Inflammation & wound healing Flashcards
(346 cards)
1
Q
Describe innate immunity.
A
First line of defence
Non-specific
Rapid onset
No protective immunity
No memory
Phagocyte-mediated
2
Q
Describe adaptive immunity.
A
Activated
Highly specific
Slower
Protective immunity possible
Memory possible
Lymphocyte-mediated
3
Q
What mechanical mechanisms feature in the immune system?
A
Body surface: skin, fur Cilia in respiratory tract Air movement in respiratory tract Flushing by liquids: tears, urine, D++ Mucus as barrier
4
Q
What physiological means aid the immune response?
A
pH changes + extremes Pyrexia kills some infectious agents
5
Q
What molecular defences contribute to the immune system?
A
- defensins - lysozyme + sweat gland secretions - myeloperoxidase system - acute phase proteins - complement system - interferons
6
Q
What cells contain the myeloperoxidase system?
A
Phagocytes
7
Q
State one role of interferons.
A
Interfere with viral growth
8
Q
Describe defensins.
A
Small proteins (15-22 AA) Active against bacteria, fungi + viruses Found in many tissues + cells (especially phagocytes + epithelial cells)
9
Q
Describe lysozymes.
A
Family of enzymes which attack peptidoglycan cell walls of bacteria Secreted in tears, saliva + mucus Sebum from sebaceous glands: waxiness stops bacterial attachment to skin
10
Q
What are acute phase proteins? What is their biological significance?
A
Proteins whose levels fluctuate in response to tissue injury
May act by binding to organisms + aiding removal by phagocytes = opsonisation
Response is general + non-specific
e.g. C-reactive protein (CRP)
11
Q
Describe myeloperoxidase and its function within the immune system.
A
Enzyme found mainly in lysosomes in granulocytes + macrophages
Kills bacteria + other pathogens by production of toxic hypochlorite + singlet O2
12
Q
What is complement? What is the importance of complement?
A
Series of proteins which have multiple protective actions against microorganisms:
- opsonisation
- lysis of bacteria
- recruitment of other cell types to sites of infection
13
Q
What are interferons? What function do they have within the immune system?
A
Cytokines = intercellular hormones
Significant role in fighting viral infections + tumours
Produced early on in viral infections
IFN-a & IFN-ß produced by virally infected cells
IFN-gamma is produced by activated lymphocytes
Generate antiviral resistance in unifected tissue cells + recruit immune cells
14
Q
What roles do commensal bacteria offer within the immune system?
A
Inhabit mucosal surface, especially GI + respiratory tract
Also found on skin
Prevent attachment of pathogenic bacteria → blocks their invasion + infection
15
Q
What type of cells are responsible for ingesting and killing microorganisms?
A
Macrophages
16
Q
What do mast cells do?
A
Have receptors for IgE ab
Increase vascular permeability
17
Q
What kind of cell can kill tumour cells, viral infected cells or ab-coated cells?
A
NK (natural killer) cells = form of lymphocyte
18
Q
Describe the process of phagocytosis.
A
- Attachment by non-specific receptors
- Pseudopodia forming a phagosome
- Lysozyme fusion + killing of microorganism
- Release of microbial products
19
Q
Describe the role of antigens in adaptive immunity.
A
Immune system reacts to presence of ag
Possess epitopes - variable immunogenicity
Antibodies are acquired following prior exposure to ag
Requires lymphocytes
Features: specificity
self/non-self discrimination
memory
20
Q
Describe the features of adaptive immunity.
A
Memory enables 2º response to same ag
2º response is faster, stronger (better binding + greater response by cells), generates more memory cells
All memory + specificity resides in lymphocytes populations
21
Q
What role do eosinophils play within the immune system?
A
Anti-parasite immunity
22
Q
What function do polymorphonuclears + monocytes have in the immune response?
A
Phagocytosis
Ag presentation
23
Q
What 2 kinds of adaptive immunity are there? What agents mediate these kinds?
A
Humoral immunity - mediated by B-lymphocytes
Cellular immunity - mediated by T-lymphocytes
24
Q
What are the major internal lymphoid organs?
A
Thymus
Bone marrow
Spleen
Lymph nodes
25
State the major surface lymphoid organs.
Salivary glands
Respiratory tract
Mammary glands
Intestines
Urogenital system
26
What 4 sites of lymphocyte development are there?
Thymus
Bone marrow
Peyer's patches
Bursa of Fabricius (only found in chickens)
27
Give 5 examples of sites in the body where lymphocytes respond to ag.
Tonsils
Spleen
Lymph nodes
Peyer's patches
Bone marrow
28
Where in the body do T-lymphocytes mature? And B-lymphocytes?
T-lymphocytes mature in _thymus_
B-lymphocytes mature in **bone marrow**
29
What does humoral immunity entail? What kind of lymphocytes are involved?
Production of ab
Involves B-lymphocytes
30
What happens with cell-mediated immunity? What type of lymphocytes are involved?
Produces cytotoxic effects
Requires T-lymphocytes
31
What two different categories of lymphoid organs are there? Describe them.
**1º (central) lymphoid organs**
- where B- + T-lymphocytes mature into ag-recognising cells
- lymphocytes acquire ag-specific receptors
**2º (peripheral) lymphoid organs**
- ag-driven lymphocyte proliferation + differentiation
32
Describe the thymus. How does the adult organ differ from the developing thymus?
Small thoracic organ near to heart
Site of T-lymphocyte maturation + selection
Lymphocytes are transported to thymus via blood
Active in young animals, then shrinks + atrophiesm producing fewer T-cells
Contains **Hassal's corpuscles**
_Adult:_ contains many fatty + atrophied areas
still functional; greatly reduced in size
33
Describe the thymic structure.
T-lymphocytes are in intimate contact with epithelial cells - useful for selection
Immature T-lymphocytes mature within thymus cortex
34
What percentage of T-lymphocytes survive the 'thymic journey'?
Only 5%
35
What are Hassal's corpuscles?
Composed of flat non-secreting epithelial cells arranged in concentric keratinised layers
Seen in medulla of thymus
36
What does the cortex of the thymus contain?
Densely populated with immature T-lymphocytes of various sizes
Scattered macrophages - removing apoptotic lymphocytes
37
Where does thymic selection of T-lymphocytes occur? Describe the process.
Having migrated from the cortex to the medulla, T-lymphocytes encounter _macrophages_ and _dendritic cells_
These cells perform thymic selection ⇒ mature functional T-lymphocytes
These then enter the circulation + migrate to 2º lymhoid organs where they encounter + respond to ag
38
What types of cells do immature T-lymphocytes have to navigate past in order to survive thymic selection to reach maturity?
Enter thymic cortex: encountering thymocytes + cortical epithelial cells
Within medulla: they encounter medullay epithelial cellsm dendritic cells + macrophages
This selection process removes most of self-reactive T-lymphocytes
39
Where do dendritic cells originate from?
Bone marrow
40
Describe the Bursa of Fabricius.
Only found in birds
Is an organ located near the cloaca
Site where B-lymphocytes undergo maturation → ab-producing B-lymphocytes
41
What route does lymph take within the body?
