The specific immune response
• • Effects after few days
• • Leads to a state of immune memory
• • High specificity- improve during the course of respons
- A response to a specific immune stimulus (antigen)
- The immune system can "remember" invaders and react more promptly to
second exposures to infection.
-- Only an exposure to the same antigen will activate this memory response.
- The specific immune system is NORMALLY distinguishes between self- and
non-self and only reacts against non-self.
Humoral adaptive immunity
- ANTIGENS (Ag, antigenic determinants) - substances that induce a specific
immune response and subsequently react with the products of a specific immune
- ANTIBODIES (Ab, Immunoglobulins, Ig) - protein molecules that are produced
by plasma cells in response to an antigen and can bind specifically to that
-- Are proteins that serve as molecular weapons of defence.
- antibodies have a specific shape and are made out of
regions that are very specific to
the pathogen and have a region that is different from other
- Recognition: They can recognize their specific antigen.
Their recognition works to
create a pocket that the antigen can fit into.
-- Have very specific shape
-- Contain four polypeptide (protein) chains arranged in a Y shape
-- The antigen binding site consists of combination of residues from the heavy
and the light chain
-- Have variable (top of Y) and constant regions (other part)
Antigen Binding Site
| | Y
- Light Chain (two extended arms: V)
- Heavy Chain ( the base of the two extending arms (|)
NATS NOVEMBER 23, 2011Humoral Adaptive Immunity-Antibodies recognize
foreign pathogens and help to destroy theySteps: -Neutralization: the
attachment protein is blocked by antibodies to stop the cells from infecting other
cells. Antibodies can block bacteria and virus cells. -Agglutination: antibodies
cells have two binding sites. Collect together many pathogens and then get rid of
them at once.-Precipitation: clumps together molecules dissolved in bodily fluids
and destroys them all together. -Activation of complement: you can create
holes in the membrane of bacteria and it bursts and dies.-40 years ago the way
to see interaction between bacteria and antibodies was by taking the bacteria
and letting it grow, then adding a drop of antibodies. They you see the tube
becomes cloudy nd you cant see through because interactions between bacteria
type of interactions so you had to do these tests (Agglutination, Precipitation)at
Function of Antibodies- an antibody molecule has two related functions in
humoral immunity-recognize and bind to a certain antigen- By binding to it, help
to counter its effect- Neutralization: Ab “neutralizes” toxins, binds to attachment
molecules- Agglutination: Create complexes of cells- Precipitation: create
complexes of molecules- Opsonization: Ab binds to pathogen surface molecules
and link them to phagocyte cell.- Complement Activation: occurs on antibody
bound to pathogens. Complement alsowork in the acquired immunity as well.
** Opsonization by Antibodies (Ab)- to increase the efficiency of the interaction
Lymphocytes- we have billions of antigens and we need a strong immunity
when a relevant infection is around- when were are making an antibody that is
specific to an antigen, this antibody must be produced by 1 lymphocyte. This
specific cells only knows how to make antibodies for one specific antigen,
nothing else.- to recognize approximately trillion of possible antigens, individuals
and specifically- each lymphocyte has 1 specific antibody that it expresses for its
lifetime- this creates a bit of a problem because in order to make an effective
amount of antibodies, to mount an effective response, we need to have sufficient cells specific for the antigen in question (100,000’s to millions)- it is not possible
having 1 million x1 trillion (10~15) cells in the body just for specific immunological
response. -our entire body consists of 10~14 cells. We need to be ten times as
large just for the immunesystem- the body needs to find another way in order to
give us this specific activity against all kinds of pathogens that are around now or
may be around. - The Solution: Clonal Selection of Lymphocytes(what Prof said
outloud) -we have trillions of cells that can recognize different antigens and they
are located in lymphnodes doing nothing until the relevant antigen is around.
When it’s around the antigen binds to the B Cell they create antibodies and
secrete them out and the B Cells create 2 new cell( clone them selves) and have
the ability to secrete antibodies outside of the cell. They’re still considered as B
Cells but they get another name to describe that they are a bit different. As
Summary of Clonal Selection: - the immune system has an extremely low
frequency of cells specific for each of trillion of specificities (5-10/cell)- when a
cell encounters its specific Ag, it replicates extensively, turning ~5-10 cells into
millions of progeny- Rare antigen-specific cells can increase in number so that
they get the ability to effectively fight the pathogen that elicited the response.
Clonal selection and immunity
- Primary response is about clonal selection
-Our immune system has a chemical memory of infections.
Immunological memory is the ability of the immune system to respond more
quickly and effectively to pathogens that have been encountered previously
-The primary immune response takes several days to produce effector cells via
- clonal selection produces also memory cells, which can last decades in the
- The secondary immune response can be developed when the same antigen is
- Initiated much faster due to the presense of memory cells.
- In the primary response the major class of AB produced is Igm.
- In the secondary response it is IgG
The Body's Defenses ALL IN ONE- Summary
The First Line of Defense (nonspecific)
• Mucous Membranes and their Secretions
◦ Stomach acid
The Second Line of Defense (nonspecific)
• Phagocytic White Cells
◦ monocytes / macrophages
• Antimicrobial Proteins
◦ cytokines (interleukins)?
• The Inflammatory Response and Fever ◦ histamines
◦ cytokines (interleukins)
The Third Line of Defense: The Immune system (specific mechanisms)
• Lymphocytes (Cellular response - a 2 prong attack on invaders)
◦ B-cells - antibodies
◦ T-cells - help stimulate B-cells, other T-cells directly attack infected cells or are
involved in self-regulation of the immune system.
