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Adaptive Immunity Chapter 17 Tortora
 

Adaptive Immunity Chapter 17 Tortora

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    Adaptive Immunity Chapter 17 Tortora Adaptive Immunity Chapter 17 Tortora Presentation Transcript

    • Adaptive Immunity: Specific Defenses of the Host Chapter 17 Tortora
    • Immunity
      • Protection against disease (etc)
      • The immune system recognizes foreign substances and develops an immune response against them.
      • Innate or nonspecific immunity seems to have an inherited (genetic) component
      • Adaptive or specific immunity adapts to a particular invader or foreign substance
    • Types of acquired immunity
      • Acquired immunity can be acquired passively or actively
      • Active or passive can be acquired naturally or artificially
      • Naturally acquired active immunity-exposure to antigens (you get sick and recover)
      • Naturally acquired passive immunity-natural transfer of antibodies from mom to child (breast feeding and in utero)-this is short lived.
    • Immunity continued
      • Artificially acquired active -get a vaccination which introduces specially prepared antigens into the body
        • Doesn’t cause disease but stimulates your reaction
      • Artificially acquired passive -introduce antibodies into the body
        • These are derived from serum so are called antisera
        • Often inject a horse with antigen and then use the horse antibody (spider and snake antivenom)
    • Dual nature of the immune system
      • First Nobel prize winner was Emil von Behring who discovered immunity can be passed from one organism to another (now called humoral immunity)
      • Scientists later discovered this was due to antibodies (1930’s)
      • Cell mediated immunity is governed by lymphocytes
      • Humoral immunity (antibody mediated) involves the production of antibody
    • Humoral immunity
      • B cells or B lymphocytes are responsible for antibody production
      • This provides resistance to bacteria and viruses and bacterial toxins
      • B stands for the Bursae of Fabricius
      • Antibody or immunoglobulins recognize different types of antigen
    • Cell mediated Immunity
      • Involves T cells (T lymphocytes) that act against foreign cells or tissue
      • T cells mature in the thymus gland
      • Also regulate the activation and proliferation of other immune system cells
      • Cell mediated immune response is directed against bacteria and viruses inside phagocytic cells or infected host cells, fungi, protozoa, and helminths
      • This also causes rejection in implanted tissue
    • Antigens and antibody
      • Antigen is any foreign substance
      • We recognize ‘ self’ and don’t attack it ( MHC antigen)
      • Antibody is produced by B cells and combines with antigenic determinant or epitopes on the antigen
      • Some antigens are small (a molecular weight of less than 10,000) and won’t trigger a response unless attached to a carrier. These small antigens are HAPTENS.
      • The antibody reacts with the hapten, not the carrier.
    • Nature of antibody
      • Antibodies are proteins made in response to antigen that recognize and bind to antigen
      • The valence of an antibody is the number of antigen binding sites
      • Most humans are bivalent
      • Antibodies are members of a group of soluble proteins called immunoglobulins or Igs.
    • Antibody structure
      • A bivalent is the simplest structure for an antibody so it is referred to as a monomer
      • A monomer usually has 4 protein chains
      • Two of these are identical light chains (L) and two are identical heavy chains (H)
      • Light and heavy refer to molecular weights
      http://courses.washington.edu/conj/immune/antibody.htm Citation for picture
    • Antibody structure continued
      • Variable regions (V) are located at the end of the Y’s arms
      • Their structure reflects the specific antigen they recognize, and these are specific to the two antigen binding sites (bind to epitopes)
      • The stem and lower portion of the Y are the constant regions (C)
      • These are the same for a particular class of Ig
      • There are 5 major types of C regions, giving us 5 major classes of immunoglobulin
      • The Fc regions (on the stem) are important in immunological reactions
    • Classes of Ig
      • IgG -80% of all serum antibody, cross blood vessel walls and enter tissue fluids
        • Cross placenta to protect fetus
        • Protect against circulating bacteria, viruses, neutralize toxin, trigger complement, and enhance phagocytic cells
      • IgM 5-10% of serum antibody and is shaped like a pentamer
        • First to respond to initial antigen exposure. Subsequent exposure results in increased IgG
        • Valuable in diagnosis because it is early to respond.
    • Classes continued
      • IgA -5-10% of serum antibody, but most common in fluids like saliva and breast milk (helps keep baby safe while it develops its own immune system)
        • Prevent attachment of viruses and/or bacteria to mucosal surfaces
      • IgD -0.2%, found on surface of B cells and act as antigen receptors (no known function in serum)
      • IgE -0.002% of serum antibody, Fc portion binds to mast cells and basophils (allergic reactions),
        • Increases during parasite or allergy
    • B cells and Humoral immunity
      • This antibody mediated immunity is carried out by B cells
      • HOW?
      • B cell exposed to antigen and become activated
      • B cells divide and produce clones called plasma cells
      • Plasma cells produce antibody to that specific antigen (say you have measles for instance, it won’t work against chicken pox)
      • Some turn into memory cells so that you can have long term immunity to that disease.
    • More on B cells
      • B cells come from stem cells in bone marrow (adult) and liver (fetus)
      • Mature B cells are found in spleen and lymph nodes
      • Recognize antigen by antigen receptors on cell surface
      • Apoptosis -programmed cell death
      • We make 100 million lymphocytes a day, so equal number must die. Any that don’t encounter antigen quickly go through apoptosis
    • Activation of antibody producing clones
      • Each B cell can only produce an antibody against a particular antigen
      • A mature B cell can have 100,000 IgM or IgD antibody bound to it’s surface
