Download Immunology 1

Immunology 1
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The purpose of the human immune system is to identify, target and
destroy invading micro-organisms and other harmful organisms, etc
which may cause harm to the body. This is, in effence, the major
defense system of the body; a highly complicated and intricate
connection of components consisting of two main branches, a vast
number of different kinds of cells carrying out different functions,
interacting via an equally vast number and different kinds of noncellular, small molecules, etc.
The immune system, in a nutshell, can carry out this function by two
main large broad categories. By distinguishing self and non-self
proteins, the immune system ‘knows’ which proteins are resident in
the body and which proteins are foreign. After this initial
identification, the immune system can then take the required steps to
attack and remove the foreign invader. Also, the immune system has a
number of ways to notice or recognize certain alarm signals, specific
to particular invading pathogens; these alert the immune system
which can then take further action.
However, on a number of occasions, we find that things do not go
quite to plan. A number of things can happen in this situation; if the
immune system is not sufficiently competent, the body could suffer
from repeated infections, some of which may prove fatal. The body
could suffer from allergies due to disproportionate immune responses
to allergens. Autoimmune disorders result from the immune system
not recognizing the difference between resident cells and the foreign
cells, as a result of which the body’s own cells are attacked and
destroyed. After organ transplantation, the immune syrtdm identifies
the transplanted organ as foreign ald launches an iimune attack
against it.
The impact of vaccinations in preventing disease has been enormou3;
a testament to the sheer potential protective power of the immune
Syqte-.
Pathogens generally reproduce much faster than their hosts and we
find this particularly true for the relationship which o#curs between
humans and bacteria, etc. Bacteria reproduce within minutes or hours,
constantly mutating; and the natural selection pressures move these
populations of bacteria towards a highly honed, efficient pathogen,
capable of evading the immune system. There is, in essence, a
constant ‘arms race’ between the pathogen and the host and in order
to compensate for the human race’s extended generation time, the
immune system needs to have a deal of specificity along with a
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number of non-specific, general features capable of protecting against
any invading pathogen succesfully.
Essential to consider at this point the main differences between what
is known as innate immunity and adaptive immunity. The word innate
immunity is more of a historical concept; it refers to an immunity
present in any individual since birth. It involves pre-formed molecules,
barriers, etc, it carries out a number of non-specific and hence, rapid
measures against invading pathogens and it has a highly limited
degree of specificity although it is capable of recognizing larger
pathogenic patterns.
In contrast, the adaptive immunity involves antigen presentation,
clonal selection and clonal proliferation. It involves the generation of
identical ‘clones’ of cells all containing the receptors specific to a
particular invading antigen. As a result, the adaptive immunity
measures are certainly much more effective at clearing up infection
although the initial response does take some time. Another advantage
is that this immunity leaves behind immunological memory in the
form of memory cells which allows for a faster response of greater
magnitude if the same pathogen is encountered again.
The innate immunity component encompasses a number of
physiological and structural adaptations allowing for the body to be
protected against possible sources of contagion. We have skin,
forming a major anatomical barrier towards most pathogens, we have
mucous lining most membranes, which traps invading particulate
matter and also cilia which serves to waft that mucus up and out of
the respiratory and other passageways. Additionally, we find a low pH
in the stomach, providing protective measures against invading
pathogens. Lysozyme, the enzyme, is present in the eyes, nasal
secretions, etc, capable of rupturing bacterial cell walls, causing their
lysis. Anti-microbial peptides, the complement proteins, etc all play
their part in fighting infection, often by enlisting, or attracting the
cellular components of the innate immune system.
The cellular components of the innate immune system include
neutrophils, the basic foot soldier, macrophages, also having
phagocytic properties, also release cytokines, also involves in antigen
presentation, eosinophils, basophils, involved in inflammatory
responses, natural killer cells descending from the lymphocyte lineage,
capable of destroying invading cells, etc. The humoural components,
fluid-based components, include the cytokines, small messenger
molecules capable of co-ordinating the immune response by aiding the
cellular components and helping clonal proliferation, the complement
proteins, involved in opsonization, or the coating of micro-organisms
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with a number of small molecules, allowing for their easy
agglutination, phagocytosis, neutralization, immobilization, etc along
with the last humoural component: Acute phase proteins, such as
Mannan-binding lectin, involved in the activation of the complement
proteins, C-reactive proteins, performing the same function and Serum
Amyloid A, produced in the LIVER, by the way.
