CHAPTER 16 THE ADAPTIVE IMMUNE RESPONSE

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Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

WHY IS THIS IMPORTANT? 

The adaptive immune system protects us from many infections.



The adaptive immune system has memory so we are not infected by the same pathogen a second time. 

This is why vaccinations work.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

OVERVIEW

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

Microbiology: A Clinical Approach [9780815365143] © Garland Science

INTRODUCTION 

The adaptive immune response is the second level of immunity. 

It involves lymphocytes.



It is a response to specific antigens.



It is extraordinarily specific.



It can adapt to any infection.



It has memory. 

This confers life-long immunity.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

INTRODUCTION: Types of Response 

The innate response is a prerequisite for the adaptive immune response.



The adaptive immune response has two types of response: 

Humoral – production of antibodies



Cellular – killing and regulation of infected cells

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

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INTRODUCTION: Antigens 

There are two types of antigens: 

Self



Nonself



Self antigens are part of the immunological memory and cause tolerance.



Nonself antigens are any molecules that are not self.

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Microbiology: A Clinical Approach [9780815365143] © Garland Science

INTRODUCTION: Lymphatic System



The adaptive response is associated with the lymphatic system. 

It covers the entire body.



It involves lymphocytes and lymphoid structures.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

INTRODUCTION: Lymphatic System

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

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COMPONENTS OF THE ADAPTIVE RESPONSE 

Cells involved in the adaptive response arise in the bone marrow. 



They differentiate from stem cells.

Dendritic cells are the most important cells in the adaptive immune response. This is because: 

They have enormous surface areas.



They take up and process antigens.



They present antigens to T cells.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

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COMPONENTS OF THE ADAPTIVE RESPONSE

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Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

COMPONENTS OF THE ADAPTIVE RESPONSE 

Immature dendritic cells migrate from bone marrow into blood and tissues.



They use phagocytosis and micropinocytosis to capture both self and nonself antigens.



They eventually migrate to regional lymph nodes where they are responsible for: 

Presentation of antigens to lymphocytes.



Triggering of adaptive response.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

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COMPONENTS OF THE ADAPTIVE RESPONSE

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COMPONENTS OF THE ADAPTIVE RESPONSE 

Presentation of self antigens maintains tolerance.



Presentation of nonself antigens sends signals to T cells. 

The adaptive response begins.

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ISBN: 978-0-8153-6514-3

DIFFERENTIATION AND MATURATION OF LYMPHOCYTES



Common lymphoid precursor gives rise to: 

T cells



B cells



Natural Killer cells



B cells can differentiate into plasma cells.

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DIFFERENTIATION AND MATURATION OF LYMPHOCYTES



There are two types of T cell: 

Cytotoxic (Tc)



Helper T cells

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DIFFERENTIATION AND MATURATION OF LYMPHOCYTES 

There are two types of helper T cells: 

Th1



Th2 



These activate the B cells and macrophages.

T cells are naive until they encounter antigens. 

Co-stimulatory signals must also be present.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

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DIFFERENTIATION AND MATURATION OF LYMPHOCYTES 

When B cells and T cells mature, they acquire specific antigen receptors. 

The B cell receptor is an immunoglobulin molecule.



The T cell receptor is similar to Ig.





It has two antigen binding sites.

It has only one antigen binding site.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

DIFFERENTIATION AND MATURATION OF LYMPHOCYTES

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

Microbiology: A Clinical Approach [9780815365143] © Garland Science

DIFFERENTIATION AND MATURATION OF LYMPHOCYTES



T cells mature in the thymus gland.



B cells mature in the bone marrow.



When mature, both circulate through the blood and tissues looking for antigens.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

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STRATEGIC LYMPHOID STRUCTURES 

Strategic lymphoid structures are found in places where pathogens enter. 

GALT – gut associated lymphoid tissue 

Examples include the tonsils, adenoids, appendix, and Peyer’s patches.

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STRATEGIC LYMPHOID STRUCTURES 

Strategic lymphoid structures are found in places where pathogens enter. 

