The Adaptive Immune Response Specific Defense The Adaptive Immune Response

Specific Immunity Augments mechanisms of nonspecific defense Has memory about specific pathogens Second encounter with same pathogen B lymphocytes –humoral immunity T lymphocytes-cell mediated immunity

3rd Line of Defense Acquired immunity-develops over lifetime Naturally acquired active immunity Exposed to microbe

Acquired Immunity Naturally acquired passive immunity Antibodies from mother Placenta -IgG Colostrum-IgA

Artificially Acquired Immunity Active-vaccines Live attenuated vaccines-mutated microbes Serial passage in cell cultures Adaptation to low temperatures-25 C

Artificially Acquired Immunity Inactivated or killed vaccines Non infective Lower immune response Passive- immune serum Lasts few weeks to months Destroyed by host

Antigens Immunogens-provoke an immune response Most proteins or polysaccharide Larger the molecule the better the immune response Foreign molecules usually or “nonself” Components of microbes Food allergens Dust-microbes, pollen etc.

Properties of Antigens 3 dimensional shapes of regions where antibody binds Antigenic determinants or epitopes Stimulate immune response 6-8 aa or monosaccharides Larger more complex molecules are better antigens Haptens-small molecules-hormones, peptides

Types of Antigens Exogenous antigens Endogenous antigens Microbes reproduce within cells Immune response occurs only if

Types of Antigens Autoantigens Antigens found on normal cells Immune response against oneself Leads to inflammation of tissues-lupus

Lymphocytes Produced in red bone marrow-2 types B lymphocytes T lymphocytes Based upon surface glycoproteins-CD4, CD8 T lymphocytes mature in thymus Self T cells undergo apoptosis B lymphocytes mature in bone marrow Found mainly in spleen, lymph nodes ,bone marrow Circulate in blood

Antibodies Proteins made in response to antigen by B cells-plasma cells Ig or antibodies part of humoral response Bind to a specific antigen Most effective before microbe, toxin enters cells Measure antibody titer -quantity of antibody needed to produce a reaction Detectable with specific antigen  

Immunoglobulins (IgGs) Structure Bivalent antibody-monomer 2 antigen binding sites 4 peptide chains 2 light chains and 2 heavy (longer) chains Joined together by disulfide bonds Molecule looks like letter Y

Structure Stem of antibody-Fc region Lower portions of heavy chains Only 5 types of heavy chains 5 classes of antibodies named from chain Fc regions of adjacent abs bound to microbe can bind complement and destroy organism

V-Variable Regions Arms of heavy & light chains vary in amino acid sequences from one B cell to another Same for every antibody produced by that B cell Area that forms antigen binding site Fab regions

Immunoglobulin Classes IgG protect against circulating bacteria and viruses neutralizes bacteria toxins triggers complement when bound to ag , enhances phagocytosis cross placenta and instill passive immunity to fetus

IgM Stays in blood and lymph Involved in ABO blood group ags response Reacts with C, enhances phagocytosis First ab to respond to initial ag

IgM Used in diagnosis of disease Does not cross placenta IgM indicates acute infection IgG past infection Does not cross placenta

IgA Most common in mucus membranes and body secretions In all, most abundant in body Secretory IgA is dimer,2 monomers connected by J chain

IgA Function-prevent attachment of pathogens to mucosal surfaces IgA immunity is short lived so respiratory infections’ immunity not long Found in colostrum Does not cross placenta Does not activate complement

IgD 0.2% of abs Found in blood and lymph and on surface of B cells Act as antigen receptor on B cells Initiates the immune response Does not activate complement

IgE Low concentration in serum Not important in neutralization, opsonization or agglutination Acts as signal molecule Attaches to receptors on basophils, mast cells Trigger release of histamine-inflammation Important in allergic responses Also on eosinophils-parasites

Humoral Immunity Antibody mediated immunity B cell exposed to extracelluar antigens Becomes activated-differentiates into clone of plasma cells Produce antibodies T helper cells activate B cells T dependent antigens

T-Dependent Antigens Processing of exogenous antigens (protein) Antigen determinant binds with MHC molecules in a vesicle Complex inserted in CM with antigen presented on outside of B cell Activated T helper cells binds to antigen

Clonal Selection B cell binds antigen Proliferates into clone with same receptor on surface If T dependent antigen (proteins), T helper cell will activate B cell to produce plasma cells Some become memory cells for long term immunity Self tolerance B & T cells that react with self antigens removed during early development

T-Independent Antigen B cells can bind directly to large antigens –capsule ( CH2O ) Initiate clonal expansion T cells not always activated & T cell memory may not occur Small antigens such as viruses B cells need help from helper T cells

Secondary Immune Response On second encounter with antigen Population of memory cells will proliferate and differentiate into plasma cells No need for APCs Get a rapid and effective response

Memory Cells Long lived cells with BCRs complementary to specific ag determinant Can survive months or years Primary response-abs produced slowly May survive for months or more Ends when plasma cells die

Apoptosis Programmed cell death Rid body of excessive B & T cells etc. Prevent leukemia Rid of self cells without eliciting inflammation

Antibody Function Ag binding sites complementary to antigens Antigen binds to antibody Results in activation of complement, stimulation of inflammation, cytolysis, & phagocytosis-nonspecific Results in agglutination, neutralization & opsonization

Mechanisms of Inactivation Agglutination-cause ags to clump together IgM is more effective because of many binding sites

Mechanisms of Inactivation Neutralization IgG abs inactivate viruses by blocking attachment to host cells Neutralize bacterial toxins by blocking active site on toxin (antitoxin) Toxin or microbe can’ t bind to target cells

Mechanisms of Inactivation Opsonization ag such as bacterium is coated with abs that enhance its ingestion and lysis by phagocytic cells Neutrophils & macrophages have receptors for Fc region of antibodies

Cell Mediated Cytotoxicity Antibody dependent: target cell is coated with antibodies NK, macrophages, neutrophils and eosinophils will bind to Fc of antibodies Cells especially eosinophils release chemicals that lyse large pathogens

Types of T Cells Helper T Cells: CD4 glycoprotein Cytotoxic T cells: CD8 Antigen presented on surface of antigen presenting cells (APC) Macrophages & dendritic cells

T Lymphocytes In thymus each T cell generates multiple copies with specific T cell receptor TCR has 2 different polypeptide chains with groove between Antigen binding site Act directly against endogenous invaders Do not secrete Ig but produce cell mediated immune response Antigen must be presented by host cell

Helper T Cells Help in regulating activity of B cells and T cells 2 types-TH1 & TH2 TH1’s cytokines assist cell mediated immunity: cytotoxic T cells, macrophages & NK cells TH2’s cytokines activate B cells Assist antibody mediated immunity T dependent antigens

Cytotoxic T cells Leave lymphoid tissue & go to infected site Destroy infected cells upon contact Antibodies cannot attack infected cells T cell binds to MHC-antigen on cell Releases perforin forms pore in cell Cell lyses, afterwards apoptosis occurs