Immune deficiencies Flashcards
What is an immune deficiency?
Impairment in part or function of immune system, leading to increased susceptibility to infectious disease
What are the two types of immune deficiencies?
Primary Immunodeficiency
- Inherited/congenital due to gene mutations affecting immune function
Secondary Immunodeficiency
- Acquired due to age, chronic disease, infections, or therapeutics
How do primary immune deficiencies present?
Clinically apparent early in life (congenital defects)
Can lead to increased mortality depending on mutation severity
Often breed-associated but rare
Types include SCID (Severe Combined Immunodeficiency) & CLAD (Canine Leukocyte Adhesion Deficiency)
What is CLAD (Canine Leukocyte Adhesion Deficiency) and how does it affect the immune system?
Autosomal recessive disorder
Single nucleotide mutation in beta-2 Integrin gene
Common in Irish Setters
Abnormal blood clotting & impaired immune system
Prevents WBCs from adhering to pathogens, leading to persistent infections
Persistent neutrophilia, but neutrophils can’t function properly
Diagnosis: Genetic testing for breeding management
Describe SCID (Severe Combined Immunodeficiency) in Basset Hounds
Mutation for key cytokines (IL-2, 4, 7, 9, 15)
Leads to immune system failure
Describe SCID (Severe Combined Immunodeficiency) in Jack Russel Terriers
Mutation for Lymphocyte formation
Inhibits immune response
Describe SCID (Severe Combined Immunodeficiency) in Arabian horses
Mutation impacts T & B cell receptors
Inhibits somatic mutation to different antigens
Clinical diagnosis not straightforward
Pyrexia, respiratory complications, diarrhoea
How can primary immune deficiencies be diagnosed in clinical practice?
Blood work – Check for neutrophilia, lymphopenia
Vaccine response – If no response, immune deficiency is suspected
Recurrent infections – Suggests inability to mount immune response
Breed susceptibility – Consider known predispositions
What are causes of secondary immune deficiencies?
Age-related decline
- Reduced CD4+ T cells (memory cells)
- Persistent antibody titres for known pathogens, but poor response to new pathogens
Specific infections
- e.g. Feline Immunodeficiency Virus (FIV)
Chronic stress
- Glucocorticoid release suppresses immune function
Increased infection susceptibility
Malnutrition
- Reduced leptin → impaired T-lymphocyte function
Define pathogenicity
Ability of microbe to damage host
Define virulence
Measure of how effectively a pathogen causes damage
When do bacterial infections cause clinical signs?
When pathogenicity exceeds host defences, leading to tissue damage
Damage occurs due to:
- Bacterial toxins (local or systemic effects)
- Inflammatory & immune responses
What is the difference between paracellular & transcellular bacterial invasion?
Paracellular invasion – Bacteria move between cells by loosening or breaking cell junctions
Transcellular invasion – Bacteria enter through cell, pass through it & exit on other side
What are the possible outcomes of bacterial infection?
Host clears infection
Carrier state (persistent infection)
Clinical disease (acute, subacute, chronic)
What are key clinical signs of bacterial infections?
Systemic signs – Pyrexia, increased HR & RR
Local signs – Pain, heat, swelling, erythema
Pus formation → Neutrophil response (acute infections)
Granulomas → Macrophage response (chronic infections)
Cardiovascular signs
- Congested mucous membranes (brick red/dark red)
- Toxic line (purple line in horse gums near teeth)
What are the two main categories of clinical pathology in inflammation?
Blood-based pathology – Analyses changes in circulating immune cells & proteins
Tissue-based pathology (cytology) – Examines cellular changes in inflamed tissues
What are key neutrophil changes seen in blood during inflammation?
Neutrophil count – Increased in response to infection
Left shift – Increased immature neutrophils (band cells) in response to severe inflammation
Toxic change – Abnormal neutrophil maturation due to strong inflammatory demand
What is the difference between bacteraemia and septicaemia?
Bacteraemia – Presence of bacteria in the bloodstream, but not necessarily multiplying
Septicaemia – Bacteria actively replicating in circulation, leading to systemic infection
Diagnosis – Rarely visible on blood smears, confirmed via blood culture
How do neutrophils appear in inflamed tissues?
Number assessment:
- Subjective: Microscopic examination
- Objective: Counting in effusions using lab analysers
Degenerate neutrophils – Seen in bacterial infections (cells take up water, nuclei swell)
Non-degenerate neutrophils – Seen in sterile inflammation (e.g. autoimmune disease)
What is the role of macrophages in inflamed tissues?
Clear debris & pathogens from inflamed areas
Increased macrophage count suggests chronic inflammation
Activated macrophages have foamy/lightly vacuolated cytoplasm
What determines the number of neutrophils in circulation?