BALT – bronchial associated lymphoid tissue 

Associated with the respiratory portal of entry



Most available portal of entry

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STRATEGIC LYMPHOID STRUCTURES 

Strategic lymphoid structures are found in places where pathogens enter. 

MALT – mucosal associated lymphoid tissue 

Associated with mucous membranes



An important portal of entry

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

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STRATEGIC LYMPHOID STRUCTURES 

Peyer’s patches are the most important part of GALT. 

They contain M cells.



M cells are antigen collecting cells.



Under M cells are germinal centers. 

Filled with B cells



Surrounded by T cells

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

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RELATIONSHIP BETWEEN INNATE AND ADAPTIVE IMMUNE RESPONSES 



The innate immune response deals with infection first. 

It must hold off infection until the adaptive response begins.



It helps regulate the adaptive response via chemokines and cytokines.

Innate response cells present antigens to the adaptive response.

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Microbiology: A Clinical Approach [9780815365143] © Garland Science

DEVELOPMENT OF LYMPHOCYTE POPULATIONS 

Both B and T cells are formed in bone marrow. 

B cells mature there.



T cells mature in the thymus.



There is always a supply of new B cells.



The thymus atrophies at puberty.



T cells are long lived.



Maturation requires specific signals.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

CLONAL SELECTION OF LYMPHOCYTES 

Clonal selection is the process by which some lymphocytes are destroyed and others are maintained.



It takes place in the bone marrow for B cells and in the thymus for T cells.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

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CLONAL SELECTION OF LYMPHOCYTES 



Precursor cells produce lymphocytes. 

Each lymphocyte is specific for a different antigen.



Specificity is generated through genetic rearrangement.

Clonal deletion is part of selection. 

Lymphocytes that react with self are deleted.



The mechanism is not understood.

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ISBN: 978-0-8153-6514-3

Microbiology: A Clinical Approach [9780815365143] © Garland Science

CLONAL SELECTION OF LYMPHOCYTES 



Lymphocytes that remain after clonal deletion mature. 

Each is specific for a nonself antigen.



If an antigen is encountered, the lymphocyte is activated. 

It begins to divide and proliferate.



It forms a clone of cells specific for one antigen.

Lymphocytes that never encounter antigen eventually die.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

CLONAL SELECTION OF LYMPHOCYTES 

Three important points about clonal selection: 

It generates a vast number of different antigen receptors.



Each receptor is specific for a different antigen.



All progeny of that lymphocyte will have the exact same receptor.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

CLONAL SELECTION OF LYMPHOCYTES

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ISBN: 978-0-8153-6514-3

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SURVIVAL OF LYMPHOCYTE POPULATIONS: B Cells 



Millions of B cells are produced each day. 

Their survival depends on signals from peripheral tissues.



These signals cause activation and proliferation or death.

B cells that never get stimulated undergo apoptosis.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

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SURVIVAL OF LYMPHOCYTE POPULATIONS: T Cells



T cells get survival signals from two places: 

Specialized epithelial cells in the thymus



Dendritic cells in peripheral lymphoid tissue



These occur during development.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

SURVIVAL OF LYMPHOCYTE POPULATIONS: T Cells 

Once signaled, T cells stop migrating and become activated. 

They become larger and multiply.



They multiply fourfold every 24 hours for 3-5 days.



Each one can differentiate into an armed effector T cell.



They can migrate into tissue or stay in the node.

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SURVIVAL OF LYMPHOCYTE POPULATIONS: T Cells 

Some activated effector T cells eventually die.



Some will become memory cells.





This is a safety precaution.

These respond very fast the second time an antigen is encountered.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

RESPONSES TO ANTIGEN FOR T OR B CELLS



This requires a second co-stimulatory signal. 



This comes from innate response cells.

No second signal causes lymphocyte inactivation – anergy.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

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RESPONSES TO ANTIGEN FOR T OR B CELLS



After inactivation, lymphocytes cannot be reactivated. 

