Specific Defense The Adaptive Immune Response. Specific Immunity Augments mechanisms of nonspecific...
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Transcript of Specific Defense The Adaptive Immune Response. Specific Immunity Augments mechanisms of nonspecific...
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– 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