Immune Response Kim

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    SPECIFIC HOST

    DEFENSES: THEIMMUNE RESPONSE

    Shalimar Kim P. Inay

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    The Immune Response

    Immunity - Ability of an organism to recognizeand defend itself against specificpathogens or

    antigens.

    Immune Response - it involves production ofantibodies and generation of specialized

    lymphocytes against specific antigens.

    Antigen - Molecules from a pathogen or foreign

    organism that provoke a specific immuneresponse.

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    Defense against Pathogens in the

    body

    Nonspecific Resistance

    External barriers

    Leukocytes and macrophages

    Antimicrobial proteins

    Fever

    Specific Immunity

    General aspectCellular immunity (Recognition, Attack, Memory)

    Humoral immunity (Recognition, Attack, Memory)

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    Immune System

    Humoral (Antibody-Mediated) Immunity

    Involves production of antibodies against foreignantigens.

    Antibodies are produced by a subset of lymphocytescalled B cells.

    B cells that are stimulated will actively secreteantibodies and are calledplasma cells.

    Antibodies are found in extracellular fluids (blood

    plasma, lymph, mucus, etc.) and the surface of Bcells.

    Defense against bacteria, bacterial toxins, and virusesthat circulate freely in body fluids, before they entercells.

    Also cause certain reactions against transplanted

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    Antigens

    Most are proteins or large polysaccharides from a

    foreign organism.

    Microbes: Capsules, cell walls, toxins, viral capsids,

    flagella, etc. Nonmicrobes: Pollen, egg white , red blood cell surface

    molecules, serum proteins, and surface molecules from

    transplanted tissue.

    Lipids and nucleic acids are only antigenic whencombined with proteins or polysaccharides.

    Hapten: Small foreign molecule that is not antigenic. Must becoupled to a carrier molecule to be antigenic. Once antibodies areformed they will recognize hapten.

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    Antigens

    Epitope

    Small part of an antigen that interacts with an

    antibody.

    Any given antigen may have several epitopes.

    Each epitope is recognized by a different

    antibody.

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    Epitopes: Antigen Regions that

    Interact with Antibodies

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    Antibodies

    Proteins that recognize and bind to aparticular antigen with very high specificity.

    Made in response to exposure to the antigen.

    One virus or microbe may have severalantigenic determinant sites, to which differentantibodies may bind.

    Each antibody has at least two identical sites

    that bind antigen: Antigen binding sites. Belong to a group of serum proteins called

    immunoglobulins (Igs).

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    Antibody Structure

    Monomer: A flexible Y-shaped molecule with fourprotein chains: 2 identical lightchains

    2 identical heavychains

    Variable Regions: Two sections at the end of Ysarms. Contain the antigen binding sites (Fab).Identical on the same antibody, but vary from oneantibody to another.

    Constant Regions: Stem of monomer and lowerparts of Y arms.

    Fc region: Stem of monomer only. Importantbecause they can bind to complement or cells.

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    Antibody Structure

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    Immunoglobulin Classes

    IgG

    Most abundant, about 80% of all antibodies in the

    blood; found in blood, lymph, and intestines;

    monomer (one unit) structure. Protects againstbacteria and viruses by enhancing phagocytosis,

    neutralizing toxins and trigerring the complement

    system. It is the only class of antibody to cross

    placental from mother to fetus; conferringconsiderable immune protection in newborns

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    Immunoglobulin Classes

    IgA

    Found mainly in sweat, tears, saliva, mucus,

    breast milk, and gastrointestinal secretions.

    Smaller quantities are present in the blood andlymph. Makes up 10-15% of all antibodies in the

    blood. Occurs as monomers and dimers (two

    units). Levels decrease during stress, lowering

    resistance to infection. Provides localizedprotection of mucuos membranes against

    bacteria and viruses

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    Immunoglobulin Classes

    IgM

    Makes up 5-10% of all antibodies in the blood; also

    found in lymph. Occurs as pentamers (five units);

    first antibody class to be secreted by plasma cellsafter an initial exposure to any antigen. Activates

    complement and causes agglutination and lysis of

    microbes. Also present as monomers on the

    surfaces of B cells, where they serve as antigen

    receptors. In blood plasma, the anti-A and anti-B

    antibodies of the ABO blood group, which bind to A

    and B antigens during incompatible blood

    transfusions are also IgM antibodies.

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    Immunoglobulin Classes

    IgD

    Mainly found on the surfaces of B cells as antigen

    receptors, where it occurs as monomers, involved

    in activation of B cells. About 0.2% of allantibodies in the blood

    IgE

    Less than 0.1% of all antibodies in the blood.

