Immunology - Part 3B (After Midterm)

Front 1

In autoimmunity, what are lesions the result of?

Back 1

Hypersensitivity reactions

Front 2

What are some examples of normal immune responses to unusual or abnormal antigens that can be considered autoimmunity?

Back 2

* Previously hidden self-antigens are released through tissue damage
* Cross-reacting autoantibodies
* Molecular alterations

Front 3

What are some examples of normal immune responses to unusual or abnormal antigens that can be considered autoimmunity?

Back 3

Loss of regulation due to lymphoid tumors or defect in CD95 or its ligand

Front 4

What are the most important genes that influence naturally occurring autoimmune disease?

Back 4

MHC genes

Front 5

Are certain dog breeds being predisposed to autoimmune diseases an artificial phenomenon?

Back 5

Yes, phenotypic selection can result in inbreeding and lack of genetic diversity

Front 6

What is the mechanisms behind tissue damage in autoimmunity?

Back 6

Hypersensitivity reactions

Front 7

What is an example of a Type I hypersensitivity response to autoimmunity?

Back 7

Milk ALLERGY in cattle - dairy cow allergic to casein protein in milk

FYI: In Type I hypersensitivity, TH2 cells trigger B cells to make IgE which is inappropriate response.

Front 8

Review:
What type of hypersensitivity response is mediated by IgG or IgM?
What are some easy examples of this type hypersensitivity reactions?

Back 8

Type II Hypersensitivity

Transfusion reactions
Hemolytic disease of Newborn (neonatal isoerythrolysis)
Immune-mediated cytopenias

Front 9

hypersensitivity which may cause agglutination or hemolysis or stimulate opsonization and phagocytosis of the cells??

Back 9

Type II hypersensitivity: may cause agglutination or hemolysis or stimulate opsonization and phagocytosis of the cells

Front 10

What are some examples of Type II hypersensitivity response to autoimmunity?

Back 10

1. Immune-mediated cytopenia
2. Myasthenia gravis (musc.weakness)
3. Lymphocytic thyroiditis in dogs
4. Pemphigus folieacous (autoimmune blistering disease of skin & mucous membranes)

Front 11

What disease involves autoantibodies against RBCs?

Back 11

Immune-mediated Hemolytic Anemia

Front 12

What disease involves autoantibodies against platelets?

Back 12

Immune-mediated thrombocytopenia

Front 13

What disease involves autoantibodies against leukocytes?

Back 13

Immune-mediated leukopenias

Front 14

What kind of test can be used to detect immune mediated hemolytic anemia?

Back 14

Coomb's test
(trying to detect "bad" Ab which attach surface of RBC)
- if these Ab present, will to see agglut. of RBC

Front 15

What can cause false negatives in a Coomb's test for immune mediated hemolytic anemia?

Back 15

Long term glucocorticoid therapy

Front 16

What autoimmune disease is caused by antibodies against the acetylcholine receptor on muscle cells?

Back 16

Myasthenia gravis

Front 17

How do you treat myasthenia gravis?

Back 17

Treat with anti-cholinesterase

Front 18

What is the result of lymphocytic thyroiditis in dogs?

Back 18

Causes hypothyroidism

Front 19

How do you treat lymphocytic thyroiditis in dogs?

Back 19

Replacement therapy with synthetic T4, no cure

Front 20

What type of hypersensitivity response is the result of lymphocytic thyroiditis in dogs?

Back 20

Type II
Type IV

Front 21

What is the mechanism behind pemphigus folieaceous?
(autoimmune blistering disease of the skin and mucous membranes )

Back 21

Ag-Ab interaction allows for activation of complement, as part of the Type-II response

pemphigus foliaceus = type 2 h.s. rxn = cytotoxic h.s.; Ab mediated hypersensitiivty

Front 22

Does pemphigus foliaceus have an immune-mediated response where antibody binds cell antigen and activates complement?

Back 22

Yes; Ab mediated hypersensitiivty

note: pemphigus foliaceus is type 2 h.s. rxn = cytotoxic h.s.

Front 23

What type of autoimmune response causes autoantibodies to form immune COMPLEXES with autoantigens which then can cause inflammation?

Back 23

Type-III hypersensitivity
(see next question)

Front 24

Review:
What is the cause of a type III hypersensitivity reaction?

Back 24

Type-III hypersensitivity
(can be localized e.g. Arthus reaction from injection of tetanus toxin when have Ab
OR generalized in circulation e.g. Serum sickness, Glomerulonephritis)

Front 25

Review:
If the complexes of the a type III hypersensitivity reaction form in the circulation what type is it?

Back 25

Generalized Type-III

= Ab-Ag complex in blood vessel !

Front 26

Review:
What are the three mechanisms of Type-III hypersensitivity reactions?

Back 26

Immune complex formation
Immune complex deposition
Immune complex-mediated inflammation

Front 27

What are some examples of Type III hypersensitivity?

