Rationale Week 8 and Week 9

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RATIONALE:

The main difference between immunoglobulin and antibody is that


immunoglobulin has a transmembrane domain in order to be
The lymphoid cells of the body reside in the lymph nodes, the
attached to the plasma membrane whereas antibody does not have
spleen, the mucosal surfaces, and the circulation. They derive from
a transmembrane domain.
multipotential hematopoietic stem cells, with their production
moving progressively from the yolk sac in the embryo to the liver
The immune response of lymphocytes is triggered by materials
in the fetus, and, finally, to the bone marrow in the infant through
called immunogens, which are macromolecules capable of
adult ages The various lymphoid cells are conveniently identified
triggering an adaptive immune response by inducing the formation
by the presence of unique protein markers on their surfaces that
of antibodies or sensitized T cells in an immunocompetent host.
endow those cells with particular functions.
Immunogens can then specifically react with such antibodies or
sensitized T cells. The term antigen refers to a substance that reacts
The α- and β-subunit TCR proteins have variable, joining, and with an antibody or sensitized T cells but may not be able to evoke
constant regions an immune response in the first place. Thus, all immunogens are
(α also contains a diversity region), with corresponding encoding antigens, but the converse is not true.
regions in the TCR gene that undergo rearrangement, resulting in
high specificity binding for a particular antigen. The CD3 proteins Serum amyloid A (SAA) is the other major protein besides CRP
assist transduction of the signal to the interior of the cell when an whose concentration can increase almost a thousandfold in
antigen binds to the TCR on the lymphocyte surface. A small response to infection or injury. It is an apolipoprotein that is
percentage of T lymphocytes have a TCR composed of γ- and δ- synthesized in the liver and has a molecular weight of 11,685
subunits that similarly interact with CD3. These cells are generally daltons. Normal circulating levels are approximately 5 to 8 ug/mL.
found at mucosal surfaces of the gastrointestinal and respiratory In plasma, SAA has a high affinity for HDL cholesterol and is
tracts. T cell proliferations may be characterized as neoplastic transported by HDL to the site of infection. SAA appears to act as
(clonal) or benign (polyclonal) according to whether their DNA a chemical messenger, similar to a cytokine, and it activates
shows predominantly a single form of TCR gene rearrangement or monocytes and macrophages to then produce products that increase
a complete spectrum of such rearrangements, as normally occurs in inflammation. It has been found to increase significantly more in
a heterogeneous lymphocyte population. bacterial infections than in viral infections. Levels reach a peak
between 24 to 48 hours after an acute infection. SAA can also be
increased because of chronic inflammation, atherosclerosis, and
Natural killer (NK) cells constitute 10% to 15% of lymphocytes cancer. Because SAA has been found in atherosclerotic lesions, it
in the peripheral blood. They are neither T cells nor B cells and is now thought to contribute to localized inflammation in coronary
were formerly called null cells. NK cells are characterized by the artery disease. Elevated levels may predict a worse outcome for the
surface markers CD16 and CD56, which are commonly used for patient.
their identification. CD16 is the Fc receptor for IgG; hence, NK
cells are able to lyse selectively those cells that are coated with
antibodies (antibody-dependent cell-mediated cytotoxicity, which
is important in some hypersensitivity reactions). NK cells also
secrete cytokines such as IFN-γ. NK cells are recognizable on
examination of standard stained blood smears as large granular
lymphocytes.

Acute-phase reactants are normal serum constituents that increase


rapidly because of infection, injury, or trauma to the tissues. Most
of the acute phase reactants are positive acute phase reactants
(increases during inflammation) except: albumin, prealbumin,
transferrin, retinol-binding protein, and antithrombin. These are
negative acute phase reactants and they decrease in inflammation.

The Centers for Disease Control and Prevention (CDC) has


recommended that a CRP concentration of less than 1 mg/L is
associated with a low risk for cardiovascular disease; 1 to 3 mg/L
is associated with an average risk; and greater than 3 mg/L is
associated with a high risk. Normal levels in adults range from
approximately 0.47 to 1.34 mg/L. A mean for people with no
coronary artery disease is 0.87 mg/L. Thus, monitoring CRP may
be an important preventative measure in determining the potential
risk of heart attack or stroke.

