1
Q
Study of diseases caused by immune mechanics
A
Immunopathology
2
Q
primarily involved in defending the body against infections
A
Immune system
2
Q
may also result to production of abnormal, aberrant, excessive or inappropriate
immunologic response resulting to tissue damage and are called immunopathologic
reactions
A
Immune system
3
Q
Immune system acts in what 2 ways
A
A. provide immunity- associated with beneficial effects
B. Production of hypersensitivity or excessive immune reaction or in some cases,
deficiency I immune function which are termed immuno- deficiency states
4
Q
Components of the Immune System
A
Humoral response
Cell mediated response
5
Q
Humoral response involves what
A
Antibodies
6
Q
Humoral Response
Mechanism
A
a.presence of an antigen (Ag)
b) Ag is a processed by Ag- presenter cells (macrophages & dendritic cells)
c) processed Ag is presented to B-lymphocytes
d) sensitized B-lymphocytes undergo transformation into lymphoblast (large cells)
and then into plasmablasts (Ab secreting plasma cells); transformation is also
aided by a helper T-cell
e) plasma cell from Ab
7
Q
Are plasma proteins (gamma globulins)
A
Antibodies
8
Q
plasma proteins (gamma globulins) are also called
A
Immunoglobulins (Ig)
9
Q
5 kinds of Ig
A
Ig G, Ig M, Ig A, Ig D, and Ig E
10
Q
Ig that are common in the plasma
A
Ig G, Ig M
11
Q
Ig that are common on mucosal surfaces and secretions
A
Ig A, and Ig D
12
Q
Ig E is usually bound to
A
Mast cells or basophils
13
Q
Structures of an Antibody Molecule
A
2 heavy chain of amino acids & 2 light chains bound by disulfide bonds in a
Y- shaped molecule
13
Q
2 Fragments of an Antibody Molecule and what do they contain
A
- Fab fragments (2) – contain Ag-binding sites which are highly specific and
selective - Fc fragments – contains receptors for complement (C) and effector cells
14
Q
Function of Antibodies
A
- Bind and inactivates Ag
- Provides attachment sites for effector cells and substances of immune system
so that they can come close to the antigen and acts against it - Complement activation
- Opsonization- antibodies binds with
- Antibody dependent cytotoxici
15
Q
Cell mediated response involves
A
sensitized T- lymphocytes
16
Q
Subclasses of T lympocytes
A
a) Suppressors T- cells
b) Helper T-cells
c) Cytotoxic cells
17
Q
Functions of suppressors T cells
A
-Capable of suppressing the functions of helper & cytotoxic T-cells there by
preventing them from producing excessive immune reactions
− Classified as regulatory cells
18
Q
What do the helper t cells produce that serves as major regulators of all immune functions
A
Lymphokines
18
Q
Most numerous t lympocytes
A
Helper t cells
19
Q
Act directly by killing microorganisms and sometimes even the body’s own cells
A
Cytotoxic T cells
20
Q
Cytotoxic T cells are also called what
A
killer cells
21
Q
Effector Substances
A
A. Complement
B. Lymphokines
21
Act by attaching to organisms or cells containing their binding- specific Ag and
secrete hole- forming proteins- perform or they may secrete cytotoxic substances
Cytotoxic T-cells
22
Which do not belong
A. Gut epithelial cells
B.hepatocytes
C.macrophages
D. Neutrophil
D.
