Immunology Exam 2 Flashcards
What are killed vaccines (inactivated)?
The agent in the vaccine has been killed. They often contain an adjuvant to enhance the immune response
What does the EPA regulate?
Topical insecticides
What is vaccine potency?
The vaccine containes the required amount of antigens and adjuvants needed to induce immunity
Maternal Antibodies _____Antibody production in the newborn
inhibits
What type of vaccines usually have adjuvants?
Killed vaccines
What are some things that can happen to a vaccine or the way it was administered?
- Storage Temp
- exposure to light
- improper diluent used
- mixing of vaccines
- Vaccines administered concurrently
- Freeze thawing of reconstituent vaccine
- bacterial contamination of multi-dose vial -administered the wrong route
- Different strain
What is active immunity?
Immunity that is produced as a result of antigen stimulated immune response in the individual
What is an example of a type II hypersensitivity?
RBC (Transfusion reactions, Hemolytic disease of the newborn, anemia) other cells types like skin
What is a cytokine?
• Protein messenger molecules - low molecular-weight secreted proteins that regulate intensity and duration of innate and adaptive immune responses
Key Role of ILC3 and TH17
Extracellular bacteria and fungi
What are the disadvantages of MLV’st
- can revert to virulence
- May be virulent in a immunosupressed animal
- may be immunosupressive
- may cause abortion
- can be contaminated with other live viruses
- must be handled carefully to maintain viability
What is a colony Stimulating Factor?
stimulate colony formation in bone marrow, stimulate stem
cell differentiation
Define Antibody
An immunoglobulin protein molecule synthesized on exposure to antigen which can then bind to that antigen
What does it mean when we detect high levels of IgM in an antibody test?
Recent infection
How does allergen specific immunotherapy work?
expose the organism to small amounts of the antigen to cause a local degranulation reaction
What are the two types of passive immunity?
Maternal Transfer
By injection
When can you see systemic effects of proinflammatory cytokines?
in moderate amounts and act on hypothalamus
Where does antibody synthesis occur?
In plasma cells (thousands per minute)
What are the basic components of lateral flow immunodiagnostic test?
Ex: Heartworm test
as the heartworm antigen passes by it picks up the antibody labeled in red and then picks up the antibody with blue color. If there is antigen then the red and blue line show.
How is the innate immune response activated?
by danger signals from the pathogen or tissue damage
What factors influence vaccine efficacy in the presence of maternal antibody?
- Maternal antibody titer
- Immune mechanisms
- characteristic of the pathogen
- immune competence of the young animal
What charcteristics of the vaccine influences vaccine efficacy in the young animal?
MLV/vs. killed Adjuvant rte. of administration antigenic mass number of doses
What does lack of parasites contribute to?
Type I hypersensitity
What turns down the cytokine response?
Feedback inhibitory mechanisms
What are the factors that can decrease resistance and increase suceptibility to bacterial pneumonia?
- Genetics
- Distress
- Viruses
- Age
- Coccicia
- Poor nutrition
- Paracites
Explain how vaccines can fail due to an overwhelming challenge dose
- Poor sanitation in diarrheal viruses
2. Poor ventilation in respiratory viruses
What are the cellular components of the innate immune response?
cellular components (setinal cells, phagocytes and granulocytes, innate lymphoid cells
A person with very high levels of antibody to tetanus toxin is at risk for an adverse vaccine reaction following a tetanus toxoid booster. The reaction begins to manifest 6-8 hours after the booster and is characterized by acute inflammation at the site of the booster (can cause swelling and pain which resolves in a day or two). Give the immunologic basis for this reaction and include the cells and molecules involved. Do your best to include the type of hypersensitivity, inciting cause of inflammation, and the cells and molecules that result in inflammation.
Type of Hypersensitivity: Type III (Arthus Reaction)
Cells: Neutrophils and mast cells
Molecules: Complement fixation components, mediators released from the mast cells and oxygen radicals produced by the neutrophils causing damage
Complexes form and invade tissues
Timing 2-8 hrs.
What are the major sentinel cells?
Dendritic, macrophages, mast cells
- Give an explanation for a potential mechanism of action for hyposensitization therapy for Type I hypersensitivities.
Allergy Shots: getting injected with small amounts of the allergen they have made IgE to. Over time the goal is to get the immune system to switch away from IgE. They want the immune system to make TH1 cells and IgG.
What does the classical pathway require?
Antibody
What is autoimmune disease?
The adaptive immune system attacks self molecules or cells
What is the difference between a normal vaccine reaction and an immediate type hypersensitity reaction?
A immediate type reaction will be very rapid and may cause swelling of the muzzle, and face. I can also be systemic and mount an anaphalactic response
What are some clinical manifistations of Type III hypersensitivites
Serum sickness or Autoimmune disease
Define Hypersensitivity
An immune mediated damaging inflammatory response to a normally innocuous antigen
What is immunodeficiency?
Failure to protect from infections or cancer
When type of protective immunity is considered a circulating antibody?
IgG or IgM that provides protection
Why are proteins good antigens?
they are complex; they have positive/negative charges, hydrophobic areas, etc.
What antibodies are complement fixing?
IgM and IgG
How does • Production and secretion of interferon by one cell protects nearby cells ?
including activating proteins in the neighboring cells that inhibit viral replication
How are cells destroyed in a Type II hypersensitivity?
An antibody attacks a cell surface in the body: Phagocytosis of the cell (rbc) or if a tissue cell the neutrophils and macrophages can attack the cell on lacation. If we get enough antibodies complement system is activated.
Define passive immunity
Antibodies passed from one individual to another
What is perceived vaccine failure?
You think the vaccine failed but it really didn’t
What is a defensin?
A small cationic antimicrobial peptide that can insert and poke holes in bacteria
What are the types of cytokines?
Interleukins (IL1,IL2,IL3IL4) Interferons Chemokines Colony Stimulating Factors Growth Factors
Cellular response to cytokines is ______
tightly regulated
what questions should you ask in terms of protective immunity when vaccinating?
What are the important antigens you must have in your vaccine to induce protective immunity? and what type of antibodies
Are polysaccarides good antigens?
not as good as protein, because it is not complex, usually has repeating structures and no charge
In herd immunity what type of responses can you get?
- Most animals produce an adequate immune response
- Some animals produce an poor immune response and will be poorly protected
- A few animals produce a superior immune response
What is a membrane attack complex?
has a hydrophobic exterior and hydrophilic interior (poke a hole in the bacterial cell membrane)
How long do neutrophils live for?
1-2 days and then enter tissues and do not return to circulation
Antibiotic
A chemical compound obtained from microorganisms that can prevent growth or kill bacteria
What are antibodies?
large proteins with antigen binding sites and Fc portion that is responsible for the biological functions of antibody
What are new technology vaccines?
DNA Vx, RNA particle vaccines and Live vectored vaccines (Chimeric) Live gene deleted Non replicating recombinent antigen vx (virus like particle, Genetically engineered) nucleuic acid mediated
What part of immunity are basophils a part of?
innate
If you did a serology test for IgE antibodies would you see them in high numbers during a reaction?
