Figure 21.1

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


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


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


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


Innatedefenses

Internaldefenses


Margination.Neutrophils clingto capillary wall.



1 2


Innatedefenses

Internaldefenses



Diapedesis.Neutrophils flatten andsqueeze out of capillaries.



1 2 3


Innatedefenses

Internaldefenses



Diapedesis.Neutrophils flatten andsqueeze out of capillaries.

Chemotaxis.Neutrophilsfollow chemicaltrail.Capillary wallBasementmembraneEndothelium


1 2 3

4


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


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)


Antigenic Determinants

• Parts of antigen that are immunogenic

• Antibodies and lymphocyte receptors bind to them


Antigenic determinantsAntigen-bindingsitesAntibody A

Antibody BAntibody C

Antigen


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


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


MHC Proteins

• Classes• Class I MHC proteins, on most all cells

• Class II MHC proteins, on certain cells in immune response


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


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


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


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.


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


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


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


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)


Fate of the Clones

• Secreted antibodies• Circulate in blood or lymph

• Bind to free antigens

• Mark the antigens for destruction


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


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


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.


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

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Figure 21.1