Immunology AI Flashcards
What are the expected events after injection of a vaccine in a healthy animal?
- Virus infects host cells, causing lysis of some cells
- Viral proteins are taken up by resident dendritic cells and processed for presentation on MHC molecules
- Dendritic cells are activated when their PRRs recognise typical viral structures or DAMPs released from dying cells
- Dendritic cells carrying viral antigens migrate to local lymph nodes
- Dendritic cells interact with naïve T cells in the lymph node, activating any T cells that recognise the viral antigens on their MHC molecules
- Activated T cells provide help to B cells in the lymph node that also recognise viral antigens
- Activated B cells differentiate into plasma cells and produce antibodies specific for the virus
- Antibodies and activated T cells clear the virus from infected tissues.
Why is vaccination able to make use of the memory response of the immune system?
Immune responses develop more quickly and effectively after repeated exposure to the same antigens.
What are memory T and B cells?
They are long-lived cells produced during immune responses that are able to respond directly to their antigen, permitting more rapid production of antibodies by B cells, production of cytokines by CD4+ T cells, or generation of activated cytotoxic (CD8+) T cells.
What route of vaccination is commonly used in veterinary practice?
Most vaccines used in veterinary practice are administered by subcutaneous injection, where they will be absorbed systemically to generate an immune response in the lymph nodes and spleen.
Why is stimulation of local, mucosal immunity important for pathogens that normally infect mucosal surfaces?
Protective immunity depends on stimulation of local, mucosal immunity. Immune responses can be generated in mucosa-associated lymphoid tissue (MALT), rather than in the lymph nodes or spleen.
Where are mucosa-associated lymphoid tissues typically found in the body?
Mucosal tissues of the respiratory, gastrointestinal, and urogenital tracts.
What are autoinflammatory diseases and how are they different from autoimmune diseases?
Autoinflammatory diseases are caused by inappropriate activity of the innate immune system without activation of T cells or other components of the adaptive immune system. Autoimmune diseases, on the other hand, involve the immune system attacking normal cells and tissues.
Why are some diseases in veterinary medicine described as ‘immune-mediated’?
Some diseases in veterinary medicine are described as ‘immune-mediated’ because it isn’t clear whether they are autoimmune or autoinflammatory. Detailed research studies are often lacking to establish the exact cause of these diseases.
What is the association between autoimmune haemolytic anaemia and chronic lymphocytic leukaemia?
There is a strong association between the development of autoimmune haemolytic anaemia and underlying chronic lymphocytic leukaemia, where the malignant B cells produce autoantibodies causing red blood cell destruction.
Why do thymomas frequently develop myasthenia gravis?
Thymomas frequently develop myasthenia gravis due to the inappropriate production of antibodies against the acetylcholine-gated ion channels in the neuromuscular junction.
How do some drugs increase the risk of autoimmune reactions?
Some drugs increase the risk of autoimmune reactions by possibly changing the expression of genes that regulate the immune system or altering the structure of normal proteins in the body, causing the immune system to identify them as foreign.
Do vaccinations have a proven association with autoimmune disease in dogs and cats?
No, there is no proven association between vaccination and autoimmune disease in dogs and cats, although it is frequently reported anecdotally and included as a warning in the datasheet of some vaccine products.
What is molecular mimicry and how does it relate to autoimmune diseases?
Molecular mimicry is when bacteria or pathogens have molecular structures that are similar to normal host molecules. In some cases, the immune response against the pathogen may ‘cross-react’ with host tissues, leading to immune-mediated damage.
What role does the microbiome play in shaping the immune system?
The microbiome, consisting of bacteria, viruses, and fungi in the gut, upper respiratory tract, and on the skin, interacts with the immune system to shape its development and immune responses. Mice raised in sterile conditions, without a microbial community, have a decreased risk of many autoimmune diseases.
Are there any recommended interventions targeted at the microbiome for dogs and cats with immune-mediated diseases?
Currently, there is insufficient evidence to recommend probiotics, antibiotics, or any other intervention targeted at the microbiome in dogs and cats diagnosed with an immune-mediated disease.
What diagnostic tests may be considered when presented with a dog or cat showing signs of an autoimmune disease?