No because they are not in the circulation and reside on mast cells.
How long before the adaptive immune response kicks in?
Several days to weeks
Where do lymphocytes circulate?
between the lymph and blood
How is active immunity activated via natural infection?
Exposed to pathogen and innate response is activated
B cells and T cells respond with antibodies, t cell cytokines and/or cytotoxic t cells
What are released when a vaccine is given?
Proinflammatory cytokines
What is a hypersensitivity reaction?
Immune mediated diseases such as allergies
This is when the adaptive immune system attacks molecules that are not dangerous
What is cytokine production induced by?
various signals
What are the Important Properties for Strong Antigens (immunogen)?
Foreigness
Size >10,000 MW
Molecular Complexity
Rigidity/Degradability
What is the duration of immunity of a vaccine dependent on?
- presence of the antibody
- Presence of effector and memory lymphocytes (B cells, TH1, TH2, TH17, CTL, or Gamma Delta T Cells)
- Health Status
- Characteristics of the pathogen (virulence and dose)
- Two dogs, Wrigley and Bush, are in for intradermal skin testing for allergies. Explain why Wrigley developed wheal and flare to ragweed and Bush did not and why they both developed wheal and flare to histamine.
This is an example of a type 1 hypersensitivity which is mediated by IgE. Therefore, Wrigley has been previously exposed to the antigen, resulting in the presence of the IgE ragweed antibodies on his mast cells in the dermis. This induced the response. Bush has not been previously exposed so he did not have the antibodies present to cause the reaction. Histamine is already present within the granules of mast cells and the cells of the body naturally have receptors for it to mediate mast cell action. Therefore, any dog would have a reaction to histamine injections because their receptors are not dependent on antibodies or previous encounters. Histamine is used in this situation as a positive control of the wheel and flare response.
Type 1 Interferons
Innate system cytokines
What are some examples of cytokines?
IL1, interferon alpha, interpheron gamma, GM-CSF (granulocyte-monocyte colony stimulating factors)
If we vaccinate all heathy animals we can then _____the effect unhealthy animals
minimize
What does it mean when we see high titers of IgG in a
The infection occurred a few weeks ago
What cell is responsible for the early phase immediate type (Type I) hypersensitivity reaction and what are its special features?
Mast Cells-it degranulates
what is important for a successful immune response?
Communication between adaptive and innate response
What are the cellular components of adaptive iimmunity?
Cytotoxic T cells
TH cell cytokines
Gamma Delta T Cells
- What is the difference between a COVID 19 PCR test, rapid antigen immunodiagnostic test, and an antibody test?
PCR-Looks for Portions of RNA from the virus
Rapid Antigen Test-Looks for a specific antigen (less sensitive)
Antibody Test-Tells us whether the patient already has antibodies for the infection
What are adjuvants?
Something that is added to vaccines to enhance immunity or alter the immune response to co-administered antigen
How is complement regulated?
The components of complement are short acting and are quickly hydrolyzed into inactive states. Many molecules can inactivate complement components
What are the key components in a type III hypersensitivity?
IgG and soluable antigens
What sytemic effects do you see with moderate amounts of pro-inflammatory cytokines?
Fever Sickness behavior action on the liver stimulates the bone marrow to produce more neutrophils neutrophilia Acute phase proteins
How is the Alternative pathway for complement initiation activated?
C3b binding on the cell wall of bacteria, fungi and some viruses
What are advantages to killed vaccine and bacterins?
- Safer
- No reversion to virulence
- no contamination with live viruses
- less likely to be immunosupressive
- less likely to cause abortion
- more stable in handling
If you know the pathogenic mechanism you can figure out the ________
defensive mechanism
What are the pathways for activation of complement?
Classical, Lectin and Alternative
What does the USDA regulate?
Vaccines and diagnostics
What is a true vaccine reaction?
Due to the vaccine or way it was administered
What are some antigen tests?
- Isolation and identification
- PCR
- ELISA
Why do some individuals develop type I hypersensitivity and others do not?
We don’t know the whole story but genetics is part of it along with environment (too clean)
How long does it take a mast cell to degranulate?
5 seconds to start and 1 minute for lots of granules
What is the biggest host factor that cause vaccines to fail?
Presence of the maternal antibody
Is the innate immune response antigen specific?
No
What are the major phagocytic cells?
Neutrophils, macrophages, dendritic cells
What defense mechanism do killed vaccines usually induce?
Neutralizing antibody and Th 1 cytokines
Key role of ILC2 and TH2
Helminthic parasites/allergy
Where can the veterinary vaccine regulations be found?
Virus-Serum-Toxin Act in title 9 of the code of federal regulations
What defensive mechanism would be activated when the pathogen is a parasite?
TH2 and IgE
What agency regulates pharmaceuticals and animal devices?
FDA
What are platelets important for?
Blood Clotting but no role in immune response
What do antibodies form against in SLE?
DNA
What does the USDA say that licensed biologicals must be?
Pure
Safe
Potent
Efficacious
Which types of vaccines induce the endogenous antigen pathway of presentation?
MLV
Live vectored
DNA vx
RNA particle vx
When selecting the optimal technology for new technology vaccines, what should you consider?
- Understand antigen processing and presentation
- pathogenic mechanisms
- defense mechanisms
- protective antigens
What is the function of cytokines?
Protein messenger molecules
Where are Mast cells located?
In tissues
What is hemolytic disease of the newborn?
The mother has developed rbc cell type of the father and newborn also has rbc type of father. When the newborn receive colostrum a reaction will occur
What are eosinophils important in?
Parasite defense and contribute to allergy symptoms
What type of protective immunity is usually activated for viruses?
cytotoxic T cells
At what point do MLV vaccines start to work in young animals
12 weeks but with a 2 weeks period of vuneralbility
What defensive mechanism would be activated when the pathogen is a virus that replicates very rapidly?
Type 1 and 2 interferons
What is the timing of a type IV hypersensitivity?
DTH 24-48 hrs.(TB testing)
What defensive mechanism would be activated when the pathogen infects epithelial cells?
Gamma delta T cells
What are the primary mediators in the type I hypersensitivity response?
Granule contents (Histamine, Proteases, and Chemostatic Factors)
If you are concerned about influenza, you may check a serum sample two to three weeks later, what will you be looking for?
o You would not expect to find IgM for influenza in the serum sample due to its short half-life of about 5 days. On the other hand, a serum sample collected those two to three weeks later could still indicate levels of IgG for influenza due to its half-life of around three weeks.
What does C3 break down to?
Spontaneously breaks down to C3a and C3b
T/F immunologic memory is faster than a primary response
True
Who would you call if you have issues with the safety of a vaccine?
USDA center for biologics or company veterinarian
How many cytokines exist?
over 60
What can the adaptive immune response develop?
Memory and tolerance
How long does it take for long lived plasma cells to be produced?
2 or 3 weeks
Name the proinflammatory cytokines.
IL-1,
TNF,
IL-6 and HMGB-1 (high mobility group box protein-1, also called “alarmin”, and is released from damaged tissue cells).
What defensive mechanism would be activated when the pathogen adheres to the mucosa?
