IMMUNE SYSTEM

Immunity
• Ability to resist damage from foreign substances as
microorganisms and harmful chemicals
• Categories
– Innate or nonspecific resistance
• Mechanical mechanisms: Prevent entry or remove microbes
• Chemical mediators: Promote phagocytosis and inflammation
• Cells: Involved in phagocytosis and production of chemicals
– Adaptive or specific immunity
• Specificity: Ability to recognize a particular substance
• Memory: Ability to remember previous encounters with a
particular substance and respond rapidly
 Mechanical Mechanisms and
Chemical Mediators of Innate
Immunity
• Mechanical • Chemical
Mechanisms Mediators
– Skin, tears, saliva, – Complement
mucous membranes, • Group of 20
mucus proteins
• Circulate in blood
in inactive form
• Become activated
in cascade form:
Classical or
Chemical of Innate Immunity &
their Function

22-4
Complement Cascade
 Innate Immunity: Cells
• Macrophages (monosit 5X)
White blood cells
– Monocytes that leave blood,
– Most important
enter tissues
cellular components – Specific name: Microglia, Dust
of immune system cell, Kupffer cell
– Methods – Large phagocytic cells
• Chemotaxis – Skin, mucous & serous
• Phagocytosis membrane, around blood &
• Neutrophils Lymphatic vessels
– Phagocytic and first – Reticuloendothelial system
(sinus?)
cells to enter
infected tissue • Basophils (motile) and Mast
– 126 billions per day leave cells
the blood, pass through the – Promote inflammation
Inflammatory Response
 Inflammatory Response
• Tissue injury regardless of type can cause
inflammation
• Response initiated by chemical mediators that
produce vasodilation, chemotactic attraction,
increased vascular permeability
• Types
– Local: Symptoms are redness, heat, swelling, pain, loss of
function
– Systemic: Symptoms are increase in neutrophil numbers,
fever (by pyrogen of microbes, macrophage, neutrophils) and shock
(by increased vascular permeability  large amount of fluid are lost
from the blood into the tissue), death
 Adaptive Immunity
• Involves the ability to recognize, respond to, and
remember a particular substance
• Stimulants
– Antigens: Large molecules
• Foreign: Not produced by body, introduced from outside
• Self-antigens: Produced by body
– Haptens: Small molecules (Ex: Arsenilic Acid) that
capable to conyugate with a larger molecule (carrier; Ex:
BSA)
• Types
– Humoral or Antibody-mediated: B cells
– Cellular or Cell-mediated: T cells
Innate vs Adaptive Immunity
Origin and Development
of Lymphocytes
• B and T cells
– Originate in red bone
marrow
– Move to lymphatic
tissue from processing
sites and continually
circulate
– Clones are small
groups of identical
lymphocytes
 Origin and Development
of Lymphocytes
• Positive selection
– Ensures survival of lymphocytes that react against
antigens
• Negative selection (mostly occur during prenatal develop.)
– Eliminates lymphocytes that react against self-antigens
• Primary lymphatic organs (red bone marrow, thymus)
– Where lymphocytes mature into functional cells
• Secondary lymphatic organs (diffuse lymphatic
tissue, lymph node, lymphatic nodules, tonsils,
spleen)
– Where lymphocytes produce an immune response
Antigenic Determinants

• Antigenic determinants
– Specific regions of a
given antigen recognized
by a lymphocyte
• Antigenic receptors
– Surface of lymphocyte
that combines with
antigenic determinant
 Major Histocompatibility
Complex (MHC)
• Most lymphocyte activation involves glycoproteins of cell
surfaces called MHC molecules
– Class I molecules display antigens on surface of nucleated cells,
resulting in destruction of cells
– Class II molecules display antigens on surface of antigen-
presenting cells (B cells, Macrophage, Monocyte, Dendritic Cell), resulting in
activation of immune cells
Antigen Processing
Costimulation
Cytokines
Proliferation of Helper T Cells
Proliferation of B Cells
 Lymphocyte Inhibition

• Tolerance: To prevent the immune system

from responding to self-antigens
– Provoked by
• Deletion of self-reactive lymphocytes (Negative Selection)
• Preventing activation of lymphocytes (No binding
and/or costimulation)
• Activation of Suppressor T cells (release suppressive
cytokines to kill antigen-presenting cells)
Antibody-Mediated Immunity
• Antibodies or
Immunoglobulins (Ig)
– Classes: IgG, IgM,
IgA, IgE, IgD
– Structure
• Variable region: Part
that combines with
anitgenic determinant
of antigen
• Constant region:
Responsible for
activities
Actions of Antibodies
Antibody Production
 Cell-Mediated Immunity

• Antigen activates effector T cells and produces memory T cells

• Cytotoxic T cells lyse virus-infected cells, tumor cells, and
tissue transplants
• Cytotoxic T cells produce cytokines, which promote
phagocytosis and inflammation
Interactions and Responses of
Innate and Adaptive Immunity
 Acquired Immunity
• Active natural immunity
– Results from natural exposure to an antigen
• Active artificial immunity
– Results from deliberate exposure to an antigen
• Passive natural immunity
– Results from transfer of antibodies from a mother to
her fetus or baby
• Passive artificial immunity
– Results from transfer of antibodies (or cells) from an
immune animal to a nonimmune one
 Ways to Acquire
Adaptive Immunity
 Effects of Aging

• Little effect on lymphatic system

• Decreased ability of helper T cells to
proliferate in response to antigens
• Decreased primary and secondary antibody
responses
• Decreased ability of cell-mediated
immunity to resist intracellular pathogens
 Immune System Problems
• Hypersensitivity reactions (atopy, anaphylaxis,
cytotoxic reaction, immune complex disease)
• Autoimmune disease (the immune system fails to
differentiate between self-antigens and foreign antigens: molecular
mimicry?; type I diabetes vs rheumatoid arthritis, rheumatic fever,
Graves’ disease, systemic lupus erythematosus, and myasthenia gravis.
• Severe combined immunodeficiency
disease (SCID; both B and T cells fail to differentiate  kept
in a sterile environment or is provided with a compatible bone marrow
transplant)
• Transplantation MHC = HLA ?
host-versus-graft rejection vs graft-versus-host rejection
– Acute rejection (several weeks)
–
 Immune System Problems
• Hypersensitivity reactions
Atopy: is a localized IgE-mediated hypersensitivity reaction (by pollen)

Anaphylaxis: is a systemic IgE-mediated reaction and can be

lifethreatening (by drugs e.g., penicillin; and insect stings)

Cytotoxic reaction: IgG or IgM combines with the antigen on the surface
of a cell, resulting in the activation of complement and subsequent lysis
of the cell (Ex: incompatible blood types)

Immune Complex Disease: too many immune complexes are formed 

too much complement is activated, and an acute inflammatory response
develops  Complement attracts neutrophils to the area of inflammation
and stimulates the release of lysosomal enzymes  cell lysis
 Immune System Problems
• Tumor
Tumor antigen  destroyed by NK cell &
Macrophage

• Transplantation MHC = HLA ?

host-versus-graft rejection vs graft-versus-host rejection
– Acute rejection (several weeks)
– Chronic rejection
Teng-kyu