LN 06 (Immunopathology) Flashcards
abnormal, aberrant, excessive or otherwise inappropriate immunologic response that leads to pathological changes to tissues
immunopathologic reactions
study of diseases caused by or resulting from immune mechanisms, and is
concerned primarily with untoward consequences of immune reactions
immunopathology
consists of effector cells and substances that provide
protection to an individual following antigenic challenge
immune system
mediated largely by antibodies and
other effector substances such as complement
humoral response
mediated by sensitized lymphocytes and cells of the reticulo-endothelial system
cellular response
macromolecules that are either
natural or synthetic in origin that are capable of inducing immune response
antigens (immunogens)
bind to preformed antibodies or sensitized immune cells and can
induce an immune response when coupled to a carrier protein
haptens
process the antigen and present the
same to B lymphocytes
antigen presenting cells (macrophages, dendritic cells)
B-lymphocytes or B-cells are produced in
bone marrow
b cells undergo a series of transformation into an antibody secreting plasma cell through
the aid of inducer
T-lymphocytes
they synthesize the antibodies
plasma cells
antibody molecules found greatest in plasma
IgG, IgM
antibody molecules mostly found on mucosal surfaces
and body secretions
IgA, IgD
antibody molecules surface bound to specific cells such as basophils and mast cells
IgE
contain the antigen binding sites
Fab
contains receptors for complement and effector cells of antibody molecule
Fc
provide some sort of scaffold where
effector cells and substances of the immune system in particular complement can come in close contact with the antigen for the expression of their biological functions
Fc fragment
major humoral component of innate immunity and a mediator of inflammation
complement
largely produce the antibodies
B cells
mediate cellular reactivity
T cells
two functional classes of T
cells
- helper or inducer T cells
- cytotoxic or suppressor T cells
Interleukin 2 is called as
T cell growth factor
Activated T cells secrete _____ that stimulates the production of IL-2 receptors and the proliferation of T cells
IL-2 or T cell growth factor
secrete IL-4, IL-5, and IL-6
helper T cells
these are B cell growth factors that promote proliferation and maturation of B cells
IL-4, IL-5, and IL-6
surface glycoproteins that functions as adhesion molecules and as co-receptors for
antigen
CD4 and CD8
CD4 positive T cells
helper cells
CD8 positive cells
cytotoxic or suppressor cells
glycoproteins present on all nucleated cells and
platelets
Class I antigens
exist as bimolecular protein complexes restrictedly found in antigen presenting cells, B cells, and some activated T cells
Class II antigens
These proteins do not
function as histocompatibility antigens
Class III antigens
protein components of the complement system
(C2, C4 and Bf) that are coded for within the MHC
Class III antigens
regulates the cell-to cell
interaction in the immune
responses
MHC
facilitate interactions
between lymphocytes and
macrophages in the process of immune recognition
Class II antigens
able to recognize antigens only in the form of antigenic peptide complexed with Class II antigens on the surface of antigen presenting cells
T helper cells or CD4+
recognize antigens presented on the surface as antigenic peptide complexed with Class I MHC molecules
Cytotoxic cells
Complement consists of plasma proteins synthesized by (3)
- hepatocytes
- macrophages
- gut epithelial cells
classical pathway is initiated by the binding of antigen-antibody complexes to C1 that self-activates and cleaves C4 and C2 into
C3 convertase
a C3 fragment released and increases vascular permeability
C3a
forms a complex called C5 convertase that splits C5 into C5a and C5b
C3b
increases vascular permeability and attracts
polymorphonuclear and mononuclear leucocytes
C5a
initiates the terminal
sequence C5b-C9 forming the membrane attack complex (MAC)
C5b
affect irreversible lesions on cell membranes leading to cytolysis
Membrane attack complex
initiated by a variety of substances without the formation of antigen- antibody complexes
Alternate pathway
Alternate pathway involves (3)
- C3
- factor B
- other proteins
mediates and regulates the growth, differentiation, and function of cells involved in immunity, hemopoiesis,
and inflammation
cytokines
cytokines secreted by lymphocytes
lymphokines
cytokines secreted by macrophages and monocytes
monokines
a cytokine that carries messages between lymphocytes
interleukin
chemotactic cytokines produced by macrophages, monocytes and T cells that attract
leucocytes to the site of inflammation or infection
Chemokines
symptoms occur after the release of pharmacologically active compounds from mast cells and basophils
Type I hypersensitivity
precipitated when the antigen is transmitted parenterally or in food, and are associated with signs and symptoms
of anaphylaxis
systemic reaction
best exemplified by a positive skin-test
reaction (wheals and flares), and allergic rhinitis following inhalation of dust or
pollen particles
local reactions
Anaphylaxis in dogs shows concentrated mas cells in hepatic veins, resulting to: (2)
- portal hypertension
- visceral pooling of blood
Necropsy of dog with anaphylaxis would reveal massive congestion of the (2)
- liver
- intestines
In cats, anaphylaxis takes the form of
- broncho-constriction
- pulmonary edema
necropsy of anaphylaxis in cats reveal (3)
- pulmonary emphysema
- hemorrhages
- edema
One of the signs of anaphylaxis in cats in scratching of the face. Caused by?
