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Immuno > Immunodeficiency Week 10 > Flashcards

Immunodeficiency Week 10 Flashcards

1
Q

What is a Immunodeficiency Diseases

A

Defects in one or more components of the immune system can lead to serious and
often fatal disorders - immunodeficiency diseases

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2
Q

How many groups are immunodeficiencies classified? what are they?

A

2
Primary
Secondary or Acquired

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3
Q

What is a primary immunodeficiencies

A

The primary immunodeficiencies are genetic defects that result in an increased
susceptibility to infection that is frequently manifested in infancy and early childhood
but is sometimes first clinically detected later in life

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4
Q

What is a secondary or acquired immunodeficiency?

A

Secondary, or acquired, immunodeficiencies are not inherited diseases but
develop as a consequence of malnutrition, disseminated cancer, treatment with
immunosuppressive drugs, or infection of cells of the immune system

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5
Q

What is the principal consequence of immunodeficiency

A

The principal consequence of immunodeficiency
is increased susceptibility to infection

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6
Q

What are the consequences of a deficient humoral immunity?

A

Deficient humoral immunity usually results in
infection by encapsulated, pus-forming bacteria
and some viruses

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7
Q

What are the defects in cell-mediated immunity?

A

defects in cell-mediated immunity lead to infection
by viruses and other intracellular microbes or the
reactivation of latent infections

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8
Q

Where do you find combined deficiencies?

A

Combined deficiencies – all classes of microbes

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9
Q

What are “opportunistic” infections?

A

Opportunistic infections; susceptible to cancer

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10
Q

Features of Immunodeficiencies affecting T or B Lymphocytes:
Susceptibility to infection in a B cell deficiency includes:

A

Pyogenic bacteria (otitis, pneumonia, meningitis, osteomyelitis)
enteric bacteria and viruses
some Parasites

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11
Q

Features of Immunodeficiencies affecting T or B Lymphocytes:
Susceptibility to infection in a T cell deficiency includes:

A

Pneumocystis jiroveci
many viruses
atypical myobacteria
fungi

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12
Q

Features of Immunodeficiencies affecting T or B Lymphocytes:
Serum Immunoglobulin Levels in a B Cell Deficiency are….

A

reduced

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13
Q

Features of Immunodeficiencies affecting T or B Lymphocytes:
Serum Immunoglobulin Levels in a T Cell Deficiency are….

A

normal or reduced

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14
Q

Features of Immunodeficiencies affecting T or B Lymphocytes:
DTH reactions to common antigens in B Cell Deficiency are…

A

Normal

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15
Q

Features of Immunodeficiencies affecting T or B Lymphocytes:
DTH reactions to common antigens in T Cell Deficiency are…

A

Reduced

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16
Q

Features of Immunodeficiencies affecting T or B Lymphocytes:
Morphology of lymphoid tissues in a B Cell Deficiency are…

A

Absent or reduced follicles and germinal centers (B cell zones)

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17
Q

Features of Immunodeficiencies affecting T or B Lymphocytes:
Morphology of lymphoid tissues in a T Cell Deficiency are…

A

Usually normal follicles, may be reduced parafollicular cortical regions (T cell zones)

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18
Q

Primary (Congenital) Immunodeficiencies are…

A

Primary immunodeficiencies are monogenic diseases caused by germline mutations
in genes that regulate the development or function of the immune system

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19
Q

Most Primary immunodeficiencies exhibit….

A

the majority of primary immunodeficiencies exhibit an autosomal recessive
inheritance

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20
Q

Autosomal recessive alleles are often seen when?

A

Autosomal recessive alleles are often seen in consanguineous families when the
same mutation is inherited from both parents

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21
Q

What is the situation when offspring are of NONCONSANGUINEOUS marriages?

A

in offspring of nonconsanguineous marriages, one defective allele of a specific gene
is inherited from one parent and a different defective mutation in the same gene is
inherited from the other parent

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22
Q

Some primary immunodeficiencies are associated with what?

A

Some primary immunodeficiencies are associated with autosomal dominant
inheritance

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23
Q

Primary immunodeficiency diseases –> what?

