Transcript Specific Resistance = Immunity

Specific Resistance =
Immunity
Immunology = study of a host’s specific defenses, i.e. immunity.
Lymphocytes (review)
Antigens & Antibodies
Acquired Immunity
Humoral Immunity: B-cell Function
Cell-Mediated Immunity: T-cell Function
Lymphocyte
B cells:
Interact with antigens;
may develop a clonal
population of memory
cells or become
stimulated, divide and
mature into antibody
producing plasma cells.
Antibody functions are
called Humoral Immunity.
T cells:
Act
as either “helpers” in
communicating the
presence of an antigen;
or cytotoxic agents to
destroy infected cells.
These functions are
called Cell-Mediated
Immunity.
100 million produced per day
therefore others must die (apoptosis
= programmed cell death)
Antibody Monomer
Structure:
Immunoglobin (Ig) = antibody
Many possible antibodies
with different antigenic
binding sites due to variable
region diversity of long and
short chains.
Antigen-Antibody
Interaction
Antigen = a substance with unique 3D
form that causes antibody formation in
B cells (lymphocytes).
Antigens may possess one or more
types of reactive molecular
components, called antigenic
determinants or epitopes.
Antigen binding sites on the antibody
Fab fragments specifically recognize
and chemically interact with an epitope.
Because a single antibody recognizes a
single epitope, there may be multiple
antibodies generated against an antigen
with more than one epitope.
Antigens can be
pieces of or whole
microbes or viruses.
i.e. epitopes
Antigens can be derived from very small molecules called haptens,
which without some carrier molecule or cell would not elicit an
immune response alone. Examples of haptens include drugs and/or
toxins (e.g. some venoms). Think of a heptan as functioning as the
epitope for an incomplete antigen (carrier molecule).
Antibody Classes
• IgG (80%; monomer; passive
to fetus/newborn);
• IgM (<10%, pentamer of IgG,
effective in agglutination);
• IgA (< 15%; dimer; on B cell
surface involved in activation;
released into fluid/mucus
secretions);
• IgD (minor; monomer; on B
cell surface involved in their
activation); and
• IgE (minor; monomer; on mast
cells and basophils; involved in
allergic response).
vaccine
antiserum
Passive = antibodies supplied to host from external sources, possibly prior to the
presence of any foreign antigen in the host.
Active = Foreign antigen introduced to host, which then stimulates immune response.
Humoral Immunity: B Cells
Each B cell produces a
different IgD&M on its
surface.
Some antigens require
involvement of helper T
cells for B cell activation.
Long-lived cells, stored in large numbers in
lymph nodes; host is now “primed” for any
second response by the same antigen.
(particularly when
stimulated by helper
T cell’s interleukin-2)
T-independent
versus
T-dependent
Antigens
• Antigens that are large
multivalent polymers that bind
multiple IgD&M on a B cell
surface will directly stimulating
humoral immunity independent of
any helper T cell involvement.
• Smaller protein antigens with
too few epitopes for multiple
IgD&M binding and direct
stimulation of B cells will require
involvement of helper T cells and
there interleukins; they are
dependent on T cells for
stimulating humoral immunity.
(see more below)
Antigens fall into one of two broad types!
(Protein; polysaccharide;
glycoprotein)
B cell
IgD & IgM
Immune
complex
forms:
ADCC:
1) Antibodies bind to
parasite surface.
2) Fc region
receptors on surface
of eosinophils,
macrophage and
natural killer cells
bind to antibody.
3) Release of
cytokinins, perforins
and other lytic
enzymes to damage
parasite tissues.
4) Liberation and /or
phagocytosis of
other parasite
antigens to further
activate immunity.
Cell-Mediated Immunity: T Cells
•
Helper T cells (TH) are needed to stimulate production of cytotoxic T cells
(TC) and humoral immunity (B cells) to T-dependent antigens.
•
Important to this system is the ability for lymphocytes to distinguish
normal host cells (“self”) from microbes or infected host cells. The major
histocompatibility complex (MHC) on the surface of all host cells
functions as a “self flag”. TH cell receptors (CD4+) bind to class II MHCs
and Tc cell receptors (CD8+) to class I MHCs.
•
Events in cell-mediated immunity:
1) Antigen presenting cells (APC; macrophage and dendrites)
phagocytize antigen carrying microbe, virus, or carrier molecule.
2) Antigen fragment with a unique epitope combines with the MHCs at
the APC surface for presentation to helper T cells. Simultaneously,
APC secrete IL-I.
3) A TH cell with a specific receptor for that epitope binds to the class II
MHC on the APC, which together with IL-1 results in proliferation of
that particular TH cell clonal population.
Cell-Mediated Immunity: T Cells
4) The active clonal population of TH cells secretes IL-2 and other cytokinins.
5) These signals stimulate specific B cells to proliferate and mature to antibody
secreting plasma cells (see details below for T-dependent antigens).
6) These signals also stimulate specific Tc cells to proliferate and activate. The Tc cells
involved have their own receptors for binding to class I–MHC on infected hosts.
The role of TH cells in
humoral immunity to
T-dependent antigens.
• TH cell receptors unique to the epitope
and MHC of concern may bind to B cells
with complementary surface features.
• These bound B cells are stimulated by
IL-2 to proliferate and mature to plasma
cells that secrete antibodies to the Tdependent antigen.
Cytotoxic T Cells:
1) They bind to infected target host cells (typically due to virus or
intracellular bacterium) expressing the antigen-MHC via Tc cell receptor.
They also bind to cells with non-self MHC (e.g. tranplants; tumor cells).
2) Binding stimulates secretion of extracellular enzymes (perforins) to
degrade the target cell plasma membrane.
3) Grazymes (proteolytic enzymes) are released by Tc cells and enter
infected cell through pores and induce apoptosis.
4) Rupturing of the membrane kills the target cell and releases Tc cell.
Immunity
Overview