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MICR 201 Microbiology for Health Related Sciences . Microbiology- a clinical approach by Anthony Strelkauskas et al. 2010 Chapter 16: The adaptive immune response. Why is this chapter important?.

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Micr 201 microbiology for health related sciences

MICR 201 Microbiology for Health Related Sciences

Microbiology- a clinical approach by Anthony Strelkauskas et al. 2010

Chapter 16: The adaptive immune response


Why is this chapter important
Why is this chapter important?

  • The adaptive immune response is a very powerful system that protects us from a multitude of infectious organisms.

  • It has the gift of memory, which provides rapidly a more powerful reaction if the same pathogen is seen again. This is the basis for vaccinations.

  • Without the adaptive immune response we would not survive.



Introduction initiation of the adaptive immune response
Introduction: initiation of the adaptive immune response

  • The adaptive immune response is the second line of defense.

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

    • Alerts and activates the adaptive immune response via cytokines and chemokines.

    • Presents antigens

  • Dendritic cells are the most important innate cells for the proper development of an adaptive immune response. This is because:

    • They take up and process antigens.

    • They migrate to lymph nodes and present antigens to T cells.

    • They have enormous surface areas and can interact with many different T cells.


Introduction overview
Introduction: overview

  • The adaptive immune response involves lymphocytes which develop from the hematopoietic stem cell in the bone marrow

    • B-lymphocytes (B cells)

    • T-lymphocytes (T cells)

  • It is a response to specific antigens via highly specific antigen receptors

    • Antibody molecule on B cells

    • T cell receptor on T cells

  • It can adapt to any infection.

  • It has memory.

    • This confers life-long immunity.


Introduction types of adaptive immune response
Introduction: types of adaptive immune response

  • The adaptive immune response has two types of response:

    • Humoral – production of antibodies by B cells

    • Cellular – strengthening immune cells and killing and regulation of infected cells by T cells


Introduction antigens
Introduction: antigens

  • Antigen is any molecule that can induce a specific adaptive immune response.

    • Originally defined as antibody generating agent

  • There are two types of antigens:

    • Self

    • Non-self

  • During early cell development or maturation lymphocytes are schooled to become tolerant for self antigens.

    • B cells mature in the bone marrow

    • T cells mature in the thymus



Introduction lymphatic system
Introduction: lymphatic system

  • The adaptive response is associated with the lymphatic system.

    • It patrols (almost ) the entire body.

    • It involves lymphocytes and lymphoid structures such as lymph nodes.


Introduction lymphatic system1
Introduction: lymphatic system

The strategic placement of these lymphoid structures makes it possible for the adaptive immune system to deal with potential pathogens from almost any place that is involved in infection.


Introduction lymphoid structures
Introduction: lymphoid structures

  • Strategic lymphoid structures are found in places where pathogens typically enter.

    • GALT – gut associated lymphoid tissue

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

    • BALT – bronchial associated lymphoid tissue

      • Associated with the respiratory portal of entry

      • Most available portal of entry

    • MALT – mucosal associated lymphoid tissue

      • Associated with mucous membranes

      • An important portal of entry


Peyer s patches
Peyer’s patches

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

  • They contain M cells (M for microfold).

  • M cells are antigen collecting cells.

  • Under M cells are germinal centers

    • Filled with B cells

    • Surrounded by T cells


M cells and peyer s patches
M cells and Peyer’s patches


Development differentiation and maturation of lymphocytes
Development, differentiation, and maturation of lymphocytes

  • There are two types of T cell:

    • Helper T cells (TH)

    • Cytotoxic (CTL)


Development differentiation and maturation of lymphocytes1
Development, differentiation, and maturation of lymphocytes

  • Helper T cells differentiate into subtypes including:

    • TH1 cells

    • TH2 cells

  • TH1 cells activate macrophages to synthesize more antimicrobial factors

  • TH2 cells instruct B cells to make large amounts antibodies which in turn block pathogens from entering the body and improve phagocytosis


Development differentiation and maturation of lymphocytes2
Development, differentiation, and maturation of lymphocytes

  • Cytotoxic T cells kill host cells that have been taken over by specific microbes

    • Virus infected

    • Cells infected with intracellular bacteria

    • Protozoan infected cells

  • Cytotoxic T cells kill similar to NK cells, they command the target cell to commit suicide. However, they only target specific cells which they recognize with their antigen receptor.


Development differentiation and maturation of lymphocytes3
Development, differentiation, and maturation of lymphocytes

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

    • The B cell receptor is an immunoglobulin (antibody) molecule.

      • It has two antigen binding sites.