Fluid filters from capillaries and drains into lymphatic vessels to become _lymph_
Lymph eventually drains into venous blood after passing through 2º lymphoid organs
42
What functions does lymph have?
Drains interstitial fluid
Transports dietary lipids
Facilitates immune responses by draining ag from tissues to lymph nodes, and eventually blood
43
Where do the lymph nodes receive lymphocytes from?
10% from lymph
90% from circulation, entering via **high endothelial venules**
44
Describe the features of lymph nodes.
Highly efficient at trapping ag entering via afferent vessels
Lymphocytes are retained for up to 24hrs
ag react with macrophages, T- & B-lymphocytes → immune response
Composed of cortex → paracortex → medulla
45
What constituents form a lymph node?
Germinal centres
Subcapsular sinuses
1º & 2º follicles
Associated artery + vein
Dividing trabeculae + medullary cords
46
Describe the structure of the spleen.
Red pulp = open sinusoids containing RBCs
White pulp = mainly composed of lymphocytes
Red pulp surrounds white pulp
47
What does MALT (mucosa-associated lymphatic system) comprise?
Tonsils
Peyer's patches
Appendix
- very dense areas of lymphocytes
48
Where are MALT areas found?
Found in many areas of GIT, respiratory tract and genito-urinary tract
49
Describe the tonsils.
Lacks a capsule or afferent lymphatics
Have lymphoid follices + germinal centres
Found in vatious forms around upper respiratory tract
Contain lymphocytes and macrophages
50
Describe the features of Peyer's patches.
Found in ileal submucosa of SI
Visible to naked eye
Germinal centres prominent as sites of ab-production
Detect ag that diffuse across intestinal epithelia via M-cells
51
What hormones are produced by the thymus to support T-lymphocytes growth and differentiation?
Thymosin
Thymulin
Thymopoeitin
52
What is an epitope?
The immune reactive part of an antigen
53
Define an antigen.
Any agent that is capable of binding specifically to components of the immune system.
54
What is an immunogen?
Any agent capable of inducing an immune response.
55
What are the key interactions needed for ab-production?
Ag + specific lymphocyte
Lymphocytes with each other + _accessory cells_
56
What is the humoral defence composed of?
B-lymphocyte + ag → ab-production (plasma cell)
57
What is a plasma cell?
A fully differentiated B-lymphocyte which produces a single type of ab
58
Describe the process of achieving humoral immunity.
Clonal expansion occurs when ag meets small resting lymphocyte
Lymphocyte multiplies + matures
Activated, expanded B-lymphocytes become **plasma cells** - exit lymphoid tissues and migrate to areas of infection to secrete ab
Some lymphocytes become _memory cells_ instead to enable a strong 2º immune response on re-challenge
59
Describe the structure of a basic immunoglobulin.
Symmetrical unit comprised of 2 heavy chains + 2 light chains
60
How many different classes of heavy immunoglobulin chain are there? Name them.
5 different classes:
IgM = micro
IgD = delta
IgG = gamma
IgA = alpha
IgE = epsilon
61
What fragments constitue an Ig molecule?
**Fab** = fragment ag binding
**Fc** = fragment crystallisable
62
What kind of bond is present between heavy-heavy and heavy-light chains of Ig molecules?
Disulphide bridges
63
What can both heavy and light chains be further sub-divided into?
Constant and variable regions of heavy chain
Constant and variable regions of light chain
64
At what region do ab bind to ag?
Variable regions of light and heavy chains
65
What is the name of the section of the Ig molecule between the Fac and Fc regions?
Hinge region
66
What is another name for the antigen binding site on an Ig molecule?
Hypervariable region = actual ag bindingsite on Ig, found in variable region
## Footnote
*\* this will bind epitope of ag*
67
What part of an Ig molecule dicatates its biological function?
Heavy chain end of Ig molecule
68
How is IgA transported across mucosal epithelium?
Via a transport vesicle that utilise secretory component
69
What does the valency of interaction between ag + ab depend on?
Number of ag being bound by ab
70
What is another term used for the valency of interaction between ag + ab?
Avidity = overall binding strength between an ab + ag
71
What are antisera?
A blood serum containing ab against specific ag
Injected to treat or protect against specific diseases
Polyclona as many epitopes stimulate many B-lymphocytes
72
What type of cells produce ab? Where do ab generally terminate?
B-lymphocytes produce majority of ab
Ab tend to end up in fluids
73
What different forms of ab are there?
Soluble and membrane-bound forms
74
What are Ig produced by and in what situation?
Produced by B-lymphocytes that have been expose to ag
Ig are specific to ag
75
What are the 4 phases of a 1º antibody response?
1. Lag phase
2. Log phase
3. Plateau
4. Decline
76
What is antibody switching? Describe the process.
Following first encounter with ag, B-lymphocyte secretes IgM
Lots of memory cells are also generated - many of these have switched from IgM ⇒ IgG (or IgA) expression
Upon 2º response, secretion of high affinity ab which is mainly IgG in most tissues
77
What is the theory behind vaccination?
That 1º immune responses will generate memory cells + protection through 2º ab response
= **acquired immunity**
\* mimics 1º infection
78
State the different funtions of antibodies.
- Prevent pathogen attachment
invasion of host cells
replication
toxin production
- Activate complement system
- Opsonisation by Fc + complement receptors
- Cytotoxic for pathogen + infected cells (NK)
79
What happens in the body between 1º and 2º immune responses?
Animal learns which ab is most effective - regulated by specficity of lymphocytes
\* **antibody switching**
80
What is complement comprised of?
System of proteins - normally inactive molecules that are activated in series (*through a cascade*)
Mainly produced by liver
Mainly found in body fluids including circulation
81
What are the problems associated with complement?
Its capacity to harm the host:
e.g. swelling of joints
canine rheumatoid arthritis- disruption of hyaline cartilage
- cell lysis
- attraction of phagocytes to site of ab production/localisation
- induction of anaphyltoxins in tissues
- activation of phagocytes + mast cells
- smooth muscle contraction
82
What mechanisms of protection does complement have?
1. Opsonisation
- bind to pathogen to promoto phagocytosis by phagocytes bearing complement receptors
2. Chemoattractant
- recruits phagocytes in situ
3. Lysis
- damages certain bacteria by perforating membrane
83
How does amplification work within complement activation cascades?
Each stage of complement is a substrate which becomes an enzyme on activation, whose substrate is the next complement stage
84
Name the 3 pathways that result in complement activation.
Classical pathway
Lectin pathway
Alternative pathway
85
Describe the classical pathway.
1. IgG or IgM antibody binds to an antigen
2. Complement component C1q binds to ag-bound ab
3. C1q activates C1r → activates C1s → C1s binds + cleaves C2 + c4
4. C2a + C4a split off
5. C2b + C4b attach to protein close to ab - repeated many times, freeing complexd to actiave further molecules
6. C3 binds to C2b → C3a splits off
7. C3b splits many copies of C5 → each C5 binds to nearby C2b + C4b
8. C5b is target for binding of C6, C7, C8+ C9
9. C5b-C9 forms **membrane attack complex** → penetrates cell membrane, allowing ionic leakage
86
What are the components of a membrane attack complex?
C5b
C6
C7
C8
C9
87
What is result of the classical complement pathway?