Basophils are the least numerous of WBCs found in peripheral


blood, representing less than 1% of all circulating WBCs. The
smallest of the granulocytes, basophils are slightly larger than
RBCs (between 10 to 15 μm in diameter) and contain coarse,
densely staining deep-bluish-purple granules that often obscure the
nucleus. Constituents of these granules include histamine,
cytokines, growth factors, and a small amount of heparin, all of
which have an important function in inducing and maintaining
allergic reactions. Histamine contracts smooth muscle and heparin
is an anticoagulant. In addition, basophils regulate some T helper
(Th) cell responses and stimulate B cells to produce the antibody
IgE. Basophils have a short life span of only a few hours in the
bloodstream; they are then pulled out and destroyed by
macrophages in the spleen.

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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.

Antigen-presenting cells include dendritic cells, B-cells,


macrophages, fibroblasts, hepatocytes, mast cells.

The role of T cells is to produce cytokines that contribute to


immunity by stimulating B cells to produce antibodies, assisting in
killing tumor cells or infected target cells, and helping to regulate
both the innate and adaptive immune response. NK cells are also
capable of recognizing any foreign cell and represent the first line
of defense against virally infected cells and tumor cells. Although
NK cells have traditionally been considered part of the innate
immune system because they can respond to a variety of antigens,
it appears that they also have the capability to develop memory to
specific antigens in a similar manner to T 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.

Innate Immunity Adaptive Immunity


Neutrophils, Basophils, Lymphocytes:
Eosinophils, Monocytes, - B-cells
Macrophage, Mast cells, - T-cells (T-helper, T-
Dendritic cells cytotoxic, T-regulator)
NK cells
APRs, phagocytosis, TLRs,
Complement, Inflammation,

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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.

Survivors of selection exhibit only one type of marker, either CD4


or CD8. It is not certain why one marker is downregulated, but it
may depend on which MHC protein the cell interacts with, how
strongly they react, and to which cytokines they are exposed.
CD4+ T cells recognize antigen along with class II MHC protein,
whereas CD8+ T cells interact with antigen and class I MHC
proteins. The two separate mature T-cell populations created differ
greatly in function. T cells bearing the CD4 receptor are mainly T IgA is found in mucous secretions as a dimer stabilized by the J-
helper (Th) cells, whereas the CD8+ population consists of piece. IgA is synthesized locally by plasma cells and dimerized
cytotoxic T cells. Approximately two-thirds of peripheral T cells intracellularly. IgM is also held together by a J-piece, but it exists
express CD4 antigen, whereas the remaining one-third express as a pentamer.
CD8 antigen. Th1 cells pro- duce interferon gamma (IFN-γ),
interleukin-2 (IL-2), and tumor necrosis factor-β (TNF-β), which
protect cells against intracellular pathogens by activating cytotoxic
lymphocytes and macrophages. Th2 cells produce a variety of
interleukins, including IL-4, IL-5, IL-6, IL-9, IL-10, and IL-13.
The essential role of the Th2 cells is to help B cells produce
antibodies against extracellular pathogens and to generally regulate
B-cell activity.

In the spleen, immature B cells develop into mature cells known as


either marginal zone B cells or follicular B cells. Marginal B cells
remain in the spleen in order to respond quickly to any blood-borne
pathogens they may come into contact with. Follicular B cells
migrate to lymph nodes and other secondary organs. Unlike
marginal B cells that remain in the spleen, follicular B cells are
constantly recirculating through- out the secondary lymphoid
organs. In addition to IgM, all mature B cells exhibit
immunoglobulin D (IgD), another class of antibody molecule, on
their surface. Both IgM and IgD have the same specificity for a
particular antigen or group of antigens. These surface
immunoglobulins provide the primary activating signal to B cells
when contact with antigen takes place. IgD is not required for B-
cell function, but it may prolong the life span of mature B cells in
the periphery. Unless contact with antigen occurs, the life span of a
mature B cell is typically only a few days. If, however, a B cell is
stimulated by antigen, it undergoes transformation to a blast stage
that eventually forms memory cells and antibody-secreting plasma
cells. This process is known as the antigen-dependent phase of B-
cell development. The production of antibodies by plasma cells is
called humoral immunity.

The basic structure of all immunoglobulins is two light chains


joined to two heavy chains by disulfide bonds. The amino terminus
of both the heavy and light chains, together, constitutes the Fab
fragment (fragment of antigen binding). The carboxy-terminus of
the heavy chains constitutes the Fc fragment. The hinge region is
the area at the center of the "Y," near the carboxy- terminus of the
light chains.

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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.

Cytokines are the chemical messengers that regulate the immune


system, orchestrating both innate immunity and the adaptive
response to infection. They are small proteins produced by several
different types of cells that influence the hematopoietic and
immune systems through activation of cell- bound receptors.