A

Primary immunodeficiency diseases clinical history of repeated infections

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24
Q

Diagnoses of Primary (Congenital) Immunodeficiencies are quite easily made by what? (3 things)

A

measurement of serum Ig levels,
flow cytometry of immune cells,
or assessment of neutrophil function in vitro

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25
Q

Diagnoses of Primary (congenital) immunodeficiencies in Primary T cell immunodeficiencies are made by what? (2 things)

A

reduced numbers of peripheral blood T cells,
low proliferative responses of blood lymphocytes to polyclonal T cell
activators

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26
Q

Primary (Congenital) Immunodeficiencies may result from what types of defects? (2 things) defect in what development and activation and defect in effector mech of what?

A

defects in lymphocyte development or activation
defects in the effector mechanisms of innate and adaptive immunity

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27
Q

Defects in Innate Immunity are: (define and name)

A

Defects in NK Cells and Phagocytes -

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28
Q

Defects in Innate IS
Chediak-Higashi syndrome CHC

Who gets it?
What is it?
How does it behave:
What happens?

A

Inherited disease of Hereford, Japanese Black, and Brangus cattle; mink, persian cats, white tigers, humans, etc.

it is a RARE AUTOSOMAL RECESSIVE DISORDER which results in recurrent infections by pyogenic bacT, albinism, excessive bleeding etc.

mutation in the lysosomal trafficking regulator (LYST)

Neutrophils, monocytes, lymphocytes–>GIANT LYSOMES–>rupture–>tissue damage

CD8 t cells and NK cells CANNOT EXCREETE THEIR GRANZYME-RICH GRANULES

PARIENTS WILL BE MORE SUSEPTIBLE TO RESPITORY INFECTIONS AND TUMORS

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29
Q

Autoimmunity: what occurs with random gen of AG binding receptors?

A

Random gen of AG binding receptors –> makes lymphocytes capable of binding and responding to self-AG.

Autoimmune DZ–>develop spontaneously.

2 major catagories include :
*Normal IR to Unusual AG
*Abnormal IR to normal AG

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30
Q

Autoimmunity stems from 2 sources:

A

Hormonal influences and Genetic predisposition

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31
Q

Normal immune response is divided into 2 subsets:

A

Previously hidden antigens and Molecular Mimicry

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32
Q

Abnormal immune response results in:

A

failure of regulatory control

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33
Q

Autoimmunity, a normal immune response and previous hidden antigens; they can be found in 3 subsets… what are they

A

Tissue Damage–>intracellular molecules

Molecular structural
alterations

Newly-synthesized antigens

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34
Q

Autoimmunity, a normal immune response and molecular mimicry what is the subset?

A

Microbial cross-reactions

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35
Q

Autoimmunity, abnormal immune response and failure to regulate what are the 3 subsets?

A

Failure to apoptosis
virus infections
microchimerism

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36
Q

Autoimmunity
normal IR
Explain:

A

IR to an AG that has been previously hidden (ex:sperm) OR a result of cross reactivity between an infectious agent and a normal body component

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37
Q

Normal IR
Do we have naturally occurring auto AB? why?

A

to allow for homeostasis and regulation (IgM/IgG) AB against protein fragments or proteins that are damaged due to oxidation (ROS)
Keep in mind some autoimmune responses have a physiological function

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38
Q

Normal IR
What is Cryptic AG?

A

-Nontolerant T Cells meet previously hidden autoAG

–T cells are only tolerant if they are first exposed to these AutoAG (AIRE GENE!!)

–Ex: testes injury–>may allow for the proteins to reach the BS–>then come in contact with AG-sensitive cells –>autoimmune response

–EX: heart attack–>AutoAB will be produced against the mitochondria of the myocardiocytes

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39
Q

Normal IR
-AG generated due to molecular changes: how can it be triggered?

A

can be triggered by the development of completely new epitopes on normal proteins.

POP QUIZ: what is an epitope?

A: the specific target against which an individual antibody binds. When an antibody binds to a protein, it isn’t binding to the entire full-length protein. it is binding to a segment of the protein known as an epitope. Another word for epitope is antigenic determinant–part of the antigen that is recognized by the immune system, specifically by antibodies, b cells or t cells,

EX. Rheumatoid factors (RFs) and immunocongluttins (IK)

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40
Q

Normal IR
RF: autoAB against immunoglobulins. Explain:

A

Produced when large amounts of immune complexes are generated–>autoimmune dz
–Rheumatoid arthritis, systemic lupus erythematosus

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41
Q

Normal IR
IK: autoAB directed against the complement components c2, c4, c3 explain:

A

occurs whenever these factors =activated

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42
Q

Normal IR
Receptor Editing explain:

A

REMEMBER B AND T CELLS ARE SPECIAL AND UNDERGO RANDOM GENE REARRANGEMENT.