Complement-mediated lysis
H2O + ions enter cell → cell to swell + lysis
88
Which component of the classical pathway is also crucial to the other pathways?
C3
89
What is C1 molecule comprised of?
C1q
C1r
C1s
90
What is another name for the lectin pathway?
MBL pathway = mannan-binding lectin
91
What is needed for the MBL pathway?
A pattern recognition receptor
= protein produced by liver
- recognises patterns on infective processes
92
Describe the lectin pathway.
1. Initiates complement cascade by bindign to pathogen surfaces
2. Cleaves C2 + C4 to activate C3
93
What potential factors can initiate the alternative pathway of complement activation?
**Pathogen components**
- many gram- bacteria
- lipopolysaccharides from gram- bacteria
- many gram+ bacteria
- fungal cell walls
- some viruses + parasites
**Non-pathogens**
- complexed IgG + IgA
- anionic polymers
- pure carbohydrates
94
What are the various outcomes for activation of C3?
C3a is produced:
- when combined with C5 ⇒ **inflammatory response**
- mast cells are degranulated → increases vascular permeabilty
C3b is also produced:
- **opsonisation** - C3b remains on microbial cell wall + is recognised by phagocytes → phagocytosis
- **lysis** - C3b activates C5 → formation of membrane attack complex → cell lysis
95
What does degranulation of mast cells result in the release of?
Histamines
Heparins
96
How can the process of opsonisation be improved in its efficiency?
Binding of activated complement via C3
Binding of ab (Fc)
97
What causes mast cells to degranulate?
Binding of C3a + C5a
98
What are C3s + C5a known as?
**Anaphylatoxins**
99
What local events are associated with anaphylatoxins (C3a + C5a)?
- increased vascular permeability
- adhesion + chemotaxis of neutrophils + monocytes
- smooth muscle contraction
- degranulation of mast cells
100
What is chemotaxis?
The process by which phagocytes are attracted to the site of inflammation.
101
Which of the complement components has the greatest potency?
C5a \> C3s \> C4a
102
What are the biological functions of the complement components C3a, C4a & C5a?
Increased vascular permeability → increased fluid leakage from BV, extravasation of Ig + complement molecules
Increased cell adhesion molecules
Increased migration of macrophages, PMN leucocytes + lymphocytes
103
What does extravasation refer to?
The leakage of fluid from within a contained area
e.g. blood vessel
104
Which complement functions are dependent on the activation of C3?
1. Lysis
2. Opsonisation
3. Activation of inflammatory response
4. Clearance of immune complexes
105
What happens to macrophages and neutrophils following the process of phagocytosis?
Macrophages persist
Neutrophils are end-stage cells that die having consumed the foreign body or microbe
106
Name the different complement control mechanisms.
Lability - self-destruct ifthey do not achieve activation over a certain distance
All cells have surface protection provided by specific complement receptor proteins
Factor I: cleaves C3
Factor H: cleaves C3
C1 inhibitor: binds C1r + stops C2 & C4 from binding
C3b receptor on RBCs
107
What are PAMPs?
Pathogen-associateed molecular patterns
= molecules on pathogens recognised by receptors on cells of innate immue response.
*e.g. bacterial lipopolysaccharide*
108
What are PRRs?
Pattern recognition receptors
= primitive part of immune system, found on phagocytes + mast cells, these identify + bind PAMP
\* no memory
109
What are monocytes?
Large phagocytic WBC with a simple oval nucleus + clear, greyish cytoplasm
110
Define a macrophage.
A large phagocytic cell found in stationary form in the tissues, or as a mobile WBC especially at sites of infection
111
What is a mast cell?
A cell filled with basophilic granules, found in numbers in connective tissue and other substances during inflammatory + allergic reactions
112
What proportion of B- and T-lymphocytes are seen in the circulation?
B-lymphocytes at 20%
T-lymphocytes at 80%
113
How many different kinds of T-lymphocyte are there? What are their functions?
**Helper T-lymphocytes** - assist both ab-production + cytotoxic T-lymphocyte effects; associated with CD4
**Cytotoxic T-lymphocytes** - kill infected host cells + tumours; associated with CD8
114
What kind of lymphocytes are associated with CD4?
Helper T-lymphocytes
115
What kind of lymphoctes are associated with CD8?
Cytotoxic T-lymphocytes
116
How do T-lymphocytes recognise ag?
Through specific receptors = TCR (T-cell receptors)
117
What are TCR composed of?
Variable + constant domains
Single ag-binding site
a- + ß-chains
CD3 complex
Accessory molecule of CD4 or CD8
118
How does a B-lymphocyte ag-receptor compare to a T-lymphocyte ag receptor?
B-lymphocyte receptor - binds surface Ig
2 identical ag recognition sites
T-lymphocyte receptior - 1 ag recognition site
119
What is the importance of B-lymphocyte development in the bone marrow?
- regulate construction of an ag-receptor
- ensures each cell has only 1 specificity
- checks + disposes of self-reactive B-lymphocytes
- exports useful cells to periphery
- provides a site for ab-production
120
Describe the process of removing self-tolerant B-lymphocytes.
**Clonal deletion**
- small pre-B cell assembles Ig
- immature B-cell recognises multivalent self-ag
- clonal deletion occurs by apoptosis
121
What is an MHC (major histocompatibility complex)?
Cell surface molecules used for tissue typing in transplantation
Defines an individual molecularly
MHC genes code for expresses membrane proteins
Highly polymorphic
122
What are the functions of MHC?
Cell communication within immune cell populations
Control type + degree of immune response
MHC proteins present ag to T-lymphocytes
123
What are the distinguishing features between the different classes of MHC?
Class 1: expressed on most nucleated cells
presents proteins to CD8+ cytotoxic T-cells
Class 2: expressed on APCs, macrophages, B-cells + activated T-cells
presents proteins to CD4+ helper T-cells
124
Describe the different selection processes that occur in the thymus affecting T-lymphocyte maturation.
**Positive selection:**
T-cells that can react to self MHC carrying peptides are allowed to live.
Those that cannot undergo apoptosis
**Negative selection:**
T-cells that react strongly to self-ag are eliminated.
*\* only T-cells that can react to MHC but do not bind strongly to self-ag emerge as mature T-cells*
125
What are the functions of mature T-lymphocytes?
Cytotoxic to infected cells = CD8
Activate macrophages = CD8
Help ab-production by B-cells = CD4
cytotoxicity by other T-cells = CD4
126
What is the significance of APCs (antigen-presenting cells)?
Expresses ag to helper T-cells → proliferate
Cytotoxic T-cells will kill these cells
127
What are the 3 main types of APC?
Dendritic cells
B-lymphocytes
Macrophages
128
Describe the main features of APCs.
They lack ag-specific receptors
Process + present ag to T-lymphocytes so that they can react
Present ag via MHC on their surface
Capable of killing own cells if infected
129
Describe the components needed for T-cell recognition of ag.
MHC molecule present peptide
Ag is peptide-bound to molecule
TCR recognises MHC + peptide
130
What is the role of cytokines?
Control of immune responses
131
What are cytokines? What is the name given to those are produced by leucocytes?