When presented with a dog or cat showing signs of an autoimmune disease, clinicians may consider performing a thorough history, including exposure to drugs and toxins, physical examination, and checking all peripheral lymph nodes.
What is the difference between immune-mediated (IMHA) and autoimmune (AIHA) diseases in dogs and cats?
In dogs and cats, diseases such as haemolytic anaemia are described as immune-mediated (IMHA) if they are specific for a normal self-antigen, while they are described as autoimmune (AIHA) if they are caused by an autoimmune response.
What are the general clinical features of autoimmune and autoinflammatory diseases?
The general clinical features of autoimmune and autoinflammatory diseases may differ depending on their causes. Autoimmune diseases depend on the location of the targeted self-antigen, while autoinflammatory diseases exhibit features similar to an acute phase response.
Give an example of an autoimmune disease where the antigen is expressed in a single location.
Autoimmune (lymphocytic) thyroiditis is an example of an autoimmune disease where the antigen is expressed in a single location, specifically the thyroid gland.
What autoimmune disease in dogs exhibits immune responses against nuclear proteins produced throughout the body?
Systemic lupus erythematosus, a rare autoimmune disease in dogs, exhibits immune responses specific for nuclear proteins produced in practically every cell in the body.
What are the clinical signs of autoinflammatory diseases?
Autoinflammatory diseases typically display features of an acute phase response, including intermittent fever, lethargy, malaise, generalized lymph node enlargement, and occasionally joint pain and arthritis.
What combination of mechanisms can some diseases involve?
Some diseases can involve a combination of autoinflammatory and autoimmune mechanisms, where they may begin as an autoinflammatory disease and progress to an autoimmune response if T cells become activated.
Which disease causes pyrexia, joint pain, swelling, inflammation, and deposition of amyloid proteins in multiple tissues?
Shar Pei fever, also known as Shar Pei Autoinflammatory Disease (SPAID), causes pyrexia, joint pain, swelling, inflammation, and deposition of amyloid proteins in multiple tissues.
What is the cause of primary hypoadrenocorticism in most cases?
In most cases of primary hypoadrenocorticism, the cause is an autoimmune response directed against antigens found only in the adrenal glands.
What are the learning objectives of this module?
The learning objectives are to distinguish between the innate and adaptive responses, describe the major cell types associated with innate and adaptive immune responses, interpret the major components of adaptive immune response, describe the types of functions of antibodies, explain what immunity neonatal animals possess due to transplacental and transmammary transfer, describe the major changes that occur in the immune system with a vaccine, describe the different types of vaccine available, with reference to those clinically available, and distinguish between autoimmune and autoinflammatory diseases.
What does the immune system protect against?
The immune system provides protection against infectious pathogens, some cancers, and is responsible for removing senescent cells and debris in the blood and central nervous system.
How can the immune system be defined?
The immune system can be defined by its structural components, meaning the cells and tissues that contribute to the immune system, or by its functional elements and actions, regardless of which cells and tissues are actually performing these actions.
What are the barriers to infection in the normal mammalian body?
The normal mammalian body provides several barriers to infection at the skin and internal mucous membranes. These include physical separation of exogenous organisms from critical internal organs, as well as physical and chemical properties of these surfaces that prevent colonization of bacteria and other pathogens.
What are innate immune responses?
Innate immune responses are not specific to a single antigen but are activated by molecular signatures shared by many different pathogens. They occur rapidly and consistently because they are initiated by cells that are already resident in the tissue.
What are the clinical features of inflammation?
The typical clinical features of inflammation are described using a set of Latin terms. One of these features is dolor, which refers to the pain caused when inflammatory mediators activate receptors on neurons.
What are some cytokines that may be released into the blood in large quantities?
Interleukin-1β (IL-1β), TNFɑ, and interleukin-6 (IL-6).
What is the purpose of the acute phase response?
To direct the body’s resources towards fighting infection and create an environment that is not conducive to pathogen replication.
What are the typical features of the acute phase response?
Pyrexia, increased serum c-reactive protein (CRP), mild non-regenerative anemia, and inflammatory leukograms consisting of neutrophilia with monocytosis.
What causes the increase in neutrophils and monocytes in dogs with tissue inflammation?
The effect of inflammatory cytokines on myeloid progenitors in the bone marrow, increasing the production of mature myeloid cells.