This is another safety measure.



This is all part of tolerance.

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LYMPHOID TISSUES 

Lymphocytes move through blood to the lymphoid tissues.



T and B cells are found in specific locations. 

B cells are found in follicles.



T cells surround follicles in paracortical areas.



These are in the outer cortex.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

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LYMPHOID TISSUES



Lymphocytes circulate continuously through the lymphoid tissue.



They either find their specific antigen or die.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

LYMPHOID TISSUES: B Cells 

B cells are constantly produced in the bone marrow. 

Most of them die when they reach the peripheral tissue.



They are constantly replaced and therefore the number remains constant.

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LYMPHOID TISSUES: T Cells 

T cells leave the thymus fully mature.



They are produced in smaller numbers than B cells.



T cells have a long life span. 

They are thought to be self-renewing in peripheral tissue.

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ANTIGEN PRESENTATION: MHC 

For presentation to occur, the antigen must be bound to the major histocompatibility complex (MHC). 



The MHC is found on antigen presenting cells.

There are two types of MHC: 

Class I is found on all cells except immune cells.



Class II is found only on immune cells.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

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ANTIGEN PRESENTATION: T Cells 

T cell receptors must recognize both the antigen and the MHC. 



This is referred to as the antigen-MHC complex.

There are two types of T cells: 

Helper T cells have CD 4 antigens.



Cytotoxic T cells have CD 8 antigens.

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ANTIGEN PRESENTATION: T Cell & MHC Interaction



Cytotoxic T cells bind Class I MHC molecules.



Helper T cells bind Class II MHC molecules.



The MHC is a co-receptor.

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ANTIGEN PRESENTATION: Delivery 

Antigens are delivered by the MHC in different ways: 

Class I molecules associate with cytoplasmic antigens. 



They present to cytotoxic T cells.

Class II molecules associate with antigens from phagocytic cell vesicles. 

They present to helper T cells.

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T CELL RESPONSE TO SUPERANTIGENS



T cells can respond to superantigens. 

These are distinct classes of antigens produced by many pathogens.



They provoke a response beneficial to the pathogen.

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T CELL RESPONSE TO SUPERANTIGENS 

Superantigens do not need to be bound to the MHC to be recognized. 

They can bind to the outside of MHC molecules.



They cause massive overproduction of cytokines.



They cause systemic toxicity and suppression of the adaptive response.

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THE HUMORAL (B CELL) RESPONSE



The humoral response is carried out by B lymphocytes.



It involves the production of the antibody.



In most cases, activation of B cells requires help from T cells.

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THE HUMORAL RESPONSE: Activation



After activation: 

Some B cells proliferate and differentiate into plasma cells.



Some B cells become memory cells.



Plasma cells produce massive amounts of antibody.

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THE HUMORAL RESPONSE: Antibodies 

Antibodies are found in the blood and in extracellular spaces.



They contribute to the adaptive response in three ways: 

Neutralization 

Neutralizes toxins and viruses



Prevents bacterial attachment (staying in)



Opsonization



Complement





Facilitates uptake of pathogens by phagocytic cells

Activates the classical pathway

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THE HUMORAL RESPONSE: Antibodies

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THE IMMUNOGLOBULIN MOLECULE Antigen receptors on B cells are called immunoglobulins (Ig).  All Ig molecules have a Y shape. 



They are composed of 4 polypeptide chains. 

Two light chains



Two heavy chains



The 4 amino terminal ends make up the antigenbinding site.



Remainders of the heavy chains make up the constant region.

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THE IMMUNOGLOBULIN MOLECULE

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THE IMMUNOGLOBULIN MOLECULE: Binding



Antibodies bind antigens. Binding: 

Is based on contacts between the antigen and binding site.



Depends on the size and shape of the antigen. 

Binding is along the side of large antigens.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

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THE IMMUNOGLOBULIN MOLECULE: Binding 

Antibodies are generally made against epitopes. 



Epitopes are small surface regions of antigens.

