 First response to particular antigen called

primary response
› May take a week or more to develop
 Immune system remembers pathogen on
subsequent exposure
› Termed secondary response
 Adaptive immunity divided into
› Humoral immunity
 Eliminates extracellular pathogens
› Cellular immunity
 Eliminates intracellular pathogens
 Overview of humoral immunity
› Mediated by B lymphocytes
 a.k.a B cells
› Develops in bone marrow
› B cells may be triggered to proliferate into
plasma cells
 Plasma cells produce antibodies
 Antibodies produce when antigen bonds B cell receptor
› Some B cells produce memory cells
 Overview of cellular immunity

› Mediated by T lymphocytes
 a.k.a T cells
› Matures in thymus
› Divided into 2 subsets
 Cytotoxic T cells
 Helper T cells
 T cell receptors help with antigen recognition
 Lymphoid system collection of tissues and
organs designed to bring B and T cells in
contact with antigens
› In order for body to mount appropriate response,
immune cells must encounter antigen
 Lymphoid system includes
› Lymphatic vessels
› Secondary lymphoid organs
› Primary lymphoid organs
 Lymphatic vessels
› Carry lymph to body tissues
 Lymph formed as result of body’s circulatory
system
› Lymph travels through vessels to lymph
nodes
 Material such as protein is removed
 Fluid portion empties back into blood stream
 Secondary lymphoid organs
› Sites where lymphocytes gather to
encounter antigens; organs include
 Lymph nodes
 Spleen
 Tonsils
 Adenoids
 Appendix
› Organs situated strategically
 Allows for initiation of immune response from
nearly any place in body
 Primary lymphoid organs
› Bone marrow and thymus are primary
lymphoid organs
 Location where stem cells destined to
become B and T cells mature
 B cells mature in bone marrow
 T cells mature in thymus
 Once mature, cells leave primary lymphoid
organs and migrate to secondary lymphoid
organs
 Coined from compounds that elicit
antibody production
› Antibody generator
 Includes an enormous variety of materials
 Today, term used to describe any
compound that elicits an immune response
› Antigen that causes immune response termed
immunogen
 Proteins and polysaccharides induce string
response
› Lipids and nucleic acids often do not
 Recognition of antigen directed at
antigenic determinant or epitope
 Structure of the Antibody (Ab)
› Basic Y-shaped structure
› Made of four chains of amino acids held together by disulfide
bonds
 Two chains are heavy
 Two chains are light
› Each heavy and light chain has a constant region
 The constant region is known as Fc region
› Each heavy and light chain has a variable region
 Variable region is unique to each Ab
 This region binds to a specific Antigen and is known as “Fab”
region
 Protective outcomes of
antibody-antigen binding
› Neutralization
 Prevents toxin from interacting
with cell
› Immobilization and
prevention of adherence
 Antibody bonding to cellular
structures to interfere with
function
› Agglutination and
precipitation
 Clumping of bacterial cells by
specific antibody
 Bacteria more easily
phagocytized
 Protective outcomes of
antibody-antigen binding
› Opsinization
 Coating of bacteria with
antibody to enhance
phagocytosis
› Complement activation
 Antibody bonding triggers
classical pathway
› Antibody-dependent cellular
cytotoxicity
 Multiple antibodies bind a cell
which becomes target for
certain cells
 Five classes of Ab
› IgM
 First Ab to respond to infection
 5 – 13% of Ab in circulation
 Structure: pentamer
 Five monomer units joined together at the constant
region
 Found on the surface of B lymphocytes as a
monomer
 Only Ab that can be formed by the fetus
 Five classes of Ab
› IgG
 Dominant Ab in circulation
 80 – 85% Ab in circulation
 Structure = monomer
 Only Ab that can cross the placenta
 The antibody of memory!!!!!