Back 27

1. SLE (Systemic Lupus Erythematosus) or Canine Lupus (common in German Shepherds)
2. Rheumatoid arthritis ((see notes… used as example of molecular alteration leading to autoimmunity)
3. Some causes of glomerulonephritis

Front 28

What type of hypersensitivity / autoimmune response is caused by auto-reactive T-cells attacking tissue? (delayed)

Back 28

Type IV hypersensitivity

Front 29

Some examples of Type __ hypersensitivity autoimmune diseases?
Multiple Sclerosis
Polymyositis
Insulin-dependent Diabetes mellitus (IDDM)
Lymphocytic thyroiditis

Back 29

These are type IV hypersensitivity autoimmune diseases:
Multiple Sclerosis
Polymyositis
Insulin-dependent Diabetes mellitus (IDDM)
Lymphocytic thyroiditis (also type 2 HS?)

note: type 4 involves attacking own tissue with t-cells

Front 30

• Result: Lymphocytes unresponsive to IL-2, as receptor is defective…. but they can produce IL-2.

Back 30

X-linked SCID

(Severe combined immunodeficiency)

fyi: ~ aka "bubble boy disease"

Front 31

Review:
What is a reaction to intravenous injected proteins (usually in antiserum) derived from another species e.g. horse serum?

What type of hypersensitivity is this?

Back 31

Serum sickness - get major Ab-Ag complexes forming in vessels

* this is generalized type III h.s. rxn

Front 32

What are the general components of any Type-IV hypersensitivity?

Back 32

Antigen sensitized Th1 CD4 lymphocytes and CD8 lymphocytes
Th1 cytokines
Activated macrophages
Response peaks at 72 hours
(DTH)

Front 33

What type IV hypersensitivity autoimmune disease is the result of self-reactive Th1 cells reacting against myelin basic protein?

Back 33

Multiple Sclerosis

Front 34

What type IV hypersensitivity autoimmune disease is common in german shepherds and is the result of autoreactive T-cells and autoantibodies?

Back 34

Polymyositis
> diffuse inflammation of skeletal muscles; often see hypergammaglobulinemia, positive titers for elevations of anti-muscle antibodies (also demonstrable by indirect immunohistology). Generalized weakness which worsens on exercise. These patients also have a stiff stilted gait, lameness and pain on muscle palpation. Some loss of skeletal muscle mass is evident. Megaesophagus may be present with regurgitation and aspiration pneumonia.

Front 35

What is some evidence that some tumor cells are immunogenic?

Back 35

Immunity can be acquired through immunization with killed tumor cells
Immunity is specific for the antigens of the original tumor used for immunization
Immunity can be lasting (memory)

Front 36

What is the main defense against tumor outgrowth?

Back 36

Innate immune system (NK cells and macrophages)

Front 37

How might u diagnose Pemphigus folieacous (autoimmune blistering disease)?

Back 37

1. biopsy
2. Immunofluorescent or immuoperoxidase test to identify auto-antibodies (equine IgG) directed against desmoglein 1 in the superficial epidermis

Front 38

What would you expect to see in biopsy?

Back 38

intraepidermal vesicles with loss of intercellular connections, such as desmosomes, resulting in loss of cohesion between keratinocytes

Front 39

Treatment for Pemphigus folieacous ?

Back 39

* Glucocorticoids are given to suppress the immune system and reduce inflammation
* Antibiotics may need to be given to reduce secondary bacterial infections

Front 40

What is some evidence that the immune system helps to protect against cancer?

Back 40

patients with HIV-AIDS more likely to develop cancer, transplant patients are on immunosuppressive drugs and these people more likely to develop cancer.

Front 41

Not all cancers are more likely to emerge in immunosuppressed individuals, what are examples of this?

Back 41

in humans lung or breast cancer do not develop more frequently in immunodeficient people

Front 42

How can immunity to tumor cells acquired?

Back 42

through immunization with killed tumor cells

Front 43

What is immunity specific for?

Back 43

the antigens of the original tumor used for immunization

Front 44

T/F Both the innate immunity and the adaptive immunity help prevent the overgrowth of tumor cells

Back 44

True; but innate immunity is more important

Front 45

What is the main defense against tumor outgrowth is what system?

Back 45

innate system through the action of NK cells and macrophages

Front 46

What are NK cells regulated by?

Back 46

cytokines!

• NK cells can be activated almost immediately by interferons from virus-infected cells and by IL-12 from macrophages.

Front 47

Triggering of NK cell cytotoxicity (attack infected cells) results from what?

Back 47

change in the balance between activating and inhibitory signals to the NK cells

Front 48

Do NK cells express antigen-specific receptors?

Back 48

No

Front 49

How can NK cells bind to antibodies that is bound to a tumor antigen on surface of tumor cell, and can thus help with ADCC?

Back 49

have Fc receptors for the Fc region of antibody

Front 50

What molecules are not expressed by normal healthy cells, but by some tumor cells, virus-infected cells and cells undergoing other kinds of stress.

