IMMUNOPATHOLOGY 6 Flashcards
(116 cards)
1
Q
primarily serves to defend the animal body against infections.
A
immune system
2
Q
These untoward responses of the immune system that result
to tissue injuries are called
A
immunopathologic reactions
2
Q
is the study of diseases caused by or resulting from immune mechanisms, and is
concerned primarily with untoward consequences of immune reactions.
A
immunopathology
2
Q
The immune system consists of
A
effector cells and
substances that provide
protection to an individual
2
Q
There are two responses
of the immune system:
A
humoral response
cellular response
2
Q
e mediated largely by antibodies and other effector substances such as complement,
A
humoral response
3
Q
mediated by sensitized lymphocytes and cells of the reticulo-endothelial system.
A
cellular response
4
Q
(also known as immunogens)
A
Antigens
5
Q
are macromolecules that are either natural or synthetic in origin that are capable of inducing immune response.
-are usually microbial or foreign proteins or polysaccharide
A
Antigens
6
Q
are simple molecules that bind to preformed antibodies or sensitized immune cells and can
induce an immune response when coupled to a carrier protein.
A
Haptens
7
Q
usually, macrophages and dendritic cells process the antigen and present the
same to B lymphocytes
A
antigen presenting cells (APC)
8
Q
The sensitized B-cells undergo a series of transformation into an antibody secreting plasma cell through the aid of inducer T-lymphocytes
(another lymphocyte clone subpopulation)
A
8
Q
The plasma cells synthesize the antibody, a plasma protein belonging to the gamma globulin fraction of serum
A
8
Q
next two are found on mucosal surfaces and body secretions
A
IgA and IgD
8
Q
The first two have their greatest
concentration in the plasma,
A
IgG and IgM
9
Q
specific clones of white
blood cell lymphocytes
produced in the bone marrow.
A
B-lymphocytes or B-cells
9
Q
surface bound to specific cells such asbasophils and mast cells.
A
IgE
9
Q
An antibody molecule consists of :
A
two identical heavy chains of amino acids and
two identical light chains chemically linked by disulfide bonds in Y configuration
9
Q
The antigen-binding site at the Fab fragments bind specifically and selectively to the
determinants of the antigen molecule that initiated the production of the antibody.
A
9
Q
Is a major humoral component of innate immunity and a
mediator of inflammation normally present in the plasma in inactive form that are
activated to mediate or amplify the reaction.
A
Complement
10
Q
Enzyme studies showed that there are two fragments:
A
fab and fc
10
Q
contain the antigen binding sites
A
Fab
11
Q
that contains receptors for complement and effector cells
A
Fc
12
Q
is mediated largely by sensitized lymphocytes.
A
cellular response
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Two types of lymphocytes are recognized:
b cells
t cells
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that mediate cellular
reactivity.
t cells
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There are two functional classes of T
cells:
helper/inducer T cells and
the cytotoxic/suppressor T-cells
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largely produce the antibodies
B-lymphocytes
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The helper T cells also secrete IL -4, IL-5, and IL-6 (B cell growth factors) that promote the proliferation and maturation
of B cells.
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Activated T cells secrete interleukin-2
(IL-2 or T cell growth factor) that stimulates the production of IL-2
receptors and the proliferation of T cells.
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Helper cells are CD4 positive T cells,
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cytotoxic/suppressor T cells are CD8 positive cells.
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are surface glycoproteins that functions as adhesion molecules and as co-receptors for
antigen
CD4 and CD8
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Studies of the immune reactions towards organ transplantation showed this capability is under fine control in specific locus of the genes called
major histocompatibility
complex
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In humans, this locus is located at chromosome 6 and is called the
human lymphocyte antigen complex (HLA complex)
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This chromosome region
codes for surface proteins in body cells called
histocompatibility antigens or transplantation antigens.
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MHC gene products are classified into three categories:
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are glycoproteins present on all nucleated cells and
platelets.
class I antigens
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exist as bimolecular protein complexes restrictedly
found in antigen presenting cells (monocytes, macrophages, dendritic
cells), B cells, and some activated T cells.
class 2
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are protein components of the complement system
(C2, C4 and Bf) that are coded for within the MHC. These proteins do not
function as histocompatibility antigens.
class 3
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significantly influences immune reactivity.
It regulates the cell-to cell
interaction in the immune
responses (Figure 6.4-MHC
restriction on antigen
recognition)
MHC
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Class II antigens
facilitate interactions among
lymphocytes and
between lymphocytes and
macrophages in the process of immune recognition.