A mucosal antibody (IgA)
What is the most important C component in the Alternative pathway and also has the highest concentration in the blood.
C3
What tests detect antibodies?
- Elisa
2. Neutralization /inhibition assays
What are the advantages of Live vaccines?
- More rapid protection
- Longer immunity
- One dose is sufficient
- No adjuvant required
- Better induction of cell mediated immunity (esp. cytotoxic T-cells)
- Better able to stimulate IgA
- May stimulate interferon
- Less expensive
Where are short lived plasma cells found?
lymphoid tissues
Where are endotoxins found?
Gram negative Bacteria
What are the secondary mediators in a Type I hypersensitivity response?
Membrane phospholipids that make arachadonic acid and PAF that release Leukotrienes and prostaglandin
T/F classical pathway occurs during primary response
False-antibody is not present
What is a plasma cell?
A fully differentiated B cell
If we given an animal a modified live vaccine at 6 weeks and the animal is receiving materal antibodies, will the vaccine work?
No because materal antibody titer is still too high
How does complement increase vascular permeability?
- endothelium allows neutrophils, macrophages and lymphocytes to easily exit the blood vessel and enter the tissues
- allows fluid containing antibody and components of complement to easiliy get to the site of infection
What is the • Interferon autocrine effect?
can result in infected cell increasing MHC1 presentation which will increase the likihood of a cytotoxic T cell recognizing the cell to kill
When is the innate response more effective?
In the presence of adaptive immunity
What are mucosal antibodies?
IgE on mast cells under the mucosal surface
IgA in the mucosal layer
Are mammalian DNA good Antigens?
not good , simple, flexible, easily degraded, not foreign
What do dendritic cells do?
phagocytose microbes and play a role in processing and presenting antigens to T cells
● Antibody molecules are different enough between animal species to be immunogenic, e.g. equine antibodies are immunogenic in humans. Think about the important characteristics of immunogens. What makes a good immunogen/antigen?
A good antigen is large (>10,000 MW), foreign, complex, rigid, and degradable.
What are primary lymphoid tissues?
Where T and B cells become educated to determine which antigen they will recognize
What does the Law mean by safety of vaccines?
Freedom from properties causing undue local or systemic reactions when used as recommended or suggested by the manufacturer
What type of vaccine can break through maternal antibodies sooner?
Intranasal
What are B lymphocytes are part of?
Adaptive immunity
- Humira (adalimumab) and Enbrel (etanercept) are commonly advertised on TV and in magazines for treatments for inflammatory diseases such as rheumatoid arthritis. What are the mechanisms of action of these two drugs?
Both of these drugs use similar mechanisms of action to accomplish the same goal. They both minimize free tumor necrosis factor (TNF) in the synovial fluid. TNF is responsible for the excessive inflammation in joints associated with rheumatoid arthritis. While both drugs bind TNF to inhibit its ability to bind cell receptors and exhibit action, Humira only targets the specific TNF-alpha. Enbrel will target TNF-alpha and -beta.
What are the two types of active immunity?
Natural infection
Vaccination
What function of the complement system does MAC function under?
Lysis of bacteria
What is a lectin?
A protein that binds to a carbohydrate
What do sentinel cells produce?
Pro-inflammatory cytokines
When does the innate immune response take affect?
immediately
- Provide some explanations for why vaccination for diseases such as measles have been so effective and induce immunity that lasts years, but vaccination for influenza is much less effective and yearly boosters are recommended.
-There are a variety of factors that contribute to immunity. For the individual receiving the vaccine, genetics, health status when receiving the vaccination, and health status when exposed all play a role in how the individual’s immune response. This also extends to the pathogen as well where virulence, dose, and antigenic drift and shift effect the outcome of immunity. One large difference between measles and influenza is that measles is given via a live-attenuated vaccine and demonstrates little mutation. It is considered a relatively stable virus which allows for longer immunity. On the other hand, influenza’s mutations due to antigenic drift and shift allows the virus to change immunity to the strain(s) of the virus that are present in the vaccine.
When is the adaptive immune response most effective?
when innate defense mechanisms are in play
- Explain why in an O negative (no A or B antigen on her RBCs and no Rh factor) human mother prevention of hemolytic disease of the newborn (fetus) in humans focuses only on the Rh antigen and not the antibodies the mother has to the A and B blood group antigens.
If the mother is exposed to Rh antigen the mother may make IgG antibodies that can cross over the placenta than it can damage the baby RBC’s. We do not have to worry about this in livestock animals because antibodies cannot cross the placenta but will be in the colostrum.
What do T cells do when immunologic memory has taken place?
T helper and T cytotoxic clones have expanded, matured, and are circulating
How are cells destroyed in a Type IV hypersensitivity?
cytotoxic T cells
Where are dendritic cells located?
• Along vessels
What is schedule is recommended to vaccinate cats and dogs?
every 3 weeks
What causes the post vaccination illness?
Pro-inflammatory cytokines
Describe some therapies for Allergies?
- Avoidance
- Symptomatic (Singulair, Atopica, Xolair)
- Allergy specific immunotherapy
What are interferons less successful in defending?
Slow moving viruses
What happens during immunologic memory?
Antigen specific clones of B and T lymphocytes have expanded and matured
Define atopy
Allergies to ragweed, house dust mites and inhaled antigens that produces pruritus and dermatitus in canines
What type of immunity are monocytes a part of?
innate
What should we take into consideration when we decide when and how to vaccinate?
Maternal Antibody
What is a sentinel cell?
“guard” cells found in tissues under the skin and mucus membranes, alert the body to invasion by pathogens or to cellular damage
what are new technology vaccines?
Based on genetics
- Rituximab (anti-CD20) is a monoclonal antibody used in people with B cell non-Hodgkin’s lymphoma. Explain how this immunotherapy helps treat B cell non-Hodgkin’s lymphoma, i.e., what is the function of the antibody and how does it lead to death of the lymphoma cells. CD20 is a surface molecule and is found on lymphoma cells. It is also used as a marker for B cells.
Rituximab is used to target the specific antigens of the non-Hodgkin’s Lymphoma tumor to destroy or reduce the size of the tumor. This can be done through the opsonization of the lymphoma cells for phagocytosis, the monoclonal antibody drug can bind to lymphoma cells allowing natural killer cells to enter and kill the cell, or the cell can die through complement fixation. Neutrophils and macrophages could also kill the cells post opsonization. The antibody binding could also induce antibody-dependent cellular cytotoxicity.
Poison ivy contact dermatitis is a type IV hypersensitivity. The urushiol oil of the plant is a small lipid soluble chemical. It covalently binds to extracellular host proteins and also crosses the host cell membranes and covalently binds to intracellular proteins; the newly formed molecule induces an immune response. Based on the description of this immunogen, describe how the antigen is “seen” by the immune system, what cells of the immune response are stimulated.
The Hapten fastens itself to host proteins (extracellular and intracellular) and is now seen as a new antigen. Extracellularly it will present itself on MHC II stimulating TH cells. If it crosses the cytoplasm it will present itself on MHC I and CD8 positive cells will be stimulated along with cytotoxic T cells.
