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 cellsplasma 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