23
components of complement and give their function
a. Receptors unit – able to recognize activate Ab molecule
b) Receptors site – enable it to bind to the surface of cells
c) Effector molecules – responsible for the biological action of the C
24
2 pathways protein (Complement) components are activated
Classical pathways
Alternative activation pathway
25
How can classical pathwaybe activated
Activated by the presence of Ag-Ab complex after contact with Fc portion of Ab bound Ag
26
How is Alternative activation pathway activated
Properdin- a serum protein
Protein factors labeled as factor B, D, H, I
Cell wall antigen of bacteria, fungi, helminth & tumor cells
Aggregated immunoglobulin
27
the C3-C5 fragments are activated and forms what
C5-C9 component
28
C5-C9 component leads to the formation of
Membrane Attack Complex (MAC)
29
The role of Membrane Attack Complex (MAC)
responsible for irreversible lesions on cell membrane for cytolysis
30
effects of the complement
a) Increase in vascular permeability (C3a, C5a)
b) Enhanced phagocytosis (C3b)
c) Chemotaxis (C3a, C5a, C567)
d) Platelet aggregation (C3b)
e.)Cytolysis (C56789 or MAC)
31
act on other cells of the immune system and on bone marrow cells
Lymphokines
31
Lymphokines is produced by
helper T-cells
32
Lymphokines
Examples
Mitogenic factor- stimulates non-immune T-cells to undergo transformation, mitotic proliferation
Macrophage aggregating factor- prevents the migration of macrophages & promote their aggregation at the reaction site
Chemotactic factor- attracts effector cells e.g. eosinophils, lymphocytes, macrophages to sites of reaction
Lymphotoxin- responsible for cytotoxic effect on target cell
Helper factor- promotes differentiation of sensitized B-cells into Ab producing cells
33
4 types of IMMUNOPATHOLOGIC REACTIONS
Type 1 or Immediate hypersensitivity
Type II or Cytotoxic/Cytolytic Reactions/ Antitissue Antibody Injury
Type III or Immune Complex Reactions
Type IV or Delayed Hypersensitivity
34
Immediate hypersensitivity is also termed
Allergy and anaphylaxis
35
What happens in immediate hypersensitivity
Due occurrence of reaction after exposure to the antigen, IgE with its complementary Ag will bind to circulating basophils and tissue mast cells since they have receptors that can bind with the Fe portion of the IgE molecule
Binding of IgE, Ag and basophil or mast cell is followed by biochemical events that result to degranulation (or exocytosis of granules) of basophil or mast cell.
Note: there has to be 2 or more IgE molecules with an Ag
36
binding of IgE, Ag and basophil or mast cell will result to what
degranulation of basophil or mast cell
37
granules contain vasoactive substances like
a. histamine
b. eosinophil chemotactic factor
c. kallikrein
d. prostaglandin D2
e. kinins
f. platelet aggregating factor
38
Example of localized reaction in Type 1
presence of skin lesions like wheals and flares
39
Example of systemic reaction in Type 1
allergic rhinitis after inhalation of pollen or dust particles
40
For the systemic reactions to occur antigen must be administered through
parenteral or via the food
41
symptoms of anaphylaxis in dog
mast cells are concentrated around hepatic vessels resulting to portal hypertension and visceral pooling; they also show the following signs: vomiting, defecation, urination, collapse and muscular weakness, depressed respiration and coma
42
necropsy findings in dog due to anaphylaxis
congestion of the liver and intestines
43
symptoms of anaphylaxis in cat
anaphylaxis is in the form of bronchoconstriction and pulmonary edema; other signs include dyspnea, scratching of the face due to histamine release, salivation,
44
symptoms of anaphylaxis in ruminants
result to systemic hypotension and pulmonary hypertension with dyspnea, urination, defecation, and bloating
45
symptoms of anaphylaxis in horse and swine-
systemic and pulmonary emphysema, peribronchiolar edema and edematous hemorrhagic enterocolitis.
46
Type II or Cytotoxic/Cytolytic Reactions/ Antitissue Antibody Injury
mechanisms:
a. Complement-dependent cytotoxicity
b. Antibody- dependent cellular cytotoxicity
47
Complement-dependent cytotoxicity involves the combination of these 2 antibodies
IgG and IgM
48
What happens in Complement-dependent cytotoxicity
There is a combination of IgG and IgM antibodies with antigenic determinants on cell membranes
49
antibodies binded on antigen on cell membrane is seen in
Ex:
immune mediated glomerulonephritis
50
Antibodies binded on exogenous antigen which is ADSORBED on the cell membrane is seen in
Ex:
drug induced hemolytic anemia
51
What happens in Antibody- dependent cellular cytotoxicity
Ab and Ag attaches on Fab site while Fc end of antibody interact with cytotoxic cells like macrophages, PMN’s and natural killer cells
This allows for closer contact between target cell and cytotoxic cell to readily destroy target cell
52
Antibody- dependent cellular cytotoxicity ex:
isoimmune hemolytic anemia in foals
Immune mediated anemia
drug induced hemolytic anemia
thrombocytopenia
53
fetal red blood cells gain entry to maternal circulation thus sensitizing the mare’s immune system so that after parturition and suckling of colostrum by the foal, the Ig in the colostrum binds with the foal’s RBC’s thereby destroying them
isoimmune hemolytic anemia in foals
54
Example of cases of immune mediated anemia
trypanosomiasis and babesiosis
55
drug inducing hemolytic anemia
penicillin, quinine, amino- salicylic acid and phenacetin
56
Drugs causing thrombocytopenia
sulfonamide, phenylbutazone, aminopyrine, phenothiazine and chloramphenicol
57
result from combination of an antibody to an antigen or an immune complex
Type III or Immune Complex Reactions
58
Type III or Immune Complex Reactions
2 major types of reactions:
a. Arthus Reaction
b. Circulating Immune- Complex Disease
59
Explain the Arthus Reaction
Occurs when Ag or immune complexes are deposited within tissues that results to acute inflammatory reaction that starts as an erythematous, edematous swelling to local hemorrhage and thrombosis and can end in necrosis.