    • The T cell receptor is related to immunoglobulins , but

      • It has only one antigen binding site.



Clonal selection of lymphocytes
Clonal selection of lymphocytes

  • Once lymphocytes passed schooling and are found not to react with self they are released into the bloodstream and they continuously circulate the lymphatic system.

  • If an antigen is encountered and fits to the antigen receptor on the lymphocyte, 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.


  • Clonal selection of lymphocytes1
    Clonal selection of lymphocytes


    Proliferation and differentiation of lymphocytes into effector cells
    Proliferation and differentiation of lymphocytes into effector cells

    • Once signaled, lymphocytes stop migrating and become activated.

    • They become larger and multiply.

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

    • They differentiate into effector cells

      • B cells become Plasma cells that are antibody factories.

      • T cells become armed effector cells that put out a huge amount of cytokines (TH) or kill the target cells (CTL)

    • Some will differentiate into memory cells that are able to quickly become effector cells upon re-stimulation


    Co stimulatory signals are required for lymphocyte activation
    Co-stimulatory signals are required for lymphocyte activation

    • The consequences of lymphocyte activation are dramatic.

    • As a safeguard, antigen that binds to the antigen receptor is not enough to trigger a full adaptive response.

    • Other danger signals must be present, called co-stimulatory signals:

      • Pro-inflammatory cytokines

      • Other cell surface molecules expressed only under stress

      • TLR binding.

    • Once the infection is cleared lymphocytes are no longer stimulated and will die by apoptosis

    • Lymphocytes never activated also die by “neglect”, or also entering the apoptotic pathway.


    Antigen presentation to t cells
    Antigen presentation to T cells activation

    • B cells recognize native antigens.

    • T cells cannot detect native antigen. They can see antigen only after it has been processed (degraded, taken apart) into short amino acid stretches and placed onto a specialized molecule, the major histocompatibility complex (MHC).

    • There are two types of MHC:

      • Class I is found on all cells.

      • Class II is found only on specialized antigen presenting cells

        • Monocytes/macrophages, dendritic cell, B cells


    Antigen presentation delivery

    TH activation

    CTL

    Antigen presentation: delivery

    • Antigens are delivered by the MHC in different ways:

    • Class I molecules associate with cytoplasmic or endogenous antigens.

      • They present to cytotoxic T cells.

      • These antigens are derived from microbes replicating in the host cell.

    • Class II molecules associate with antigens from phagocytic cell vesicles or exogenous.

      • They present to helper T cells.

      • These antigens are degradation products from the phagolysosome.

    MHC I

    MHC II


    Antigen presentation t cells
    Antigen presentation: T cells activation

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

      • This is referred to as the antigen-MHC complex.

    • Additional molecules are required to make sure that the right T cell acts on the right target cell

      • T helper cells should only act on immune cells that need help to deal with the invading microbe

      • Cytotoxic T cells should only kill infected cells that have been taken over by the microbe.

    • To guarantee this there are additional molecules involved in the formation of the antigen-MHC complex.

      • CD 4 on T helper cells binds to MHC class II

      • CD8 on cytotoxic T cells binds to MHC class I


    Mhc i ii and cd 8 4 interaction
    MHC activation I/II and CD 8/4 interaction

    TH

    CTL

    Induce apoptosis

    INFg

    Cytotoxic

    granules

    Cytokines

    Any nucleated cell

    Ag presenting cell

    Note: antigen and antigen receptor are omitted.


    Effector t cells
    Effector T cells activation


    T cells respond to superantigens
    T cells respond to activationsuperantigens

    • T cells can respond to superantigens.

      • These are distinct classes of antigens produced by many pathogens.

    • 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.

    • Example: toxic shock syndrome toxin


    Toxic shock syndrome
    Toxic shock syndrome activation

    • First described in menstruating women using certain types of tampons

    • High fever, rash, skin peeling in palms, shock, multiple organ failure

    • Staphylococcus TSST production triggered in high absorbency tampons

    • TSST resorption through vaginal mucosa


    T helper cells
    T helper cells____________. activation

    • bind to antigen presented on MHC I.

    • express CD8.

    • Release INFg to stimulate macrophages.

    • All of the above is correct.

    • None of the above is correct.


    Nk cell and ctl are alike in all of the following except
    NK activation cell and CTL are alike in all of the following except_______.

    • that they both induce apoptosis in the target cell.

    • that they release cytotoxic granules.

    • they recognize only specific infected cells.

    • that they can kill more than one cell.

    • All of the above are correct.


    The humoral b cell response
    The activationhumoral 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.

      • Some B cells proliferate and differentiate into plasma cells.