Antibody binding involves hydrophobic and electrostatic forces. 

Hydrogen bonds are also involved.

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IMMUNOGLOBULIN ISOTYPES 

There are 5 isotypes: 

IgG



IgM



IgA



IgD



IgE

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IMMUNOGLOBULIN ISOTYPES

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IMMUNOGLOBULIN ISOTYPES 

The constant region of any immunoglobulin has three main functions: 

Recognition by specialized receptors on phagocytic cells



Forming antigen-antibody complexes that initiate classical complement pathway



Delivering antibody to tissues and secretions

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DISTRIBUTION AND FUNCTION OF IMMUNOGLOBULINS 

Most antibodies are distributed by diffusion.



Some are distributed by specialized transport mechanisms. 

These are used to bring the antibody to the epithelial surfaces including: 

Digestive tract



Lungs

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DISTRIBUTION & FUNCTION OF IMMUNOGLOBULINS: IgM 

IgM is the first antibody to be produced. 

IgM can be in a pentamer structure.



It is usually found in blood.



It is an excellent activator of the complement system.



It is the primary response to bloodborne pathogens.



It is also found in pleural spaces.





This has ten binding sites and great binding strength.

This protects against environmental pathogens.

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DISTRIBUTION & FUNCTION OF IMMUNOGLOBULINS: IgG 

IgG, IgA, and IgE are all smaller than IgM.



The principle isotype of IgG is found in the blood and extracellular fluid.





They can easily diffuse out of the blood.

It is very effective for opsonization and complement activation.

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DISTRIBUTION & FUNCTION OF IMMUNOGLOBULINS: IgA



IgA is the principle antibody in secretions. 

It is found in the respiratory and digestive tracts.



It is not very effective in activating the complement system.

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DISTRIBUTION & FUNCTION OF IMMUNOGLOBULINS: IgE 

IgE is found in low levels in the blood and extracellular fluids. 

It binds tightly to mast cells just below the skin and mucosa.



It is also found along the blood vessels in connective tissue.



After antigen binding, powerful chemical mediators are released. 

They cause coughing, sneezing and vomiting.

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DISTRIBUTION & FUNCTION OF IMMUNOGLOBULINS: IgD



IgD is found in very small amounts in the blood. 

It is found on the surface of B cells.



It is involved as an early antigen receptor.

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DISTRIBUTION & FUNCTION OF IMMUNOGLOBULINS: Transcytosis



Immunoglobulins can move across epithelial barriers – transcytosis. 

It occurs most frequently with IgA. 

IgA is secreted as a dimer.



It is held together by a J chain and a secretory piece.

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DISTRIBUTION & FUNCTION OF IMMUNOGLOBULINS: Transcytosis

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DISTRIBUTION & FUNCTION OF IMMUNOGLOBULINS: Newborns 



IgA is found in colostrum. 

It is transferred from mother to child.



It protects against newly encountered bacteria.

Newborns also get maternal IgG for further protection. 

IgG can cross the placenta.

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DISTRIBUTION & FUNCTION OF IMMUNOGLOBULINS: Bacterial Toxins



IgG and IgA can neutralize bacterial toxins. 

They bind the toxin molecule and prevent it entering the cell.

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DISTRIBUTION & FUNCTION OF IMMUNOGLOBULINS: Blocking Attachment



IgG and IgA can block viral and bacterial attachment. 

IgA acts at the mucosal surfaces.



IgG acts in tissues.

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DISTRIBUTION & FUNCTION OF IMMUNOGLOBULINS: Cell Activation 

Antibody can also activate the following cells: 

NK cells



Basophils



Mast cells



Activation triggers the release of mediators.



It is important in parasitic infections.

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ACTIVATION OF BASOPHILS AND MAST CELLS BY IgE A substantial amount of IgE is bound to mast cells and basophils.  When bound to antigen, antibody causes the release of histamine. 