60
occurs when antigen is administered intravenously to animals with increased levels of circulating antibodies results to formation of immune complexes in the circulation
Circulating Immune- Complex Disease
61
In Circulating Immune- Complex Disease, most complexes are phagocytosed by
mononuclear phagocytic system
62
When soluble complexes are deposited on walls of blood vessels it results to
vasculitis
63
disease that manifest Immune Complex Reactions
1. SLE
2. swine fever
3. pyometra
4. bacterial endocarditis
5. canine distemper
6. lymphosarcoma
7. mastocytoma
8. dirofilariasis
64
It results due to the deposition of immune complexes in glomerular basement membrane
Membranous Glomerulopathy
65
due to infection or vaccination with live CAV-1; results to localized effects (a type of Arthus reaction) within uveitis. Corneal edema and opacity; cornea isinfiltrated with virus- Ab complexes
hepatitis blue eye
66
Type IV or Delayed Hypersensitivity manifest after how many hours of post exposure
24 to 72
67
Type IV or Delayed Hypersensitivity is mediated by
sensitized T- cell/ lymphocytes
68
2 phases in the production of Delayed Hypersensitivity
Inductive Phase
Amplification phase
69
involves the accumulation of sensitivity antigen deposition
Inductive Phase
69
follows interaction of antigen with 1 cell that produce lymphokines that are responsible for this phase
Amplification phase-
70
an important feature of Delayed Hypersensitivity
cytotoxicity which is an essential process in host defense against viral and fungal infection and in spontaneous tumor rejection
71
diseases that produce Delayed Hypersensitivity
allergic contact dermatitis and flea allergy- most common in dogs and cats
tuberculin hypersensitivity
organ or tissue transplant rejection
graft vs. host disease
72
Criteria for considering Adverse Drug Reactions as hypersensitivity
1.hypersensitivity reaction occurs after initial exposure to a drug
2.After the reaction has been established the same reaction may be produced by minute amounts of the same drug
3. The same reaction recurs upon repeated exposure to the drug
4.The reaction does not resemble the pharmacological action of the drug
5.The symptoms are suggestive or may be similar to known hypersensitivity response
73
Predisposing Factors to the development of Adverse Drug reactions:
Host Factors
Drug Factors
Route of administration
Dose of duration of exposure
74
Genetic make- up of the animal is responsible for:
Difference in drug metabolism that result to the production of metabolites that can lead to hypersensitivity
Variations in the capacity to respond to an immune challenge
Difference in tissue receptor sites that may be related to the hypersensitivity reaction
Production of mediators of the immune system that influence variations in the severity of hypersensitivity reactions
75
failure of an individual to recognized its own tissue or when an immune response is directed against the body’s own tissues
Autoimmunity
76
results from disordered regulation and interaction of B&T cells in response to antigenic stimulation
Autoimmunity
77
mechanism of AID
excess of T-cell activity or a deficiency of suppressor T-cell
78
sensitizing antigens involved are
self- antigens
79
Mechanisms of occurrence of AID
T- cell bypass mechanism
Sequestered Antigen Release
Loss of Suppressor T- cell Activity
80
Explain the 3 Mechanisms of occurrence of AID:
T- cell bypass mechanism- most self- antigens or auto- antigens circulate in very low doses and prolonged exposure to them results to selective tolerance in T- cells so only B cells are able to bind to the auto- antigens or to be stimulated by them in the presence of inducer T- cell signals
Sequestered Antigen Release
Auto antigens comes from tissues that are separated from blood vessels and lymphatics by membrane barriers such in the lens of the eye, the brain and developing fetus so that protein components of cells were hidden from immuno –competent cells. However, certain disease processes may damage these tissues so auto- antigens are released and stimulate non- tolerant cells of immune system to produce autoantibody or cell mediated tissue injury or both
Loss of Suppressor T- cell Activity
