Rationale Week 8 and Week 9
Rationale Week 8 and Week 9
Rationale Week 8 and Week 9
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T-cell maturation in the thymus. T-lymphocyte precursors (TP) Phagocytosis, ADCC
enter the thymus at the corticomedullary junction. They migrate External barriers, nose hair,
upward in the cortex and begin development of the T-cell receptor. pH of skin, Competitive
A small percentage of precursors develop gamma-delta chains, inhibition
whereas the majority develop alpha-beta chains and become
double-positive (DP) (both CD4 and CD8 are present). Positive There are no surface markers that are unique to NK cells, but they
and negative selection takes place through the CD3/T-cell receptor express a specific combination of antigens that can be used for
for antigen. If positively selected, the T cell becomes single- identification. Two such antigens are CD16 and CD56. CD16 is a
positive (SP); that is, either CD4+ or CD8+. Further interactions receptor for the nonspecific end of antibodies. Because of the
with macrophages or dendritic cells take place to weed out any T presence of CD16, NK cells are able to make contact with and then
cells able to respond to self-antigen. Surviving CD4+ and CD8+ lyse any cell coated with antibodies.10 NK cells are also capable of
cells exit the thymus to the peripheral blood. recognizing any foreign cell and represent the first line of defense
against virally infected cells and tumor cells.
Dendritic cells are so named because they are covered with long
membranous extensions that make them resemble nerve cell
dendrites. They were discovered by Steinman and Cohn in 1973.
Progenitors in the bone marrow give rise to dendritic cell
precursors that travel to lymphoid as well as nonlymphoid tissue.
They are classified according to their tissue location in a similar
manner to macrophages. After capturing an antigen in the tissue by
phagocytosis or endocytosis, dendritic cells present the antigen to
T lymphocytes to initiate the adaptive immune response in a
similar way as macrophages. Dendritic cells, however, are
considered the most effective APC in the body, as well as the most
potent phagocytic cell.
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Ficoll-Hypaque Density gradient centrifugation is used to separate
the monocytes in whole blood using a density agent (Ficoll-
Hypaque; density/specific gravity of 1.0772, 1.0767, and 1.0758
at 20 ºC, 22 ºC, and 25 ºC, respectively.)
Lymphocytes used routinely in HLA serologic typing assays are
readily obtained from peripheral whole blood by layering onto a
Ficoll-Hypaque gradient to separate the blood cells by density
centrifugation.
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Rheumatoid Arthritis can be characterized as a chronic, symmetric,
and erosive arthritis of the peripheral joints that can also affect
multiple organs such as the heart and the lungs. These patients are
positive for rheumatoid factor (RF) or antibodies to CCP.
RF is an antibody that is most often of the IgM class and is
directed against the FC portion of IgG. It has been postulated that
RFs may play a role in the pathogenesis of RA by increasing
macrophage activity and enhancing antigen presentation to T cells
by APCs. Antibodies to cyclic citrullinated proteins (anticyclic
citrullinated peptide antibody [anti-CCP or ACPA]) are a
second major type of antibody associated with RA. Anti-CCP
antibodies can react with citrulline-containing components of the
matrix, including filaggrin, keratin, fibrinogen, and vimentin, and
are thought to correlate with the pathogenesis of RA. In RA,
autoantibodies such as RF and anti-CCP are thought to combine
with their specified antigen, and the resulting immune complexes
become deposited in the joints, resulting in a type III (or immune
complex) hypersensitivity reaction. The complement protein C1
binds to the immune complexes, activating the classical
complement cascade. During this process, C3a and C5a are
generated, which act as chemotactic factors for neutrophils and
macrophages. The continual presence of these cells and their
associated cytokines leads to chronic inflammation, which
damages the synovium itself.
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scattering will form a straight line if plotted on a graph. DNAse B antibodies. Hemagglutination represents a positive test,
Nephelometers typically measure light scatter at angles ranging indicating that antibodies to one or more of these antigens are
from 10 degrees to about 90 degrees. If a laser beam is used, light present.
deflected only a few degrees from the original path can be
measured. Although the sensitivity of turbidity has increased,
nephelometry is more sensitive, with a lower limit of detection of 1
to 10 mg/L for serum proteins. Many automated instruments use a
technique called rate nephelometry for the measurement of serum
proteins. In this instance, the rate of scattering increase is measured
immediately after the reagent antibody is added. This rate change
is directly related to antigen concentration if the concentration of
antibody is kept constant.
An antibody mixture is
placed in the central
well. Unknown antigens
are placed in the outside
wells. The antibodies
and antigens all diffuse
radially out of the wells.
(A) Serological identity.
If the antigens are
identical, they will react
with the same antibody
and the precipitate line
forms a continuous arc.
(B) Nonidentity. If the
antigens share no
identical determinants,
they will react with
different antibodies and two crossed lines are formed. (C) If
antigen 3 has a determinant in common with antigen 1, one of the
antibodies reacts with both antigens. Another antibody that reacts
with different determinants on antigen 1 (absent on antigen 3)
passes through one precipitation line and forms the spur on the
other line. The spur formed always points to the simpler antigen
with fewer antigenic determinants.
