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

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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