Intercellular hormones
Interleukins - produced by one leucocyte to affect another
132
Which of the APC is the most effective + most potent?
Dendritic cells
133
How do the TH1 and TH2 reaction pathways affect one another?
They are antagonistic
Inhibitory effect determined by cytokine production
134
What is the role of NK cells?
To recognise cells lacking in MHC class 1
Effective vs. tumours, some viruses
135
Which MHC class presents ag to helper T-cells?
Class 2 - assists ab-production + cytotoxic T-cell activity
136
Which of the classes of MHC presents ag to cytotoxic T-lymphocytes?
Class 1 - enables killing of infected host cells
137
What different pathways are there for processing ag?
**Endogenous pathway**
- host cells process infective agents + express on cell surface with _MHC class I_
- targeted by Tc - host cell is killed
**Exogenous pathway**
- macrophages digest infective agent + produce peptides to present on surface _MHC II_
- or to be picked up by other cells (e.g. dendritic cells) to be presented to Th cells to activate them
138
By which pathway can all APICs present ag to Th cells?
Exogenous ag can be presented
Using MHC II
139
Which of the APCs tend to process ag (via endogenous pathway)?
Macrophages
Dendritic cells
140
What type of APCs tends to present ag?
Dendritic cells - circulate around body + localise in lymph nodes
141
Describe the process of ag-processing.
Usually needed to degrade large proteins or organism prior to presentation by APC
Not all degradation is performed by APC
All APC can present ag in association with MHC I
142
State an advantage + a disadvantage of dendritic cells as APCs.
Advantage: excellent + highly potent APC
Disadvantage: poor at processing large ag
143
What happens when T-lymphocytes are activated?
Blast cells are generated
IL-2 receptor expression is increased
IL-2/4 synthesis is increased
- drives clonal proliferation ⇒ many effector +/- memory cells
144
What different kinds of helper T-lymphocyte are there?
TH1 - assist T-lymphocyte functions (Tc + macrophage activation) for **intracellular infections**
TH2 - assist B-lymphocytes to make ab for _extracellular infections_
145
How do cytotoxic T-cells respond to ag?
Identify ag-presentation by MHC I on infected cells ⇒ induces apoptosis within target cells
146
How do NK cells respond?
Are cytotoxic lymphocytes that recognise cells without MHC I - commonly seen with tumours + some virally infected cells
Induces apoptosis within target cells
147
How do immune cells communicate?
Through direct cell-cell contact induced by peripheral lymphoid tissues trapping and concentrating ag-containing phagocytic cells
148
What are the 4 phases of immune responses?
1. Recognition phase
2. Activation phase
3. Effector phase
4. Memory phase
149
Describe the effector phase of an immune response.
- lymphocytes are specifically activated to perform functions for eliminating ag
- work with other non-lymphoid effector cells (neutrophils, phagocytes)
- complement - lysis + phagocytosis of microbes
- cytokines - enhance function of phagocytes + other lymphocytes; stimulate inflammation
150
Describe the recognition phase of the immune response.
Binding of foreign ag to specific receptors on mature lymphocytes
151
Describe the memory phase of an immune response.
Lymphocytes with a high affinity for ag are in the correct site if a repeat infection should occur with the same ag
152
Describe the activation stage of an immune response.
All lymphocytes undergo proliferation + differentiation
Lymphocytes migration to sites of ag entry and persistence
153
What factors regulate an immune response?
Ag
Ab
MHC genes
Lymphoyctes e.g. Treg
154
What is Treg?
A CD4 (helper) lymphocyte
155
Describe Treg and its role within an immune response.
Has surface CD4 + CD25
Switches off immune response - regulatory role
Prevents state of autoimmunity
Selected in thymus
156
Describe passive immunity.
Offers short-term protection as ab wane wiithin recipient
No cell-mediated immunity; ab only
Risk of hypersensitivity with foreign serum
Blocks inducation of active acquired immunity
157
Where is passive immunity acquired from?
**Natural:** MDA in colostrum or via placenta
**Artificial:** injection of ab (sera) from resistant ⇒ suscpetible animal
158
By what means is active acquired immunity achieved?
Natural infection
Artificial immunisation: living organisms vs dead vaccines
159
What is the main concern with vaccinating animals?
That they may not be able to withstand 1º infection
160
What does an anamnestic response refer to with regards to passive immunity?
Refers to the enhanced reaction of the body's immune system to an ag which is related to one previously encountered
161
Which of the Ig molecules provide the main protective ab?
IgG or IgA
162
What should an ideal vaccine do?
Provide prolonged strong immunity
Immunity sholud be conferred to any foetus carried
Free of side effects
Cheap, stable + easy to apply
Produces immunity distinguishable from natural infection (DIVA)
163
What are the essential components to a vaccine?
- stimulation of APCs
- both B + T cells stimulated
- helper + effector responses to several epitopes
- vaccine ag should persist in appropriate sites in lymphoid tissues
164
State the reasons for avoiding vaccination.
- poor natural/artificial immunity offered
- immunity doesn't prevent infection → carrier state
- ab contribute to disease
- vaccine causes disease by infection
- vaccine ag interferes with serodiagnosis
165
What are the disadvantages of killed vaccines?
- less immunogenic than live vaccines
- have to be administered more often
- not effective by natural infection route
- require adjuvant for effective immunity
166
By what methods can pathogens be modified to attentuate them for use in vaccines?
Heat
Culture
Chemical
167
What are the advantages to using killed vaccines?
Safer than attenuated vaccines
Give better ab responses compared to cell-mediated immunity
168
How can a virus be attentuated for vaccine usage?
Pathogenic organism with gene for virulence factor
- virulence gene removed - deletions, knock-outs
- avirulent organism lacking gene for virulence factor is placed into vaccine
169
What are the different routes for administering vaccines?
SC
IM
IN
Aerolisation
Water
Feed
170
What are the benefits of subcutaneous vaccines?
Skin contains specialised, monocyte-derived epidermal cells
= Langerhans cells - precursors of dendritic cells
- capture + process ag in skin
- travel in lymph to lymph node → follicular dendritic cells
- stimulate T-cells very effectively
171
What is the significance of adjuvants within vaccines?
Added to increase effectiveness of killed vaccines
- promote APCs
172
State 4 reasons why vaccinations might fail.
Incorrect administration
Wrong time period
Wrong vaccine used
Insufficient quantity of vaccine used
Passive immunity still efficacious
173
What is one of the problems, seen in particular with cats + FeLV vaccination? How is this dealt with?
Post-vaccinal sarcoma - relatively rare
With FeLV vaccine, this is injected into muscle of HL as this is easier to amputate should a sarcoma result than one localised to the scruff of the neck
174
What is the basic outline for foetal immunology?
Thymus appears first
2º lymphoid organs develop
Cell-mediated immunity develops at same time as ab production
175
How do the levels of macrophages + PMNs in neonates compare to levels in the adult?
PMN - similar level + function in neonate to adult levels
Macrophages - phagocytic ability impaired
\* thought to be due to increase in glucocorticoids - may also impair abilities of APC
176
What does tolerance refer to?
A lack of immune response to specific ag
177
By what means does transfer of immunity to offspring occur?