Complement factors C3a and C5a are anaphylatoxins that are


known to initiate inflammation. C4a’s function is still unknown
apart from being an anaphylatoxin.

Class I MHC molecules are found on all nucleated cells; these


molecules associate with foreign antigens, such as viral proteins,
synthesized within a host cell. This is known as the endogenous
pathway for antigen presentation. Class I MHC molecules consist
of an α chain encoded by the MHC complex, as well as a second Prozone and Postzone would result in a false-negative reaction to
lighter chain called β2–microglobulin, encoded by a gene on agglutination and precipitation reactions.
chromosome 15. Class I molecules present antigen to CD8+ T
cells, triggering a cytotoxic reaction. External defenses are structural barriers such as skin, mucous
membranes, cilia, and secretions such as lactic acid and lysozyme
that keep microorganisms from entering the body. Internal
defenses include both cells capable of phagocytosis and acute-
phase reactants that enhance the process of phagocytosis. Cells that
are most active in phagocytosis include neutrophils, monocytes,
macrophages, and dendritic cells.

Turbidimetry is a measure of the turbidity or cloudiness of a


solution. A detection device is placed in direct line with an incident
light, collecting the light after it has passed through the solution.
This device measures the reduction in light intensity caused by
reflection, absorption, or scatter. Scattering occurs when a beam of
light passes through a solution and encounters molecules in its
path. Light then bounces off the molecules and travels in all
directions. The amount of scatter is proportional to the size, shape,
and concentration of molecules present in solution. It is recorded in
absorbance units, a measure of the ratio of incident light to that of
transmitted light. The measurements are made using a
spectrophotometer or an automated clinical chemistry analyzer.

Nephelometry measures the light that is scattered at a particular


angle from the incident beam as it passes through a suspension.
The amount of light scattered is an index of the solution’s
concentration.
The relationship between antigen concentration, as indicated by
antigen–antibody complex formation, and the amount of light

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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.

Affinity is the initial force of attraction that exists between a single


Assays that measure lysis, the end point of complement activation,
Fab site on an antibody molecule and a single epitope or
are functional tests that are frequently run in conjunction with
determinant site on the corresponding antigen. The strength of
testing of individual components. The hemolytic titration (CH50)
attraction depends on the specificity of antibody for a particular
assay is most commonly used for this purpose.
antigen. One antibody molecule may initially attract numerous
different antigens, but it is the epitope’s shape and the way it fits
CH50 assay measures the amount of patient serum required to lyse
together with the binding sites on an antibody molecule that
50% of a standardized concentration of antibody-sensitized sheep
determines whether the bonding will be stable. When the affinity is
erythrocytes. Because all proteins from C1 to C9 are necessary for
higher, the assay reaction is more sensitive because more antigen–
this to occur, absence of any one component will result in an
antibody complexes will be formed and visualized more easily.
abnormal CH50, essentially reducing this number to zero. New
Cross-reactivity happens when the antibodies react to the antigen
microbead assays allow for the simultaneous detection of multiple
which resembles the original antigen. The more the cross-reacting
cytokines in a single tube. Each bead type has its own fluorescent
antigen resembles the original anti- gen, the stronger the bond will
wavelength, which, when combined with the fluorescent secondary
be between the antigen and the binding site.
antibody bound to a specific cytokine, allows for the detection of
Affinity is determined by the three-dimensional fit and
up to 100 different analytes in one tube. The use of a multiplexed
molecular attractions between one antigenic determinant and one
bead array enables simultaneous measurement of a multitude of
antibody-binding site.
biomarkers; these include acute-phase reactants such as CRP;
proinflammatory cytokines; Thl/Th2 distinguishing cytokines such
Avidity represents the overall strength of antigen–antibody binding
as IFN-gamma, IL-2, IL-4, IL-5, and IL-10; other nonspecific
and is the sum of the affinities of all the individual antibody–
acting cytokines; and CSFs.
antigen combining sites. Avidity refers to the strength with which a
multivalent antibody binds a multivalent antigen and is a measure
Opsonization is the coating of foreign particles with serum
of the overall stability of an antigen–antibody complex. A high
proteins.
avidity can actually compensate for a low affinity.
Cytokines released from lymphocytes were called lymphokines,
ASO tests detect antibodies to the streptolysin O enzyme produced
cytokines released from monocytes and macrophages were called
by Group A streptococcus. A single ASO titer is considered to be
monokines, and cytokines secreted by leukocytes that mainly act
moderately elevated if the titer is at least 240 Todd units in an adult
on other leukocytes were called interleukins.
and 320 Todd units in a child. The streptozyme test is a slide
Chemokines are a large family of cytokines that have the ability to
agglutination screening test for the detection of antibodies against
recruit specific cells to a particular site.
streptococcal antigens. The streptozyme test measures antibodies
against five extracellular streptococcal antigens: anti-streptolysin
The given clinical scenario is indicative of Type IV
(ASO), anti-hyaluronidase (AHase), anti-streptokinase (ASKase),
hypersensitivity, which is also known as delayed-type
anti-nicotinamide-adenine dinucleotide (anti-NAD), and anti-

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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.