*Do NK cells do this too? y/n

As a result autoreactive AG receptors can be created :(

Immature B cell–>produces a receptor that binds to selfAG–>B cell will fail to continue to develop–>light chain receptor will undergo recombination–>no longer self reactive.

**REMEMBER B CELLS GET A 2 CHANCE

This does not occur in mature B cells–>these cells –>apoptosis

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43
Q

Normal IR
Molecular mimicry
what is it?
How does it occur?
example

A

Sharing of epitopes between an infectious AG and an autoAG

Bcell–>binds to foreign AG and can cross react w/autoAG
**THIS REQUIRES T HELPER CELLS

Ex. T.cruzi and mammalian neurons and cardiac muscle

CDa/18 shares an AG determinant w/ (see diagram in notes)

44
Q

Abnormal IR
Failure of regulatory control
explain:

A

Hidden epitopes, sustained response is necessary for Dz to develope through

Autoimmune dz and lymphoid tumors

-Myasthenia gravis–>thymic carcinoma

45
Q

Abnormal IR
Infectious induced autoimmunity
explain what types of infections:

A

NZB mice–>persistent infection with a type of c retrovirus–>production of autoAB against nucleic acids and RBC

Strep, Pyogenes, lyme dz, lepto may also trigger autoimmune heart dz, arthritis, uveitis

46
Q

Abnormal IR
Microchimerism
Explain:

A

During pregnancy–>mothers and fetuses exchange cells–>fetal cells can persist in the moms body for years–>moms cells are in offspring

Y chromosomal DNA has been detected in Golden Retrievers suggesting persistent fetal microchimerism

47
Q

Autoimmunity
Flu vax–>guillain-barre syndrome
explain:

What are the genetic predisposing factors?

A

rabies vax of beagle pups–> increased risk of antithyroglobulin AB 6 mo later

Vax–> autoimmune hemolytic anemia

vax w/potent adjuvants–>low levels of autoAB

Genetic Predisposing factors:
-MHC–>are the most NB genes that influence naturally occurring autoimmune dz
*Inc restricted MHC polymorphism–>inc autoimmune sus
*Diabetes mellitus associated w/DLA-A3,A7,A10 and DLA-B4

48
Q

Immune-mediated inflammatory Dz

what is it?
examples of it include what?

A

Extensive and uncontrolled inflammation caused by innate autoimmunity.

-Systemic lupus erythematosus
-Discoid lupus erythematosus
-Sjorgens syndrome
-Autoimmune polyarthritis
_immune vasculitis

49
Q

Organ-specific auto immune diseases
Autoimmune ENDOCRINE diseases include:

A

-lymphocytic thyroiditis
-hyperthyroidism
-lymphocytic parathyroiditis
-autoimmune diabetes mellitus
-atrophic lymphocytic pancreatitis
-autoimmune adrenalitis

50
Q

Organ-specific auto immune diseases
Autoimmune NEUROLOGICAL diseases include:

A

-equine polyneuritis
-canine polyneuritis
-necrotizing meningoencephalitis
-degenerative myelopathy
-cerebellar degeneration

51
Q

Organ-specific auto immune diseases
Autoimmune EYE diseases include:

A

-Equine recurrent uveitis
-Uveodermatological syndrome
-Immune-mediated ketatoconjunctivitis

52
Q

Organ-specific auto immune diseases
Autoimmune SKIN diseases include:

A

-Alopecia areata
-Pemphigus vulgaris
-Pemphigus foliaceus
-Bullous pemphigoid

53
Q

Additional organ specific autoimmune diseases can occur where? (4 places that are not endocrine, neurological, eye, skin)?

A

Reproductive
Nephritis
blood diseases
muscle diseases

54
Q

tissue graft rejection

4 types of grafts:

A

autograft
isograft
allograft
xenograft

55
Q

tissue graft rejection
what is an autograft

A

-from the same individual
-does not trigger immune response

56
Q

tissue graft rejection
what is isograft

A

-from an identical twin
-does not trigger immune response

57
Q

tissue graft rejection
what is allograft

A

-from a genetically different individual of the same species
-different MHC and Blood group
-STRONG REJECTION
-most frequent type of graft
-typically rejects in 1-2 weeks

58
Q

tissue graft rejection
what is xenograft

A

-from a different species
*biochemical and immunological rejection
-is rapid and intense within hours

59
Q

tissue graft rejection
Genetics
Are identical grafts rejected?