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hypersensitivity. This type of hypersensitivity is characterized by a
delayed immune response, typically mediated by T lymphocytes,
and it is associated with autoimmune diseases. In the case
described, the development of insulin-dependent diabetes mellitus
(IDDM) suggests an autoimmune response against the beta cells of
the pancreas, and this is commonly associated with Type IV
hypersensitivity.
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The scientist known for radioimmunoassay is Rosalie Yalow. prevent the attachment of the C5b-7 complex to the cell membrane.
Rosalie Yalow, along with Solomon Berson, developed the Decay-accelerating factor (DAF) is a cell surface protein that
radioimmunoassay (RIA) technique, for which she was awarded functions to inhibit the activation of the complement system by
the Nobel Prize in Physiology or Medicine in 1977. RIA is a destabilizing and dissociating C3 convertase enzymes. DAF helps
powerful technique for measuring the concentration of various protect cells from complement-mediated lysis, but it does not
substances in biological samples, using radioactively labeled specifically prevent the attachment of the C5b-7 complex to the
antibodies. cell membrane. Homologous restriction factor (HRF) is a protein
that binds to the C8 component of the complement system,
The gauge of needle commonly used in quantitative serum VDRL inhibiting the polymerization of C9 and preventing the formation
(Venereal Disease Research Laboratory) testing is Gauge 19. This of the membrane attack complex. While HRF plays a role in
gauge size is appropriate for drawing blood samples for various regulating complement, it does not specifically prevent the
laboratory tests, including VDRL, and is commonly used for attachment of the C5b-7 complex to the cell membrane.
venipuncture.
Hepatocellular carcinoma (HCC) is best determined by an increase
In B-cell development, Pro-B cell rearrangements of genes coding in AFP (Alpha-fetoprotein). AFP is a tumor marker that is often
for heavy chains occur on chromosome 14. The genes involved in elevated in cases of HCC and is used as a diagnostic and
the recombination of heavy chains are located on chromosome 14. monitoring tool for this type of liver cancer. An elevated AFP level
can indicate the presence of HCC or its progression. The other
The non-specific immune response with antiviral activity is markers listed, such as CEA, PAP, and HCG, are associated with
Interferon. Interferons are a group of signaling proteins that play a different types of cancer and may not be as specific for HCC.
crucial role in the body's defense against viral infections. They are
part of the innate immune response and have antiviral properties. The size of a pore that C5b678 can able to create in cell membrane
in order to initiate cell lysis is 70-100 angstroms.
A graft derived from a different class but an identical individual is
called Xenograft. Xenografts involve the transplantation of tissue
or organs from one species to another. In this case, the individuals
may be from different classes or species, but they are genetically
identical, which can reduce the risk of graft rejection. Heterograft
(also known as Allograft) refers to the transplantation of tissue or
organs between individuals of the same species but with different
genetic backgrounds. This is the most common type of graft and
includes transplants between unrelated or genetically non-identical
individuals. Examples include kidney transplants from one human
to another, where the donor and recipient are not genetically
identical. Autograft refers to the transplantation of tissue or organs
from one part of an individual's body to another part of the same
individual. This type of graft is often used in procedures like skin
grafts, where a section of a person's skin is taken from one area and
transplanted to another, such as for wound coverage. Isograft
involves the transplantation of tissue or organs between genetically
identical individuals. This typically occurs between identical twins
or, in the case of animals, between genetically identical siblings.
Isografts are not subject to immune rejection since the donor and
recipient share identical genetic backgrounds.