histamine
occur in ruminants following anaphylaxis
- Systemic hypotension
- Pulmonary hypertension
anaphylaxis is manifested as systemic and pulmonary hypertension
horse and swine
Necropsy of anaphylaxis in horse and swine reveals (3)
- pulmonary emphysema
- peri-bronchiolar edema
- edematous hemorrhagic enterocolitis
type of hypersensitivity produced by the combination of antibody with antigen resulting in the formation of immune
complexes
Type III - Immune complex reactions
Diseases that may result to the expression of Type III reactions in the form of
membranous glomerulopathy
- Equine infectious anemia
- Swine fever
- Pyometra
- Bacterial endocarditis
- Canine distemper
- Lymphoma
- Mastocytoma
- Dirofilariasis
syndrome in dogs following infection or vaccination with live canine adenovirus (CAV-1)
blue eye
do not become clinically detectable until 24 to 72 hours post exposure to an antigen
Type IV - Delayed Hypersensitivity
involves the accumulation of sensitized T cells at the site of antigen deposition
inductive phase
caused by the elaboration of lymphokines by these cells
amplification phase
prominent component of Type IV, and is an important process in host defense against viral and fungal infections, and in
spontaneous tumor rejection
Cytotoxicity
Type IV is involved clinically in condition such as (4)
- allergic contact dermatitis
- tuberculin hypersensitivity
- organ and tissue transplant rejection
- graft-vs-host disease
More common example of Type IV reaction in dogs and cats
- Flea allergy
- Allergic contact dermatitis
Untoward immune response towards administration of drugs
Adverse drug reactions
one of the most fascinating features of the immune system
be able to distinguish “self” from “non self”
Studies of the immune reactions towards organ transplantation showed this capability is under fine control in specific locus of the genes called
major histocompatability complex
In humans, MHC is located in
Chromosomes 6
In humans, MHC is located at chromosome 6 and is called the
human lymphocyte antigen complex (HLA complex)
This chromosome region codes for surface proteins in body cells called
histocompatibility antigens or
transplantation antigens
MHC gene products are classified into three categories
Class I antigens
Class II antigens
Class III antigens
significantly
influences immune reactivity
MHC
antibody molecule consists of two identical heavy chains of amino
acids and two identical light chains chemically linked by
disulfide bonds in Y-configuration
contain the antigen binding sites
Fab
When antigen enters body, APC process it into antigenic fragments that expresses
epitopes or its antigenic determinants
presented at the surface of the APC to receptors for antigen on helper T cells
Class II antigen
B cells receptor for antigens is composed of surface membrane bound
monomeric IgM programmed during B cell maturation in the gut associated
lymphoid tissues in mammals
gene rearrangements of small coding segments to produce a large amount of diverse receptor for antigen binding
bursa of Fabricius in avian species
It is the main effector pathway of the immune response and has a receptor unit able to recognize antibody molecules
complement
paramount function of the immune system
recognize foreign antigens and protect the individual
re-exposure to the same antigen could bring about untoward, excessive or aberrant immune responses that result to
tissue injury
hypersensitivity reaction
What happens after antibody attaches to the Fab portion
Fc portion of the antibody is then free to interact with cytotoxic cells having an Fc receptor
condition wherein fetal red blood cells gain entry to the maternal circulation
isoimmune hemolytic anemia (in foals)
Clinical examples of Antibody-dependent cytotoxicity
- trypanosomiasis
- babesiosis
- drug-induced
hemolytic anemia - drug-induced thrombocytopenia
Adverse Drug Reactions criteria
- The onset of hypersensitivity state does not occur until sometime after initial exposure to a drug;
- After the reaction has been established, the same may be elicited by minute amount of the drug in question;
- The same reaction recur upon repeated exposure to the same drug;
- The reaction does not resemble the known pharmacological action of the drug; and
- The symptoms are suggestive of known forms of hypersensitivity reaction.