      • When antigen binds to antigen receptor, the B cell proliferates into clones that will recognize this one antigen (clonal selection)
      • Each B cell has the ability to respond to 100 million antigens thanks to the variable region, but once it has responded it can only make clones for ONE type.
    • Antigen/antibody complex
      • B cells usually require the help of a helper T cell
      • An antigen that requires the helper T cells for antibody production is called a T-dependent antigen
      • B cell contacts the antigen and is processed inside the B cell
      • Fragments of the antigen combine with MHC and are displayed on the B cell surface.
      • The T cell comes in contact with the antigenic fragment/MHC presented on the B cell and activates the T cell
      • The T cell produces cytokines that in turn activate the B cell to produce clones, some of which become the plasma cell.
    • Antigen-antibody binding and results
      • Antigen/antibody complex is formed quickly
      • Binding targets the antigen for phagocytosis or complement
      • Agglutination is clumping of antigens to make them easier for phagocytes to digest
      • Neutralization-IgG antibodies inactivate viruses by blocking their attachment to a host
      • Opsonization-antigen is covered by antibody to aid in ingestion/digestion by phagocytic cells
      • IgG and IgM trigger complement
    • T cells and Cell mediated Immunity
      • The chemical messengers of immune cells are called cytokines
      • These chemical messengers allow the cells to communicate with each other
      • There are 60 different cytokines identified to date
      • Some cytokines help the communication between leukocytes and are called interleukins
      • There are 18 of these (IL-1, IL-2 etc) (see table 17.3)
      • Another group is called chemokines that help induce leukocytes to migrate into infected areas.
    • Cellular components of immunity
      • T cells are the key component
      • They develop from stem cells in bone marrow and mature in the thymus gland
      • After maturation they migrate to lymphoid organs
      • T cells respond to specific antigen, multiply as clones into effector T cells, and destroy the invader
    • Types of T cells
      • Helper T- have central role in immune response, these activate macrophages and help form cytotoxic T cells
      • Cytotoxic T destroy target cells on contact by producing perforin that lysis a bacterial or viral infected cells
      • Delayed hypersensitivity T involved in allergic reactions and tissue rejection,
      • Suppressor T are involved in stopping the reaction once the danger is passed. (Now called regulatory T cells).
      • Another way to classify T cells is by the type of surface receptor called CD (clusters of differentiation)
      • Two are CD4 and CD8.
    • Nonspecific cellular components
      • Natural killer cells or NK cells -lymphocytes that can destroy other cells, especially tumor cells and other viral infected cells
      • Activated macrophages are stimulated macrophages that have been activated by the cytokines produced by helper T cells
      • These macrophages can be activated by digesting antigen too.
      • Macrophages often act as antigen presenting cells (APC’s)
      • This is identified by the T cells
    • Interrelationship between cell mediated and humoral immunity
      • Antibody production depends on macrophages and T cells (T dependent antigen)
      • 1. antigen is ingested and presented by the APC
      • 2. The helper T cells reacts with this MHC-antigen complex
      • 3. This activates the T cell and it begins to proliferate and produce cytokines.
      • 4. The cytokines activate macrophages, CD8 cells, and natural killer cells
    • continued
      • 5. IL-2 influences a B cell to differentiate into a plasma cell that produces antibody
      • Sometimes antigen can stimulate B cells directly without the help of T cells. This is called T independent antigen
      • In this case the antigen reacts directly with the B cell receptors.
      • This is usually weaker
    • Immunological memory
      • Intensity of the antibody mediated humoral response is reflected by antibody titer
      • This is the amount of antibody in the serum after infection has been cleared
      • There is no detectable titer in the serum for 4-7 days (initial infection)
      • IgG peaks in 10-17 days, and titer increases
      • This is the primary response
      • If you are exposed again, the memory response peaks in 2-7 days and is much greater!
    • When the immune system goes haywire!
      • Hypersensitivity -antigenic response beyond the normal response due to previous exposure (sensitization) by an allergen
      • 4 types:
        • Type I-anaphylatic reactions
        • Type II cytotoxic reactions
        • Type III-Immune complex reactions
        • Type IV-delayed cell mediated (delayed hypersensitivity)
        • http://www.cehs.siu.edu/fix/medmicro/hyper.htm
    • Type I
      • Occur quickly (2-30 minutes) after exposure
      • May be localized or systemic
      • Localized reactions include hives, hay fever, asthma
      • Systemic includes shock and breathing difficulty (death can result)
      • Over reactive IgE ( you inherit the sensitivity but may have a completely different allergy)
    • Type II
      • Involve activation of complement by IgG or IgM antibodies within an antigenic cell
      • This causes lysis of the cell
      • Common type II reactions are transfusion reactions (ABO blood group)
      • Erthryoblastosis fetalis or hemolytic disease of the newborn (Rh negative mom has a second Rh positive baby, the second baby is likely to develop this)
    • Type III
      • Form when certain ratios of antigen and antibody occur
      • Usually involves IgG
      • IF there is a slight excess of antigen, the soluble complex that forms is small and escape phagocytosis
      • It this happens the complex may become trapped in the basement membrane beneath cells, activating complement and inflammation
      • Neutrophils enter and release enzymes that can damage the cells within 2-8 hours.
      • An example is glomerulonephritis which damages kidney glomeruli causing kidney failure
      • Another is serum sickness following injection of antitoxin produced by an animal
    • Type IV
      • Caused by T cells
      • Delay may be a day or more
      • Include allergic contact dermatitis (allergic to latex)
      • T B tine test