    Occurs as monomers, located on mast cells andbasophils. Involved inn allergic and

    hypersensitivity reactions. Provides protection

    against parasitic worms

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    Antigen(Ag)- Antibody(Ab)

    reactions

    It is the reaction between an antigen and an

    antibody when they come in contact.

    This occurs when antigens enter the body.

    When antigens enter the body, signals are

    sent out and in response to that antibodies are

    made specifically to destroy the antigens.

    It is part of the Adaptive(Specific) immunity

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    B cells and Antibodies

    When a B cell encounters its triggering antigen(alongwith collaborating T cells and accessory cells), it givesrise to many large plasma cells. Every plasma cell isessentially a factory for producing antibody. Each ofthe plasma cells descended from a given B cells

    manufactures millions of identical antibody moleculesand pours them into the bloodstream.

    A given antibody matches an antigen much as a keymatches a lock. The fit varies: sometimes it is veryprecise, while at other times it is little better than thatof a skeleton key. To some degree, however, theantibody interlocks with the antigen and therebymarks it for destruction.

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    How Do B Cells Produce Antibodies?

    B cells develop from stem cells in the bone

    marrow of adults (liver of fetuses).

    After maturation B cells migrate to lymphoid

    organs (lymph node or spleen).Clonal Selection: When a B cell encounters an

    antigen it recognizes, it is stimulated and divides

    into many clones called plasma cells, which

    actively secrete antibodies.

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    Humoral Immunity

    Clonal Selection

    Clonal Selection: B cells (and T cells) that

    encounter stimulating antigen will proliferate into

    a large group of cells.Clonal Deletion: B and T cells that react against

    selfantigens appear to be destroyed during fetal

    development. Process is poorly understood.

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    Antigen-Antibody Binding

    Consequenses

    Antigen-Antibody Complex: Formed when anantibody binds to an antigen it recognizes.

    Agglutination: Antibodies cause antigens(microbes) to clump together.

    IgM (decavalent) is more effective that IgG (bivalent).

    Hemagglutination: Agglutination of red blood cells.Used to determine ABO blood types and to detectinfluenza and measles viruses.

    Opsonization: Antigen (microbe) is covered withantibodies that enhances its ingestion and lysis byphagocytic cells.

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    Antigen-Antibody Binding

    Consequenses

    Neutralization: IgG inactivates viruses by binding

    to their surface and neutralize toxins by blocking

    their active sites.

    Antibody-dependent cell-mediated cytotoxicity:Used to destroy large organisms (e.g.: worms).

    Target organism is coated with antibodies and

    bombarded with chemicals from nonspecific

    immune cells. Complement Activation: Both IgG and IgM trigger

    the complement system which results in cell lysis

    and inflammation.

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    Immunological Memory

    Antibody Titer: Amount of antibody in theserum

    Pattern of Antibody Levels during infection

    Primary ResponseAfterinitialexposure to antigen, no antibodies are

    found in serum for several days.

    A gradual increase in titer, first of IgM and then of

    IgG is observed.Most B cells become plasma cells, but some B

    cells become long living memory cells.

    Gradual decline of antibodies follows.

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    Immunological Memory

    Secondary Response

    Subsequent exposure to the same antigen

    displays a faster and more intense antibody

    response. Increased antibody response is due to the

    existence of memory cells, which rapidly produce

    plasma cells upon antigen stimulation.

    R l ti hi B t C ll

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    Relationship Between Cell-

    Mediated and Humoral Immunity

    Antibody Production

    T-Dependent Antigens: Antibody production requires assistance from T helper cells.

    A macrophage cells ingest antigen and presents it to TH

    cell.

    TH cell stimulates B cells specific for antigen to become plasmacells.

    Antigens are mainly proteins on viruses, bacteria, foreign redblood cells, and hapten-carrier molecules.

    T-Independent Antigens: Antibody production does not require assistance from T cells.

    Antigens are mainly polysaccharides or lipopolysaccharides withrepeating subunits (bacterial capsules).

    Weaker immune response than for T-dependent antigens.

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    Relationship Between Cell-

    Mediated and Humoral Immunity

    Antibody Dependent Cell Mediated

    Cytotoxicity Target cell is covered with antibodies, leaving Fc

    portion sticking outwards. Natural killer and other nonspecific cells that have

    receptors for Fc region are stimulated to kill targeted

    cells.

    Target organism is lysed by substances secreted byattacking cells.

    Used to destroy large organisms that cannot be

    phagocytosed.