- Placental transfer - primates receive IgG only
- 5% placental: 95% colostral - dogs, cats
- 100% colostral - ruminants, pigs, horses
178
What is the organ responsible for supplying mammary glands with Ig?
Supramammary lymph nodes ⇒ mammary ducts
179
How does Ig reach colostrum from the circulation?
Specialised FcR in mammary gland draws ig from serum to add to colostrum
180
What is the minimum amount of colostrum needed by calves + foals within 6hrs of birth?
1L colostrum minimum
181
How does absorption of colostrum occur?
- ingested and passes into GIT where enzyme levels are low/blocked so that proteins can reach SI
- neonates have specialised Fc receptor on intestinal epithelia for brief period following parturition
- Igs are bound, actively _pinocytosed_ → reaches circulation + lymphatics
182
At what point following parturtition do circulating Igs reach their peak?
12-24hrs post-partum
183
When is the greatest risk of infection posed to newborn animals?
In between decline of passive immunity + stimulation of active immunity of immue system
184
By what means can colostrum be assessed?
Hydrometer/colostreter - measures specific gravity to correlate with TP or Ig content
Refractometers - measures protein content through degree of light refraction
185
Describe the test used to making a rapid assessment of Ig levels in foals.
**Zinc sulphate turbidity test**
- the cloudier the solution, the greater the concentration of Ig
**Radial immunodiffusion (RID)**
- measures foal serum Igs
- _failure of passive transfer_ = when IgG \< 2mg/mL
- partial transfer = when IgG 2-4 mg/mL
- adequate transfer = when IgG \> 4 mg/mL
186
At what serum concentration is failure of passive transfer deemed to have occurred? What concentration is considered adequate? And partial transfer?
\< 2 mg/mL for failure of passive transfer
2-4 mg/mL is partial passive transfer
\> 4 mg/mL is adequate transfer
187
What means of Tx are there for FPT?
Provide additional colostrum:
- bottle or nasogastric tube
- only suitable for neonates up to 15hrs old
Over 15hrs old:
* \* no oral absorption is occurring*
- use IV plasma - commercially available with high specific ab titres
- both IV plasma + commercial plasma must be free of anti-erythrocyte ab
188
What are the different considerations for treating FPT?
Age of foal - affects course of Tx
If younger than 15hrs, give additional colostrum via nasogastric tube or bottle
If older than 15hrs, requires IV plasma - from healthy animal to provide sera Igs
189
Describe CMI in colostrum.
Many lymphocytes present - mostly T
May survive up to 36hrs in intestine of neonate calf
Some penetrate to local lymph nodes → circulation
Enables some CMI + humoral immunity
190
Why would non-suckled calves produce ab sooner than suckled calves?
MDA inhibit ab production
191
Describe the normal neonatal immune response.
GI lymphoid tissue responds well to ingested ag
Passive immunisation inhibits development of immune response
192
What is the 1/2 life of cat + dog ab in their neonate offspring?
8-10d
193
How is passive immunity achieved in the chick?
Serum IgG is transferred from serum to yolk within ovary
IgM + IgA are picked up in oviduct - remain within albumin to be ingested by neonate chick
194
What kind of relationship does commensalism describe?
A neutral relationship
195
What term is used to describe the occurrence of symbiotic pathogens becoming pathogenic if weakness occurs in host animal?
Opportunistic pathogens
196
What are the distinguishing features of prokaryotes?
No defined nucleus
Cell lacks compartmentalisation
Only have one circular chromosome
197
Describe the difference between gram+ and gram- bacteria.
_Gram+_
Appears purple when stained with crystal violet
Thick peptidoglycan wall retains stain
_Gram-_
Appears pink when stained with crystal violet
Thin petidoglycan wall therefore poor stain retention
198
Describe the main features of bacteria.
Plasmids
Cell envelope
Flagella
Pili
Capsule + slime layers
Endospores
199
What mechanisms of the innate immune system are there to combat bacteria?
Acute phase proteins (opsonins)
Complement - alternative pathway
Phagocytosis by neutrophils
Macrophage activation
PAMPs recognised by PRRs
200
What are PAMPs?
Conserved molecular motifs on pathogens
e.g. lipopolysaccharides, flageillin
201
What are the mechanisms that recognised PAMPs?
Toll-like receptors (TLRs) + PRRs on host cells
202
Describe the role of TLRs.
Found on monocytes/macrophages, mast cells + B-cells
Recognise PAMPs on bacteria
Triggering of TLRs → cytokines + inflammation
Capable of some recognition of bacteria, though lack specificity
203
Describe the process of phagocytosis.
Macrophages ingest + degrade particulate ag through the use of long pseudopodie that bind + engulf bacteria
Engulfed bacteria are degraded when the phagosome fuses with a vesicle containing proteolytic enzymes ⇒ phagolysosome
204
By what means do bacteria avoid phagocytosis?
Bacterial capsule
Protein A - binds IgG, activates C3 → decreases complement
M-protein - blocks complement activation + reduces opsonisation
205
What mechanisms can bacteria utilise to promote their survival within host cells?
Infiltrate phagolysozomes
Manipulate host cytokine responses - altering balance of Th1 + Th2
Causes TH2 \> TH1
206
What happens to pathogens if TH1 cells are stimulated?
TH1 cells direct response to inhibit IC pathogens
TH1 cells secrete IFN-gamma to activate macrophages + Tc cells
207
What happens to pathogens if TH2 is promoted?
TH2 suppresses activation of macrophages
TH2 promote strong ab-response based on neutralising IgGs
\* most effective to combat EC pathogens
208
Compare the 2 main methods of acquired immunity to bacteria: humoral vs. cell-mediated.
_Ab-mediated (humoral)_
- neutralises toxins
- kill bacteria - IC method by macrophages
- opsonises bacteria
- essential protection for neonates
_Cellular immunity_
- mainly Th1 responses
- direct killing by Tc + NK cells
209
Give 4 examples of bacteria that hide within hosts cells to avoid the host immune system.
Chlamydophila psittaci
Salmonella
Rickettsia
Bartonella
210
By what means can bacterial avoid ab-defences of host?
IgA protease which cleaves ab found in mucosal secretions
Antigenic variation - turns pili on/off
Mimic host - look like self-ag
Biofilm formation
211
How can bacteria cause injury to host tissues?
Secreted exotoxins
Membrane-bound endotoxins
Non-specific immune stimulation
Specific humoral + CMI stimulation
212
How do bacterial endotoxins cause damage to host tissues?
- can cause food poisoning even in absence of organism
- immune systems often target toxins with neutralising abs
**\* whilst endotoxins are susceptible to ab, many are so toxic that they may be fatal to host before defensive ab can be produced**
213
Describe the process of endotoxic shock.
Excessive release of cytokines can lead to:
- intravascular coagulation with consequent defective clotting
- changes in vascular permeability
- loss of fluid into the tissues
- fall in BP (risk of hypovolemia)
- circulatory collapse
- haemorrhagic necrosis - especially in the gut
* \* may be fatal*
214
How can bacterial endotoxins damage the host organism?
Lipopolysaccharide - activates macrophages to release inflammatory cytokines
Lipid A - toxic if organism enters bloodstream → massive immune cell infiltration + activation of coagulation
215
How do superantigens cause damage to host tissues?