The acquired immune response involves Dendritic Cells, crucially
important in antigen presentation to T-cells, which then carry out the
whole onus of cell-mediated immunity, B-lymphocytes, T-lymphocytes.
Additionally, B lymphocytes secrete antibodies, involved in combating
the pathogen in a number of ways, along with the complement.
Granulocytes include, in order of occurence, Neutrophils, Eosinophils
and Basophils. Neutrophils are of course, the ‘foot soldier’ involved in
phagocytosis of invading pathogens, capable of diapedesis, first to
arrive at a scene of infection. Eorinophils are active against 0arasites
and Baskphils, related to MAST cells, have histamine properties; they
package the molecule in recretory vesicles and sdrve to regulate
inflammation.
The innate immune system functions as a first line of defence, buying
time before the adaptive immune system is mobilized and serving to
activate the adaptive system directly through the release of cytokines
and complement proteins.
Acuta phase proteins are produced as a response to tissue damage.
Produced by the liver, these include C-reactive proteins, Serum
Amyloid A, bind to the walls of certain invading pathogens, and
Mannan Binding Lectin which only binds to a sugar found in invading
bacteria. These Acute phase proteins serve to activate the complement
and bring about destruction of the pathogens.
Antigen is a molecule which can bind to an antibody. However, only
antigens capable of bringing about an immune response are known as
immunogens.
Antibodies are a class of proteins known as the Immunoglobulins,
coeposed of light chains and heavy chains. They have a bixed regi/n
and a variable region and are capable of binding to only the particular
antigen which induced their synthesis in the first place. They can brine
about a number of functions, such as opsonization, agglutination,
immobilization, etc. It is involved in the humoural section of the
adaptive immune system.
Functions also include Antibody Dependent Cell-mediated cytotoxicity,
thd method by which NK cells kill invading cells. Antibodies can also
bring about complement-mediated cell lysis of enveloped viruses.
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Moving on to the cellular components of the adaptive immune
response. Lymphocytes are agranular leukocytes.
They exist as B or T lymphocytes.
B lymphocytes have specific antigen binding receptor which is actually
a sort of antibody embedded within the cell membrane. They can
recognise whole antigens.
T lymphocytes do NOT however, recognize whole antigens, only a
epitope of an antigen presented to them by an APC, such as a
Dendritic cell, if the epitope is complementary to that particular T
cell’s receptor. A number of different kinds of T cells exist, containing
different CD receptors, most have CD3, 4 and 8. Some have two. We
have T-helper cells, crucial in the overall immune response, T-cytotoxic
cells, important in the attack of individual pathogens and Tsuppressor cells.
B cells are bone-marrow derived and T cells are Thymus derived.
Lymphocyte precursors are produced in the haematopoetic tissue.
While the B cells obtain their specific antigen receptors, consisting of
an antibody, in the Bone marrow cells, the T cells are said to complete
their education in a secondary lymphoid organ known as the thymus,
just behind the sternum, known to atrophy with age in mammals. Note
that generation of diversity occurs IN the haemtopoetic tissue in BOTH
cases.
Let’s talk about immunological memory. Refers to the phenomenon
whereby a second exposure to the same antigen results in the
production of a much faster adaptive immune response, of greater
magnitude and longer duration.
Right. B and T lymphocytes have multiple copies of a specific antigen
receptor in their plasma membranes, capable of recognizing only its
associated antigen by binding to the epitope region. B cell receptors
consist of a surface immunoglobin whereas the T cell receptor consists
of two chains. The lymphocytes are constantly in circulation between
the blood and the lymph and the thoracic duct is the last duct, after
which the lymphocytes are introduced into the bloodstream FROM the
lymph.