      • Plasma cells produce massive amounts of antibody.

      • Some B cells become memory cells.


    The humoral response antibodies
    The activationhumoral 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

      • Opsonization

        • Facilitates uptake of pathogens by phagocytic cells

      • Complement

        • Activates the classical pathway


    The humoral response antibody production
    The activationhumoral response:Antibody production


    The antibody molecule
    The antibody molecule activation

    • Antibodies are also 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 antigen-binding site.

      • Remainders of the heavy chains make up the constant region that interacts with host cells

        • E.g. phagocytes



    The antibody molecule antigen binding
    The antibody molecule: antigen binding activation

    • 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.

    • Antibody binding involves hydrophobic and electrostatic forces but is never covalent.

    • Antibodies are generally made against epitopes.

      • Epitopes are small surface regions of antigens.


    Antibody immunoglobulin isotypes
    Antibody (immunoglobulin) activationisotypes

    • There are 5 isotypes:

      • IgG

      • IgM

      • IgA

      • IgD

      • IgE

    • They differ in the type of the constant region.

    • A B cell always makes IgM isotype first and then switches to other isotypes with the help of cytokines that have been released by T helper cells. The antigen binding site remains the same.


    Antibody isotypes
    Antibody activationisotypes


    Antibody isotypes1
    Antibody activationisotypes

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

      • Recognition by specialized receptors on phagocytic cells (IgG)

      • Forming antigen-antibody complexes that initiate classical complement pathway (IgM, IgG)

      • Delivering antibody to tissues and secretions (IgG, IgA)


    IgM activation

    • IgM is the first antibody to be produced.

      • IgM can be in a pentamer structure.

        • This has ten binding sites and great binding strength.

      • 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 protects against environmental pathogens.


    IgG activation

    • IgG is smaller than IgM and can easily diffuse out of the blood.

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

    • It is very effective for opsonization and complement activation.

    • It can cross the placenta and protect the unborn embryo and fetus.

      • IgG in a sick newborn does not prove infection!

      • Maternal IgG lasts for about 6 - 9 months.


    IgA activation

    • IgA is the principle antibody in secretions.

    • It is found in the respiratory and digestive tracts.

    • It is present in colostrum and milk and protects the newborn.

    • It is very effective in blocking pathogen attachment to the host and toxin inactivation.


    Transcytosis of iga
    Transcytosis activation of IgA


    IgE activation

    • 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 by the mast cell.

        • They cause coughing, sneezing and vomiting.


    IgD activation

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

    • It is found on the surface of B cells.

    • It plays a role in B cell maturation.


    Which of the following antibody isotype function is mismatched
    Which of the following antibody activationisotype & function is mismatched?

    • IgM & complement activation

    • IgG & opsonin

    • IgA & neutralization

    • IgD & placenta transfer

    • All are correctly matched.


    A newborn baby has a rash and organ anomalies. You determine antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?

    • Moderate titer ++ for IgG.

    • IgM ++ , IgG +++

    • High ++++ titer for IgG

    • High IgA +++

    • High IgD +++


    Antibody mediated cell activation
    Antibody mediated cell activation antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?

    • Antibodies can also activate the following cells to release their granules filled with bioactive molecules:

      • NK cells: IgG

      • Basophils

      • Mast cells

    IgE (important for parasitic infections)


    Activation of mast cells by ige
    Activation of mast cells by antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella? IgE

    • A substantial amount of IgE is bound to mast cells.

    • When bound to antigen, antibody crosslinking causes the immediate release ofhistamine.

      • 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.


    Activation of mast cells by ige1
    Activation of mast cells by antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella? IgE

    • Photo courtesy of Ann Dvorak


    B cell activation by t cells
    B cell activation by T cells antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?

    • 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.


    B cell primary response
    B cell primary response antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?

    • 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.


    B cell activation by t cells secondary response
    B cell activation by T cells: secondary response antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?

    • Isotype switching occurs in the secondary response.

      • IgM gives way to IgG and later on other isotypes depending on the cytokine

      • INFg: IgG

      • IL4: IgE

    • 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.

    • These activated B cells become plasma cells.

    • Some become memory cells.


    B cell primary and secondary response
    B cell primary and secondary response antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?


    Plasma cells
    Plasma cells antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?

    • Produce large amounts of antibodies of one isotype (no more switch)

    http://millette.med.sc.edu/Lab%206%20pages/Connective%20tissue%20cells.htm


    The cellular t cell response
    The cellular T cell response antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?

    • 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.


