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