A

generally never

60
Q

tissue graft rejection
Genetics
are genetically different grafts rejected?

A

always

61
Q

tissue graft rejection
Genetics
will offspring of genetically different parents reject a graft from either of the other parent

A

not reject

62
Q

tissue graft rejection
Genetics
will a graft from the offspring of two genetically different parents be rejected by the parent?

A

will be rejected

63
Q

Immunodeficiency

Primary explain:

autosomonal?
causes?
DX?
Primary t cell def:
can result in?

A

genetic defects that result in an increase susceptibility to infection

*think YOUNG (usually)

monogentetic disease caused by germline mutations–> reg the development/function of the IS

autosomonal recessive inheritance (both parents must have the allele)

some primary deficiencies are associated with autosomonal dominent inheritance (only need 1 copy of the mutation

causes: repeat infections

DX: easy, measure serum lg levels, flow cytometry of immune cells or assessment of the neutrophil function

Primary t cell def:
reduced numbers of peripheral blood t cells and low prolif response

can result in defects in:
-lymphocyte development
-lymphocyte activation
-effector mechs of innate or the adaptive IS

64
Q

Immunodeficiency

secondary/acquired explain:

A

not inherited disease but develop as a consequence of malnutrition, cancer, tx w/immunosuppressive drugs, infection

**results in an increased susceptibility to infection

65
Q

Immunodeficiency

humoral immunity deficiency
explain:

A

results in infection by encapsulated pus-forming bacT and viruses

66
Q

Immunodeficiency

cell-mediated immunity deficiency

explain:

A

results in infection by viruses and other intracellular microbes

67
Q

Defects in the innate Immune System

Pelger-huet Anomaly

who gets it?
what is it?
clinical importance?

A

Inherited disorder in humans, arabian horses, DSH, cocker spaniels and foxhounds

failure to granulocyte nuclei to segment

not very clinically important other than may be missed DX as inflammation

68
Q

Defects in the innate Immune System

Canine leukocyte adhesion deficiency (LAD)

what is LAD 1
what is LAD 2
what is LAD 3
what is CLAD

what is the result?

A

LAD 1: loss of funcion on the gene encoding for the bets 2 integrin (irish setters)
_THIS IS CLAD
-What is so important about integrins?

LAD2: defect in fucose metabolism that results in a deficiency in the carb structure–>neutrophils cant roll

LAD 3: defects in teh activation of beta integrins due to a mutation in the kindlin 3 gene

CLAD: LAD1–> result of affected in the integrin mac 1
-Neutrophils cant respond to chemo attractants–>increased risk of infection even with a high number of neutrophils
-patient typically dies young due to recurrent bacT infections

69
Q

Defects in the innate IS

Bovine Leukocyte Adhesion Deficiency BLAD

who gets it?
what is it?
what is the result?
Why does this happen?

A
  • LAD-I – described in Holstein calves – autosomal recessive disease – recurrent bacterial infections,
    anorexia, gingivitis, periodontitis, chronic pneumonia, and delayed wound healing
  • Calves die 2-7 months of age; survivors grow slowly and may develop amyloidosis
  • Large number of intravascular neutrophils but very few extravascular – even in the presence of bacteria
  • Because T cells also express CD 18, BLAD calves show poor delayed hypersensitivity responses.
    Neutrophils show reduced responsiveness to chemotactic stimuli and diminished superoxide production
    and myeloperoxidase activity
  • BLAD – point mutation in the CD 18 gene – aspartic acid is replaced by glycine – CD 18 is not
    produced – neutrophils cannot attach to the vascular endothelial cells or emigrate from blood vessels
70
Q

Defects in Innate Immunity

Canine Cyclical Neutropenia (grey Collie syndrome)

who gets it?
what happens?
Why?
result?

A
  • Autosomal recessive disease of Border Collies – diluted skin
    pigmentation, eye lesions, and fluctuation in leucocyte number
  • Hair – silver grey and the nose is grey – diagnostic feature
  • Loss of neutrophils – every 11 to 12 days and lasts 3 days
  • Followed by normal or elevated neutropil count – 7 days
  • Dogs – severe enteric and respiratory – rarely live beyond 3 y
  • Puppies – weak, grow poorly, wounds that fail to heal and
    increased mortality
71
Q

Inherited Defects in the Adaptive Immune System

Immunodeficiencies of Horses

what is it?
why?
result?