T- cells are involved in controlling B- cells functions by suppressing Bcells dependent synthesis of auto- antibodies in normal conditions, suppressor T cells clones can inhibit auto- immune response and thus delay auto immune reactions-in case of disease states, in old animals and immune deficiency, there is decreased or loss of suppressor T-cell functions so that B-cells are allowed to proliferate with resultant production of auto- antibodies and auto- reactive lymphocytes that damage the tissues
81
Types of reaction involving by-pass of T-cell specificity in the presence of competent Bcells
Binding of foreign haptens as drugs to host tissues
Infections by viruses and bacteria that alter host autoantigens
Exposure to altered or cross reacting antigens
Stimulation of competent B- cells by bacterial lipopolysaccharide
Non- specific stimulation of inducer T- cell activity by adjuvant in vaccines
Graft-versus-host reaction (non-specific stimulation of inducer T-cell activity by allogeneic cell)
82
CLASSIFICATION OF AUTOIMMUNE DISEASE
A. Organ Specific Auto Immune Disease
B. Non- organ Specific Auto- Immune Disorders
C. Disease with non- organ specific auto- antibodies but with lesions restricted to one or only a few organs
83
characterized by chronic inflammatory changes in specific organs
Organ Specific Auto Immune Disease
84
auto- antibody in this group exhibit specificity for antigens of the diseased organs
Organ Specific Auto Immune Disease
85
examples of disease processes seen in Organ Specific Auto Immune disease
primary hypothyroidism
post- vaccination encephalomyelitis (after rabies vaccination)
86
pathogenic mechanism involved in primary hypothyroidism and post- vaccination encephalomyelitis (after rabies vaccination)
T- cell bypass due to T-cell deficiency
87
characterized by widespread/ multiple pathologic changes in several different organs
Non- organ Specific Auto- Immune Disorders
88
auto- antibodies involved lack organ specificity
Non- organ Specific Auto- Immune Disorders
88
primary mechanism involved Non- organ Specific Auto- Immune Disorders
deposition of immune complexes in the vasculature in various organs and tissues
89
Non- organ Specific Auto- Immune Disorders classic example
SLE
90
mechanism of injury in Disease with non- organ specific auto- antibodies but with lesions restricted to one or only a few organs
cytotoxic T-cell activity
91
An example of Disease with non- organ specific auto- antibodies but with lesions restricted to one or only a few organs
primary biliary cirrhosis of the liver
92
AID’s are often associated with
Malignancies
Ageing
Immuno- deficient syndrome
93
Indicators for AID
presence of auto- antibodies
amyloidosis in tissues
hypergammaglobulinemia with increase in various immunoglobin subclasses
vasculitis, serositis and glomerulonephritis suggestive of immune- complex disease
presence of other disorders like endocrine disorders
94
Categories of IMMUNODEFICIENCY SYNDROMES
Primary
Secondary or Acquired
95
results from a failure of proper development of humoral or cellular immune system or both
Primary
96
diseases associated with Secondary or Acquired
Diseases due to irradiation
Infectious diseases
Iatrogenic immunosuppression by drugs that result to functional lymphoid cell depletion
Lymphoreticular malignancies
Failure of maternal transfer of immunoglobulins in neonates (by either transplacental route or through colostrum)
97
5 Mechanisms involved in Immunodeficiency Syndromes
Deficiency of lymphocytes production and or functions
Deficiency of hormones and co- factors required for lymphocytes differentiation, programming and maturation and activity
Deficiency of phagocytic cell produced and or function
Deficiency of complement particularly of C3
98
diseases that damage lymphoid tissues
Canine Parvovirus
Feline Panleukopenia due to parvovirus
Chediak- Higashi Syndrome- in dogs, result to decreased phagocytic cells
99
failure of the newborn to acquire passive immunity (via the colostrum or via the transplacental transfer of Ig) lead to immunodeficiency in perinatal life
Failure of passive immunity in neonates
100
Intestinal absorption of maternal Ig in colostrum ends within how many hours after birth in pig, horse, cattle and dog
24 to 48
101
Intestinal absorption of maternal Ig in colostrum ends up to how many days in sheep and goat
4
102
Pathology 141
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