Factors that predispose the development of ADR
- Host factor
- Drug factor
- Route of Administration
- Dose and duration of exposure
tendency of a drug to induce immune response that results in a hypersensitivity reaction
drug factor
has the greatest capacity to induce ADR
topical application of drugs
defined as a failure of the individual to recognize its
own tissues thus resulting to immune recognition and consequent immune
reactions
autoimmunity
Autoimmunity arises when?
there is disordered regulation and interaction of the T cells and the B cells in response to an antigenic challenge or stimulation
T cell and B cell interactions may be altered as a consequence of
- genetic
- viral
- environment
To prevent autoimmunity, there must be a central balance with
activity of suppressor T cell clones and inducer T cell clones
autoimmune disease characterized by chronic
inflammatory changes in a specific organ
Organ- specific autoimmune disease
Clinical examples of organ- specific autoimmune disease
- Primary hypothyroidism
- Post vaccinal encephalitis in rabies
these are characterized by
widespread pathologic changes in different organs wherein associated autoantibodies often lack organ specificity
non-organ-specific autoimmune disorder
classic example of non organ specific autoimmune disorder
Systemic lupus erythematosus
primary mechanism of injury is by immune complex deposition in the vasculature of various organs and tissues
non-organ-specific autoimmune disorder
combines the features of specific and non specific AID, and the levels of serum autoantibodies does not correlate with the severity or duration of the disease
Disorders with non-organ-specific autoantibodies and with lesions
confined to one or few organs
Disorders with non-organ-specific autoantibodies and with lesions
confined to one or few organs mechanism
cytotoxicity T cell activity
mechanism is thought to involve T cell bypass, and that a deficiency of T cells
may be a key factor in the initiation of the whole process
Organ- specific autoimmune disease
Disorders with non-organ-specific autoantibodies and with lesions
confined to one or few organs clinical example
Primary biliary cirrhosis of the liver
Autoimmune diseases are frequently associated with (3)
- malignancies
- ageing
- immunodeficiency syndromes
Autoimmune pathogenesis
- Existence of autoantibodies
- Amyloidosis in tissues
- Hypergammaglobulinemia with elevation of the various immunoglobulin subclasses
- Vasculitis, serositis and glomerulonephritis that suggest an immune
complex disease - Existence of other disorders such as endocrine disease known to be associated with autoimmune disorders.
results from a failure of proper development of humoral or cellular components of the immune system
Primary Immunodeficiency syndromes
Immunodeficiency associated with a variety of diseases including irradiation
Secondary or acquired
basic mechanisms that cause immunodeficiency
- Deficiency of hormone and co-factors required for lymphocyte differentiation,
programming, maturation and activity - Deficiency of lymphocyte production and/or functions
- Deficiency of phagocytic cell production and/or functions
- Deficiency of complement, particularly C3
- Failure of passive immunity in neonates.
Examples of infectious diseases that damage lymphoid tissues
- canine parvoviral infection
- feline panleukopenia
Intestinal uptake of maternal immunoglobulin terminates within 24-48 hours in what animals
- pig
- horse
- cattle
- dog
sensitivity of intestinal mucosal cells for colostral uptake could last up to four (4) days
Sheep and goats
most important predisposing factor to perinatal infection and
death
failure of passive transfer of maternal immunoglobulin
depend solely on colostral transfer of maternal immunoglobulin, for these species
- piglets
- foals
- calves
- kids
- lambs
these species placental cyto-architecture do not prevent the transplacental transfer of maternal immunoglobulin
kittens and pups
Depletion of cells, in particular, _______, and _______ result to a functional deficiency in the capability of the animal body to mount an immune response
lymphocytes, and/or complement
IL-1
growth of activated T and B cells
IL-2
growth of activated T, B, and NK cells
IL-3
Growth and differentiation of hemopoietic precursors
IL-4
growth of activated T and B cells
IL-5
growth of activated B cells
IL-6
growth and maturation of T and B cells
IL-10
activates macrophages and increases their expression of MHC Class I and Class II
IFN-gamma
helps activate cytolytic T cells
activates phagocytic cells, mediates local and systemic effects, including acute phase reactions of inflammation
TNF
Drug induced hemolytic anemia
- penicillin
- quinine
- amino-salicylic acid or aspirin
- phenacetin
drug-induced thrombocytopenia
- sulfonamide
- phenylbutazone,
- phenothiazine
- chloramphenicol