What is the difference between innate immune responses and adaptive immune responses?
Innate immune responses occur quickly and reliably in any damaged or infected tissue, while adaptive immune responses mount powerful responses against specific antigens and develop immunological memory.
Where do T cells undergo rounds of selection?
In the thymus.
Where do B cells undergo selection?
In the bone marrow.
What is fixed before birth and does not change during life?
The range of pathogens that can be recognized by innate immune cells due to the inheritance of genes encoding PRRs (Pattern Recognition Receptors) from parents.
What are the two types of antibodies produced by B cells?
The two types of antibodies produced by B cells are IgM and IgE.
What is the major function of IgE antibodies?
The major function of IgE antibodies is to cause degranulation of mast cells, leading to localized or systemic inflammatory responses.
What is opsonization?
Opsonization is the process of marking bacteria for phagocytosis by neutrophils.
What is antibody-dependent cell cytotoxicity (ADCC)?
Antibody-dependent cell cytotoxicity (ADCC) is the process of marking infected cells for destruction by cytotoxic (CD8+) T cells.
Which type of antibodies are particularly effective in activating the complement cascade?
IgM antibodies are particularly effective in activating the complement cascade.
How do neonatal dogs and cats obtain maternal antibodies?
Neonatal dogs and cats obtain maternal antibodies through the placenta (5-10%) and absorption across the gastrointestinal tract after ingestion of colostrum (90-95%).
What is immunosenescence?
Immunosenescence is the general trend for animals to mount less effective immune responses with increasing age, making them more susceptible to infectious diseases.
What type of cells does the thymus produce more of in neonatal dogs and cats?
The thymus produces more CD4+ T cells than CD8+ T cells in neonatal dogs and cats.
What is the process of shuffling gene segments called?
The process of shuffling gene segments is called gene rearrangement.
What is the main difference between adaptive and innate immune responses in terms of specificity?
Adaptive immune responses are much more specific to the inciting cause than innate responses.
Where does the initiation of adaptive immune responses usually take place?
The initiation of adaptive immune responses is usually confined to specialised lymphoid organs.
What do resident dendritic cells (DCs) collect in inflamed or damaged tissues?
Resident dendritic cells (DCs) collect proteins in inflamed or damaged tissues.
With what molecules do dendritic cells display digested fragments of collected proteins?
Dendritic cells display digested fragments of collected proteins in conjunction with molecules called major histocompatibility complexes (MHC, class II).
What happens when a helper T cell recognizes an antigen displayed by a dendritic cell?
When a helper T cell recognizes an antigen displayed by a dendritic cell, a strong interaction is formed between the two and the dendritic cell stimulates the T cell to proliferate and differentiate.
What are the two types of cells that B cells can differentiate into when stimulated by activated helper T cells?
When stimulated by activated helper T cells, B cells can differentiate into plasma cells or memory B cells.
Which type of antibody in mammals is the most common isotype in the serum?
The most common isotype of antibody in the serum of mammals is IgG.
What are immune complexes?
Immune complexes are large, complex aggregates composed of antibodies and antigens.
Where are immune complexes preferentially deposited?
Immune complexes are preferentially deposited in the glomerular capillaries and synovial membranes.
What can cause glomerulonephritis?
Local activation of the complement cascade and infiltration of immune cells caused by deposition of immune complexes can cause glomerulonephritis.
What can cause immune-mediated polyarthritis?
Local activation of the complement cascade and infiltration of immune cells caused by deposition of immune complexes can cause immune-mediated polyarthritis.
What cells are activated in some autoimmune diseases?
CD8+ (cytotoxic) T cells can be activated in some autoimmune diseases.
What do the activated CD8+ T cells do in autoimmune response?
Activated CD8+ T cells destroy cells bearing the antigen that stimulated the autoimmune response.
What breeds are autoimmune diseases classically seen with increased frequency in?
Autoimmune diseases are classically seen with increased frequency in the Cocker spaniel.
What environmental factors can contribute to the development of autoimmune diseases?
Environmental factors such as gender and neutering status, infections, ingestion of some drugs, and exposure to ultra-violet light can contribute to the development of autoimmune diseases.
What are the observed changes in B and T cells?