- polyclonal T-cell activators
- produced by bacteria to induce ineffective host immunity
- hyperstimulate immune system: fever, nausea, D++, V++
- leads to shock ⇒ organ failure + circulatory collapse
= cause of **toxic shock syndrome (TSS)**
216
What is the significance of serology with regards to bacterial infections?
Detects specific ab to organism - useful for Dx
- often general increases in serum Igs are seen in conjunction with severe or systemic bacterial infections
217
What are the 2 main classifications for fungi?
Moulds - filamentous, spore-forming
Yeasts - unicellular, budding mechanism for reproduction
218
Describe innate immunity of hosts to fungal infections.
- alternative complement pathway is activated
- phagocytosis is weak → bystander damage is severe due to 'frustrated' phagocytosis
219
Describe the process of acquired immunity to fungal infections in hosts.
- once infected, only T-cell responses are effective - mainly by activating local macrophages + promoting tissue repair
- some Tc responses
- fungal infections common in animals with defective T-cell immunity
220
What is the significance of macrophages releasing cytokines?
This:
- attracts other cells
- induces fluid exudate from blood
- exudate contains complement + other antimicrobial products
221
Describe the basic features of viruses.
Small particles that infect cells
Obligate IC parasites - lack reproductive machinery
Threatened by immunity or death of host
222
What different types of virus are there?
DNA viruses
RNA viruses
223
What is the infection strategy of viruses within their natural hosts?
In natural hosts - there is no disease
224
What tends to happen in 2º virus hosts?
Vira infection can be lethal
225
Give 3 examples of DNA viruses.
Herpesviridae
Adenoviridae
Parvoviridae
226
Give 6 examples of RNA viruses.
Paramyxoviridae
Orthomyxoviridae
Coronoviridae
Picornaviridae
Caliciviridae
Flaviviridae
227
What are the general steps of viral reproduction?
1. Viral invasion of host cell
2. Synthesis of new viral nucleic acids + proteins
3. Self-assembly of new viral macromolecules into virus particles
4. Virus particles released from host cell
228
What are the possible consequences for a cell infected by a virus?
Lytic infections = destruction of the host cell caused by virulent viruses
Persistent infections = do no lead to cell lysis, release viral particles slowly over a long period
Latent infections = delay between the infection process + the appearance of symptoms
Transformation = some animal viruses can change a normal cell into a tumour cell
229
What are the problems posed by viruses and treating them?
Constantly evolving due to short 1/2 - new forms appear spontaneously
Tx are very restricted or absent
Evolution selects for 'smart' viruses
230
What is the role of interferons against viruses?
Secreted within hours of infection
231
What different kinds of interferons are there?
Type 1 = IFN-a & IFN-ß
- produced by tissue cells (fibroblasts)
- stimulate NK activity against viral cells + NK secretion of IFN-gamma
Type 2 = IFN-gamma
- from activated T + NK cells
- prevents viral growth in cells by induction of NO secretion + more IC IFN production
- activates macrophages
232
What are the functions of IFN-a and IFN-ß?
- induce resistance to viral replication in all cells
- increase MHC I expression + ag presentation in all cells
- activate NK cells to kill virus-infected cells
233
Which type of cells produce IFN-a + IFN-ß?
Virally infected cells
234
What type of interferon is produced by T-lymphocytes responding to ag?
IFN-gamma
235
What does ADCC refer to?
A mechanism of CMI whereby an effector cell of the immune system actively lyses a target, whose membrane surface-ag have been bound by specific ab.
236
Which cells are responsible for ADCC (ag-dependent cell-mediated cytotoxicity)?
FcR+ cells
237
What are the functions of ab-mediated immunity?
Blocks absorption of virions to target cells
Stimulates phagocytosis of viruses
Triggers complement-mediated lysis
Triggers ADCC by FcR+ cells
Viral clumping (agglutination)
238
Which of the Igs is most important for ab-mediated immunity?
IgG
239
In what ways might ab enhance disease?
Mediate virus attachment to some cells e.g. FcR/C3b
Hypersensitivity reactions
240
What kind of cells are targeted by NK cells?
Cells whose MHC class I is reduced
241
What is the agent responsible for stimulating NK cell activity?
IFN
242
What 2 means are there for eradicating virally infected cells?
NK cells
Tc cells
Macrophage elimination
243
What mechanisms do viruses have of evading immune systems?
Interfering with IFN
Surviving phagocytosis
Evading ab responses
Inhibiting infected cell death
Inducing immunosuppression
Evading T-lymphocyte responses
Stress can activate latent infections
244
Give 2 conditions that result as adverse consequences of viral immunity.
Distemper - demyelination: brain macrophages ingest immune complexes containing distemper which releases toxic products damaging neurones
Canine adenovirus - deposition of immune complexes in cornea + PMN release damaging enzymes → opacity to eye
245
What 3 classes of parasites are there?
Protozoa
Worms (helminths)
Arthropods (insects, arachnids)
246
How do parasites damage their hosts?
Competing for cell nutrients
Disrupting tissues
Destroying cells
Mechanical blockage
247
How does a direct parasite life cycle work?
Same host is reinfected
248
What is the term used to describe infection of different hosts before the original host is re-infected?
Indirect life cycle
249
Describe the features of protozoa.
Single-celled eukaryotic microorganisms
Lack cell walls
Many possess a cyst that protects from adverse conditions
2 important sub-phyla: Sarcodina + Mastigophora
250
What methods do protozoa have for evading their host's innate immunity?
- resistance to complement
- surviving inside phagocytes
- manipulating dendritic cells
- poor PAMP expression
251
How does the host respond to parasitic infection?
- ab - control parasites numbers in blood + tissues, driven by TH2
- CMI - IC parasites controlled by TH1
* \*often both pathways are needed for effective immunity*
252
How effective are vaccinations against protozoal infections?
- limited success
- frequently requires a cocktail of species/strains for maximising vaccination success
253
What is the main problems that helminth infections present to their host immune system?
Most are EC + too large for phagocytosis
254
What is the main mechanism used to target helminth infections?
TH2 response - very strong
- release of inflammatory mediators
- high levels of IL-4, IgE, many eosinophils + mast cells at infection sites
- ag-bound IgE attach to their specific IgE FcR on mast cells → degranulation
255
How do eosinophils respond to parasite infection of the host?
IgE binds to worm
Binding of FcR to IgE triggers activation ⇒ release toxic mediators
→ breakdown of worm's cuticle
256
How is the TH2 response selected in favour of TH1 mechanism?
IL-4 driven
257
Describe the process of TH2 in eliminating parasite infections within a host.
TH2 cells suppress macrophage activation; stimulating eosinophils + mast cell action
Generates a strong ab response based on neutralising IgE + IgG
- best method for combatting EX pathogens
258
What are the roles of eosinophils + mast cells in parasite infection?
Mast cells stimulate worm expulsion
Eosinophils kill worms
259
How does CMI respond to helminth infection?
Some Tc responses
Sensitised T-lymphocytes attack by:
- macrophage attraction + activation
- Tc cells attack larvae
260
What physiological host changes are induced by anti-worm immunity?