    Cytotoxic t cell antigen encounter
    Cytotoxic antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella? T cell: antigen encounter

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

      • They are carried to the cell surface by class I 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.


    Helper t cells antigen encounter
    Helper T cells: antigen encounter antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?

    • Phagocytes take up antigens via phagocytosis. B cells take up antigen via endocytosis of antigen bound to their surface antibody .

    • Both cells degrade this exogenous antigen, load bits and pieces onto MHC II, and present it to (CD4 + ) TH cells

      • Antigen presenting cells (APC)

    • Helper T cells then differentiate into TH1 or TH2 cells.

      • TH1 cells help phagocytes to improve phagocytosis and killing.

      • TH2 cells trigger antibody production good for extracellular organism and parasites.


    Summary of t cell effector function
    Summary of T cell effector function antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?


    Immunological memory
    Immunological memory antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?

    • 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.


    Summary of the hallmarks of the lymphocytes
    Summary of the hallmarks of the lymphocytes antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?

    Specific antigen recognition

    +

    Memory

    m

    m

    m

    m

    m

    Clonal proliferation

    m

    m


    Immunity to infection
    Immunity to infection antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?

    • 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.

    • 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.


    Immunity to infection1
    Immunity to infection antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?


    Cellular cooperation in the immune response
    Cellular cooperation in the immune response antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?


    Vaccination
    Vaccination antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?

    • Vaccination is essentially an artificially derived infection.

    • Weakened or dead pathogens are administered to a healthy individual with the intent of conferring immunity.

      • Boosters are typically required.

    • In many case, antigen is derived from the toxin produced by the pathogen.

    • Most vaccinations are administered in childhood.


    Types of vaccinations
    Types of vaccinations antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?

    • Activeversuspassive

      • Antigen is administered in active vaccinations; antibodies are given in passive vaccinations

    • Live versusdeadversussubcomponent vaccines

      • An attenuated (weakened) strain is given in a live vaccine, a dead but whole cell/agent is given in a dead vaccine, and purified isolated antigenic compounds are given in a subcomponent vaccine.


    Risks of vaccinations
    Risks of vaccinations antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?

    • 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.


    Chapter 16 key concepts
    Chapter 16 key concepts antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?

    • The adaptive immune response is specific and involves both cellular and humoral responses.

    • T cells and B cells are involved in the adaptive immune response.

    • Both T cells and B cells have receptors for antigen..

    • There are lymphoid structures strategically placed in major portals of entry..

    • The adaptive immune response is connected to the innate immune response.

    • T cells mature in the thymus, and B cells mature in the bone marrow.


    Chapter 16 key concepts1
    Chapter 16 key concepts antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?

    Clonal selection and deletion are processes that allow some lymphocytes to mature while others are deleted from the body.

    T cells are initially naive and become armed effector cells after encountering their specific antigen.

    Antigen presentation involves combining antigen with class II MHC molecules.

    CD4 helper T cells recognize class II MHC molecules, whereas CD8 cytotoxic T cells recognize class I MHC molecules.

    B cells are responsible for antibody production. B cells differentiate into plasma cells that produce antibody.


    Chapter 16 key concepts2
    Chapter 16 key concepts antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?

    There are five types of antibody molecule: IgG, IgM, IgA, IgD, and IgE.

    T cells direct the production of antibody.

    CD8 cytotoxic T cells kill specifically identified targets and remember them through the development of memory cells.

    CD4 helper T cells can be divided into two groups, Th1 and Th2, each with a different helper function.

    The adaptive immune response can be divided into a primary phase and a secondary phase.


    Micr 201 class evaluation
    MICR 201 Class Evaluation antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?

    • STUDY

    • 4 units x 2-3 hours = 8-12 hours/week

    • LEARN

      • Terms, Glossary

      • Concepts

    • EVALUATION

      • Lecture

      • Chapter questions

      • Quiz, MT, Final


    Micr 201 evaluation revised
    MICR 201 Evaluation: Revised antibody titers against rubella. Which of the following results from the baby’s serum suggests that the baby had an intrauterine infection with rubella?

    • Completed:

      • Quiz #1 = 50 pts.

      • Midterm = 100pts.

    • Quiz #2 = 50 pts.:

      • Wed. May 15

      • Chapter 14,15,16,17

    • Quiz #3 = 50 pts.:

      • Wed. May 29

      • Chapter 18,19,20,21

    • Final Exam = 200 pts. :

      • Wed. June 12

      • 65%: Chapter 14-26

      • 35%: Chapter 1-13

    • Lecture, Chapter Questions

    • Use reading to understand lecture and Chapter questions


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