There is a general reduction in the numbers of B and T cells.
What is the immune system difference between German shepherd dogs and other breeds?
German shepherd dogs have a selective deficiency in the production of IgA antibodies.
Where are IgA antibodies made?
IgA antibodies are made at mucosal surfaces.
What is the concentration of IgA in German shepherd dogs compared to other breeds?
The concentration of IgA is lower in German shepherd dogs in blood and bile than in other breeds.
What has been suggested about the deficiency in IgA in German shepherd dogs?
This deficiency in IgA may increase the risk of inflammatory bowel disease in German shepherd dogs.
What does vaccination involve?
Vaccination involves administration of an attenuated version or part of a pathogen to stimulate an immune response.
What do most vaccines aim to do?
Most vaccines aim to limit the extent of disease or clear the pathogen more quickly.
What is the purpose of adjuvants in vaccines?
Adjuvants stimulate the innate immune system to ensure an immune response develops.
What could be a sign of lymphoproliferative disease?
Gross enlargement of lymph nodes.
What imaging techniques can be used to check for masses or internal lymph node enlargement in the thorax and abdomen?
Thoracic radiographs and abdominal ultrasonography.
What should be considered when there is a travel history?
Testing for infectious agents, particularly Babesia canis and Ehrlichia canis in dogs that have not traveled abroad.
In what cases should tests for infectious agents be considered even in dogs that have always been in the UK?
If there have been reports of Babesia canis and Ehrlichia canis in dogs in the UK that have not traveled abroad.
What is often requested to check for urinary tract infection?
Urinalysis with culture.
What is difficult to establish when urinary tract infections are found?
Whether UTIs are the cause for autoimmune diseases or if they are simply concurrent.
What is the term for the feeling of heat caused by increased blood flow to the tissue?
Calor
What is the term for the redness of the tissue that occurs when inflammatory mediators cause vasodilation?
Rubor
What is the term for the swelling of the tissue caused by leakage of fluid and protein across blood vessel walls?
Tumor
What is the term for the loss of normal function caused by altered blood flow or infiltration of inflammatory cells?
Functio laeso
Which cells in the tissue initiate inflammatory responses?
Tissue macrophages, mast cells, and endothelial cells
What are the molecular patterns shared by infectious agents or molecules released when tissues are damaged?
Pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs)
What are the inflammatory mediators produced by activated resident cells?
Histamine, prostaglandins, and cytokine tumor necrosis factor alpha (TNFɑ)
What are the principal myeloid cells recruited to the site of inflammation?
Neutrophils, monocytes, and eosinophils
What is Feline Immunodeficiency Virus (FIV) commonly associated with in cats?
FIV is commonly associated with immunological complications and chronic, non-regenerative anemia due to bone marrow dysfunction.
How is immune-mediated hemolytic anemia (IMHA) diagnosed in cats?
IMHA in cats is diagnosed based on a positive direct antiglobulin test (DAT) and/or in-saline agglutination since spherocytes cannot be reliably detected.
What is the significance of ‘ghost cells’ in cats with IMHA?
‘Ghost cells’ are red blood cell remnants that persist after hemolysis. While they may be associated with IMHA in cats, they are not specific to immune-mediated disease and can also be observed with oxidizing toxins like paracetamol.
Was it previously believed that IMHA in cats was more likely to be associated with an underlying disease compared to dogs?
Yes, it was traditionally suggested that IMHA in cats was more likely to have an underlying disease, but larger studies have shown that approximately 60-75% of cats with IMHA have no detectable underlying cause.
What are the possible patterns observed in bone marrow samples of dogs and cats with non-regenerative IMHA?
Bone marrow samples may reveal strongly regenerative response (erythroid hyperplasia) in the bone marrow with peripheral non-regenerative anemia, lack of a regenerative response (erythroid hypoplasia) in the bone marrow with peripheral non-regenerative anemia, or complete absence of erythroid stem cells (pure red cell aplasia) in the bone marrow.
What immediate care measures can be taken for dogs and cats with IMHA?
In cases of acute anaemia causing cardiovascular compromise, blood transfusion is indicated in dogs with signs of compromise. Packed red blood cells are preferable to fresh whole blood in dogs with IMHA.
Is there a standard trigger for blood transfusion in dogs with IMHA?