Increases no. of goblet cells
Increased mucin secretion
Increased intestinal mobility
Increased H2O influx into intestinal lumen
261
By what means can helminths evade vertebrate host immunity?
- size
- thick extracellular coat
- adsorbing host proteins
- anatomical seclusion
- molecular mimicry
- surface ag-shedding
- interference with ag-presentation
- immunosuppression
- anti-immunity mechanisms
- migration
- production of enzymes
262
How successful are vaccinations against helminth infections?
- poor host immmunity means very few effective vaccines
- drug Tx are much more common
263
What possible effects can saliva of arthropods have on hosts?
Stimulation of TH1
Induction of basophilic infiltration
TH2 response?
Impaired APC ability
264
What agent can parasites release to interfere with immune responses?
Free ag
265
What effects does the release of free ag by parasites have on parasites?
1. Block ab
2. Blockade effector cells
3. Induce B- + T-lymphocyte tolerance
4. Induce polyclonal activation to divert immune system
5. Inhibit the inflammatory response
266
What does polyclonal activation refer to?
Activation of B-cells to produce ab specific to epitope identified in response to detection of an ag
267
Describe the main features of cancer.
Damaged cells of body that no longer undergo programmed cell death
Growth is no longer controlled
Metabolism is altered
268
Describe the basic features of a tumour.
A swelling or lesions formed by an abnormal growth of cells
Might not be due to cancer
**A cancerous tumour arises from a single cell proliferating uncontrollably**
269
Suggest some potential causes of tumours.
Oncogenes
Tumour suppression genes becoming dysregulated
Carcinogens
Age
Genetic make-up
Diet
Immune deficiency
Environment - e.g. plant products
Infections - especially viruses
270
What is the definition of an oncogene?
Protein-encoding genes that trigger onset + development of cancer if they dysregulate
271
What different types of tumour are there?
Benign
Malignant → metastases
Premalignant
272
What potential mechanisms of the immune system could target tumour cells?
Macrophage activity
Dendritic cells - APC
CD8 cell-mediated cytotoxicity
NK activity
ADCC (ab-dependent cell-mediated cytoxicity)
273
What does FcR refer to?
Refers to fragment crystallisable receptors found on ab coating pathogens detected by the immune system
274
What different kinds of ag are expressed on tumour cells?
Tissue-specific ag
Reactivated gene products
Viral ag
Mutated gene products
275
What are the 3 major cell types involved with tumour immunity?
NK cells
Macrophages
CD8 cytotoxic T-lymphocytes
276
Descrive the T-cell mediated response to detected tumour cells.
Tumours express ag
Tumour cells phagocytosed by APC (macrophages)
APC expresses ag → triggers TH1 + Tc cells
Tc cells kill tumour
277
By what means can NK cells kill tumour cells?
Targeting tumour cells lacking in MHC-I
Kill tumours using ADCC
278
What 2 cytokines are needed to stimulate NK cell growth?
IL-2
IFN-gamma
279
What role do IL-2 + IL-4 have within the immune system?
Increase cytotoxic T-lymphocyte activity
280
What does TNF refer to?
Tumour necrosis factors are cytokines that can causes apoptosis
281
What role do TNF + IL-12 have within the immune system?
Induce IFN-gamma secretion by NK cells
282
What mechanisms do tumours have for escaping the patient's immune system?
- low immunogenicity
- ag modulation
- suppression of anti-tumour immune response by tumour cells or T-regulatory cells
- induction of lymphocyte apoptosis
283
What means are there for treating lymphomas?
Chemotherapy - highly effective
Vaccination
284
What is the definition of immunological tolerance?
A state of unresponsivenes to a particular ag
285
What is another term describing self-ag?
Autoantigen
286
Describe the 5 main mechanisms of post-thymic tolerance.
- self-reactive T cells ignore self-ag + sequestered ones
- self-reactive T cells abort
- self-reactive T cells rendered anergic
- self-reactive T cells deleted
- maintained by immune regulation ie. TH1/TH2/Treg
287
Describe the features of B-cell tolerance.
- self-reactive B cells removed in bone marrow + spleen
- self-reactive B cells may abort, be deleted or anergised
- some self-reactive B-cells will survive + enter circulation
- lack of T-cells helps prevent B-cell reactivity
288
What 2 kinds of immunological tolerance are there?
Central - in thymus + bone marrow
Peripheral
289
What is autoimmunity?
Loss of self/non-self discrimination within the immune system, resulting in immune responses + damage to host tissues
290
How does autoimmunity arise?
- exposure of hidden ag
- formation of new epitopes
- cross-reactivity with microorganisms
- induction by viruses
- immunoregulation deficiency
- histocompatibility ag
291
What happens in myaesthenia gravis?
Autoantibodies are prodced against Ach receptor → prevents muscle from responding to Ach
⇒ muscle wastage
292
How many different types of hypersensitivities are there?
4 types
293
What is atopy?
The genetic tendency to develop allergic diseases
- typically associated with heightened immune responses to common allergens
294
What is the normal Ig production process?
IgM production within 1º response
Switches to IgG/A production in 2º response
295
Describe type I hypersensitivity.
Mast cell degranulation occurs
- acute anaphylaxis: horse, pig cat - emphysema + intestinal haemorrhage + D++
dog - collapse of hepatic veins
- specific allergic conditions:
- urticaria
- milk or food allergy
- allergic inhalant dermatitis
- allergies to drugs, vaccines
- parasitic allergies
296
Which type of hypersensitivity is associated with frustrated phagocytosis?
Type II hypersensitivity
297
Describe the main features of type II hypersensitivity.
Damage results from ADCC by NK cells
cytotoxicity due to complement
⇒ ab + complement react to host cells/tissues
*\* tissue damage is caused by _frustrated phagocytosis_*
298
What condition is an example of type III hypersensitivity affecting the renal system?
Glomerulonephritis
299
Describe the process of type III hypersensitivity.
**Immune complex mediated -** form/deposited on host tissues
- ag-ab complex deposits on endothelium of vessel
- inflammatory sites localise to area, stimulated by cytokines
- complement + neutrophils attack ag-ab complex, whilst fibrinous necrosis of endothelium occurs
300
What kind of cells mediate type IV hypersensitivity?
T-lymphocytes
301
What molecules are NOT involved in type IV hypersenstivity?
Antibodies
302
Describe the process of type IV hypersensitivity.
Primed T-cells respond to chronic ag load by production of cytokines
- cytokines attract + activate macrophages
- macrophages damage tissues by release of proteolytic enzymes
303
What term is used to describe an ineffective immune response?
Immunodeficiency
304
What cells are responsible for rejection of transplants within a recipient body? Why is this?
Tc cells + macrophages
Differences in MHC-I + MHC-II in donor + recipient bodies
305
How many different kinds of immunodeficency are there?
1º - inherited defects
2º - extrinsic causes
306
What risks are increased in associated with immunodeficiency?
Increased susceptiblity to opportunistic infections
Increased risk of tumours
307
Give an example of an inherited deficiency.
Complement deficiency - Brittany Spaniels + Finnish Landrace lambs
- C3 deficiency
308
When are autosomal recessieve genetic disorders presented?