  



This occurs in seconds. It causes an increase in blood flow – vascular dilation. It promotes the movement of blood proteins and fluids in tissue. There is a following influx of neutrophils, macrophages, and lymphocytes.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

ACTIVATION OF BASOPHILS AND MAST CELLS BY IgE

Photo courtesy of Ann Dvorak

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

B CELL ACTIVATION BY T CELLS B cells have an antigen receptor that is a surface immunoglobulin molecule.  The bound antigen is endocytosed and degraded. 



 

It is then combined with MHC class II and sent to the surface.

The complex is recognized by helper T cells. The B cell is activated and differentiates into a plasma cell. 

It produces antibody against the antigen.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

Microbiology: A Clinical Approach [9780815365143] © Garland Science

B CELL ACTIVATION BY T CELLS: Primary Response



Naive B cells express both IgM and IgD on their surface. 

After activation, IgD disappears.



IgM is the first isotype of antibody produced.



This is the primary response.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

B CELL ACTIVATION BY T CELLS: Secondary Response 

Isotype switching occurs in the secondary response. 

IgM gives way to IgG.

The secondary response occurs when the antigen is seen again.  It is faster and more powerful than the primary response.  Helper T cells regulate the production and isotype of antibody. 

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

B CELL ACTIVATION BY T CELLS: Primary and Secondary Response

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

Microbiology: A Clinical Approach [9780815365143] © Garland Science

T AND B CELL INTERACTION



For the humoral response to work, each B cell must find a helper T cell. 

This is accomplished by trapping.



Trapping occurs in the peripheral lymphoid tissue.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

T AND B CELL INTERACTION: Trapping 

Antigens are captured and processed by antigen-presenting cells (APCs).



APCs migrate to lymph nodes and lodge in the paracortical areas.



Naive T cells move through the node.



If a T cell is presented with its antigen it is activated and remains trapped in the lymph node.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

T AND B CELL INTERACTION: Trapping 

B cells also pass through the paracortical areas.



B cells are trapped if there is an activated T cell present.



T and B cells cooperate in the paracortical area.



B cells then move to follicular areas and differentiate into plasma cells.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

Microbiology: A Clinical Approach [9780815365143] © Garland Science

PLASMA CELLS



Plasma cells have a variety of life spans 

Some live for only a few days.



Others live for significantly longer periods 

They receive survival signals from bone marrow stromal cells.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

THE CELLULAR (T CELL) RESPONSE 

The cellular immune response is generated by T cells. 

Cytotoxic T cells



Helper T cells



T cells that have not seen antigen are considered to be naive.



After encountering antigen, both types become armed effector T cells.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

CYTOTOXIC T CELLS: Antigen Encounter 



Some antigens are degraded in the cytoplasm of infected cells. 

They are carried to the cell surface by class 1 MHC molecules.



They are then presented to cytotoxic (CD8) T cells.

Cytotoxic T cells proliferate and look for any cells also expressing that antigen. 

They will kill those cells.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

Microbiology: A Clinical Approach [9780815365143] © Garland Science

HELPER T CELLS: Antigen Encounter Some pathogens multiply in intracellular vesicles and there are pathogens in extracellular fluid.  Antigens from both are taken to the surface of the APC. 

 



They are coupled with MHC class II molecules. They are then presented to helper (CD 4) T cells.

Helper T cells then differentiate into Th1 or Th2 cells.  

Th1 cells help with pathogens in vesicles. Th2 cells deal with extracellular pathogens.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

HELPER T CELLS

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

PRODUCTION OF ARMED EFFECTOR T CELLS



The arming of naive T cells can be done by: 

Dendritic cells



Macrophages



B cells

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

Microbiology: A Clinical Approach [9780815365143] © Garland Science

ARMING BY DENDRITIC CELLS 

Dendritic cells secrete chemokines. 

Chemokines attract naive T cells.



Dendritic cells present viral, fungal, and bacterial antigens.



They also participate in transplantation rejection and allergic reactions.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

ARMING BY MACROPHAGES 

Resting macrophages have few or no class II MHC molecules.



After ingesting a microorganism, they produce more.