› IgA
 Found in secretions
 10 - 13 % of Ab in circulation
 Structure
 Monomer in serum
 Dimer in secretions
 Breast milk, mucus, tears and saliva
 Five classes of Ab
› IgD
 <1% of total Ab in circulation
 Structure = monomer
 Maturation of antibody response
› IgE
 Barely detectable in circulation
 Structure = monomer
 Active in allergic reaction
 When antigen introduces
into body, only
appropriate antibody
bonds
› Initiates multiplication of
specific antigen
 Process called clonal
selection
 Repeated cycles of cell
division generates
population of copied
antibodies
 Termed clonal expansion
 Without sustained
stimulation, cells undergo
apoptosis
 Lymphocyte characteristics include
› Immature
 Antigen specific receptors not fully developed
› Naive
 Have antigen receptor but have not encountered
antigen
› Activated
 Able to proliferate
 Have bound antigen
› Effectors
 Descendents of activated lymphocytes
 Able to produce specific cytokines
 Plasma cells, T helper and cytotoxic T cells effector cells
› Memory lymphocytes
 Long-lived descendents of activated lymphocytes
 Memory cells responsible for seed and effectiveness of
secondary response
 Remembers antigen on subsequent exposure
 Antigen binds to B cell receptor
› Poises B cell to respond
 In many cases B cell needs conformation from helper T cells
 Ag enters the body and is phagocytized and processed by
macrophages
› These macrophages destroy Ag and present a portion on the
surface of the macrophage next to self Ag
 Macrophages are called antigen-presenting cells (APC)
 Processed Ag combines with specific TH with the appropriate
receptor
 APC releases substances to activate TH cell
 TH cell activates B cells to divide and differentiate
› Produce plasma cells and memory B cells
 Characteristic of primary response
› Lag period of 10 to 12 days occurs before antibody
detection in blood
 Activated B cells proliferate and differentiate into increasing
numbers of plasma cells as long as antigen is present
› Net result is slow steady increase in antibody titer
 Over time, some B cells undergo
changes enhancing immune
response including
 Affinity maturation
 Class switching
 Formation of memory cell
 Affinity maturation
› Form of natural selection
 Occurs among proliferating B cells
› Fine tunes quality of response with respect
to specificity
 B cell receptors more and more specific to
antigen
 Antibody bonds antigen more tightly
 Class switching
› B cells initially programmed to differentiate into plasma cells
 Plasma cells secrete IgM antibodies
› Helper T cells produce cytokines
 Some B cells switch programming
 Differentiate to plasma cells that secrete other classes of
antibodies
 Commonly IgG
 Formation of memory
› B cells that have undergone class switching
 Produce IgG antibody
 IgG is antibody of memory
 IgG antibody can circulate in body for years
allowing protection against specific antigens
 Characteristics of secondary response
› Memory cells responsible for swift effective
reaction of secondary response
 Often eliminate invaders before noticeable
harm is done
› Vaccine exploits phenomenon of immunologic
memory
› Some memory B cells will differentiate into
plasma cells
 Results in rapid production of antibodies
 T-independent antigens
› Can stimulate antibody
response
 Activate B cells without
helper T cells
 Few antigens are T-
independent
› B cell receptors bind
antigen simultaneously
 Leads to B cell activation
› Some polysaccharides and
lipopolysaccharides act as
T-independent antigens
 General characteristics of T cells
› Have multiple copies of T cell
receptors
 Receptors have variable sites of
antigen bonding
› Role of T cells different from B
cells
 T cells never produce antibodies
 T cells armed with effectors that
interact directly with antigen
 T cell receptor does not react
with free antigen
 Antigen must be present by
APC
 General Characteristics
› During antigen presentation, antigen
cradled in grove of major histocompatability
complex molecule (MHC molecule)
 Two types MHC
 MHC class I
 Bind endogenous antigen
 MHC class II
 Bind exogenous antigen
 General characteristics
› Two major function T cell populations
 Cytotoxic T cells
 Proliferate and differentiate to destroy infected or
cancerous “self” cells
 Have CD8 marker
 Recognize MHC class I
 Helper T cells
 Multiply and develop into cells that activate B cells
and macrophages
 Stimulate other T cells; orchestrate immune response
 Have CD4 marker
 Recognize antigen display by MHC class II
 Functions of Tc (CD8) cells
› Induce apoptosis in “self” cells
 Cells infected with virus or intracellular
microbe
 Destroys cancerous “self” cells
› Nucleated cells degrade portion
of proteins
 Load peptides into groove of MHC
class I molecule
 MHC class I molecule recognized by
circulating Tc cell
 Cell destroyed by lethal effector
function of Tc cell
 Tc cells releases pre-formed cytokines
to destroy cell
 Functions of TH (CD4) cells
› Orchestrate immune response
 Recognize antigen presented by MHC class II
molecules
 MHC class II molecules found only on APC
 If TH cell recognizes antigen, cytokines are
delivered
 Cytokines activate APC to destroy antigen
 Role of TH cells in B cell activation
› If TH cell encounters B cell bearing peptide:
MHC calls II complex
 TH cell responds by producing cytokines
› B cell is activated in response to cytokine
stimulation
 B cell proliferates and undergoes class
switching
 Also drives formation of B memory cells
 Role of TH cells in
macrophage activation
› Macrophages routinely engulf
invading microbes resistant to
lysosomal killing
› TH cells recognize macrophage
with engulfed microbes
resistant to killing
› TH cells activate macrophages
by delivering cytokines that
induce more potent
destructive mechanisms
 Natural killer cells descend from lymphoid stem
cells
› They lack antigen specificity
 No antigen receptors
 Recognize antigens by means of Fc portion of IgG
antibodies
 Allow NK cells to attach to antibody-coated cells
 Actions augment adaptive immune response
› Important in process of antibody dependent cellular
toxicity
 Enable killing of host cells with foreign protein in membrane
 Natural killer cells recognize destroyed host
cells with no MHC class I surface molecules
› Important in viral infection
 During lymphocyte development, B and
T cells acquire ability to recognize
distinct epitopes
› Once committed to specific antigen, cells
“checked out” to ensure proper function
› B cells undergo developmental stages in bone
marrow
› T cells go through process in thymus