Antibody-Mediated Immunity

Involves antigen-antibody interactions to neutralize, eliminate, or destroy foreign proteins. Anitbodies

are produced by B-lymphocytes (B cells)

Purpose

The main purpose of B-cells are to become sensitized to a specific foreign protein (antigen) and to
produce antibodies directed specifically against that protein.

 B cells have the most direct role in AMI

 Macrophages and t-lymphocytes work with Bcells to start and complete antigen-antibody
interactions
 Bcells start out as stem cells then the stem cell commits to the lymphocyte pathway.
 The lymphocyte stem cells are released from the bone marrow into the blood then they migrate
into many secondary lymphoid tissues where maturation is completed

Antigen-Antibody Interactions

Seven steps are needed to produce a specific antibody directed against a specific antigen whenever the
person is exposed to that antigen

1. Exposure or invasion- the antigen must first enter the person. Invasion must occur in such large
numbers that some of the antigen evades detection by the body’s natural nonspecific defenses
or overwhelms the ability of the inflammatory response to get rid of the invader
2. Antigen recognition- the naïve unsensitized Bcell must first recognize the antigen as non-self.
The macrophage recognizes the invading antigen as non-self and physically attaches itself to the
antigen. The macrophage presents the attached antigen to the helper Tcell. Then the helper-
tcell and the macrophage together process the antigen to expose the antigen’s recognition sites.
Then the helper tcells bring the antigen into contact with the bcell so that it can recognize it as
non-self
3. Lymphocyte sensitization- occurs when the Bcell recognizes the antigen as non-self and is now
sensitized to this antigen. A single naive Bcell can be sensitized only once. So each Bcell can be
sensitized to only one type of antigen.
After being sensitized the Bcell divides and forms two types of B-lymphocytes, each one still
sensitized to the specific antigen. One cell becomes the plasma cell- which can start immediately
to produce antibodies against the sensitizing agent, but has a short life span. The second cell is
the memory cell- it is a sensitized Bcell but does not start to function until the next exposure to
the same antigen
4. Antibody production and release- allow the antibodies to search out specific antigens.
Antibodies are produced by plasma cells, each plasma cell can make up to 300 molecules of
antibody per second. The antibody molecules are released into the blood as free antibody and
remain there for 3-30days
 Circulating antibodies can be transferred from one person to another to provide the receiving
person with immediate immunity of short duration
5. Antibody-antigen binding- antibodies are Y shaped, the tips of the short arms of the Y recognize
the specific antigen and bind to it. Each antibody can bind either to two separate antigens or to
two areas of the same antigen.
The stem of the Y is the Fc Fragment- it can bind to Fc receptor sites on WBCs.
The WBC has its own means of attacking antigens and also has the added power of having
surface antibodies that can stick to antigens
6. Antibody-binding actions- triggered by binding of antibody to antigen. The following actions take
place to neutralize, eliminate, or destroy the bound antigen
Agglutination- clumping action that results from the antibody linking antigens together, forming
large and small immune complexes. This action starts other defensive effects, first it slows the
movement of the antigen through body fluids. Second, the irregular shape of the antigen-
antibody complex increases the chance of the complex being attacked by other WBC
Lysis- cell membrane destruction, occurs now because of antibody binding to membrane-bound
antigens of some invaders. Holes are made in the invaders’ membrane, weakening the invader.
Bacteria and viruses are the non-self cells that are most damaged through lysis.
Complement activation and fixation-actions triggered by some classes of antibodies that can
remove or destroy antigens. There are 2 classes of antibody that can activate the complement
system, they are IgG and IgM. Binding from either of these to an antigen provides a binding site
for the first component of complement. Once the first complement molecule is activated, other
proteins of the complement system are activated in a cascade.
Precipitation-antibody molecules bind so much antigen that large, insoluble, antigen-antibody
complexes are formed. These complexes cannot stay in suspension in the blood. Instead they
form a large precipitate that can be acted on and removed by neutrophils and macrophages.
Inactivation- the process of making an antigen harmless without destroying it. When an
antibody binds to an antigen and covers up the antigen’s active site, the antigen is made
harmless without destroying it
7. Sustained immunity- provides us with long lasting immunity to a specific antigen. Results from
memory Bcells made during the lymphocyte sensitization stage. On re-exposure to the same
antigen, the memory cells rapidly respond. This allows a rapid and large immune response to
the antigen. Usually the invading organisms are removed completely and the person does not
become ill. Without the action of memory, people would remain susceptible to specific diseases
on subsequent exposure to the organisms and no sustained immunity would be generated.