• Antibodies (Humoral response)
Basic Features of the Immune System
The Immune system's primary role is to protect the body against damage from
any source that proves dangerous including viruses, bacteria, fungi, and other
microorganisms as well as internal threats such as cancer. Evolution continues to
improve the countermeasures parasites use to invade our bodies. Although our
immune system is also capable of evolving to meet this challenge medical and
technological advances so far have kept the legions of invaders at bay. How long
will the uneasy peace last against constant new threats such as AIDS and E.
How does the immune system identify and respond to pathogens? The first step involves the preparation of a molecule of foreign protein, referred to
as an antigen, for identification. Macrophages such as the interdigitating
dendritic cells and other so-called antigen-presenting cells, APCs, such as
macrophages scavenge materials from the blood and tissues and digest them.
Once inside these cells, small pieces of the antigens (peptides) enter a special
processing center, a vacuole called the compartment for peptide loading or
CPL, where they are bound to a special class of membrane proteins called major
histocompatibility complex (MHC) molecules. The CPL somehow attaches the
antigen to a class II MHC molecule and embeds it into the plasma membrane for
all passing immune cells to see. It is this antigenic flag around which various
MHC molecules are organized into 3 classes. (Class I molecules are found on all
nucleated cells, class II are found on B-cells and macrophages, and class III are
the various soluble proteins that make up complement.) Class I MHC molecules
act as a badge identifying all nucleated cells as "self". T-cells have molecules
called T-cell receptors which fit like lock and key to the Class I or Class II MHC
molecules on normal healthy cells. But these T-cell receptors are actually a dual
site, capable of recognizing a specific antigen which is attached to the MHC
molecule. T-cells can only be activated when the antigen-MHC site is occupied
(first signal), and a second, less understood, site is also involved (second signal).
Conversely, anytime a T-cell gets the first signal but not the second it will be
inactivated - perhaps by apoptosis. (A receptor protein coded CD28 is
The body's third and perhaps the ultimate line of defense is its immune system. It
is distinguished from the nonspecific defenses by four features: specificity,
diversity, self/non-self recognition, and memory.
a. Specificity - the immune system's ability to recognize and eliminate particular
microorganisms and foreign molecules called antigens.
b. Diversity - the ability of the immune system to respond to millions of kinds of
invaders, each recognized by its antigenic markers by a unique antibody
c. Self/Non-Self recognition. Why doesn't the immune system attack our own cells? The standard explanation is that the immune system is "trained" during its
early development to recognize the difference between self and non-self. This is
called self-tolerance. It is presumed that any lymphocytes with receptors for
molecules present in the body (self) before birth (and perhaps after) are
somehow destroyed. Thus there are no antigen receptors for an animal's own
molecules. However it may be that the immune system responds to danger,
actual damage detected as a special chemical signature caused by the rupture of
injured or dying cells.
d. Memory - refers to the immune system's ability to remember antigens it has
encountered and to react quickly and effectively against them a second time
around. This is known as acquired immunity. Acquired immunity may be active;
conferred by recovery from a particular infectious disease; or
passive&emdash;transferred from one individual to another&emdash;often
obtained through vaccination. It the case of infants mom's antibodies can pass
through the placental barrier.
When a lymphocyte first encounters an antigen it recognizes and is stimulated to
divide it initiates the Primary Immune Response. The process involves clonal
selection, the rapid development of a single line or lines of T- and B-
lymphocytes from a vast and diverse army.
But before this occurs all pathogens must slip by the:
I. The First Line of Defense
1. The skin is an effective physical barrier by being both tough (keratin resists the
digestive enzymes of invading bacteria) and poisonous (certain fatty acids are
toxic to bacteria as are secretions from sweat and oil glands which lower the pH
of the skin somewhere between 3 and 5&emdash;a hostile environment for most
pathogens). 2. The secretions of the mucous membranes in the respiratory system effectively
trap invading bacteria which can then be swept away by the ciliate lining.
3. The nasal passages and sinuses are now known to make nitrous oxide and
other nitrogen compounds which are toxic to a wide range of infectious
microorganisms. "Unlike the nose, which harbors many types of bacteria, the
sinuses...remain curiously free of intruders." The reason, recently discovered, is
that the sinuses produce nitric oxide, NO, a gas considered a pollutant in the
atmosphere is lethal even in small doses to bacterial and viruses, binding
strongly to their vital enzymes. NO is made by the sinus' epithelial cells. (July '96,
4. Most invaders cannot withstand the strong acid (HCl) found in the stomach.
5. Anti-bacterial enzymes known as lysozymes are found in tears and other
body secretions. Lysozymes (digestive enzymes) found in the respiratory tract
and around the eyes attack the cell walls of many bacteria.
6. Urinary passages are protected by the flushing action of urine. 7. The vagina and lower intestine are protected by the symbiotic association
of mutualistic bacteria which help crowd out dangerous species by using up
available resources, out-competing the invaders or by creating a hostile
8. The inflammatory response and fever. Certain white blood cells release
molecules called pyrogens which set the body's thermostat at a higher
temperature. While a high fever is dangerous a moderate one inhibits the growth
of some microorganisms (possibly by decreasing availability of iron) and can
II. Secondary /Tertiary Defenses: Nonspecific and Specific
1A. Nonspecific, Chemical Secondary Defenses
1. Histamine - speeds release of other agents both chemical and cellular and
initiates the inflammatory response. Histamines (which are blocked by
antihistamines) initiate the redness and swelling associated with inflammation
and infection. Histamine is released by injured basophils and mast cells that are
found in connective tissue. Histamine triggers local vasodilation and makes the
capillaries leakier. Prostaglandins which are also released promote blood flow to
2. Cytokinins (kinins or lymphokines)- attract phagocytes, increase inflammatory response. Released by injured cells, these short polypeptides increase
circulation and capillary permeability; attract white blood c