A
  • Both cell- and antibody-mediated resonses are defective – genetic lesion at the point prior to thymic
    and bursal cell processing stem cell lesion
  • Defect in thymic development failure to mount cell-mediated immune responses – normal Ab
  • Lesion in the B cell – impaired antibody responses

Severe Combined Immunodeficiency (SCID)
* Foals fail to produce functional T or B cells and have very few circulating lymphocytes
* Suckle successfully – aquire maternal Ig
* Born healthy – begin to siken by 2 months of age – all die 4 to 6 months – overwhelming infection
* Bronchopneumonia – equine adenovirus, Rhodococcus equi, and Pneumocystis

72
Q

Inherited Defects in the Adaptive Immune System

Immunodeficiencies of Horses
Immunoglobulin deficiencies

what is it?
what happens?
why?

A
  • Primary agammaglobilinemia is rare in foals – animals have no B cells and very low serum Ig
  • Lymphoid tissues have no primary follicles, germinal centers or plasma cells
  • Foals – recurrent bacterial infections but may susvive for up to 18 months
  • Develop septicemia or recurrent respiratory tract infections (Klebsiella pneumoniae and R. equi)
  • Most foals – Arabian – genetic basis
73
Q

Inherited Defects in the Adaptive Immune System

Immunodeficiencies of Horses
Common Variable Immunodeficiency

what is it?
who gets it?
what happens?
why?

A
  • Late onset B-cell lymphopenia as a result of impaired B cell production in the bone marrow
  • Horses where four genes – E2A, PAX5, CD19, and IGD have significantly reduced expression
  • Resemble primary immunodeficiencies but usually occur in animals over 3 years of age
  • Recurrent infections not responsive to medical treatment – bacterial meningitis
  • Serum – only trace levels of IgG, IgM and very low IgA; normal T cell number but undetectable B cells
  • Necropsy – no B cells in lymphoid organs, blood or bone marrow
74
Q

Inherited Defects in the Adaptive Immune System

Immunodeficiencies of Horses
Foal Immunodeficiency Syndrome

what is it?
who gets it? what happens?
why?

A
  • B cell immunodeficiency and profound anemia, hematocrit and B cell numbers decline over 4-12 w
  • Animals lack germinal centers and plasma cells – Fell and dales ponies
  • The B cell numbers declines to les than 10% of normal and serum Ig levels drop – maternal Ab
    catabolization
  • Severe respiratory disease – opportunistic – adenivirus plus severe diarrhea – Cryptosporidium
  • Foals die or are euthanized by 1 to 3 months of age
  • Autosomal recessive disease – mutation in a gene coding for sodium/myoinositol co-transporter
75
Q

Inherited Defects in the Adaptive Immune System

Immunodeficiencies of Cattle
Severe Combined Immunodeficiency

who gets it?
what happens?
why?

A
  • Angus calf – normal when born – suckeled normally – 6 weekes – pneumonia and diarrhea
  • Lymphopenic and severely hypogammaglobulinemic (undetectable IgM and IgA and low IgG)
  • The animal died within a week with systemic candidiasis – syndrome closely resembles equine SCID

Selective IgG2 Deficiency

Hereditary Parakeratosis

  • Black Pied Danish and Fresian cattle – born healthy – few weeks – exanthema, hair loss and parakeratosis
76
Q

Inherited Defects in the Adaptive Immune System

Immunodeficiencies of Pigs
Porcine SCID

who gets it?
what happens?
why?

A
  • Inbred Yorksire pigs – normal while suckling but gradually overcome by opportunistic infections
  • Reduced growth, skin lesions and respiratory distress – not survive beyond 60 days
  • Thymus not visible, lymph nodes were small; B and T cells lacked in the bloodstream but had normal
    number of NK cells and neutrophils – no antibody response to viral infections
  • Two spontaneous mutations in the Artemis gene (H12 and H16)
77
Q

Inherited Defects in the Adaptive Immune System

Immunodeficiencies of Dogs
Combined immunodeficiencies

who gets it?

what is it?

what happens?

why?