No, there is no standard trigger for transfusion as it depends on factors like the speed of onset of anaemia, the severity of the anaemia, and the severity of clinical signs.
How can Babesia canis be detected in red blood cells?
Babesia canis can be detected in red blood cells in fresh blood smears by a trained pathologist.
What is the recommended action if a dog has a travel history to (Southern) Europe or an area with reported cases of B. canis?
It is recommended to have a blood sample examined at an external laboratory and request polymerase chain reaction (PCR) for B. canis.
Which breed of dogs are born with defects in enzymes required for normal metabolism inside red blood cells?
Dogs of some breeds, such as English Springer spaniels, are born with defects in enzymes required for normal metabolism inside red blood cells.
What is the most common disease causing severe haemolysis in dogs after exercise or excitement?
The most common disease causing severe haemolysis in dogs after exercise or excitement is phosphofructokinase (PFK) deficiency.
Which breed has been diagnosed occasionally with phosphofructokinase (PFK) deficiency?
English Springer spaniels have been diagnosed occasionally with phosphofructokinase (PFK) deficiency.
What is the other reported disease that can cause mild, chronic haemolytic anaemia in dogs?
The other reported disease that can cause mild, chronic haemolytic anaemia in dogs is pyruvate kinase (PK) deficiency.
Which breed is known to have a reported association with pyruvate kinase (PK) deficiency in the UK?
West Highland white terriers are known to have a reported association with pyruvate kinase (PK) deficiency in the UK.
What are some causes of haemolysis other than phosphofructokinase (PFK) deficiency or pyruvate kinase (PK) deficiency?
Some other causes of haemolysis include severe acute leptospirosis, oxidising toxins like zinc, onions, and paracetamol in cats, and Mycoplasma haemocanis transmitted by tick bites.
What is ITP?
ITP stands for immune-mediated thrombocytopenia, a condition characterized by a low platelet count due to immune destruction of platelets.
What are some variants of ITP?
Some variants of ITP include Angiostrongylus vasorum, which is associated with lungworm infestation, and a ‘non-regenerative’ form in dogs where megakaryocytes in the bone marrow are targeted.
How can lungworm infestation be detected in dogs suspected of having IMTP?
Lungworm infestation can be detected using either a SNAP test on blood or Baermann flotation of a fecal sample in dogs suspected of having immune-mediated thrombocytopenia (IMTP).
In the study mentioned, what was the difference between dogs with regenerative and non-regenerative forms of IMTP?
Dogs with non-regenerative forms of IMTP had a poorer prognosis, were more likely to require blood transfusion, and were more likely to be anemic at the time of presentation compared to dogs with normal numbers of megakaryocytes in the bone marrow.
Is primary IMTP common in cats?
Primary immune-mediated thrombocytopenia (IMTP) is rarely reported in cats and seems to be much less common than in dogs.
What are some other underlying causes of thrombocytopenia in cats?
Other underlying causes of thrombocytopenia in cats include feline leukemia virus and feline immunodeficiency virus infections.
What immediate treatment is advised for dogs with confirmed thrombocytopenia?
Dogs with confirmed thrombocytopenia should be handled carefully, and jugular venepuncture should be avoided. It is also advisable to administer a gastric acid suppressant, such as omeprazole, and dogs with IMTP and anemia may require blood transfusion.
Are platelet transfusions a viable treatment option for thrombocytopenic dogs?
Platelet transfusions are not a viable treatment option for thrombocytopenic dogs due to the short half-life of platelets and their susceptibility to damage or activation during transfusion.
What are the two possible causes of neutropenia?
Neutropenia may be caused by decreased production of neutrophils in the bone marrow or by increased consumption or destruction of neutrophils in the periphery.
What is the typical appearance of a ‘left shift’ in neutropenia?
The bone marrow responds to peripheral destruction of neutrophils by increasing production and releasing immature (band) neutrophils into the circulation, producing a ‘left shift’.
What is one common cause of neutropenia?
Severe bacterial infections and sepsis are often a common cause of neutropenia.
Why is it important to collect diagnostic samples prior to starting antimicrobials?
Collecting diagnostic samples prior to starting antimicrobials helps establish whether an infection is the cause or result of the neutropenia.