The major component of mast cell granules is Histamine.


Histamine is a key inflammatory mediator released by mast cells in
response to various stimuli, such as allergens or injury, and it plays
a central role in allergic reactions and immune responses.

Mast cells and basophils have surface receptors (FcεRI) that


specifically bind to the Fc (constant) region of IgE antibodies. This
binding to IgE antibodies sensitizes the mast cells and basophils,
leading to their activation when the IgE antibodies encounter their
specific antigens. This interaction plays a crucial role in allergic
responses and hypersensitivity reactions.

Based on the signs and symptoms described for Patient X, the


possible diagnosis could be Chronic Hepatitis.
The presence of jaundice, hepatomegaly, palpable spleen, and a
history of potential exposure to contaminated water (swimming in
the lagoon during flood rescue operations) are suggestive of a
liver-related condition. Chronic Hepatitis, often caused by
Hepatitis B or Hepatitis C viruses, can manifest with these
symptoms and can lead to hepatomegaly, splenomegaly, and
jaundice. Additionally, the history of Hepatitis B immunization at
15 years of age suggests the possibility of a prior Hepatitis B
infection that might have developed into a chronic form. AST,
Anti-HAV IgM, Anti-HEV Antibody and ALT can confirm the
diagnosis.

Clinical manifestations in a patient with secondary syphilis include


Condylomata lata.
Condylomata lata are raised, wart-like lesions that can occur in
secondary syphilis. On the other hand, Condyloma acuminatum
is not typically associated with syphilis; it is more commonly seen
in genital warts caused by certain strains of the human
papillomavirus (HPV).

The strain used in the FTA-ABS (Fluorescent Treponemal


Antibody Absorption) test as a sorbent is Reiter strain. This strain
is a specific strain of Treponema pallidum, the bacterium
responsible for syphilis, used in the FTA-ABS test to absorb non-
specific antibodies and enhance the test's specificity for detecting
antibodies associated with syphilis. Nichols strain is the
pathogenic strain.

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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.

The tick-over pathway is one of the ways in which the


complement system is constantly active and can rapidly respond to
infections and pathogens. It involves the spontaneous activation
and inactivation of C3, providing continuous immune surveillance.
The other options mentioned do not specifically describe this
process.

The properdin pathway is a specific part of the complement


system that plays a role in amplifying the activation of complement
proteins, especially in the alternative pathway. It stabilizes and
extends the activity of complement C3 convertase enzymes. While
it is important for the complement system's function, it doesn't
directly describe the continuous production and inactivation of C3.
Protease activity pathway: This term is quite general and does
not specifically describe the process of constant production and
spontaneous inactivation of C3. Protease activity is a characteristic
of complement proteins involved in their activation and function.

CD59 (also known as protectin) is the specific molecule that


prevents the attachment of the C5b-7 complex to the cell
membrane by inhibiting the formation of the membrane attack
complex (MAC). CD59's primary function is to protect host cells
from being damaged by the complement system. S protein
(vitronectin)plays a role in the regulation of the complement
system. It acts as a cofactor for factor I in the degradation of C3b
and C4b, contributing to the inhibition of complement activation.
While it helps regulate complement, its primary function is not to

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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.

The CD8 is not a natural process of our body for


immunosuppression. CD8 (cluster of differentiation 8) T cells, also
known as cytotoxic T cells, play a role in the immune response by
directly attacking and destroying infected or abnormal cells. They
are primarily involved in cell-mediated immunity and are not
associated with immunosuppression. T regulatory cells, also
known as suppressor T cells, are a subset of T cells that help
regulate and suppress excessive immune responses to prevent
autoimmunity and maintain immune homeostasis. MHC
restriction is a key component of T cell recognition and activation.
It helps ensure that T cells recognize foreign antigens while not
attacking self-antigens. It does not, in itself, induce
immunosuppression. Neuroendocrine factors can influence
immune responses, including immunosuppressive effects. For
example, stress-related hormones can suppress immune function.