A
  • Jack Russel terriers – SCID phenotype – lymphopenia, agamaglobulinemia, thymic and lymphoid aplasia
  • Autosomal recessive condition – point mutation stop codon formation and premature termination of
    the peptide chain
  • X-linked SCID – Basset Hounds and Corgi – stunted growth, susceptibility to infections and absence of
    lymph nodes
  • Born normal – 6-8 weeks develop pyoderma, otitis – pneumonia, enteritis or sepsis – 4 months
  • X-linked – breeding of a carrier female to a nomal sire – half the males in each litter affected and all
    females – phenotipically normal
78
Q

Inherited Defects in the Adaptive Immune System

Immunodeficiencies of Dogs
Immunoglobulin deficiencies

who gets it?

what is it?

what happens?

A
  • Selective IgM deficiency – Doberman Pinschers – high IgA, low IgG and very low IgM
  • Selective immunodeficiencies of IgA – mostly in German Sheperds and Shar-Peis – deficiencies in
    mucosal immunity
  • Cavalier King Charles Spaniels with Pneumocystis pneumonia had reduced IgG levels compared to
    normal dogs
79
Q

Inherited Defects in the Adaptive Immune System

Immunodeficiencies of Dogs
T-cell deficiencies

who gets it?
what happens?
why?
result?

A
  • Family of inbred Weimaraners – immunodeficiency and dwarfism
  • Normal at birth – at 6-7 weeks developed a wasting syndrome – emaciation and letargy
  • Thymuses – atrophied and lacked a cortex; normal Ig levels, Th cells activity unimpared
  • Growth hormone treatment caused thymic cortical regeneration and clinical improvement
  • Disease – due to a deficiency of growth hormone as a result of a lesion in the hypothalamus – the thymus
    requires growth hormone to function
80
Q

Secondary (Aquired) Immunodeficiencies

what is it?

how common are they? why?

what causes them?

examples

A
  • Deficiencies of the immune system often develop because of abnormalities that are not genetic but
    acquired during life
  • Acquired immunodeficiency diseases are, in fact, more common than congenital immunodeficiencies
    and are caused by a variety of pathogenic mechanisms
  • Disorders in which immunodeficiency is a frequent complicating element include malnutrition, cancer,
    and infections
  • Viruses that invade the immune system are – affect primary lymphoid tissues
  • affect secondary lymphoid tissues
  • Chickens – infectious bursal disease virus (IBDV) destroys lymphocytes in the bursa of Fabricius
  • IBDV is not completely specific for bursal cells; it also destroys cells in the spleen and thymus
81
Q

Secondary (Aquired) Immunodeficiencies

  • Loss of lymphocytes

what is this?

A

Loss of lymphocytes – common in virus infections since viral survival and persistence may require
immunosupression

82
Q

Secondary (Aquired) Immunodeficiencies

Lymphopenia

where do you find this?

A

Lymphopenia – in feline panleukopenia, canine parvovirus-2, feline leukemia ans African Swine Fever

83
Q

Secondary (Aquired) Immunodeficiencies

Bovine viral diarrhea virus (BVDV)

what is this/what does it do?

A

Bovine viral diarrhea virus (BVDV) causes destruction of both T and B cells

84
Q

Secondary (Aquired) Immunodeficiencies

Equine herpesvirus-1

what is this?

A

Equine herpesvirus-1 causes a drop in T-cell numbers and depresses cell-mediated responses in foals

85
Q

Secondary (Aquired) Immunodeficiencies

Bovine herpesvirus-1 (BHV-1)

what is this?

A

Bovine herpesvirus-1 (BHV-1) also causes a drop in T cells and depresses macrophage cytotoxicity
and IL-1 synthesis

86
Q

PRRS causes destruction of what, and leads to what?

A

Alveolar macs and causes enzootic pneumonia

87
Q

Secondary (Aquired) Immunodeficiencies

Porcine Reproductive Respiratory Syndrome (PRRS)

what is this?

A

Porcine Reproductive Respiratory Syndrome (PRRS) – destruction of alveolar macrophages – severe
enzootic pneumonia

88
Q

Virus-induced immunosupression

Canine distemper virus (CDV)

what is this?
what does it do?
how does it happen?
what result?