Balance between production & usage:
- How fast neutrophils enter from the bone marrow
- How fast neutrophils leave to tissues
Species differences: Some species have higher neutrophil reserves than others
Describe the neutrophil response to inflammation in dogs & cats
High marrow neutrophil reserves → Can quickly respond to inflammation
Rapid neutrophil production if needed
Neutropenia (low neutrophils) is rare, seen only in severe cases where demand exceeds production
Describe the neutrophil response to inflammation in cattle
Low neutrophil reserves → Slow response to inflammation
Early inflammation → Neutropenia due to slow replenishment
Chronic inflammation → High neutrophil count due to long-term stimulation
Cattle are good at walling off infections (e.g. abscesses in thorax/abdomen)
Describe the neutrophil response to inflammation in horses
Intermediate marrow reserve – Between dogs/cats and cattle
Moderate neutrophil regenerative capacity
More likely than dogs/cats to show mild neutropenia in early inflammation
What does the term “left shift” mean in neutrophil maturation?
Left shift occurs when immature neutrophils appear in circulation due to high demand
Instead of only mature segmented neutrophils, you see:
- Band neutrophils (mild left shift)
- Metamyelocytes, myelocytes, or earlier precursors (severe left shift)
Indicates strong inflammatory stimulation
What is the difference between a regenerative and degenerative left shift?
Regenerative Left Shift:
- Increased mature neutrophils with some immature forms.
- Bone marrow keeps up with demand = Better prognosis.
Degenerative Left Shift:
- More immature neutrophils than mature ones.
- Bone marrow cannot keep up with demand = Poor prognosis
What does “toxic change” in neutrophils indicate?
Not caused by bacterial toxins, but linked to severe inflammation
Driven by cytokine stimulation during strong inflammatory responses
More severe toxic change = worse prognosis
What are the morphological features of toxic neutrophils?
Foamy cytoplasm – Due to dispersed organelles
Diffuse cytoplasmic basophilia – Persistent cytoplasmic RNA staining blue
Döhle bodies – Blue-grey cytoplasmic structures (rough endoplasmic reticulum/RNA)
- can be normal in cats
Asynchronous nuclear maturation – Mature-looking segmented nucleus, but immature chromatin structure
How is toxic change different from a left shift?
Toxic change – Morphological abnormalities in mature and immature neutrophils due to severe inflammation
Left shift – Increased numbers of immature neutrophils in circulation due to high demand
Both can appear together in severe infections
What do neutrophil inclusions indicate?
Uncommon findings in blood smears but may indicate infection, inflammation, or genetic disorders
Some infections directly invade neutrophils, while others cause secondary morphological changes
Give examples of causes of neutrophil inclusions
Bacterial
- Ehrlichia, Anaplasma
Viral
- Canine distemper
Protozoa
- Toxoplasma, Hepatozoon
Fungi
- Histoplasma
Hereditary/metabolic
- Chediak-Higashi, Birman cat anomaly, mucopolysidosis
What happens in septic shock?
Severe systemic inflammation due to infection
Cytokines & endotoxins cause metabolic failure & circulatory collapse
Leads to poor oxygen delivery, organ dysfunction & lactate accumulation
How do cytokines and endotoxins affect cellular metabolism in sepsis?
Cytokines & endotoxins inhibit pyruvate dehydrogenase, preventing pyruvate from entering the Krebs cycle
Instead, pyruvate is converted to lactate, leading to lactate accumulation
Cells switch to anaerobic metabolism due to oxygen extraction failure
How does vasodilation contribute to tissue hypoxia in septic shock?
Widespread vasodilation → Blood moves too slowly in some areas, too fast in others
Oxygen bypasses hypoxic tissues, leading to poor oxygen extraction
Venous blood remains oxygen-rich, but tissues still suffer from hypoxia
How does severe inflammation lead to coagulation abnormalities?
Cytokine storm activates clotting cascade
Leads to disseminated intravascular coagulation (DIC)
Platelets become hyperactive, causing microthrombosis & depletion of clotting factors
What happens in DIC (Disseminated Intravascular Coagulation)?
Excess clot formation → Microthrombosis & organ damage
Clotting factor depletion → Uncontrolled bleeding
Often seen in sepsis, systemic inflammation, and trauma
How does DIC create a vicious cycle of inflammation?
- Inflammation activates neutrophils
- Neutrophils release DAMPs (damage-associated molecular patterns)
- DAMPs promote coagulation & reduce fibrinolysis
- Coagulation further stimulates inflammation, worsening process
Why is FIV tested using an antibody test while FeLV is tested using an antigen test?
FIV detection:
- Virus isn’t present in large numbers in blood
- Antibody testing more reliable for detecting exposure
FeLV detection:
- Virus circulates in the blood
- Antigen testing detects active infection
How is FIV transmitted between cats?
Main route: Deep bite wounds (saliva-to-blood transmission)
Less common: Mother-to-kitten transmission during birth or nursing
Not easily spread through casual contact, grooming, or shared food bowls
How does age-related immune deficiency impact disease susceptibility?
Reduced CD4:CD8 ratio → Fewer naive T cells to respond to new infections
More memory cells but weaker primary immune response
Impaired mucosal defence (e.g. weakened lung clearance mechanisms)
Increased susceptibility to infections and slower recovery
