Immunology Flashcards
what are the 3/4 mechanisms of immunopathology
• Immunodeficiency = ineffective immune response
• Hypersensitivity reaction = overactive immune response
• Autoimmunity = inappropriate reaction to self
(also immune cell neoplasia)
what are the 3 general features of immunodeficiency diseases
o Increased susceptibility to infection
o Increased incidence of autoimmune disease
o Prone to virally induced cancers e.g. feline leukaemia virus
examples of innate immune system deficiencies
abnormal phagocyte function
complement deficiency
adaptive immune system deficiencies
B cell immunodeficiency (decreased immunoglobin production)
T cell immunodeficiency (decreased cell mediated immunity)
Combined – B and T cell (SCID)
primary vs secondary immunodeficiency diseases
primary are congenital, rare, and clinical signs develop after weaning
secondary are acquired, more common, and involve the animal initially having functional immunity, but subsequently the immunity becoming defective
causes of secondary immune deficiencies
o Failure of passive transfer
o Medical intervention e.g. chemotherapy, immunosuppressive drugs
o Infection of immune cells e.g. canine distemper virus, FIV, FeLV
o Hypercortisolaemia and stress
o Chronic disease = lymphoid depletion
o Environment e.g. starvation, malnutrition
o Old age (immunosenescence)
potential causes of failure of passive transfer
o Lack of colostrum ingestion – failure to suckle
o Lack of colostrum production – e.g. premature birth
o Absorption failure by newborn – something wrong with GIT
diagnostic approach to failure of passive transfer
• Index of suspicion based on history, signalment
• Measure IgG concentrations – stall-side testing kit
• Complete blood count
o Abnormal white blood cell count
o Toxic changes in white blood cells
• Serum biochemistry
o Low globulin concentrations
treatment of failure of passive transfer
IV administration of plasma containing immunoglobins (oral admin won’t work after 24 hours post-parturition as GIT is no longer able to absorb)
Antibiotics to treat infection
prevention of failure of passive transfer
• Prevention better than treatment
• Ensure the dam is healthy and vaccinated
• After birth, verify that the foal stands and nurses
• 12-18 hours after birth measure serum immunoglobins
o >8g/L = adequate
o <4g/L = failure
o 4-8g/L = partial failure
Iatrogenic immunosuppression
Acquired immunodeficiency due to administration of immune suppressant medication
Secondary opportunistic infections can occur - UTI, skin infections, blood stream infections
If an infection results, lower the dosage of the immune-suppressing meds and give antibiotics
hypersenstivity reactions
undesirable / harmful responses produced by normal immune system mechanisms.
Evolved to protect against infection – but overreact and react to harmless things, and react to self (autoimmunity) – can cause tissue injury and serious disease.
autoimmunity
an immune response directed against self-tissue, due to failure of self-tolerance.
Immune-mediated disease / autoimmune disease
the inflammation, tissue damage and resultant clinical signs that result from autoimmunity.
What’s the difference between autoimmunity and autoimmune disease?
Autoimmunity doesn’t always result in disease, but autoimmune disease is always due to autoimmunity.
What is the difference between autoimmunity and hypersensitivity?
Related abnormalities of the immune system
In autoimmunity, the immune system is reacting to self (no stimulus)
In hypersensitivity, the immune system is overreacting to a stimulus
why does autoimmunity occur?