The correct sequence for the complement cascade according to


activation is C142356789. This sequence represents the classical
pathway of the complement system, which is initiated by the
binding of C1 to antigen-antibody complexes or other activating
substances. The numbers correspond to the various complement
components activated in sequence.

The region of the Fc (Fragment crystallizable) portion of an


antibody that specifically binds with complement is CH2. The
CH2 domain of the Fc region contains the binding site for
complement proteins, allowing antibodies to activate the
complement system when bound to antigen-antibody complexes.

The Mancini method (Endpoint method), also known as radial


immunodiffusion, is a quantitative technique used to measure the
concentration of a specific antigen in a sample. In this method, an
antibody against the target antigen is incorporated into a gel
medium. The antigen from the sample diffuses into the gel and
forms a circular or radial precipitin ring. The diameter of this ring
is directly proportional to the concentration of the antigen in the
sample. The Mancini method is widely used for the quantitative
determination of various antigens, including serum proteins,

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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.

Sensitization refers to the initial step in immunological reactions


when an antigen and antibody first come into contact. During this
phase, antibodies (such as IgG or IgM) recognize and bind to
antigens, forming antigen-antibody complexes. This binding is the
first step in initiating immune responses, including complement
activation and phagocytosis. The Zone of Equivalence is a state
that occurs when there is an optimal ratio of antigen and antibody.
In this zone, all available antibodies are fully occupied by antigens, The structure formed by the fusion of engulfed material and
leading to the formation of large antigen-antibody complexes. enzymatic granules within phagocytic cells is called a
These complexes are neither in excess nor in deficiency, and this phagolysosome. In a phagolysosome, the ingested material is
state allows for the optimal interaction and cross-linking of exposed to lysosomal enzymes, which break it down and facilitate
antibodies and antigens. Lattice formation refers to the formation its digestion. This process is essential for the destruction of
of large, cross-linked complexes of antigen-antibody interactions. pathogens and cellular debris by phagocytic immune cells like
In some cases, when antigen and antibody are present in excess, macrophages and neutrophils.
they can form lattices or networks of interconnected complexes.
This can occur, for example, in the precipitation reactions observed Selective IgA deficiency is considered one of the most common
in immunodiffusion tests like the Ouchterlony double diffusion, primary immunodeficiency disorders. It is characterized by a
where the lattice formation results in visible lines or precipitates. decrease in or absence of IgA, an immunoglobulin class that plays
a crucial role in mucosal immunity. Individuals with selective IgA
A positive HLA-B27 test indicates an increased risk for developing deficiency may be prone to recurrent bacterial infections,
ankylosing spondylitis (AS), but it does not necessarily mean that especially in mucosal areas like the respiratory and gastrointestinal
the individual has the condition. HLA-B27 is a genetic marker that tracts. Bladder cancer (Bladder CA tumor) and rheumatoid factor
is associated with an increased susceptibility to AS and several are not typically related to primary immunodeficiency disorders.
other autoimmune diseases, but it is not a definitive diagnostic test Recurrent bacterial infections are a common feature of primary
for AS. Many people who are HLA-B27 positive do not develop immunodeficiency disorders, including selective IgA deficiency.
AS, and the presence of other clinical symptoms and diagnostic
criteria is typically required to confirm the diagnosis. Zeta potential is affected by multiple factors:
1. The sialic charge on the red cell surface: The sialic acid
Dendritic cells are immune cells that originate from myeloid residues on the surface of red blood cells can contribute to the zeta
progenitor cells in the bone marrow. They are part of the innate potential. These negatively charged sialic acid groups influence the
immune system and play a crucial role in antigen presentation and electrostatic repulsion between red blood cells, affecting their zeta
the initiation of adaptive immune responses. Dendritic cells are potential.
known for their ability to capture, process, and present antigens to 2. The effect of a macromolecular media such as albumin: The
T cells, which is essential for the immune system's recognition and presence of macromolecules in the surrounding medium, such as
response to pathogens and foreign substances. Lymphoid albumin, can influence the zeta potential of particles, including red
progenitor cells, on the other hand, give rise to lymphocytes, blood cells. Albumin may affect the surface charge and the
including T cells, B cells, and natural killer (NK) cells. Dendritic

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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.

BRAF gene - metastatic melanoma


KRAS gene - colorectal cancer
EGFR gene - non-small cell lung cancer; NSCLC
ALK gene - NSCLC
HER2 gene - breast cancer
ESR1 and PGR genes - breast cancer

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