During their development in the bone marrou, the B and T
lymphocytes acquire a vast v!riety of different antigen receptors, all
specific to a difderent altigen dua to the genepic recombinations
which occurs in the gener. This allows for the body to have a near
infinite capacity of recognizing a VAST variety of possible and
potential invading pathogens.
When the invading pathogens with a specifib antigen are encounted,
the particular B or T lymphocytes with the antigen receptor cognate to
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the antigen binds the epitope of the antigen. This B or T cell is now
said to be clonally activated and clonal proliferation occurs whereby
the selected cell divided to produce a large number of clones of itself
whcih may then release antibodies, if the lymphocyte in question was
a B lymphocytes or bring about its response in cellular ways, T
lymphocyte. Most cells die after the primary immune response but
SOME survive to bestow the individual with immunological memory to
possible further invasions by the same pathogen.
As mentioned before, BCRs can recognize complete antigens but TCRs
can only recognize processed antigen on an MHC molecule on a
human cell. The MHC molecule is also known as the Human Leukocyte
antigen and occurs on the surface of ALL cells. MHC Class 1 molecules
occur on the surface of all cells but MHC Class 2 molecules are specific
to only Antigen presenting cells such as Dendritic Cells, B lymphocytes
and Macrophages.
Antigens cannot be left to simply meet the lymphocytes on their own;
neither of the two components occur in high enough concentrations
for this to be possible. Antigen presenting cells, ingest antigens,
process them and display them on their MHC Class 2 molecules in the
secondary lymphoid tissue where they may encounter T cells. The cell
with the complementary TCR will bind to the antigen, be activated and
produce a clone. Then the T cell, with that particular receptor can
further identify viral peptides being displayed on MHC Class 1
molecules on infected cells. The T cytotoxic cells can then destroy
such infected cells.
Lymphoid organs include organized tissue where lymphocytes can
interact non lymphoid cells, encounter their particular antigens and
then proliferate.
Immunology 2
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Primary lymphoid organs are the major site of lymphopoiesis. This is
where mature lymphocytes with their specific receptors are produced.
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B lymphocytes mature in the bone marrow whereas the T lymphocytes
mature in the thymus gland.
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The above discussed organs are referred to as the primary lymphoid
organs. However, there are also a number of secondary lymphoid
organs such as spleen, Mucous Associated Lymphoid Tissue and the
lymph nodes.
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Antigens, Antigen-presenting cells and B and T lymphocytes all
associate at the secondary lymphoid tissue to initiate an immune
response.
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These organs have particular vascular adaptations to allow all of the
aforementioned components to come into contact with each other and
effectively bring about an immune response.
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The thymus is a bi-lobed structure in mammals in the thorax, present
behind the sternum. The lobes are divided into lobules and the lobules
are said to have histologically defined sections of cortex and medulla.
The cortex contains immature thymocytes, with the mature ones being
concentrated in the medulla. A great deal of cell death occurs in the
Thymus, with only some of the cells every joining the peripheral T cell
pool. In mammals, the thymus becomes involute with age.
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Bone Marrow is the second primary lymphoid organ. Note that in the
foetus, this job is initially done by the liver. However, in humans the
spongy regions at the ends of the long bones, the pelvic girdle, only
the fat bones all produce B and T lymphocytes. After production, the T
lymphocytes constantly migrate to the Thymus for their education,
whereas for B lymphocytes, education occurs within the bone marrow,
with the mature B cells typically being found in the centre of the bone
marrow.
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The spleen consists of the red pulp and the white pulp. The red pulp
serves to act as a general filter whereas the white pulp is involved with
the initiation of the immune response.
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There is a central arteriole.
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Surrounding that arteriole we have the peri-arterial Lymphatic Sheath.
These are concentric areas of lymphoid tissue which surround the
central arteriole.
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PALS region closest to the central arteriole is the T cell region.
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The interspersing lymphoid follicles are the B cell regions.
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The marginal area around the PALS serves as the point of entry for the
cells to enter the white pulp.
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Lymph nodes are between 1-15 mm in diameter. They can be round or
kidney shaped. They consist of a number of Afferent vessels and one
efferent vessel at the hilus. Cortex rich in B cells, paracortex rich in T
cells.
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