediated) immunity
Copyright © 2010 Pearson Education, Inc.
Antigens
• Substances that can mobilize the adaptive defenses and provoke an immune response
• Most are large, complex molecules not normally found in the body (nonself)
Copyright © 2010 Pearson Education, Inc.
Antigenic Determinants
• Parts of antigen that are immunogenic
• Antibodies and lymphocyte receptors bind to them
Copyright © 2010 Pearson Education, Inc. Figure 21.7
Antigenic determinantsAntigen-bindingsitesAntibody A
Antibody BAntibody C
Antigen
Copyright © 2010 Pearson Education, Inc.
Haptens (Incomplete Antigens)
• Small molecules (peptides, nucleotides, and hormones) • Not immunogenic by themselves• Are immunogenic when attached to body
proteins• Cause the immune system to mount a harmful
attack • Examples: poison ivy, animal dander,
detergents, and cosmetics
Copyright © 2010 Pearson Education, Inc.
Self-Antigens: MHC Proteins
• Proteins (self-antigens) on cell surface of s
• Example: MHC proteins• Coded for by genes of major histocompatibility
complex (MHC) and unique
Copyright © 2010 Pearson Education, Inc.
MHC Proteins
• Classes• Class I MHC proteins, on most all cells
• Class II MHC proteins, on certain cells in immune response
Copyright © 2010 Pearson Education, Inc.
Cells of the Adaptive Immune System
• Two types of lymphocytes• B lymphocytes (B cells)—humoral immunity
• T lymphocytes (T cells)—cell-mediated immunity
• Antigen-presenting cells (APCs)• Do not respond to specific antigens
• Play essential auxiliary roles in immunity
Copyright © 2010 Pearson Education, Inc. Figure 21.8
1
2
3
Red bone marrow: site of lymphocyte origin
Secondary lymphoid organs: site ofantigen encounter, and activation to becomeeffector and memory B or T cells
Primary lymphoid organs: site ofdevelopment of immunocompetence as B orT cells
Lymphocytes destined to become T cellsmigrate (in blood) to the thymus and develop immunocompetence there. B cells develop immunocompetence in red bone marrow.
Immunocompetent but still naive lymphocytes leave the thymus and bone marrow. They “seed” the lymph nodes, spleen, and other lymphoid tissues where they encounter their antigen.
Antigen-activated immunocompetent lymphocytes (effector cells and memory cells) circulate continuously in the bloodstream and lymph and throughout the lymphoid organs of the body.
Redbone marrow
Bone marrowThymus
Lymph nodes,spleen, and otherlymphoid tissues
Immaturelymphocytes
Adaptive defenses Humoral immunityCellular immunity
Copyright © 2010 Pearson Education, Inc.
T Cells
• T cells mature in the thymus under negative and positive selection pressures• Positive selection• Selects T cells capable of binding to self-
MHC proteins (MHC restriction)• Negative selection• Prompts apoptosis of T cells that bind to
self-antigens displayed by self-MHC• Ensures self-tolerance
Copyright © 2010 Pearson Education, Inc. Figure 21.9
Adaptive defensesPositive selection: T cells must recognize self major histocompatibility proteins (self-MHC).
Antigen-presentingthymic cell
Failure to recognize self-MHC results in apoptosis (death by cell suicide).
Recognizing self-MHC results inMHC restriction—survivors are restricted to recognizing antigen on self-MHC. Survivors proceedto negative selection.
Recognizing self-antigen results in apoptosis. This eliminates self-reactive T cells that could cause autoimmune diseases.
Failure to recognize (bind tightly to) self-antigen results in survival and continued maturation.
MHCSelf-antigen
T cell receptor
DevelopingT cell
Cellular immunity
Negative selection: T cells must not recognize self-antigens.
Copyright © 2010 Pearson Education, Inc.
Antigen Receptor Diversity
• Lymphocytes make up to a billion different types of antigen receptors• Coded for by ~25,000 genes
• Gene segments are shuffled by somatic recombination
• Genes determine which foreign substances the immune system will recognize and resist
Copyright © 2010 Pearson Education, Inc.
Antigen-Presenting Cells (APCs)
• Engulf antigens
• Present fragments of antigens to T cells
• Major types• Dendritic in connective tissues and epidermis
• Macrophages in connective tissues and lymphoid organs
• B cells
Copyright © 2010 Pearson Education, Inc.
Macrophages and Dendritic Cells
• Present antigens and activate T cells• Macrophages mostly remain fixed in the lymphoid
organs
• Dendritic cells internalize pathogens and enter lymphatics to present the antigens to T cells in lymphoid organs
• Activated T cells release chemicals that• Prod macrophages to become insatiable phagocytes
and to secrete bactericidal chemicals
Copyright © 2010 Pearson Education, Inc. Figure 21.11 (1 of 2)
Primary response(initial encounterwith antigen)
Antigen bindingto a receptor on aspecific B lymphocyte (B lymphocytes with non-complementary receptors remain inactive)
Proliferation toform a cloneActivated B cells
Plasma cells(effector B cells)Secretedantibodymolecules
Memory B cell—primed to respond to same antigen
Adaptive defenses Humoral immunity
Antigen
Copyright © 2010 Pearson Education, Inc.
Clonal Selection
1. B cell is activated when antigens bind to its surface receptors and cross-link them
2. Receptor-mediated endocytosis of cross-linked antigen-receptor complexes occurs
3. Stimulated B cell grows to form a clone of identical cells bearing the same antigen-specific receptors(T cells are usually required to help B cells achieve full activation)
Copyright © 2010 Pearson Education, Inc.
Fate of the Clones
• Secreted antibodies• Circulate in blood or lymph
• Bind to free antigens
• Mark the antigens for destruction
Copyright © 2010 Pearson Education, Inc.
Immunological Memory
• Primary immune response• Occurs on the first exposure to a specific
antigen
• Lag period: three to six days
• Peak levels of plasma antibody are reached in 10 days
• Antibody levels then decline
Copyright © 2010 Pearson Education, Inc. Figure 21.11
Primary response(initial encounterwith antigen)
Antigen bindingto a receptor on aspecific B lymphocyte(B lymphocytes withnon-complementaryreceptors remaininactive)
Proliferation toform a cloneActivated B cells
Plasma cells(effector B cells)
Secretedantibodymolecules
Memory B cell—primed to respondto same antigen
Clone of cellsidentical toancestral cells
Subsequentchallenge by same antigenresults in more rapid response
Secondary response(can be years later)
MemoryB cells
Plasmacells
Secretedantibodymolecules
Adaptive defenses Humoral immunity
Antigen
Copyright © 2010 Pearson Education, Inc. Figure 21.12
Time (days)
Anti-bodiesto A
First exposureto antigen A
Second exposure to antigen A;first exposure to antigen B
Anti-bodiesto B
Primary immuneresponse to antigenA occurs after a delay.
Secondary immune response toantigen A is faster and larger; primaryimmune response to antigen B issimilar to that for antigen A.
Copyright © 2010 Pearson Education, Inc. Figure 21.13
PassiveActive
Humoralimmunity
ArtificiallyacquiredInjection ofimmune serum (gamma globulin)
Naturallyacquired
Antibodiespass from mother tofetus via placenta; or to infant in her milk
ArtificiallyacquiredVaccine;dead or attenuated pathogens
Naturallyacquired
Infection;contact with pathogen