genetic disposition
epigenetics - age, sex, lifestyle, diet
environmental triggers - infection, drugs, vaccines, cancer
primary vs secondary autoimmune disease
primary = no obvious triggers / idiopathic
secondary = suspected secondary to an obvious trigger
types of immune system neoplasia
lymphocyte neoplasia - lymphoma, lymphosarcoma, lymphoid leukaemia
plasma cell neoplasia - multiple myeloma, extramedullary plasmacytoma
macrophage and dendritic cell neoplasia - histiocytoma, histiocytic sarcoma
adverse effects of immune cell neoplasia
immunodeficiency (not very important)
local effects - disruption of physiologic function of affected tissues
paraneoplastic syndromes - hypercalcemia, hypoglycaemia, anaemia, thrombocytopenia, hyperglobulinaemia
lymphoma
very common in small animal medicine
(the most common cancer in cats)
lymphoma = clonal proliferation of neoplastic lymphocytes
WHO classification of lymphoma
stage 1 = single lymph node affected
stage 2 = regional lymphadenopathy
stage 3 = generalised lymphadenopathy
stage 4 = liver and/or spleen involvement
stage 5 = blood, bone marrow or other organ involvement
substages of WHO classification
a = without systemic signs
b = with systemic signs
Lymphadenomegaly
Submandibular, prescapular and popliteal lymph nodes are palpable in a normal dog
In a dog with lymphoma, the axillary and superficial inguinal lymph nodes may also be palpable
Pathophysiology of hypercalcaemia of malignancy
neoplastic cells produce parathyroid hormone-related peptide (PTH-rp)
PTH-rp has the same effects in the body as PTH
(increased calcium reabsorption in kidneys, increased calcium resorption from the bone)
results in hypercalcaemia
why does hypercalcaemia of malignancy cause PU/PD
• Hypercalcaemia blocks ADH action on renal collecting ducts
o Nephrogenic diabetes insipidus
o Polyuria, with secondary polydipsia
Pathophysiology of paraneoplastic hypoglycaemia
neoplastic cells produce insulin-like peptides
high insulin concentrations = glucose is moved intracellularly, glycogenolysis and hepatic glucose production is suppressed
results in hypoglycaemia
this can cause neurological signs - weakness, trembling, behaviour changes, seizures
Pathophysiology paraneoplastic anaemia
anaemia is common in lymphoma patients but is likely multifactorial
- anaemia of inflammatory disease (iron deficiency, RBC lifespan shortened)
- IMHA (autoimmunity triggered by lymphoid pathology)
- microangiopathic haemolytic anaemia (more common with histiocytic sarcoma, RBC injured as they travel through capillary beds infiltrated by neoplastic cells)
diagnosis and staging of lymphoma
cytology first (start with least invasive) - usually with fine needle aspirate, differentiate neoplastic vs reactive lymph node
histopathology from a biopsy sample
PARR - PCR for clonal antigen receptor rearrangement, can be done if histopath or cytology inconclusive
Leukaemia
neoplastic leukocytes in the peripheral blood
2 main types of leukaemia
lymphoid leukaemia - acute and chronic lymphoblastic leukaemia
myeloid leukaemia
Acute lymphoblastic leukaemia
Poorly differentiated lymphoblasts in circulation and bone marrow
Concurrent cytopenias common (anaemia, thrombocytopenia, neutropenia)
Treatment with multi-agent chemotherapy and supportive care
Aggressive cancer with poor prognosis
Chronic lymphocytic leukaemia
Well-differentiated, small, mature lymphocytes in circulation and bone marrow
Most T-cell (although B-cell origin reported)
Treatment with less aggressive chemotherapy
Long survival time expected
Multiple myeloma
systemic proliferation of malignant plasma cells within the bone marrow
uncommon
Extramedullary plasmacytoma
plasma cell neoplasm outside the bone marrow
local and systemic pathophysiology of multiple myelomas
Local disease = osteopenia and cortical lysis = bone pain and fractures
Systemic disease = paraneoplastic syndromes
- Hypercalcaemia of malignancy
- Monoclonal gammopathy -> hyperviscosity syndrome
Diagnosis of multiple myeloma
Clinical signs (non-specific): bone pain, lameness, PU/PD (if hypercalcaemic), behaviour / neurologic abnormalities (if hyperviscosity)
Routine blood tests: hypercalcaemia (common but not always), high serum globulin concentration
Serum protein electrophoresis – monoclonal gammopathy
Radiographs or CT – lytic lesions in bone (usually multiple)
Bone marrow cytology – identifies neoplastic plasma cells
Monoclonal gammopathy
(Serum protein electrophoresis)
• Neoplastic plasma cells secrete large quantities of gamma globulins
• Detected as a spike in serum electrophoresis
Histiocytic disease complex:
3 clinically recognised syndromes
- Canine cutaneous histiocytoma complex (benign neoplasia)
- Canine reactive histiocytosis (not neoplastic)
- Histiocytic sarcoma complex (malignant neoplasia)
breeds predisposed to histiocytic sarcoma
bernese mountain dogs, rottweilers, golden retrievers
histiocytic sarcoma
Disseminated, neoplastic transformation of antigen-presenting cells (dendritic cell origin)
localised vs systemic histiocytic sarcoma
Localised histiocytic sarcoma: affects a single tissue or organ – with solitary or multiple foci
Systemic histiocytic sarcoma: called “disseminated histiocytosis”
- Previously called malignant histiocytosis
- Considered disseminated once it has spread beyond the draining lymph node
- Multi-system, rapidly progressive disease with simultaneous involvement of multiple organs
- Discrete mass formation (sarcoma lesions) in spleen, LNs, lung, BM, periarticular tissue, brain
Haemophagocytic histiocytic sarcoma
Originates in the splenic red pulp and bone marrow macrophages
- Diffuse splenomegaly
- Neoplastic histiocytes phagocytose RBCs and platelets
- Erythrophagocytosis results in severe cytopenias
- Often suspected to have IMHA / ITP
- Lack discrete masses in spleen and at metastatic sites e.g. liver, lung
Worst prognosis of the two forms
- Median survival time two weeks