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T helper cells (CD4+) are able to recognize antigens only in the form of antigenic peptide complexed with Class II antigens on the surface of antigen presenting cells.
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Cytotoxic T cells recognize antigens presented on the surface as antigenic peptide complexed with Class I MHC
molecules.
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consists of plasma proteins belonging to the beta-globulin
fraction of the plasma and is normally synthesized by hepatocytes, macrophages,
and gut epithelial cells.
Complement
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The complement components are labeled C1, C2, C3, C4, C5, C6, C7, C8
and C9.
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It is activated via two pathways:
Classical Pathway
Alternate Pathway.
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is initiated by the binding of antigen antibody complexes to C1 that self-activates and cleaves C4 and C2 into C3
convertase.
classical pathway
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C3 splits into two fragments
C3a and C3b.
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a is released and
increases vascular permeability
C3a
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forms a complex called C5 convertase that splits C5 into C5a and C5b.
C3b
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increases vascular permeability and attracts
polymorphonuclear and mononuclear leucocytes.
C5a
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initiates the terminal
sequence C5b-C9 forming the membrane attack complex (MAC) that effect
irreversible lesions on cell membranes leading to cytolysis.
C5b
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is initiated by a variety of substances (including
bacterial polysaccharides, zymosan, and IgA) without the formation of antigen antibody complexes, or the participation of C1, C2, and C4.
alternate pathway
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is a generic term for polypeptide messenger molecules secreted by lymphoid and non-lymphoid cells that mediates and regulates the growth, differentiation, and function of cells involved in immunity, hemopoiesis,
and inflammation.
Cytokines
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immune system is to recognize foreign antigens and protect the individual.
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cytokines secreted by macrophages and monocytes
Monokines
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are cytokines secreted by lymphocytes
Lymphokines
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cytokine that carries messages between lymphocytes.
Interleukin
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are chemotactic
cytokines produced by macrophages, monocytes and T cells that attract leucocytes to the site of inflammation or infection.
Chemokines
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These responses that result in tissue injury are called
hypersensitivity reactions
(allergic or immunopathologic reactions)
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Four types of reactions
Immediate hypersensitivity
cytotoxic reaction
immune complex reaction
delayed hypersensitivity
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also known as anaphylaxis
Type I hypersensitivity reactions (
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The mode of antigen contact determines whether a given reaction is either
local or systemic
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are best exemplified by a positive skin-test
reaction (wheals and flares), and allergic rhinitis following inhalation of dust or
pollen particles.
Local reactions
44
Circulating basophils
and tissue mast cells
possesses receptors
capable of binding the
Fc portion of the IgE
molecule
type 1
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occur after the release of pharmacologically active compounds from mast cells
and basophils.
type 1
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precipitated when the antigen is
transmitted parenterally or in food, and are associated with signs and symptoms of anaphylaxis
Systemic reactions
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DOG
the mast cells are concentrated around hepatic veins such
such that portal hypertension and
visceral pooling of blood occur.
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Other signs in the dog include
vomiting, defecation, urination, depressed respiration, and coma.
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Necropsy of affected
animal would reveal
massive congestion of the liver and intestines.
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Other signs in the cat include
dyspnea, scratching of the face due to histamine release, excessive salivation, vomiting, incoordination and collapse.
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In cats, anaphylaxis takes the form of
broncho-constriction and pulmonary
edema.
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Necropsy would reveal
pulmonary emphysema, hemorrhages and edema.
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occur in ruminants following anaphylaxis.
Systemic hypotension and pulmonary hypertension
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Presenting signs include
dyspnea, urination, defecation,
and bloating.
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in foals ,A clinical example of this type of reaction is that of
isoimmune hemolytic anemia
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In the horse and swine, anaphylaxis is manifested as systemic and
pulmonary hypertension.
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Necropsy would reveal
pulmonary emphysema, peri
bronchiolar edema, and edematous hemorrhagic enterocolitis.
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antibody attaches to the target antigen through its
Fab antigen combining sites
antibody-dependent
Cytotoxicity
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Complement dependent
reactions usually involve the
combination of IgG and IgM
with antigenic determinants
present on cell membranes.
Type II – Cytotoxic/Cytolytic Reactions
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s. In this condition, fetal red blood cells gain entry to the maternal circulation
sensitizing the mare’s immune system.
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This type of
hypersensitivity reactions
is produced by the
combination of antibody
with antigen resulting in
the formation of immune
complexes.
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In animals, chronic diseases such as
equine infectious anemia, swine fever, pyometra, bacterial endocarditis, canine distemper, lymphoma, mastocytoma,
and dirofilariasis
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syndrome in dogs following
infection or vaccination with live canine adenovirus (CAV-1) is another example of immune complex reactions
“blue eye”
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Type IV reactions usually do not become clinically detectable until 24 to 72 hours post exposure to an antigen.