A
  • Virus that destroys secondary lymphoid organs – predilection for lymphocytes - lymphopenia
  • Major cellular receptor is CD150 – expressed on activated B and T cells
  • tonsils – bronchial lymph nodes to the blood stream – kills T and B cells
  • Invades the thymus, spleen, lymph nodes – destroys more cells – thymic atrophy, depleted
    lymphocytes in spleen and tonsils
  • CD4+, CD8+ and CD21+ B cells – most affected
  • Supresses production of IL-1 and IL-2, IL-12 and B-cell maturation
  • Immunosupresion – clinical disease – dogs develop Pneumocystis pneumonia – supressed animals
  • Also causes demyelinating leukoencephalomyelitis; demielinization is enhanced by Cytotoxic CD8+
89
Q

Virus-induced immunosupression

Retrovirus infections in primates

Simian Immunodeficiency virus (SIV)

are there many of these?

what happens?

why does it happen?
result?

A
  • More than 40 lentiviruses – isolated from nunhuman primates – simian immunodeficiency viruses (SIV)
    selectively invades CD4+ T cells
  • The viruses stimulate a strong but ineffective immune response- immunodeficiency syndrome similar to
    AIDS in humans – are believed to be transmitted sexually
  • Clinical progression is slow - animals develop lymphadenopathy, severe wheight loss, severe chronic
    diarrhea, lymphomas and opportumictic – Pneumocystis, Mycobacterium, Candida and Cryptosporidium
  • Macaques are depleted of CD4+ T cells, macrophages and dendritic cells
  • Two cellualar receptors – CD4 and CCR5
  • 25% of infected do not mount an immune response and die 3-5 m severe encephalitis; the rest mount
    immune response – 1-3 y after. No spontaneous recovery
90
Q

Virus-induced immunosupression

Type D Simian Retrovirus

is it common?
how does it work?
what happens?
who gets it?
what results?

A
  • More common than the lentiviruses – transmitted by biting – broader tropism than SIVs – in addition to
    macrophages and lymphocytes can also infect fibroblasts, epithelial cells, and the brain
  • Profound drop in serum IgG and IgM and severe lymphopenia
  • Generalized lymphadenopathy, hepatomegaly, and splenomegaly
  • Loss of lymphocytes from the T-dependent areas of the secondary lymphoid organs
  • Similar changes to AIDS in humans
  • Opportunistic agents such as Pneumocystis, cytomegalovirus, C. parvum or C. albicans cause infection
  • Some monkeys develop tumors – fibrosarcomas
  • Half develop neutralizing antibodies and survive, the other die – septicemia or diarrhea with wasting
    *transmitted via biting, affects macs, lymphocytes, fibroblasts, epi cells and the brain.
    *50% survival rate
91
Q

Retrovirus infections in cats FIV + FeLV

Feline leukemia virus (FeLV)

what is it?
who gets it? how?
what happens?
what result?

A
  • Oncogenic retrovirus with a unique surface protein – feline oncornavirus cell membrane antigen
    (FOCMA) – expressed on FeLV-infected cells
  • On exposure to FeLV, about 70% of cats become infected, but the remaining 30% do not
  • Of the infected cats, 60% become immune and 40% become viremic
  • Of the viremic, 10% cure spontaneously and 90% remain infected for life
  • Initial transient viremia and spread in lymphoid organs – lymphopenia and neutropenia 1-2 weeks after
    infection
  • FeLV causes multiple cancers – lymphosarcomas, reticulum cell sarcomas, erythroleukemias and
    granulocytic leukemias
92
Q

Other causes of Secondary Immunodeficiencies

what are they and examples?

A
  • Bacterial infections – Mannheimia hemolytica, the actinobacilli, and some streptococci
  • Parasitic infectations – Toxoplasma or trypanosomes, Trichinella spiralis, and Demodex
  • Toxin-induced immunosuppresion – polychlorinated biphenyls, iodine, lead, cadmium, DDT
  • -mycotoxins – Fusarium; aflatoxins – Aspergillus
  • Malnutrition, obesity, trace elements, vitamins
93
Q

Organ Transplants
Pathogenesis of graft rejection

what are the 2 possible responses?

A

Innate or adaptive

94
Q

Organ Transplants
Pathogenesis of graft rejection

what is innate response?

A

-surgical trauma and ischemia
–increase MHC expression
–DAMPS
–Cytokines and inflammatory mediators

TLR

MICA (stress) can activate NK cells

95
Q

Organ Transplants
Pathogenesis of graft rejection

Adaptive response:
what is the direct pathway and an indirect pathway?