What investigations are commonly performed to exclude sepsis or a septic focus in a dog with neutropenia?
Imaging of the thorax and abdomen, collection of sterile urine sample for culture, collection of sterile samples from abnormal sites, echocardiography, and collection of blood samples for blood culture.
What is the pathogenesis of Immune-Mediated Neutropenia (IMNP)?
The pathogenesis of IMNP involves an autoimmune response against normal antigens on the surface of neutrophils, resulting in production of antibodies that facilitate their phagocytosis and removal by phagocytes in the spleen.
What is one recommended test for detection of anti-neutrophil antibodies in suspected IMNP?
Flow cytometry test for detection of anti-neutrophil antibodies is recommended in suspected IMNP cases.
What other tests are recommended to rule out other causes of neutropenia in IMNP cases?
Testing for vector-borne pathogens, sampling the bone marrow to exclude pathology or neoplasia, and investigations to exclude underlying causes for immune-mediated neutropenia.
What is immune-mediated polyarthritis?
Immune-mediated polyarthritis is a condition that may occur in cats, but is less common than in dogs. It is characterized by inflammation in multiple joints.
Which clinical syndrome is commonly reported in young adult male neutered cats with polyarthritis?
A particular clinical syndrome called periosteal proliferative polyarthritis (PPP) is commonly reported in young adult male neutered cats with polyarthritis.
What causes erosive lesions in cats with polyarthritis?
Polyarthritis in cats can cause erosive lesions, particularly affecting the distal joints (carpi and tarsi).
What percentage of dogs with steroid-responsive meningitis arteritis (SRMA) may experience inflammation of the peripheral joints?
As many as 30% of dogs with SRMA may experience inflammation of the peripheral joints.
What is the immediate treatment approach for dogs and cats with suspected immune-mediated polyarthritis (IMPA)?
Before receiving diagnostic results, dogs and cats with suspected IMPA can be administered analgesic and antipyretic medication like paracetamol to improve their quality of life.
What type of medication can be concurrently used with steroids for analgesia in dogs with IMPA?
Paracetamol can be used concurrently with steroids for analgesia in dogs with IMPA, unlike conventional NSAIDs.
What is the safe and suitable dose of dexamethasone for anti-inflammatory treatment in dogs with strong suspicion of IMPA?
A safe and suitable dose of 0.1 mg/kg dexamethasone IV once daily can be administered for anti-inflammatory treatment in dogs with strong suspicion of IMPA.
What are multi-systemic immune-mediated diseases?
Multi-systemic immune-mediated diseases are immune-mediated diseases that appear to affect multiple different tissues due to autoimmune responses directed against several different antigens.
What are the major clinical and clinicopathological features of immune-mediated haemolytic anaemia in dogs and cats?
The major clinical and clinicopathological features of immune-mediated haemolytic anaemia in dogs and cats need to be described.
What clinical tests can be used to make a definitive diagnosis of IMHA in dogs?
The clinical tests that may be used to make a definitive diagnosis of IMHA in dogs should be described.
What are the other possible causes of haemolysis in dogs?
The other possible causes of haemolysis in dogs and how they may be excluded with appropriate tests need to be discussed.
What are the major clinical and clinicopathological features of immune-mediated thrombocytopenia and neutropenia in dogs and cats?
The major clinical and clinicopathological features of immune-mediated thrombocytopenia and neutropenia in dogs and cats should be described.
How can a definitive diagnosis of IMTP and IMNP in dogs be made?
The clinical tests that may be used to make a definitive diagnosis of IMTP and IMNP in dogs should be discussed.
What are the other possible causes of thrombocytopenia and neutropenia in dogs?
The other possible causes of thrombocytopenia and neutropenia in dogs and how they may be excluded with appropriate tests need to be discussed.
What are the major clinical and clinicopathological features of immune-mediated polyarthritis and multi-systemic diseases in dogs and cats?
The major clinical and clinicopathological features of immune-mediated polyarthritis and multi-systemic diseases in dogs and cats should be described.
How can a definitive diagnosis of IMPA, erosive polyarthritis, and SLE in dogs be made?
The clinical tests that may be used to make a definitive diagnosis of IMPA, erosive polyarthritis, and SLE in dogs should be discussed.
