Defense & Barriers 2: SA Immunodeficiency Flashcards
immunodeficiency definition
= a state in which the body’s ability to fight INFECTIOUS DISEASES or CANCER is COMPROMISED or ABSENT
PRIMARY immunodeficiency definition? how common is it?
SECONDARY immunodeficiency can be caused by what 8 things?
PRIMARY immunodeficiency… = CONGENITAL or INHERITED, but RARE!!
SECONDARY immunodeficiency…
1. Hyperadrenocorticism (Cushing’s)
2. Iatrogenic (GCCs, cyclosporine, etc.)
3. Malnutrition
4. Barrier damage
5. Severe cutaneous or systemic disease
6. Immunosuppressive viruses (FeLV, FIV)
7. Non-viral infections
8. Stress (psychological & physical)
what disease should we suspect in neonates, juveniles or young adults with recurrent infections?
PRIMARY immunodeficiency
in what situations should we suspect IMMUNODEFICIENCIES? (7)
- INCREASED FREQUENCY or SEVERITY of infection
- CHRONIC/PROLONGED course of infection
- INCOMPLETE CLEARING between infection episodes
- Incomplete/no response to treatment
- Infections with usually NON-PATHOGENIC/OPPORTUNISTIC ORGANISMS
- SEVERE, ATYPICAL manifestations
- Adverse reactions to MODIFIED LIVE VACCINES
5 common clinical signs of immunodeficiency?
what ABOUT all of them indicates immunodeficiency?
5 clinical signs?
1. Respiratory disease
2. Otitis externa
3. Pyoderma
4. Vomiting/diarrhea
5. Ill thrift
IN ALL CASES, THEY DO NOT RESOLVE WITH APPROPRIATE TREATMENT IF PATIENT IS IMMUNODEFICIENT
what CLINICAL SIGNS/DISEASES should we expect if there are immunodeficiencies in THESE parts of the immune system…
neutrophils?
NK cells?
cytotoxic T cells?
complement?
NEUTROPHILS = extracellular recurrent bacterial infections
NK cells = tumors
CYTOTOXIC T CELLS = more prone to viruses
COMPLEMENT = phagocytic defect
DIAGNOSTICS for immunodeficiency…
CBC values? (3)
neutrophil testing? (what 4 things does it test/how do they work? include 2 points for last marker)
CBC…
1. neutropenia
2. neutrophilia
3. lymphopenia
neutrophil testing? = determines FUNCTIONALITY of neutrophils
- ADHESION = via flow cytometry
- CHEMOTAXIS = moving of neutrophil TOWARDS infection
- PHAGOCYTOSIS
- BACTERICIDAL activity
–> Feed neutrophils opsonized bacteria and see if they can break them down via OXIDATIVE BURST
–> Can use a GREEN FLUORESCENCE ASSAY to TRACK OXIDATIVE BURST
= the HYDROGEN PEROXIDE produced will FLUORESCE GREEN
describe this chart, what it’s testing for/how it works
also describe the leftmost tube vs. the rightmost tube
this is a TOTAL HEMOLYTIC COMPLEMENT (CH50)
this complement assay aims to determine if SERUM COMPLEMENT COMPONENTS in the CLASSICAL PATHWAY are CAPABLE OF LYSING ANTIBODY-BOUND SHEEP RBCs
LEFTMOST = NO COMPLEMENT ACTIVATION, so RBCs PELLET AT BOTTOM & SERUM IS CLEAR
RIGHTMOST = COMPLEMENT ACTIVATION so RBCs LYSED & Hb released
what is this? (2)
describe what’s going on (2)
this is a RADIAL IMMUNODIFFUSION ASSAY (COMPLEMENT assay)
add patient’s SERUM and if CLEARING = COMPLEMENT ACTIVATION where ANTIGEN AND Ab BIND
BIGGER CLEARING = MORE complement activation
describe what this test is
define the LEFTMOST and RIGHTMOST peaks
how does it relate to immunodeficiency?
this is SERUM GEL ELECTROPHORESIS, which takes patient serum and SEPARATES OUT PROTEIN by SIZE AND CHARGE
LEFTMOST peak = ALBUMIN, MOST ABUNDANT PROTEIN
RIGHTMOST peak = IMMUNOGLOBULINS
in IMMUNODEFICIENCY, can determine if LACK OF IMMUNOGLOBULINS (lack of rightmost peak), OR if there’s MONOCLONAL POPULATION (neoplasia) if the IMMUNOGLOBULIN PEAK RESEMBLES ALBUMIN PEAK
what test does this describe?
after adding patient’s neutrophils, if the graph shifts…
LEFT?
RIGHT?
= BACTERICIDAL activity in NEUTROPHILS based on RELEASE OF HYDROGEN PEROXIDE in OXIDATIVE BURST
if the graph shifts…
LEFT = NEUTROPHILS HAVE BAD BACTERICIDAL ACTIVITY, more like control
RIGHT = NEUTROPHILS HAVE GOOD BACTERICIDAL ACTIVITY
lymphocyte blastogenesis…
helps determine WHAT?
how does it work? (2)
helps determine T CELL COMPETENCE
how does it work?