Problem allele is only effective when expressed in homologous manner ie. 100% offspring
When heterozygous at 50%, animal is not ill but a _carrier_
309
What are BLAD + CLAD? And what autosomal recessive condition do they both refer to?
Canine leucocyte adhesion deficiency - Irish Setters
Bovine leucocyte adhesion deficiency - Holstein cattle
- phagocyte deficiency caused by failure of granulocytes to leave blood + enter sites of infection
310
Describe the process of normal inflammation.
- cells migrate from circulation into sites of infection/inflammation to phagocytose bacteria - are attracted by several mediators
- enabled by increased expression of adhesion molecules **selectins** on vascular endothelia + _integrins_ on leucocytes by cytokines
- PMN express ***CD11b/18*** which binds to ICAM-1 on vascular endothelia to enable passage into tissues to deal with infection
311
What is the problem occurring with leucocyte adhesion deficiency (LAD)?
Absence of integrin CD11b/18 means no PMN adherence to blood vessel wall → inability to leave circulation + localise at infection sites
- infection overwhelms animal
- very high leucocytosis because PMN fail to emigrate into tissues
- caused by gene mutations, failing to produce CD11b/18
312
Describe the condition of SCID (severe combined immunodeficiency).
Seen in the Arab horse
No functional T or B-lymphocytes in circulation or tissues
Foals sicken after MDAs wane (agammaglobulinaemiac)
Autosomal recessive condition
Overwhelming infections → death at 4-6mo
313
What other forms of SCID are there?
X-linked (sex-linked) immunodeficiency in Bassett hounds + Corgis
- thymus has low number of lymphocytes ⇒ low T-cell numbers in circulation, no IgG or IgA, but normal IgM
- because X-linked, females are carriers only + disease is only seen in males
Jack Russell Terrier SCID
- autosomal recessive loss of DNA protein kinase leads to faulty recombination of ag-receptors ⇒ non-functional B & T cells, no Igs
314
What is foal immunodeficiency syndrome?
Autosomal recessive fatal genetic disease seen in Dales + Fell ponies
B-cell deficiency causes very low Igs
Foals die after loss of MDA - no survivors
Opportunistic pathogens are lethal
- carrier test is now available
315
Name 3 primary autosomal recessive defective conditions.
Genetic IgM deficiency in Arab/quarter horse foals
Thymic aplasia in nude cats - T-cell deficiency
Ehlers-Danlos syndrome - fragile hyperextendable skin + immunodeficiencies
316
Name 7 potential causes of 2º immunological defects.
1. Viruses
2. Microbial/parasite infections
3. Toxins
4. Malnutrition
5. Exercise
6. Trauma
7. Age
317
Desribe the main features of retroviruses.
Affect primary or secondary lymphoid tissues
Phospholipid envelope
RNA
Reverse transcriptase enzyme
318
Give 4 examples of small animal immunodeficiencies.
Feline immunodeficiency virus (FIV)
Feline leukaemia virus (FeLV)
Canine distemper virus
Canine parvovirus
319
Give 4 examples of canine infectious immunodeficiencies.
- Ehrlichiosis
- Anaplamosis
- Leishmaniasis
- Demodicosis
320
What are the main immunological tests used for?
Infections
Hypersensitivities
Autoimmunity
Immune function
321
What does serology test for?
Detection of specific ab to indicate the presence of a specific infection
322
What is the result of clonal selection + expansion of B cells?
Generates plasma cells + memory cells
323
What can be done to distinguish between infected and vaccinated animals?
Modify vaccine given to include extra (marker) ag targets
- requires extra serological test, but specificity is assured
324
What different forms of serological test are there?
Double immunodiffusion assays
Radial diffusion assays
Bacterial agglutination
Immunoelectrophoresis
RBC agglutination
325
Describe the process of double immunodiffusion assays.
ag + ab are placed in wells cut into agar gel and allowed to migrate towards each other
- a line of precipitation may be formed where the 2 reactants meet
- if the ag +/- ab wells contain several molecular species then multiple lines of precipitation are possible
326
What are the 3 basic patterns of precipitation possible from double immunodiffusion?
Lines of identity
Lines of non-identity
Lines of partial identity
327
How does a single radial immunodiffusion (SRID) assay work?
As the ag diffuses radially a ring of precipitation forms around the well + moves outwards
Eventually becomes stationary at _equivalence point_
328
What is immunoelectrophoresis used for?
Detecting B-lymphocytes myelomas
329
How does electrophoresis work?
Allows serum proteins to be separated by an electrical current
330
Describe the process of immunoelectrophoresis.
Patient's sera are separated by electrophoretic mobility
Then ag are detected by specific ab
331
What is myeloma?
Unrestricted multiplication of one plasma cell secreting one particular Ig
332
How would myeloma be detected?
Using immunoelectrophoresis (IEP)
- unrestricted multiplication of one plasma cell secreting a particular Ig → increase in serum conc of specific Ig
- therefore a myeloma would show a particularly thick heavy chain with corresponding thick light chain
\* an increase in a heavy chain without specific light chain increase will be **polyclonal** + probably due to infection/inflammation
333
How would polyclonal stimulation be detected in IEP?
All Igs levels would be raised in excess
334
How would immunosuppression be determined by IEP?
All Ig levels would be within a state of deficiency
335
How are positive + negative RBC agglutination results detected?
**Positive result:** RBC agglutination occurs within test tube
**Negative result:** RBC settle as 'button' within test tube
336
What different agglutination methods are there?
Bacterial
Viral
RBC
Particles coated with ag - RBC; latex particles
337
What methods can be used to label abs?
- fluorescent tags
- enzyme tags
- gold particles
- radioisotopes
338
What are the main features + advantages to using an ELISA? What does ELISA stand for?
_Enzyme-linked immunosorbent assays_
- quantifiable
- quick
- reproducible
- inexpensive
- doesn't require complex training to use
- can detect ag + ab
339
How do non-agglutination tests function?
Rely upon having reagents to detect host ab responses
- ab for detecting IgG, IgA + IgM will need to be tagged with a label for subsequent detection
340
How does immunofluorescence work? What different kinds of immunofluorescence are there?
Uses commercial ab tagged with a fluorescent molecule
e.g. FITC, rhodamine
Fluorescence is observed using UV microscope
Direct vs. indirect methods
341
How do the different methods of immunofluorescence compare?
**Direct:** detects ag in tissues
**Indirect:** detects ab in sera
342
How does a complement fixation test work?
Immune complexes bind + consume complement
Therefore depletion means no remaining complement to lyse ab-coated RBCs
343
What is the alternative name for immunoperoxidase staining? How does this method work?
*Horse radish peroxidase*
Uses wax sections
Uses LM
Good tissue architecture
Counterstaining possible
Good morphology
Coloured targets for better visibility
344
What 2 kinds of neutralising tests are there?
Virus neutralisation tests
Haemagglutination inhibition test
345
Which type of hypersensitivity is TB-testing based on?
Type IV hypersensitivity - mediated by T-lymphocytes
346
How does flow cytometry work for immunological testing?
Identifies cell surface markers - e.g. T + B-lymphocytes
Cells incubated with markers are tagged with fluorescent probes
Cells are passed through laser beam which detects different coloured cells ⇒ marker profile