The cytotoxic T cells will destroy the epithelial cells presenting that antigen. The release of the
Cytokines activate the cytotoxic T cells causing the blisters.
Key Role of ILC1 and TH1
Intracellular microbes
What is a white blood cell called?
Leukocyte
What are defensins produced by?
Epithelial and phagocytic cells
What is an interferon?
interfere with virus replication (they do more than that)
How does vaccination induce active immunity?
introduces vaccine antigens to induce immune system to make antibodies and effector T cells
What are neutrophils important for?
protection against bacterial and fungal infections (phagocytic)
Key Role of NK cytotoxic cells and CD8 CTL’s
Viral and intracellular bacteria and cancer
What factors must be known before a diagnostic test result can be interpreted properly?
Understanding the pathogen
What does it mean when a diagnostic test is measuring an antibody?
- May be due to infection or vx.
- Maternal antibodies
- can persist after infection
Titers will increase in a recent infection if paired serum samples are tests
What causes a fever?
moderate amounts of IL1 and IL6 acting on the hypothalamus
After a vaccination is given, when would you see clinical signs of proinflammatory cytokine release?
12-24 hrs
In low quantities who do pro-inflammatory cytokines do?
induce local inflammation,
What is the timing of a type III hypersensitivity?
6-8 hrs for a local vaccine reaction (resolves within 24 hrs.)
What does cytokine milieu do?
Cytokine milieu regulates cell function and trafficking (movement)
How are cells destroyed in a Type III hypersensitivity?
- The IgG reacts to soluable antigens and antibody: antigen complexes form.
- The complexes are deposited in tissues leading to immflammation and can collect at plasma filteration points such as the kidney, joints, and CSF fluid
Name the categories of vaccine failure
- Perceived
- Problems with Vaccine or way it was administered
- Factors associated with the host
- An overwhelming challenge dose
- Inadequate protection
What does Benadryl or Antihistamines do?
Block or counteract mediator effects when mast cells degranulate
Innate Immunity
Protects the naive animal
What are some mammalian proteins that are adjuvants?
IFN gamma
IL12
other cytokines
What are microbial component adjuvants?
Muramyl dipeptide
Bacterial DNA
(These stimulate Pattern recognition receptors)
What are some effects of pro inflammatory cytokine release post vaccine?
Fever, lethargy and anorexia
Why do we give booster vaccines?
Effector and memory lymphocytes taper off.
How long do lymphocytes circulate?
4 months (120 days) between blood and lymphoid tissues looking for antigens
- When a person who has not been vaccinated for rabies is bitten by a rabid animal or an animal that may be infected with rabies the post-exposure prophylaxis recommendations are:
a. Treatment of the wound - scrub with soap and water, remove foreign material, apply virucidal agent, treat with antibiotics if needed
b. Administer human rabies immunoglobulin (HRIG) on Day 0. It is recommended to infiltrate the wound with HRIG. Do not give in the same anatomical site as the rabies vaccine. HRIG is high tittered, high affinity IgG antibody that binds to the rabies virus.
c. Administer rabies vaccine for humans IM on Days 0, 3, 7, 14, and 28.
What percentage of monocytes are in the circulation?
3-7%
office it has a swollen muzzle and swollen eyes. It is having a hypersensitivity reaction to the vaccine. Explain the immunologic mechanism of the reaction and include the cells, molecules, and important mediators involved.
- Immediate Hypersensitivity reaction
- Molecules involved are the IgE on the mast cell. This causes mast cell to degranulate
- Mediators that are causing the clinical signs are
Histamines(primary), Proteases, Chemostatic)
What percentage of basophils are in the circulation?
0.5%
How do we test for IgE mediated allergies?
Intradermal skin testing (creates a local mast cell degranulation) or serology
- What immunologic defense mechanism is likely to be important to protect an animal from an organism that replicates in the cytoplasm, include a short explanation?
When a pathogen replicates in the cytoplasm, the main method of destruction of that pathogen must be the destruction of the entire cell. Therefore, cytotoxic T cells would be the main mechanism of destruction of this pathogen. The infected cell would utilize MHC class 1 to present parts of the pathogen on the surface of the cell and induce its destruction via cytotoxic T cells. TH1 cells would also be activated to help improve the cytotoxic T cell activity.
What are the clinical signs of a type IV hypersensitivity?
Either TB test for DTH or similar to poison oak.
Is previous exposure required to initiate the lectin pathway?
No-its innate immunity and no memory develops
What does Atopica do? (Cyclosporin)
Block T cell/cytokine activation
A serum sample from a horse is collected and submitted for antibody titers. The animal has a high IgM titer for West Nile virus, no IgM for Influenza, and a medium titer of IgG for influenza.
What do you think these results indicate?
o A high IgM titer for West Nile virus would be an indication of infection of the virus. Because IgM levels have a short half-life, it would be expected that the infection was recent.
The effects of a cytokine depends on ____
concentration/amt of proinflammatory cytokines produced
Why are MLV less expensive than killed vaccines?
no adjuvant and less antigen associated with it
If cytokine activity is endocrine, it is ____
at a distant location, e.g. IL3, GMCSF that act on bone marrow
What percentage of esinophils are in the circulation?
1-3%
- A person with very high levels of antibody to tetanus toxin is at risk for an adverse vaccine reaction following a tetanus toxoid booster. The reaction begins to manifest 6-8 hours after the booster and is characterized by acute inflammation at the site of the booster (can cause swelling and pain which resolves in a day or two). Give the immunologic basis for this reaction and include the cells and molecules involved. Do your best to include the type of hypersensitivity, inciting cause of inflammation, and the cells and molecules that result in inflammation.
In an individual who has high IgG from a previous tetanus vaccination, the result of receiving a tetanus toxoid booster results in the formation of a large number of immune complexes at the injection site. This is the reason why the injection site is swollen and painful following inoculation as there is basically double the innate immune response meaning more neutrophils, more proinflammatory cytokines, and more acute phase proteins. This is a form of immune complex mediated hypersensitivity where the excessive amount of IgG binds to the Ag and forms immune complexes and leads to disease.
What is a basophil made up of?
Granules and very similar to a mast cell
What is a monokine and lymphokine?
original terms for those proteins from monocytes and those from lymphocytes, respectively. These terms are rarely used anymore.
What defensive mechanism would be activated when the pathogenic mechanism is intracytoplasmic growth?
Cytotoxic T cells
What clinical signs do histamines cause?
Vasodilation, increased vascular permeability, and Bronchiole Constriction
What is an Interleukin?
between leukocytes, e.g. IL1, IL2, IL3, IL4
Is the adaptive response antigen specific
yes
If cytokine activity is paracrine, it is ____
on another cell nearby, e.g. IL12
When does adaptive or acquired immunity take place?
after antigen exposure in the presence of danger signals from the innate system
What does Xolair do?
Passive immunotherapy, anti IgE antibody
What do eosinophils contain?
Granules that stain eosinophilioic and have mediators that kill parasites
What is immune mediated hemolytic anemia?