1. separate out WBC component of blood and CULTURE with something that makes T cells STRONGLY ACTIVE & DIVIDE
- If POOR PROLIFERATION = T cell DEFECT usually due to immunodeficiency
flow cytometry…
commonality?
how does it work? (2)
what disease is this usually diagnostic for?
** MOST COMMON DIAGNOSTIC TEST AVAILABLE FOR IMMUNODEFICIENCY
how does it work?
1. use LASERS to RUN ON SUSPENSION to determine if there’s a LACK OF T CELLS due to immunodeficiency
2. enumerates T and B cells
usually diagnostic for LYMPHOMA
SECONDARY/ACQUIRED immunodeficiencies are MORE COMMON than PRIMARY immunodeficiencies, TRUE OR FALSE?
TRUE
feline immunodeficiency virus…
acronym/common name?
classification? (2)
what SPECIFICALLY does it attack?
pathogenesis? (3, first one has 3 subsets)
net effect? (2, second one has 3 subsets)
relation to lymphoma?
FIV!
classification?
1. RETROVIRUS that is also a LENTIVIRUS
2. Related to HIV but has a slower/less predictable progression to AIDS than HIV
what SPECIFICALLY does it attack?
= preferentially infects CD4 T cells (T helper cells)
pathogenesis?
1. Virus infects CD4 T cells via entry through a CD4-specific receptor, causing…
–> Decreased production of CD4 T cells
–> Decreased lifespan of CD4 T cells
–> Increased apoptosis of CD4 T ells
- CD8 T cells (virus-specific cytotoxic) and Abs will rise and CONTROL but NOT ERADICATE infection
- Can also lead to lack of IL-2, which causes immune function compromise
net effect?
1. OVERALL, FIV results in LOSS OF ALL T CELL SUBSETS (lymphoid depletion)
2. May see a rise in OPPORTUNISTIC infections in cats with FIV, such as…
–> Mycobacterium avium
–> hemotropic mycoplasma (infects RBCs and causes anemia)
–> toxoplasma gondii
** Cats with FIV are 5-6x more likely to develop LYMPHOMA
IL-2
acts as a BRIDGE between…
overall, acts as what?
what ACTION does it take? (3 subsets)
finish the sentence
bridge between INNATE and ADAPTIVE immunity
overall = acts as a CENTRAL MEDIATOR between all kinds of T cells
what ACTION does it take?
–> Helps ACTIVATE T effector cells in response to ANTIGEN, including…
1. CD8 T cells
2. NK cells,
3. Helps B cells differentiate into PLASMA CELLS
what’s something we might MISS when trying to detect FIV?
there can be a very long SUBCLINICAL stage (up to YEARS) where we don’t know cat is infected with FIV/seems otherwise healthy
most COMMON clinical sign in FIV & 3 sub-categories?
why does this occur?
= IDIOPATHIC INFLAMMATION!
1. dermatitis
2. gingivitis/stomatitis
3. enteritis
occurs because IMMUNE RESPONSE the animal IS generating is NOT EFFECTIVE at clearing virus, so LONGER, SEVERE INEFFECTIVE inflammation
what DISEASE are FIV+ more likely to get? why?
FIV+ cats are more prone to TOXOPLASMA infection because they produce LESS IL-1, IL-12, which are needed to fight toxoplasma infection, and they also MAKE MORE IL-10 (anti-inflammatory immunosuppressive cytokine)
if a cat is infected with WHAT 3 diseases should we TEST FOR FIV?
- MYCOPLASMA
- FUNGAL INFECTION (histo, crypto, opportunistic)
- TOXOPLASMA GONDII
feline leukemia virus (FeLV)..
pathophysiology? (2)
clinical signs? (3)
FeLV-AIDS? (define AIDS and then what this is)
pathophysiology?
1. INFECTS T CELLS, mostly CD4 but some CD8
2. IMPAIRED IL-2 production
clinical signs?
1. D+
2. Opportunistic infections
3. Lymphoma
FeLV-AIDS = ACQUIRED immunodeficiency syndrome, RARE but HIGHLY IMMUNOSUPPRESSIVE form of FeLV where NO ANTIBODIES ARE PRODUCED so very prone to infection
IATROGENIC causes of secondary immunodeficiency? (3 main points, first has 4 subs)
- IMMUNOSUPPRESSIVE DRUGS
(1) Corticosteroids
(2) Cyclosporine
(3) Mycophenolate
(4) Azathioprine - CHEMOTHERAPY
- RADIATION THERAPY
what UNUSUAL thing can cause immunodeficiency? 3 simple examples?
commonality?