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Anitbody Classification

 Immunoglobulins (gamma globulins)

o Globular shaped protein
 IgM (first exposure)
 Forms groups of 5 with 10 antigen-binding sites
 Initial illness lasts 5-10 days
 IgG(re-exposure)
 Produces enormous numbers
 Protects person from becoming ill again

Categories of Immunity

 Innate-native immunity (natural immunity )- any natural protective feature of a person. Can be a
barrier to prevent organisms from entering the body or it can be an attacking force that
eliminates organisms that have already entered the body.
It cannot be developed or transferred from one person to another and is not an adaptive
response to exposure or invasion by foreign proteins
EXAMPLES:
Inflammatory response, skin, mucosa, antimicrobial chemicals on the skin, complement and
natural killer cells
 Adaptive immunity- immunity that a person’s body learns to make or can receive as an adaptive
response to invasion by organisms or foreign proteins. Occurs either naturally or artificially thru
lymphocyte responses and can be either active or passive
EXAMPLE:
Antibody-mediated immunity
o Active Immunity- when antigens enter the body and the body responds by making
specific antibodies against the antigen. Can occur under natural or artificial conditions.
Natural is the most effective and the longest lasting
Artificial is developed by vaccination or immunization. Small amounts of the antigen are
placed as a vaccination into a person. Repeated but smaller doses of the original antigen
are required as a booster to retain the protection
o Passive Immunity- occurs when antibodies against an antigen are in a person’s body but
were not created there, rather the antibodies are transferred to the person’s body after
being made in the body of another person or animal. The antibodies are recognized as
non-self and eliminated quickly so it only provides immediate, short-term protection
against a specific antigen
Example of Natural passive immunity: antibodies are passed from the mother to the
fetus by the placenta or thru colostrums and breast milk
Example of Artificial passive immunity: involves injecting a person with antibodies that
were produced in another person or animal
Cell-Mediated Immunity
Provided by lymphocyte stem cells that mature in the secondary lymphoid tissues of the thymus and
pericortical areas of the lymph nodes. Certain CMI responses influence and regulate the activities of
antibody-mediated immunity and inflammation by producing and releasing cytokines. For total
immunocompetence CMI must function optimally.

Cell Types
 T-lymphocytes (Tcells)
o Helper/inducer Tcells- easily recognize self cells versus non-self cells. They secrete
lymphokines that can enhance the activity of other WBCs, most lymphokines increase
immune function. These lymphokines increase bone marrow production of stem cells
and speed up their maturation.
CD4+
o Suppressor Tcells- prevent hypersensitivity when a person is exposed to non-self cells or
proteins. Important in preventing the formation of antibodies directed against normal,
healthy self cells, which is the basis for many autoimmune system cells.
Opposite action of helper/inducer Tcells. For optimal function of CMI a balance between
helper/inducer Tcell activity and suppressor Tcell activity must be maintained
o Cytotoxic/cytolytic- destroy cells that contain a processed antigen’s major MHC. Most
effective against self cells infected by parasites, such as viruses or protozoa
o Natural Killers- have direct cytotoxic effects on some non-self cells without first being
sensitized. NK cells conduct seek and destroy missions in the body to eliminate non-self
cells. Most effective in destroying unhealthy or abnormal self cells, most often cancer
cells and virally infected body cells.
 Cytokines- small protein hormones produced by the many WBC
o Cytokines made by the macrophages, neutrophils eosinophils, and monocytes are called
monokines
o Cytokins made by Tcells are called lymphokines
o Cytokines are messengers that tell specific cells how and when to respond
o The responder cell must have a specific receptor to which the cytokine can bind.
o Pleiotropic cytokines create effects that are widespread within the immune system
o Interleukins- largest group of cytokines
o Interferons
o Colony- stimulating factor
o Tumor necrosis factor

Protection

 CMI helps protect the body through the ability to differentiate self form non-self
 Most easily recognized non-self cells are cancer cells and those of self cells infected by
organisms that live within host cells
  CMI is important in preventing the development of cancer and metastasis after exposure to
carcinogens

Transplantation Rejection
Natural killer cells and cytotoxic/cytolytic Tcells destroy cells from other people or animals, they are also
responsible for rejection of tissue grafts and transplanted organs.

 Hyperactive Rejection- begins immediately on transplantation and is an antibody-mediated

response
o Most often occurs in kidney transplantations
o Manifestations are apparent within minutes of attachment
o Process cannot be stopped once it has started
o The rejected organ is removed as soon as hyperactive rejection is diagnosed
 Acute Rejection- occurs within 1 week to 3 months after transplantation
o Antibody mediated mechanism results in vasculitis within the transplanted organ
o The second mechanism is cellular
o Diagnosis of acute rejection is made by lab tests that show impaired function of the
donated organ and biopsy
o Patient does not automatically have to lose organ
o Drug management may limit the damage to the organ and allow the graft to be
maintained
 Chronic Rejection- similar to chronic inflammation and scarring
o Smooth muscles of blood vessels overgrow and occlude the vessels
o Organ’s function is reduced
o No cure only recourse is retransplantation

Treatment

 Maintenance therapy- continuous immune suppression used after a solid organ transplant
o Combination of specific innumosuppressants- Sandimmune, Neoral, Gengraf all
cyclosporine
 Less specific – Imuran, CellCept, Myfortic
 And a corticosteroid- prednisone
 T-cell suppression- given within 2 hours before surgery and within the first few days after
surgery
 Tacrolimus(Prograf), Simulect, Zenapax
 Rescue Therapy
 ALG, an antibody produced in animal after the animal has been exposed to
human lymphocytes
 Muromonab-CD3- antibody directed specifically against the human Tcell,
generated in mice