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There are two phases in the evolution of Type IV
reactions:
inductive phase
amplification phase
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that involves the accumulation of sensitized T cells at the site of antigen deposition
inductive phase
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caused by the elaboration of lymphokines by these cells.
amplification phase
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is a prominent component of this
reaction, and is an important
process in host defense
against viral and fungal
infections, and in spontaneous tumor rejection.
Cytotoxicity
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involved in clinically diverse
conditions such as allergic
contact dermatitis, tuberculin
hypersensitivity, organ and
tissue transplant rejection, and
graft-vs-host disease.
Type IV
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A more common example of this type of reaction includes
flea allergy and allergic contact dermatitis in dogs and cats
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Untoward immune response towards administration of drugs is called
adverse drug reactions (ADR)
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There are several predisposing factors for the development of ADR, and these include
host factor, drug factor, route of administration, and dose and
duration of exposure.
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the genetic composition may determine the difference in drug metabolism that may be related to hypersensitivity to certain metabolites of the drug,
host factors
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the tendency of a drug to induce immune response that
results in a hypersensitivity reaction depends on the capacity of the drug or its metabolites to act as or form a complete antigen or hapten.
drug factors
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its dose and duration of therapy may influence ADR
route of application of the drug
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s has the greatest capacity to induce ADR followed by
intravenous, intramuscular and oral route.
Topical application of drugs
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is defined as a failure of the individual to recognize its
own tissues thus resulting to immune recognition and consequent immune
reactions.
Autoimmunity
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Most self-antigens (or autoantigens) circulate in very low doses
65
Autoimmunity arises when there is a disordered regulation and interaction
of the T cells and the B cells in response to an antigenic challenge or stimulation.
65
It was formerly believed that
many autoantigens are
secluded from immunocompetent cells of the body, and include those tissues regarded as immunologically privileged sites hidden from immune cells by blood vessels, lymphatic and membrane
barriers.
Sequestered Antigen
Release
65
can inhibit autoimmune response
and provide a
mechanism for
preventing or delaying
autoimmune reactions
in normal conditions
Suppressor T cell clones
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T cells are involved in the control and regulation of B cell functions by suppressing B cell dependent synthesis of autoantibodies.
65
However, in some
disease states
(following ageing,
immune deficiencies,
or other disease
processes), there
occurs a loss of
suppressor T cell
functions such that self-reactive B cells are
permitted to
proliferate.
66
Autoimmune diseases can be broadly categorized into three main groups:
1. Organ- specific autoimmune disease
2. non-organ-specific autoimmune disorder
3. Disorders with non-organ-specific autoantibodies and with lesions
confined to one or few organs
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are characterized by chronic
inflammatory changes in a specific organ.
Organ- specific autoimmune disease
66
The autoantibodies in this group exhibit specificity for antigens of the diseased organs, and examples include primary hypothyroidism, and post vaccinal encephalitis in rabies.
66
these are characterized by
widespread pathologic changes in different organs.
non-organ-specific autoimmune disorder
66
this group combines the features of the latter two groups, and the levels of serum autoantibodies does not correlate with the severity or duration of the disease.
3. Disorders with non-organ-specific autoantibodies and with lesions
confined to one or few organs
66
Possible autoimmune pathogenesis
must be suspected when one observes most of the following indicators:
1. Existence of autoantibodies
2. Amyloidosis in tissues
3. Hypergammaglobulinemia with elevation of the various immunoglobulin
subclasses
4. Vasculitis, serositis and glomerulonephritis that suggest an immune
complex disease
5. Existence of other disorders such as endocrine disease known to be
associated with autoimmune disorders
67
if it results
from a failure of proper development of humoral or cellular components of the
immune system,
Primary
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if it is associated with a variety of
diseases including irradiation, infectious diseases, and iatrogenic
immunosuppression by drugs resulting to depletion of functional lymphoid cells,
Secondary or acquired
69
The basic mechanisms currently recognized that
brings about an immunodeficiency state includes the following:
1. Deficiency of hormone and co-factors required for lymphocyte differentiation,
programming, maturation and activity;
2. Deficiency of lymphocyte production and/or functions
3. Deficiency of phagocytic cell production and/or functions
4. Deficiency of complement, particularly C3, and
5. Failure of passive immunity in neonates.
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colostrum after birth in the pig, horse, cattle
and dog.
24-48 hours
70
In sheep and goats
four (4) days