ENVIRONMENTAL TOXINS, such as…
1. insecticides
2. iodine
3. metals
RARE
ciliary dyskinesia…
what kind of disease is this?
pathophys?
how do dogs get this disease/at what age?
clinical signs? (5)
WHAT method is used to diagnose it? what can it do/what result is diagnostic?
what kind of disease?
= SECONDARY immunodeficiency!
pathophys?
= CILIA DO NOT BEAT in a COORDINATED FASHION, so mucociliary apparatus in LUNGS and CILIA in EARS, SOMETIMES SPERM doesn’t work!
how do they get it/what age?
INHERITED, and animals are usually young on onset
clinical signs?
1. mucoid nasal discharge
2. bronchiectasis = abnormal WIDENING of the airways causing them to fill with mucous and prone to infection
3. Secondary OTITIS MEDIA
4. Male infertility (affects cilia on SPERM)
5. RECURRENT bronchopneumonia (from a young age)
method for dx = TRANSMISSION ELECTRON MICROSCOPY of a NASAL BIOPSY is best!
1. Can visualize cross-sections of cilia and ORGANIZATION of them on the inside!
2. If NOT ALL ORIENTED IN SAME DIRECTION = DIAGNOSTIC for ciliary dyskinesia!
leukocyte adhesion deficiency…
what kind of disease is this?
AKA “what name?”
what 4 breeds predisposed? (+1 additional species)
etiology?
pathophys? (5)
AKA “Granulocytopathy syndrome”
PRIMARY immunodeficiency!
predisposed breeds?
1. Irish setter
2. Red and white setter
3. German Shepherd
4. DLH
+ 1 = COWS can get it too!
etiology?
= AUTOSOMAL RECESSIVE mutation of the CD18 molecule in INTEGRIN so NEUTROPHILS CANNOT STOP/BIND/GO TO TARGET TISSUE
pathophys?
1. When you have a bacterial infection, you need neutrophils to go to the site
- Neutrophils have to get out of blood via ROLLING/BINDING to SELECTINS (present on both the neutrophil and endothelial cell surface) on the VESSEL
- Then, SELECTINS need to bind to INTEGRINS = stops neutrophil so that it stays in same spot on endothelium
- LFA-1 is a HETERODIMER INTEGRIN made of CD11a/CD18, which then binds to ICAM (intracellular adhesion molecule)
- Once neutrophil is anchored/bound to ICAM, SQUISHES BETWEEN ENDOTHELIAL CELLS –> migrates to TARGET TISSUE
leukocyte adhesion deficiency…
clinical signs/hematology? (3 main, 4 subs on first one)
diagnosis? (2, second has 1 subset)
clinical signs/hematology?
1. RECURRENT EXTRACELLULAR bacterial infections
–> Omphalophlebitis
–> Lymphadenopathy
–> Recurrent pneumonia
–> Gingivitis
2. SEVERE LEUKOCYTOSIS (50-100K) on CBC
3. SHORTENED lifespan (~1 year)
diagnosis?
1. GENETIC TESTING for mutation!
2. Can test neutrophil expression of CD18 molecule via FLOW CYTOMETRY
–> Can STAIN neutrophils for whether they have CD18 EXPRESSION!
what DISEASE is this?
TRAPPED NEUTROPHIL SYNDROME
trapped neutrophil syndrome…
main etiology? what 2 things does this then cause?
signalment? (1)
clinical signs/hematology? (6)
diagnosis? (1)
etiology?
= from a AUTOSOMAL RECESSIVE MUTATION IN VESICLE PROTEIN SORTING 13B (VPS13B) GENE, which is REQUIRED for neutrophils to MATURE normally
this mutation then causes…
1. neutrophils to be TRAPPED in bone marrow
2. DECREASED neutrophil lifespan
signalment = COMMON in BORDER COLLIES
clinical signs/hematology?
1. MARKED neutropenia
2. Myeloid hyperplasia
3. CHRONIC extracellular bacterial infections
4. Small stature
5. Slender extremities
6. Cognitive impairment
diagnosis = DNA TEST
why does MYELOID HYPERPLASIA occur in TRAPPED NEUTROPHIL SYNDROME?
= OVERPRODUCTION of neutrophil precursors due to SHORTENED LIFESPAN of neutrophil & inability to LEAVE bone marrow
cyclic hematopoiesis…
AKA “what name?”
signalment? (2)
etiology? (weird one)
hematological finding?
what’s important to make diagnosis? (1)
prognosis? (1)
o AKA “Gray Collie Syndrome”
signalment?
1. GRAY COLLIES
2. Or any collies that have VARIABLE, CYCLICAL NEUTROPHIL counts!
etiology?
= MUTATION in adapter protein AP3B1 in neutrophil causes disrupted neutrophil elastase trafficking = NEUTROPHILS DO NOT SURVIVE
hematological finding?
1. SEVERE NEUTROPENIA every 12-14 days, +/- THROMBOCYTOPENIA
what’s important to make DIAGNOSIS? = TAKE MULTIPLE CBCs to confirm CYCLICITY
prognosis? = Usually do not survive >3 years