A normal animal develops antibodies against their own rbc called an autoantibody or foreign antibodies like drugs attack RBC
In high quantities of pro-inflammatory cytokines what happens?
cause septic shock and potentially death
The proinflammatory cytokines induce vasodilation, increased vascular permeability and upregulation of endothelial adhesion molecules. In high quantities this happens in a lot of blood vessels and leads to:
• A drop in blood pressure and low cardiac output,
• Vascular injury, thrombosis and disseminated intravascular coagulopathy (DIC); often a terminal event
• Pulmonary edema, air spaces fill with fluid, and leads to acute respiratory distress syndrome (ARDS)
- Two dogs, Wrigley and Bush, are in for intradermal skin testing for allergies. Explain why Wrigley developed wheal and flare to ragweed and Bush did not and why they both developed wheal
Histamine causes vasodilation in everyone to some extent so it is used as a positive control to see what it looks like in this animal. Wrigley has IgE on his mast cells and when the allergen is introduced degranulation occurs and he gets a reaction.
What is the cytokine milieu?
Cytokine milieu is the mixture of cytokines in the environment
What does Atopica do? (Cyclosporin)
Block T cell activation
Where are long lived plasma cells found?
Bone marrow and mucosal tissues
For the endogenous pathway, where does the antigen have to be?
In the cytoplasm
What is a growth factor?
stimulate cells to grow in vitro
What does it mean when a diagnostic test is measuring an antigen?
It indicates that the agent is in the sample but may or may not be the cause of clinical signs
A puppy develops a low-grade fever, lethargy, and mild anorexia approximately 24 hours after a vaccination. What is the immunologic basis for these clinical signs? Will you treat? If yes, what is your treatment?
- pro-inflammatory cytokines
- anti inflammatories carprofen
What does local inflammation include?
Macrophage activation, endothelium activation, complement activation
- For some diseases, with some vaccines, for example MLV viral vaccines, it is beneficial to vaccinate in the face of an outbreak.
A. Give an explanation based on what you have learned about immune responses for why this seems like it would not work
This method seems like it would not work because MLV vaccines work by inducing the body to make its own antibodies. Unfortunately, this takes a substantial amount of time for the immunological memory to be instilled in the cells of the patient. When in the presence of a substantial outbreak, there may not always be time for the body to make antibodies for itself.
Role of Gamma Delta T cells
Mucosal Protection
Why do we get fevers?
High body temperature can enhance the activity of some of the enzymes to destroy bacteria, also some viruses do not replicate as well at high temperatures
Speeds up metabolism
Where do infectious agents get drained to?
Lymph nodes
When does herd immunity wane?
Decreased vaccine efficacy or use
What is complement made of?
20-30 plasma proteins (C1,C2, C3)
What will you see if immunologic memory is produced?
Higher titer of antibody
Higher affinity for antibody
What is a monofactorial disease?
There is only one factor that you will get the disease. If you get exposed you will get the disease. The vaccines are very effective.
What are the two ways maternal transfer can happen?
- Colostral (first milk) antibodies) are ingested and absorbed accross the GI tract in some species (cow, pig, horse)
- Accross the placenta (antibody transferred) (primates and humans)
What defensive mechanism would be activated when the pathogenic mechanism is intracellular growth?
Th1 cytokines
What is an antigen?
A foreign substance that can bind to specific lymphocyte receptors an induce an adaptive immune response
Cytokine activity is _____
Receptor mediated
- What immunologic defense mechanism is likely to be important to protect an animal from an organism that grows in a phagosome of a macrophage, include a short explanation?
The main method of destruction of a pathogen that replicates in a macrophage phagosome is by initiating TH1 cells via MHC class 2. Gamma interferons from TH1 cells act on macrophages to make more lysosomal enzymes, nitric oxide, and oxygen radicals to kill the pathogen.
What are some vaccine related side effects?
Vaccine associated Feline Fibrosarcomas
Hypersensitivities (Anaphalaxysis)
Non-specific systemic side effects (pro-inflammatory cytokines)
What are the signs of anaphalaxis?
Urticaria,
How does passive transfer happen by injection?
serum antibodies from one individual is administered to another
What are the soluable components of innate immunity?
Complement
innate defense cytokines
defensins
What does the liver induce the production of during a pro-inflammatory cytokine response?
Acute phase proteins
T/F naive B and T cells can be differenciated by a light microscope
False- they are morphologically the same
Where do T cells develop?
Thymus
- C-reactive protein is a major acute phase protein and used as an indicator to monitor different diseases. What kind of information would blood levels of C-reactive protein give you regarding what is happening in the patient?
- C-reactive protein is a major acute phase protein and used as an indicator to monitor different diseases. What kind of information would blood levels of C-reactive protein give you regarding what is happening in the patient?
AVMA Principle of vaccination about who it protects
Vaccination protects a population of animals. Vaccination does not protect every individual patient even when properly vaccinated
When thinking about vaccinations what are the types of protective immunity you should consider?
Circulating antibody
Mucosal antibody
Cell-mediated antibody
Are glycoproteins and glycolipids good antigens?
o Glycoproteins and lipoproteins are good antigens because of the protein component
(b) Explain the process by which the predominant cells leave the bloodstream; include the initiating event and important molecules● The gamma interferon test for TB is a blood test. The mononuclear cells from a whole blood sample are isolated from the patient. What are the two different types of mononuclear cells identifiable with a light microscope in the blood stream (i.e. those that are not RBCs or granulocytes)? involved.
Danger signals (PAMPs/DAMPs) reach the PRR of the sentinel cells. This induces these cells to release cytokines that will react with the vascular wall near the area of infection. They (C3a, C4a, C5a) will induce vascular dilation and increase the permeability of the membrane. Other cytokines (C5a) will induce chemotaxis of the macrophages to direct them to exit the now permeable vascular walls and enter the infected tissue. macrophages will then take up the antigen and present it to the T cells to induce gamma interferon excretion.
● The TB intradermal skin test.
o Tuberculin (a purified protein from the organism) is injected into the skin dermis. In a person who is positive, 72 hours after the injection there is a palpable lump at the site where the antigen was injected indicating the animal is infected. The lump does not appear in a person that is not infected.
How is the Lectin pathway initiated?
When a mannose binding lectin (a serum protein) binds to mannose on microbes
Why are lipids poor antigens?
no charge and repeating structure
What is herd immunity?
When we vaccinate the population
Antigen
A molecule that binds to a B cell receptor, antibody, or T cell receptor
What is sensitization period?
A period that is required for a hypersensitivity to occur where the organism is first exposed to the allergen where memory T cells develop, B cells class switch and plasma cells secrete antibodies. (Immune components much be there)
Where do lymphocytes go id they can’t find their antigen in the lymph node?
thoracic duct and then back to bloodstream
What does the AVMA principle of vaccination say about the implementation of an effective vaccine program?
You must have knowledge of innunology and vaccinology which includes:
Risks and benefits
Pathobiology of infectious disease
- You are carrying a 2 x 4 and it slips out of your hands. A small piece of wood enters your skin. You can’t get the sliver of wood out and you don’t have time to deal with it. The next day your finger looks like the picture. Please explain.