A

Direct:
donor APCs mismatch with recipient T cells–>recognition of foreign material
Acute rejection

indirect:
recipient APC mismatch–>recipient T cells
Chronic rejection
Associated with minor antigenic differences

96
Q

Organ Transplants
Pathogenesis of graft rejection

Allograft rejection

what happens?

A

1- CD8+ T cells destroy vascular endothelium to graft via caspase-mediate apoptosis
*Hemorrhage–>PLT aggregation–>thrombosis–>stoppage of blood flow

  1. CD4+ T cells release TNF alpha–> apoptosis in endothelial cells
  2. Activated Macrophages: pro-inflammatory cytokines impair graft function and intensify T cell-mediated rejection
97
Q

Organ Transplants
Pathogenesis of graft rejection

Rejection syndromes

what are they? when do they occur?

A

1- Hyperacute- 48 hours after graft
2-accellerated- up to 7 days after graft
3- Acute -after 7 days

**all of these are acute b/c they use the same mechanism!

4-Chronic- several months after graft

98
Q

Organ Transplants
Pathogenesis of graft rejection

Rejection syndromes

what are the antigens?

A

Several antigens:
-blood group glycoproteins–>easier to match
-MHC molecules
-polymorphism: individuals differ in the MHC haplotype
-Endogenous antigens presented on the MHC 1
-Antibodies and T cells participate in the rejection

99
Q

Organ Transplants
Pathogenesis of graft rejection

Hyperacute Rejection

facts about it

A

1- rare
2-associated with pre-existing Abs that bind to donor endothelial Ags
3-Thrombotic occlusion of the graft vasculature
4-minues to hours after host-grafted blood vessels are anastomosed
-can be seen with imcompataible blood

100
Q

Organ Transplants
Pathogenesis of graft rejection

Rejection syndromes

Acute Rejection

facts about it

A

1- refers to both accelerated and acute rejection
2. Injury to graft mediated by alloreactive T Cells and Abs
3-inflammation=result of T cells releasing pro-inflammatory cytokines
4-Alloantibodies bind to donor endothelial antigens and cause damage
5-incomparable MHC molecules
6-a repeated graft from the same donor will involve antibodies and the complements and results in RAPID graft rejection
7-CS: Acute kidney rejection–>rapid rise in creatinine, enlarged kidney, depression, vomiting, hematuria and proteinuria

101
Q

Organ Transplants
Pathogenesis of graft rejection

chronic rejection

facts

A

-not much to do with MHC
2-arterial occlusion occurs due to proliferation of intimal smooth muscle cells
3-graft eventually fails doe to ischemic damage
4-associated with chronic inflammation
5-slowly activates immune response
6-CS: rejection of kidney, rejection creatinine and urea levels rise gradually, proteinuria

102
Q

Organ Transplants
Pathogenesis of graft rejection

Prevention of allograft rejection

A

Balance between immunosuppression to prevent rejection and not making animal more susceptible to other infection:
1- inhibit t cell signaling pathway
2-antimetabolites-metabolic toxin to kill t cell
3-function blocking or depleting anti-lymphocytic antibodies
4-co-stimulatory blockage-drugs that block t cell co stimulatory pathways
5-targeting alloantibodies and alloreactive b cells
6-anti-inflamatory–>corticosteroids

103
Q

Organ Transplants
Pathogenesis of graft rejection

Prevention of allograft rejection -DOGS

A

-Rejection in 6-14 days if untreated
-unrelated dogs with renal allografts need simultaneous bone marrow allografts from the donor animal
-median survival time is 8 months

104
Q

Organ Transplants
Pathogenesis of graft rejection

Prevention of allograft rejection –CATS

A

-without immunosuppression die in 8-34 days
-59-70% 6 mo survival
-40-50%-3 year survival

105
Q

Organ Transplants
Pathogenesis of graft rejection

Graft Diseases

Bone Marrow Allograft

A

Require Total Body irradiation or chemotherapy
-space for growing transplanted cells
-reduce intensity of rejection
-in leukemia pets–> destroys tumor

106
Q

Organ Transplants
Pathogenesis of graft rejection

Graft Diseases

Graft vs. Host Diseases

A

Caused by reaction of grafted mature T cells in bone marrow with allo-antigens of the host
-remember that recipient has been immunocompromised to get this transplant and now cannot reject grafted cells

Acute: epithelial death in the skil, liver, GI tract–> rash jaundice, diarrhea, GI hemorrhage

Chronic: fibrosis and atrophy of one or more same organs.

Immuno (13 decks)

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