Immunology Flashcards

1
Q

what are the 3/4 mechanisms of immunopathology

A

• Immunodeficiency = ineffective immune response
• Hypersensitivity reaction = overactive immune response
• Autoimmunity = inappropriate reaction to self

(also immune cell neoplasia)

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2
Q

what are the 3 general features of immunodeficiency diseases

A

o Increased susceptibility to infection
o Increased incidence of autoimmune disease
o Prone to virally induced cancers e.g. feline leukaemia virus

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3
Q

examples of innate immune system deficiencies

A

abnormal phagocyte function
complement deficiency

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4
Q

adaptive immune system deficiencies

A

B cell immunodeficiency (decreased immunoglobin production)
T cell immunodeficiency (decreased cell mediated immunity)
Combined – B and T cell (SCID)

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5
Q

primary vs secondary immunodeficiency diseases

A

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

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6
Q

causes of secondary immune deficiencies

A

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)

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7
Q

potential causes of failure of passive transfer

A

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

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8
Q

diagnostic approach to failure of passive transfer

A

• 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

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9
Q

treatment of failure of passive transfer

A

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

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10
Q

prevention of failure of passive transfer

A

• 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

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11
Q

Iatrogenic immunosuppression

A

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

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12
Q

hypersenstivity reactions

A

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.

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13
Q

autoimmunity

A

an immune response directed against self-tissue, due to failure of self-tolerance.

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14
Q

Immune-mediated disease / autoimmune disease

A

the inflammation, tissue damage and resultant clinical signs that result from autoimmunity.

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15
Q

What’s the difference between autoimmunity and autoimmune disease?

A

Autoimmunity doesn’t always result in disease, but autoimmune disease is always due to autoimmunity.

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16
Q

What is the difference between autoimmunity and hypersensitivity?

A

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

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17
Q

why does autoimmunity occur?

A

genetic disposition
epigenetics - age, sex, lifestyle, diet
environmental triggers - infection, drugs, vaccines, cancer

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18
Q

primary vs secondary autoimmune disease

A

primary = no obvious triggers / idiopathic
secondary = suspected secondary to an obvious trigger

19
Q

types of immune system neoplasia

A

lymphocyte neoplasia - lymphoma, lymphosarcoma, lymphoid leukaemia

plasma cell neoplasia - multiple myeloma, extramedullary plasmacytoma

macrophage and dendritic cell neoplasia - histiocytoma, histiocytic sarcoma

20
Q

adverse effects of immune cell neoplasia

A

immunodeficiency (not very important)
local effects - disruption of physiologic function of affected tissues
paraneoplastic syndromes - hypercalcemia, hypoglycaemia, anaemia, thrombocytopenia, hyperglobulinaemia

21
Q

lymphoma

A

very common in small animal medicine
(the most common cancer in cats)

lymphoma = clonal proliferation of neoplastic lymphocytes

22
Q

WHO classification of lymphoma

A

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

23
Q

substages of WHO classification

A

a = without systemic signs

b = with systemic signs

24
Q

Lymphadenomegaly

A

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

25
Q

Pathophysiology of hypercalcaemia of malignancy

A

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

26
Q

why does hypercalcaemia of malignancy cause PU/PD

A

• Hypercalcaemia blocks ADH action on renal collecting ducts
o Nephrogenic diabetes insipidus
o Polyuria, with secondary polydipsia

27
Q

Pathophysiology of paraneoplastic hypoglycaemia

A

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

28
Q

Pathophysiology paraneoplastic anaemia

A

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)

29
Q

diagnosis and staging of lymphoma

A

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

30
Q

Leukaemia

A

neoplastic leukocytes in the peripheral blood

31
Q

2 main types of leukaemia

A

lymphoid leukaemia - acute and chronic lymphoblastic leukaemia

myeloid leukaemia

32
Q

Acute lymphoblastic leukaemia

A

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

33
Q

Chronic lymphocytic leukaemia

A

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

34
Q

Multiple myeloma

A

systemic proliferation of malignant plasma cells within the bone marrow
uncommon

35
Q

Extramedullary plasmacytoma

A

plasma cell neoplasm outside the bone marrow

36
Q

local and systemic pathophysiology of multiple myelomas

A

Local disease = osteopenia and cortical lysis = bone pain and fractures

Systemic disease = paraneoplastic syndromes
- Hypercalcaemia of malignancy
- Monoclonal gammopathy -> hyperviscosity syndrome

37
Q

Diagnosis of multiple myeloma

A

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

38
Q

Monoclonal gammopathy

A

(Serum protein electrophoresis)
• Neoplastic plasma cells secrete large quantities of gamma globulins
• Detected as a spike in serum electrophoresis

39
Q

Histiocytic disease complex:
3 clinically recognised syndromes

A
  1. Canine cutaneous histiocytoma complex (benign neoplasia)
  2. Canine reactive histiocytosis (not neoplastic)
  3. Histiocytic sarcoma complex (malignant neoplasia)
40
Q

breeds predisposed to histiocytic sarcoma

A

bernese mountain dogs, rottweilers, golden retrievers

41
Q

histiocytic sarcoma

A

Disseminated, neoplastic transformation of antigen-presenting cells (dendritic cell origin)

42
Q

localised vs systemic histiocytic sarcoma

A

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

43
Q

Haemophagocytic histiocytic sarcoma

A

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