A. What do you see?
A local reaction to the foreign body such as inflammation, redness, pain.
B. Is this an innate or adaptive immune response?
Innate
C. What type of cells would you expect to see if you looked at a histopathology slide of the lesion?
The sentinel Cells
• Macrophages
• Dendritic Cells
• Mast Cells
I will also see neutrophils.
D. What molecules might be active, e.g. cytokines, complement?
IL-1, IL-6, Tumor Necrosis Factor, Complement
What immune response are neutrophils a part of?
innate
- For some diseases, with some vaccines, for example MLV viral vaccines, it is beneficial to vaccinate in the face of an outbreak. B. Give an explanation, based on immunology, why this could be beneficial.
This would be beneficial because a substantial outbreak will often be present to some extent in society for a long time before it is entirely eradicated. Therefore, the immunologic memory that a MLV vaccine would induce would be very beneficial to prevent individuals from contracting the disease later on in this cycle. Modified live infected cells induce an innate response which induces the release of type 1 interferons. This occurs early on and creates an antiviral state through enzymes that inhibit protein synthesis, RNA replication, and will increase mhc1 presentation on infected cells. This would cause cytotoxic T cells to kill the infected cells more efficiently. Administering cytokines on their own would not work nearly as well because it would be induced outside of the endogenous cytokine milieu.
What defensive mechanism would be activated when septicemia is present as a pathogenic mechanism?
Opsonizing antibody
What is the half life of maternal antibody?
3 weeks
What are the mechanisms for maternal antibody interference?
Negative feedback by IgG on antibody production
Neutralize modified live virus
increased removal of antigen
Where are macrophages located?
• Under skin and the epithelium of mucosal surfaces
What is complements mechanism?
Enzyme cascade and many functions to eliminate a pathogen
What does the USDA say that biologicals should not be?
Worthless
contaminated
dangerous
harmful
In a respiratory virus infection, many defense mechanisms are used, would you need to induce all of them?
No, for example in a young cat, she gets colostrum from the mother providing neutralizing antibodies that protect against most viremia.
Disadvantages of killed vaccines and bacterins
- Increased risk of hypersensitivity (endotoxin stacking and injection site)
- not as immunogenic as MLV
- Two doses required initially
- require adjuvants
- More frequent revaccination is required
- Not good inducers of cell mediated immunity or IgA
- More expensive
What are some benefits to vaccination?
- Control of emerging and exotic diseases of animal and people
- Reduce the need for antibiotics
- control of diseases in companion animals and horses
How do we get around maternal antibodies from interferring with vaccinations
use a high antigenic mass vaccine
Select a vx strain that breaks through maternal earlier
What does Benadryl or Antihistamines do?
Block or counteract mediator effects when mast cells degranulate
What is the effector Mechanism in Type II hypersensitiy?
FcR+ Cells (Phagocytes, NK cells)
What is a false vaccine reaction?
Adverse event after vx but not related to it
Acute inflammation is induced by _______
Complement
Name the 5 types of White Blood Cells
- Basophil
- Esinophil
- Monocyte
- Neutrophil
- Lymphocyte
Where are macrophages found?
In most tissues and have different functions depending on the tissue, they are phagocytotic
what is the timing of an immediate hypersensitity reaction?
5 seconds to 1 minute for mast cells to degranulate
Do mammalian cells have mannose on their surfaces?
no
T/F RBCs play a role in the immune response
False
What part of immunity are cytokines found in?
innate and adaptive
T/F veterinarian can use vaccines in animals that are not perfectly healthy
True-sometimes when they could be exposed to the disease
What are secondary lymphoid tissue?
Lymph nodes, help antigens and lymphocytes meet in an efficient way
When the tuberculin is added to these cells, if the person has been infected with M. tuberculosis, there will be measurable amounts of gamma interferon produced. In a person that has not been infected, there is not a measurable amount of gamma interferon produced. What cell type is producing the majority of the gamma interferon (be specific)?
antigen specific T Cells (TH1)
Describe the exogenous antigen pathway of presentation
- Antigen is taken up by Endocytosis
- Antigen is processed by digestion in endosome or lysosomes
- Invariant chain is presented on class II MHC
- Peptide associates with MHC and buds off
- This attaches to a CD4 T + T cell
If cytokine activity is Autocrine ____
it has activity on the cell that produced (IL2)
Which pathway do all vaccines induce in T Helper cells?
Exogenous class II MHC pathway
What immune response are eosinophils a part of?
innate
What is an example of a type III local reaction hypersensitivity?
(Arthus)
- Booster Vaccination(swelling, pain (6-8 hrs)
- Hypersensitivity pneumonitis (Farmers Lung)
What part of immunity do you see lymphoid cells?
Innate and Adaptive
What are the reasons for perceived vaccine failure?
- animal incubating disease when vaccinated
- insufficient time for immune response to occur
- misdiagnosis
What defensive mechanism would be activated when the pathogen is an exotoxin or an endotoxin or viruemia?
Neutralizing antibody
What are acute phase proteins?
Acute phase proteins are a group of proteins that increase tremendously in the first 24 hours of infections. These proteins help control the infection while the adaptive immune response is preparing to fight the infection in an antigen specific way. Increase acute phase proteins are an indication of acute inflammation.
What are the adaptive lymphocytes?
CD8 CTL’s (Cytotoxic)
CD4 (Cytokines)(TH1, TH2, TH17)
Gamma Delta T Cells
What is the half life of a neutrophil?
8-12 hours
T/F Cytokines influence the outcome of an immune response
T
How does a B cell work?
It binds to an antigen it recognizes, divides and gives rise to 5000 antibody secreting cells in 1 week.
What is primary immunodeficiency?
Geneticly related
What is a common mechanism for an adverse vaccine reaction?
Excessive induction of cytokine release
What is the half life of an eosinophil?
30 minutes
What is the bodies response to food allergies in canines?
Dermaitis
What are modified live vaccines that are attenuated?
The agent in the vaccine is alive but weakened so it can induce immunity without inducing disease
To induce herd immunity you want to
vaccinate all the healthy animals in a population, if enough animals in the herd have immunity then the infectious agent can not circulate and infect animals that do not have immunity
How do cytokines regulate innate and adaptive immunity?
• A general term for a large group of secreted proteins that mediate many aspects of the immune system, including immune cell growth and differentiation, activation of effector functions of immune cells, and cell movement
What immune responses are most suceptable to vaccine interferance by host factors?
Primary immune responses are more sucestible than secondary immune responses
- Year vaccination for influenza is recommended by the Center for Disease Control and Prevention (CDC). There is an inactivated influenza vaccine and also a live attenuated influenza vaccine. Describe the type of immune adaptive immune response you would expect from each and include your reasons.
The inactivated would use the exogenous pathway to present on MCH2 to helper T cells. This antigen will not be processed through B cells. IgG antibodies would interact with this antigen.
The live attenuated virus would induce the endogenous pathway after infecting cells. This would cause the presentation of the antigen on the MHC1 cells to cytotoxic T lymphocytes. T helper cells would also induce the exogenous pathway. This would be identified by IgA antibodies on the mucosal surfaces as well as the IgG in the blood.