They then degrade the microorganism and present antigen-class II MHC complex to T cells. 

This causes the release of co-stimulatory molecules.



These allow the activation of T cells to continue.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

ARMING OF T CELLS BY B CELLS Surface immunoglobulin on B cells is an antigen receptor.  It binds antigen and is internalized by endocytosis.  Antigen is then bound to MHC class II molecules.  The complex is moved back to the surface of the B cell.  It is presented to T cells. 



This causes the release of co-stimulatory molecules.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

Microbiology: A Clinical Approach [9780815365143] © Garland Science

ARMING OF T CELLS BY B CELLS

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

PROPERTIES OF ARMED EFFECTOR T CELLS 

There are three classes of armed effector T cells: 

Cytotoxic



Th1 helper



Th2 helper



Most of these move into the blood when they are activated.



Cytotoxins are released by cytotoxic T cells.



Cytokines are released by helper T cells.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

PROPERTIES OF ARMED EFFECTOR T CELLS

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

Microbiology: A Clinical Approach [9780815365143] © Garland Science

T CELL CYTOTOXICITY 

All viruses and some bacteria multiply in the cytoplasm of infected cells. 

Once inside a cell, pathogens are no longer susceptible to antibodies.



Cytotoxic T cells kill infected cells by inducing apoptosis in the infected cell.



They kill through cytotoxic granule release.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

T CELL CYTOTOXICITY



Cytotoxic T cells are selective and repetitive killers of target cells.



They cells also release cytokines (interferon and TNF). 

These are part of the innate immune response.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

MACROPHAGE ACTIVATION BY T CELLS 

Some bacteria proliferate in macrophages. 

They can be eliminated if the macrophage becomes activated.



Th1 helper cells provide the activation signal.



Activation increases the number of Class II molecules.



This enhances antigen presentation and increases the adaptive response.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

Microbiology: A Clinical Approach [9780815365143] © Garland Science

IMMUNOLOGICAL MEMORY Immunological memory is one of the most important properties of the adaptive immune response.  It can be seen in both T cells and B cells and is produced after infection or vaccination.  Memory is due to a persistent population of memory cells. 





Most are at rest but a small percentage is dividing at all times.

Interleukins help to maintain the memory T cell population.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

MEMORY AND EFFECTOR T CELLS 

After activation, the number of T cells increases.



As the infection subsides, the number decreases to a persistent level.



This level is 10 – 1000 times higher than the initial number before activation.



This increase is due to the increased number of memory cells.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

IMMUNITY TO INFECTION



Innate and adaptive immune responses work together as fully integrated systems to defeat infection.



The end result is the control and elimination of infection and protection from re-infection.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

Microbiology: A Clinical Approach [9780815365143] © Garland Science

IMMUNITY TO INFECTION 

The innate response works primarily in the early stages of the infection.



The adaptive immune response takes place a few days after first exposure to an antigen.



Once pathogens have established an infection, it is only the adaptive response that can get rid of them.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

IMMUNITY TO INFECTION

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

COURSE OF THE ADAPTIVE RESPONSE

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

Microbiology: A Clinical Approach [9780815365143] © Garland Science

MECHANISMS OF THE ADAPTIVE RESPONSE

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

VACCINATION Vaccination is essentially an artificially derived infection.  Weakened or dead pathogens are administered to a healthy individual with the intent of conferring immunity.  In many case, antigen is derived from the toxin produced by the pathogen.  Most vaccinations are administered in childhood. 

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

VACCINATION 

There can be risks with vaccinations. 

Some vaccines can contain adjuvants, which are chemicals designed to boost immune response.



In some people, adjuvants and some preservatives in vaccines can cause adverse reactions.



Vaccines composed of weakened pathogens may cause a small percentage of vaccinated individuals to become infected.

Microbiology: A Clinical Approach Approach, © byGarland Tony Srelkauskas Science © Garland Science

ISBN: 978-0-8153-6514-3

Microbiology: A Clinical Approach [9780815365143] © Garland Science