immunity
Important definitions
Antigen (Ag): A molecule which elicits a specific immune response when introduced into an
animal. More specifically, antigenic (immunogenic) substances are:
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4.
Generally large molecules (>10,000 daltons in molecular weight),
Structurally complex (proteins are usually very antigenic),
Accessible (the immune system must be able to contact the molecule), and
Foreign (not recognizable as "self").
Antibody (Ab): A glycoprotein produced in response to an antigen that is specific for the antigen
and binds to it via non-covalent interactions. The term "immunoglobulin" is often used
interchangeably with "antibody". We will use the term "immunoglobulin" to describe any antibody,
regardless of specificity, and the term "antibody" to describe an antigen-specific
"immunoglobulin". Immunoglobulins (Igs) come in different forms (IgA, IgD, IgE, IgG, IgM) that
reflect their structure. More information can be found here.
IgA:- Found in mucosal areas, such as the gut, respiratory tract and urogenital tract, and prevents
colonization by pathogens. Also found in saliva, tears, and breast milk.
IgM:- Eliminates pathogens in the early stages of B cell mediated (humoral) immunity.
IgG:- The only antibody capable of crossing the placenta to give passive immunity to fetus.
IgE:- protects against parasitic worms.
IgD:- Its function is less defined than other isotypes. Functions mainly as an antigen receptor on B cells .
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Pathogen
Any disease causing micro-organism.
Tolerance
Non-reactivity of the immune system, usually refers to "self" but may include foreign tissue in
organ transplants.
Autoimmunity
A failure of tolerance, the immune system reacts to self.
Chemokines
Molecules released by pathogens and infected tissues to attract cells of the immune system.
Cytokines
Signaling molecules released by one cell to cause a response in another. Signaling is extremely
important in our immune response.
Innate immunity
Protection that is always present. Includes phagocytic (cells that eat other cells) macrophages and
dendritic cells.
Adaptive immunity
Protection that arises by an immune response, including humoral immunity producing antibodies
and cellular immunity.
COMPLEMENT
Another important component of the specific immune system is a group of proteins called the
COMPLEMENT SYSTEM. Complement is a GROUP OF PROTEINS that, like the antibodies, are soluble
and reside in the serum. Complement is a COMPLEX OF ENZYMES that mainly act on foreign cells by
punching holes in their membranes to cause their LYSIS AND DEATH.
II. INNATE (NON-SPECIFIC) IMMUNITY
The elements of the innate (non-specific) immune system include anatomical barriers, secretory molecules and
cellular components. Among the mechanical anatomical barriers are the skin and internal epithelial layers, the
movement of the intestines and the oscillation of broncho-pulmonary cilia. Associated with these protective surfaces
are chemical and biological agents.
Innate ( Nonspecific ) Immunity - The term, Innate immunity, refers to the basic resistance to
disease that a species possesses - the first line of defense against infection.
The characteristics of the innate immune response include the following:
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Responses are Broad-Spectrum (non-specific)
There is no memory or lasting protective immunity
There is a limited repertoire of recognition molecules
The responses are phylogenetically ancient
Anatomic Barriers
Skin (physical barrier, low pH due to lactic and fatty acids)
epidermis - thin outer layer containing tightly packed epidermal cells and keratin (water-proofing)
completely renewed every 15-30 days.
dermis - thicker inner layer contains sebaceous glands associated with hair follicles - produce
sebum which consists of lactic and fatty acids maintaining a pH 3-5.
Mucous membranes (ciliated epithelial cells; saliva, tears and mucous secretions) - GI,
urogenital, respiratory tracts - collectively represents a huge surface area.
Physiologic Barriers
Temperature - normal body temperature inhibits growth of most microorganisms.
Elevated body temperature (fever) can have a direct effect on pathogenic microorganisms.
pH - low pH of stomach, skin, & vagina (inhibits microbial growth)
Oxygen tension
chemical factors (a few examples given below):
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Fatty acids, lactic acid
Pepsin (digestive enzyme which hydrolyzes proteins)
Lysozyme -hydrolytic enzyme found in mucous secretions - able to cleave the
petidoglycan layer of the bacterial cell wall
Anti-microbial substances which directly destroy microorganims: cryptidins and adefensins (produced in base of crypts of small intestine - damage cell membranes) bdefensins (produced within skin, respiratory tract - also damages cell membranes)
surfactant proteins A & D (present in lungs - function as opsonins which enhance the
efficiency of phagocytosis)
Interferons - group of proteins produced by cells following viral infection. Secreted by the
cells, and then binds to nearby cells and induces mechanisms which inhibit viral
replication.
Complement - a group of serum proteins that circulate in an inactive proenzyme state.
These proteins can be activated by a variety of specific and nonspecific immunologic
mechanisms that convert the inactive proenzymes into active enzymes.ssss The activated
complement components participate in a controlled enzymatic cascade that results in
membrane-damaging reactions which destroy pathogenic organisms by formation of a
membrane attack comples (MAC).
Table1. Physico-chemical barriers to infections
System/Organ
Active component
Effector Mechanism
Skin
Squamous cells; Sweat
Desquamation; flushing, organic acids
GI tract
Columnar cells
Peristalsis, low pH, bile acid, flushing, thiocyanate
Lung
Tracheal cilia
Mucocialiary elevator, surfactant
Nasopharynx and eye
Mucus, saliva, tears
Flushing, lysozyme
Circulation and
lymphoid organs
Phagocytic cells
Phagocytosis and intracellular killing
NK cells and K-cell
Direct and antibody dependent cytolysis
LAK
IL2-activated cytolysis
Lactoferrin and
Transferrin
Iron binding
Interferons
Antiviral proteins
TNF-alpha
antiviral, phagocyte activation
Lysozyme
Peptidoglycan hydrolysis
Fibronectin
Opsonization and phagocytosis
Complement
Opsonization, enhanced phagocytosis, inflammation
Serum
ACQUIRED or ADAPTIVE IMMUNITY
This refers to immunity against SPECIFIC ANTIGENS that one acquires in one of two ways, ACTIVE or
PASSIVE. These are subdivided into the following further categories:
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ACTIVE NATURALLY ACQUIRED IMMUNITY = This occurs when individuals suffer
from a natural infection of a pathogen and become immune to that pathogen upon recovery (e.g.
chickenpox).
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ACTIVE ARTIFICIALLY ACQUIRED IMMUNITY = This occurs when individuals are
actively vaccinated with an antigen that confers immunity.
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PASSIVE NATURALLY ACQUIRED IMMUNITY = This occurs when individuals receive
antibodies from their mother by a natural process, such as in BREAST MILK or in-utero transfer of
antibodies from mother to fetus. In mammals, mother's milk is know to contain a large
concentration of antibodies and other antiviral and antibacterial substance that protect the newborn
infants. Further, the mother's antibodies cross the placental barrier, particularly near the end of
term. In both these circumstances the infant is only resistant to whatever the mother is resistant to.
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PASSIVE ARTIFICIALLY ACQUIRED IMMUNITY = This occurs when individuals are
injected with POOLED serum from immune individuals that contain antibodies against a large
number of pathogens. In the case of humans, a fraction of blood serum, GAMMA GLOBULIN,
that is highly enriched in antibodies is injected into individuals that have been exposed to certain
pathogens. The GAMMA
Non-specific Immunity
Specific Immunity
Response is antigen-independent
Response is antigen-dependent
There is immediate maximal response
There is a lag time between exposure and
maximal response
Not antigen-specific
Antigen-specific
Exposure results in no immunologic memory
Exposure results in immunologic memory