Define anaphalaxis
Due to mast cell degranulation going systemic after exposure to an allergen causing bronchial smooth muscle contraction, urticaria, Heparin production and failure of blood clotting and GI muscle contraction
What do the cells do when developing immunologic memory?
The B cells switch classes
First they produce IgM and then switch to make other Ig classes
What are the functions of complement?
Lysis of bacteria
Vasodilalation and increased vascular permeability
Chemotaxis of phagocytic cells
Opsonization
How do sentinel cells work?
- They respond to danger signals and secrete proinflammatory cytokines
- Pattern Recognition receptors on the sentinels bind to the pathogen associated molecular patterns and damage associated molecular patterns
- A response is then initiated
How does efficient phagocytosis occur?
a bacteria is opsonized and then a neutrophil binds to the opsinon (C3b and IgG) and ingests the bacterium. The granules of the neutrophil fuse with the phagosome and other molecules (reactive oxygen radicals) created and kill the bacteria.
What are the types of cell-mediated immunity?
Cytokine secretion by T-Helper Cells
Cytotoxic- T Cells-For viruses
Gamma Delta T cells
What are the soluable components of adaptive immunity and what is it called?
Humoral immunity
Antibodies
what are the key phagocytic cells for killing microbes?
Neutrophils and macrophages
What are antibodies made by?
plasma cells
- Write two to three sentences or provide two to three bullet points highlighting the role of the innate immune response against SARS-CoV2 and/or in COVID-19 clinical signs. You are welcome to do your own research or use these papers. The purpose of this is to link what you are learning to this current event. Try to keep it simple. Please provide a link to your reference.
- The binding of the SARS-CoV2 to the ACE2 receptor in cells is what initiates the first inflammatory response and signals that a virus has entered the body. Studies have actually shown that predictors of poor prognosis come from increased levels of IL-6 and fibrogen. If this inflammation process were able to be blocked, then it is expected that patients would have a better prognosis as the innate system can cause immune-mediated damage which is actually more harmful than the viral damage.
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286633/
- As studies have been completed, it is believed that there is a correlation between a severe prognosis of SARS-CoV2 and dysregulated secretion of proinflammatory cytokines. This includes increased levels of IL-1β, IL-1Ra, IL-7, IL-8, IL-9, IL-10, basic FGF, GCSF, GM-CSF, IFN-ɣ, CXCL10, CCL2, CCL3, CCL4, PDGF, TNFɑ, and VEGF. However, proinflammatory cytokines are not elevated in mild to moderate cases of SARS-CoV2 determining that high concentrations is indicative of a severe case and could possibly be due to a non-regulatory complement system.
What is septicemia?
Bacteria circulating in the blood
Cytokine secretion is ____ and _______
Brief and self-limited
What could happen if there is a response to a vaccine in the presence of a maternal antibody?
- It may fail to induce detectable antibody
- May induce B cell memory
- It may induce t cell mediated immunity
- May provide protection from challenge evdn after detectable antibody is gone
What are the benefits of vaccination in terms of the animals quality of life?
It prevents suffering
How long are monocytes in the blood stream?
1-2 days then move to tissues and differentiate into a macrophage
What is unexplained pathogenesis?
increased incidence of allergies, autoimmune disease, neoplasia but we don’t know why
What is immune mediated hemolytic anemia?
A normal animal develops antibodies against their own rbc called an autoantibody or forign antibodies like drugs attack RBC
What factors increase resistance to bacterial pneumonia?
- Genetics
- Anti-leukotoxin Antibody
Anti-capsular Antibody - Cell mediated Immunity
- Immunomodulators
What are the type of lymphocytes?
B cells and T cells
What part of immunity is complement found in?
Innate
Describe the endogenous antigen pathway of presentation
- Antigen is taken up via a cytosolic protein
- Antigen is processed by peptides in the cytosol and protein digestion in proteosomes
- MHC biosynthesis–TAP is presented on MHC Class I in the ER
- Peptides are associated with the MHC and bud off
- Peptide-MHC complex attaches to CD8 and CTL
Describe the classical pathway for the activation of complement
complement fixing antibody binds antigen (IgM or IgG)
ERIG has been used in rabies prophylaxis in humans. It works well to prevent rabies; however, there can be adverse reactions following its use. o How long after the administration of the ERIG would you expect to see the adverse reaction?
You would expect to see an adverse effect several weeks post injection because the B cells must first produce the IgG. The immune response would be passive immunity which would bind the rabies antigen.
What percentage of neutrophils are in the circulation?
55-90%
Where do B cells develop?
Bone Marrow in most species
Bursa of Fabricious in Birds
Ileocael some species
what part of the immune system is the C3 pathway?
Innate
What stimilates the killing mechanism of neutrophils?
C5a
What theories explain unexplained pathogenesis?
- Long term effects of administering multiple vx concurrently
- Vaccine inducing immune dysregulation
- Environmental pollutants
- Lack of parasites
- Processed foods
- Indoor environment
- Genetics
What are some chemical adjuvants?
Aluminum hydroxide Oil emulsion(slow release)
3Give an explanation for a potential mechanism of action for hyposensitization therapy for Type I hypersensitivities.
The potential mechanism of action for hyposensitization therapy for Type I hypersensitivities could possibly involve induction of THI and IgG instead of TH2 and IgE through an allergy shot, induction of Treg cells and/or induction of sIgA. Hyposensitization therapy offers low dose exposure to the allergen by injection or sublingual exposure. In the instance of inducing TH1 and IgG in place of TH2 and IgE, IgG would bind to the allergen.This would remove or reduce the allergic response due to TH1 and IgG production and redirect the immune system to the proper immune response.
What part of immunity are antibodies?
Adaptive
What is a chemokine?
chemotactic cytokines that attract specific cells to their location
What components of complement coat bacteria and what is it called?
The process is called opsonization and C3B does the coating to make neutrophils and macrophages see the bacteria.
What is the Function and response of sentinel cells?
– Detect (PAMPS and DAMPs) and Respond (Produce pro inflammatory cytokines)
Why would we want to vaccinate in terms of food food production?
- Make sure zoonotic diseases are not transferred via GI route and to keep herds healthy
- Reduction of transmission of foodborne disease
What is a multifactorial disease?
Many factors for disease development. Example, Distress + viral infection + Bacterial Infection = Bovine Respiratory Disease
Does active immunity induce immunologic memory?
Yes
What are the key components in a type IV hypersensitivity?
Memory T Cell mediated Th1 or CTL’s
- Animals infected with Mycobacterium tuberculosis (TB), an intravesicular pathogen, will test positive on an intradermal skin test and a gamma interferon blood test. (a) If you did a biopsy of the lump, what would the predominant cell type be? (This is a memory response.)
The lump at the sight of injection would be due to an aggregation of memory TH1 cells would be present to influence the destruction of the bacteria through the excretion of gamma interferon. Neutrophils would also aggregate to the area through chemotaxis to destroy the invader.
How do cytokines act?
By binding to receptors
What are some other risks that can occur with vaccinations that are non-specific?