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Cytokines known to be endogenous pyrogens are responsible for hormones, and specific antibodies. The Fahey and McKelvey
inducing fever. IL-1 (Interleukin-1) is a well-known endogenous method (Kinetic method) is a variation of immunodiffusion,
pyrogen. IL-1 is a proinflammatory cytokine produced by various primarily used for the quantitative measurement of specific
immune cells, including monocytes and macrophages. It plays a proteins, particularly immunoglobulins (Ig). In this method,
central role in the induction of fever. When the body detects an antibodies against the target immunoglobulin classes (IgG, IgA,
infection or other immune challenges, IL-1 is released, and it acts IgM, etc.) are incorporated into agarose gel plates. Serum samples
on the hypothalamus in the brain, where it increases the body's are then added to wells in the gel. After a period of diffusion and
temperature set-point, leading to fever. IL-4 is an anti- antigen-antibody complex formation, the plates are stained, and the
inflammatory cytokine that promotes the development of Th2 size of the precipitation rings is measured. The ring size is
helper T cells and is involved in allergic and humoral immune proportional to the concentration of the specific immunoglobulin in
responses. It does not have a primary role in inducing fever; the serum sample. Ouchterlony double diffusion is a qualitative
instead, it's associated with anti-inflammatory actions. IL-5 is a technique used to determine the presence of specific antigens or
cytokine primarily involved in the activation and differentiation of antibodies and their interactions. In this method, both antigen and
eosinophils, a type of white blood cell. It is not known to be an antibody are allowed to diffuse in an agarose gel medium, leading
endogenous pyrogen or to induce fever. IL-7 is important for the to the formation of precipitation lines where they meet. The pattern
development and survival of T cells. It is not typically associated of precipitation lines reveals the relative reactivity between the
with the induction of fever. antigens and antibodies. This method is often used for
immunological profiling, including antigen identification and
IgA is the immunoglobulin that is most susceptible to proteolysis. antibody-antigen cross-reactivity studies. Nephelometry is a
IgA is an antibody isotype found in various mucosal secretions, quantitative method used to measure the concentration of particles,
such as saliva and mucus. It has a relatively shorter half-life and is such as proteins or immune complexes, in a liquid sample based on
more susceptible to proteolysis compared to other the scattering of light. In immunology, nephelometry is commonly
immunoglobulins like IgG or IgM. This characteristic is used to measure the concentration of specific proteins, including
particularly important in the context of mucosal immune responses immunoglobulins and complement components, in serum or other
where IgA plays a crucial role in defense against pathogens. biological fluids. The degree of light scattering is directly
proportional to the concentration of the particles in the sample.
Anti-Hbe (Antibodies to Hepatitis B e Antigen) is the one to first Nephelometry provides precise and quantitative results for a wide
appear during the convalescent phase of a hepatitis B virus (HBV) range of immunological assays.
infection. As the immune system begins to respond to the infection
and control HBV replication, the production of antibodies against
HBeAg, known as Anti-Hbe, starts. Anti-Hbe is an indicator of a
transition from the acute phase to the convalescent phase.
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Allotype refers to the genetic variations within the constant (C) cells and lymphocytes have distinct roles in the immune system,
region of immunoglobulin molecules, such as antibodies. Allotypes and dendritic cells are primarily derived from myeloid progenitors.
are differences in the amino acid sequences of the constant region
of heavy and light chains among individuals. These variations are Interferons are signaling proteins produced by cells in response to
inherited and can be used to identify different alleles of the same viral infections. Their main function is to interfere with viral
immunoglobulin gene. Allotypes are important in understanding replication within infected cells, essentially inhibiting the spread of
genetic diversity in antibody populations, especially within a the virus. Interferons activate antiviral defenses in neighboring
species. Idiotype pertains to the unique variable (V) region of an cells and help orchestrate the body's immune response against
antibody, which includes the antigen-binding site. It is the set of viruses.
unique amino acid sequences in the variable region of the antibody,
giving rise to the antibody's specificity for a particular antigen. Not only does the skin serve as a major structural barrier, but the
Idiotypes are specific to each individual antibody and define the presence of several secretions on it discourages the growth of
antigenic properties of the antibody. Isotype refers to the class or microorganisms. Lactic acid in sweat, for instance, and fatty acids
type of immunoglobulin that an antibody belongs to, which is from sebaceous glands maintain the skin at a pH of approximately
determined by the type of constant (C) region it has. There are 5.6. This acidic pH keeps most microorganisms from growing. In
different isotypes, such as IgG, IgM, IgA, IgD, and IgE, each with addition, human skin cells produce psoriasin, a small protein that
distinct structural and functional characteristics. Isotypes are has antibacterial effects, especially against gram-negative
significant in defining the antibody's effector functions and roles in organisms such as Escherichia coli.
the immune response. Domains are structural units within antibody
molecules. Antibodies are composed of four protein chains: two In the Weil-Felix test, Proteus vulgaris and Proteus OX-19
identical heavy chains and two identical light chains. Each of these antigens is used to detect the presence of antibodies against
chains is divided into functional and structural units called Rickettsia in a patient's serum.
domains. The most common domain in antibodies is the
immunoglobulin domain, which is a compact and stable protein The normal ratio of CD4 to CD8+ T cells in the blood is typically
structure. These domains contribute to the overall structure and 2:1. In healthy individuals, there are roughly twice as many CD4+
function of the antibody, including antigen binding and interactions T cells as CD8+ T cells. This ratio can vary within a certain range,
with other immune system components. but a substantial deviation from this balance may indicate an
immune system imbalance or underlying health condition.
CCR5 is a chemokine receptor found on the surface of certain
immune cells, including macrophages and T cells. It serves as a co-
receptor for HIV in some strains of the virus. HIV that uses CCR5
as a co-receptor is known as R5-tropic HIV. HIV's ability to bind
to CD4 and co-receptors like CCR5 or CXCr4 is a critical step in
its life cycle, as it allows the virus to enter and infect host cells.
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electrostatic interactions in the system, contributing to changes in
zeta potential.
3. The slipping plane is not a direct factor that affects zeta
potential but rather a concept related to fluid dynamics and the
movement of particles in a fluid medium.
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