Alterations in immune homeostasis:
Allergy
Autoimmune disease
post vaccinal polyneuropathy (Coon hound paralysis)
What is vaccine efficacy?
it will provide the expected level of protection when used under conditons recommended by the manufacturer
What factors are responsible for IgE production?
When an allergen is introduced, T Helper cells respond and interact with B cells causing them to switch antibody classes to IgE and from there IgE is secreted into the serum
What is a phagocytic cell?
Eat cells
- Your friend tells you she is not getting an influenza vaccination this year because last year the day after she was vaccinated with the killed influenza vaccine she came down with the flu. She does not understand why her doctor recommends getting that vaccine! How will you respond?
A. Did she get influenza from the vaccine?
B. What might have caused her to feel like she had the flu?
I would tell my friend that she should still get the flu vaccine. I would tell her that she definitely did not get the disease from the vaccine because it was a killed virus and that cannot cause infection. If the vaccine was a live attenuated one then it would be possible that it reverted back to a virulent form but still highly unlikely. She could have had the flu already but was not yet showing symptoms.
Proinflammatory cytokines could have also been released in response to the vaccine and caused similar symptoms similar to influenza. The flu she experienced could have also been a result of exposure to a form of influenza that was not included in the vaccine.
What is prutitis usually caused by during IgE mediated mast cell degranulation?
The breakdown of membrane phospholipids into arachadonic acid and then into prostaglandins which can act on nerve endings causing the itching
What are basophils important in?
Allergy and parasites
What are the isotypes of antibodies?
IgM, IgG, IgE, IgD,IgA
- A person with type O blood has antibodies to both the A and B RBC surface antigens. When a person with type O blood is given type A blood there is a transfusion reaction. The transfusion reaction is a result of the transfused RBCs being destroyed by the recipient. What type of hypersensitivity reaction is this? Describe two mechanisms for how the transfused RBCs can be destroyed.
Type II-where the antigen is on cell or cell matrix.
- complement fixation and cell lysis
- oponsination and phagocytosis and maybe agglutination
Explain what happens when an allergen is introduced in Type I hypersensitivity
- Allergen is introduced
- T helper cells process the antigen
- T helper cells interact with B cells and cause antibody class switching to IgE
- IgE antibodies are secreted into the serum and diffuses into the tissues.
- It then binds with the mast cell receptor
What is immunologic Tolerance?
In a normal immune function self molecules are not attacked and antigens present during lymphocyte maturation in utero are tolerated and the ones not present are attacked. When this is compromised autoimmune disease can occur.
What percentage of lymphocytes are in the circulation?
30%
What do we mean by vaccine purity?
it only contains approved antigens, adjuvants and preservatives and not contaminated
What is the classical pathway for complement activation an example of?
Innate (complement) and adaptive (antibody) working together
What are the innate lymphoid cells?
Cytotoxic NK cells ILC cytokines (ILC1 , ILC2, ILC3) Gamma delta T cells
What is a hypersensitivity reaction to a vaccine?
Anaphalaxis, local mast cell (edema, swelling)
T/F passive immunity has immunologic memory
F
Describe some therapies for Allergies?
- Avoidance
2. Sym
Name the types of adjuvants
Chemicals
Microbial components Mammalian Proteins
What are some physiolgical host factors that cause vaccines to fail?
- Primary immunodeficiency
- Immunosuppresive therapy
- Age
- Toxins (mycotoxins and heavy metals)
- Poor nutrition
- Stress (too hot or
- Concurrent infection
- Biological variation
- Presence of the maternal antibody
What are the two types of the adaptive immune response?
Active and passive
What produces Type 1 Interferons?
• Produced by virally infected cells within 24 hours of some viral infections
Does IgE mediated hypersensitivy occur on a first vaccine or a booster?
A booster because after the first vaccination, the animal will make igM antibodies. After the first vaccinesome time Th2 cells will respond and interact with B cells causing them to switch antibody classes to IgH
What happens during acute inflammation?
- Sentinel cells detect the PAMPs and DAMPS and release proinflammatory cytokines and complement fixation leading to increased vascular permeability and upregulation of adhesion molecules on the endothelium.
- Permeable capillaries (post-capillary venules) allow influx of fluid (complement, acute phase proteins) from the blood stream and neutrophils bind to adhesion molecules and exit out of the blood stream.
- Phagocytic cells (e.g. neutrophils) migrate to the site of infection (chemotaxis)
- Phagocytes and antibacterial exudate destroy bacteria
You have a friend whose foal did not suckle after birth. The owner had some milk replacer that she began giving to the foal after it was 24 hours old. She tells you her veterinarian initiated treatment right away and gave the foal intravenous gamma globulins. In addition, the veterinarian recommended management changes to decrease exposure to pathogens. Your friend is confused and thinks the veterinarian was over-reacting and trying to increase her bill without good reason. The basis of her distrust is your friend has had children and she never nursed those children and they only received formula and they did just fine
Please explain to your friend why she is wrong in thinking the veterinarian over-reacted, include in your explanation 1) how the foal does and does not receive passive antibodies compared to human babies and 2) why you have to give the gamma globulin’s by injection and not orally..
Animals like cattle, horses, and pigs do not experience the placental transfer of maternal antibodies like humans. It was important that the foal had suckled or the owner had at least contacted the veterinarian. It is essential that the foal drinks the colostrum (or first milk) produced by its mother as it has a high concentration of antibody. In particular, IgG is the predominant antibody in the colostrum and absorption of the antibody is highest within the first 6 hours of birth. The foal is at increased risk of infection if it does not drink the colostrum within 24 hours due to not receiving gamma globulins via placental transfer. Gamma globulins are most likely administered by injection due to faster absorption. Oral consumption would take longer as the antibody would not be absorbed until broken down in the stomach.
- A dog develops swollen ears, itchy swollen eyes and muzzle 15 minutes after being vaccinated. What is the immunologic basis for these clinical signs? Will you treat? If yes, what is your treatment?
- immediate adverse reaction due to type I
- clinical signs = release of histamine as IgE binds
- treated with diphenhydramine or epinephrine
- A horse has run into a barbed wire fence and has several lacerations. Some background information:
● Horses are quite susceptible to tetanus.
● Tetanus is caused by a toxin produced by the gram-positive anaerobic bacteria Clostridium tetani.
● The owner tells you the horse has never received a tetanus vaccination
i. Clean and disinfect the wounds
I cleaned the wound to wash away any potential pathogens that could enter the horses body. I Disinfected to inactivate or destroy any harmful microorganisms present near the wound.
ii. Administer tetanus anti-toxin by injection
Administering the antitoxin provides passive immunity (IgG - antibodies) as this horse is at risk for developing tetanus and has not received the vaccination before. (American Association of Equine Practioners, 2020)
iii. Administer a tetanus vaccination (the vaccination is tetanus toxoid, i.e., inactivated tetanus toxin) by injection
The vaccine is administered to activate active immunity. The vaccination provides the Clostridium tetani antigen so the horses immune system begins to make antibodies and T effector cells. The goal is to induce immunologic memory.
iv. Administer penicillin by injection
Penicillin is administered to the wound as it is effective against C.tetani.