Back 50

"stress" molecules, NK cells have receptors that can interact with molecules expressed by cells during stress

Front 51

What is mediated through perforins and granzymes as well as through the death receptor pathway?
(..death by apoptosis, etc)

Back 51

NK cell killing

Front 52

Macrophages activated by what are especially active against tumors?

Back 52

IFN-gamma

Front 53

Macrophages can be nonspecifically activated by what?

Back 53

BCG. thus, BCG is given in some cases to stimulate macrophages to fight cancer

Front 54

What is used to vaccinate humans against M. tuberculosis in some countries outside the US and to vaccinate some high-risk people in the US?

Back 54

BCG, modified live 'avirulent' strain of Mycobacterium bovis

Front 55

What is associated with infection by bovine papillomavirus, and is tumor of the skin epithelium and dermal fibroblasts?

Back 55

equine sarcoid

Front 56

Treatment for equine sarcoid?

Back 56

BCG

Front 57

How can tumors express proteins?

Back 57

expression of altered or new proteins, over-express a normal protein, express a protein that is normally only expressed in the fetus

Front 58

What are examples of tumors expressing altered or new proteins?

Back 58

carcinogens induce mutations so that cells produce different proteins that are no longer recognized as self-proteins, viral infections can cause the infected cell to express non-self proteins

Front 59

What abnormal antigen found in the neoplastic T lymphoid cells of cats infected with Feline Leukemia Virus?

Back 59

FOCMA (feline oncovirogenic-associated cell membrane antigen) <- example of abnormal antigen express by inf. cell

• Found on the neoplastic T lymphoid cells of cats infected with Feline Leukemia Virus (FeLV).

Front 60

What are examples of primary immunodeficiencies affecting the acquired immune system?

Back 60

severe combined immune deficiency (SCID) in horses dogs, and mice.
Hypotrichosis with tympanic aplasia in cats and nude mice

Front 61

provide inhibitory signals that block killing by NK cells.

Back 61

MHC class I

Front 62

T/F
FOCMA is coded by the viral genome and is part of the virion.

Back 62

False; although the FOCMA is coded by the viral genome, it is not part of the virion.

• FYI: FeLV-infected cats with antibody to FOCMA are relatively resistant to disease due to FeLV.

Front 63

Describe SCID (severe combined immune deficiency) in arabian foals?

Back 63

complete inability of the adaptive immune system to respond.
* Absence of functional T and B lymphocytes!!!

Front 64

Mechanisms of Acquired Immunity against tumors: (3)

Back 64

1. • Antigen-specific Cytotoxic T cells
2. • Antibody + complement activation (leading to MAC and lysis of free tumor cells)
3. • ADCC (Antibody-dependent cell-mediated cytotoxicity)

Front 65

What are examples of over-expressed self-proteins?

Back 65

Prostate-specific antigen

Front 66

What are antigens normally found on the fetus, that are formed in the adult?

Back 66

oncofetal antigens

Front 67

What are mechanisms of tumor evasion of the immune system?

Back 67

1. low immunogenicity
2. antigenic modulation or masking
3. tumor-induced immunosuppression (secrete factor TGF-B which inhibit T cells directly)

Front 68

What are examples of strategies to induce immunity to tumors?

Back 68

non-specific modulation of the immune response, expand antigen-specific T-cells, vaccination with tumor antigens

Front 69

Example of antigenic modulation or masking?
(way tumor evade immune.system)

Back 69

1. endocytosis of antigen present
(select for non-immunogenic tumor cells);
2. Production of blocking antibodies is another example

Front 70

What is it called when you remove some T-cells from patient, add IL-2 invitro to expand their numbers, and infuse it back into patient. Some of these T-cells should be the tumor antigen-specific cells (only works if there are already antigen-specific T-cells)

Back 70

Anti-tumor strategy by expanding antigen-specific T-cells

Front 71

When you vaccinate with naked DNA which codes for tumor antigens or vaccinate with DNA-transected dendritic cells. The dentricitc cells must come from the patient, why?

Back 71

has to be self-MHC (T-cells can only see antigen produced by self MHC)

Front 72

What type of immunodeficiency is a result of an inherited defect (may notice breed suseptibilities, especially in breeds with reduced genetic diversity)?

Back 72

Primary immunodeficiency

Front 73

What type of immunodeficiency is a result of some other cause, such as an infection or exposure to a toxin?

Back 73

secondary immunodeficiency

Front 74

What is an example of primary immunodeficiency?

Back 74

canine cyclical neutropenia (grey collie syndrome)

Hypotrichosis (hair loss) in cats

Front 75

What are symptoms of canine cyclical neutropenia (grey collie syndrome)?

Back 75

* Neutrophils are not only periodically decreased in numbers, but also can’t kill organisms as efficiently as normal neutrophils.
* dilution of skin pigmentation and of hair coat color.
* Eye lesions
* Fluctuations in leukocyte numbers.

Front 76

How can 'grey collie syndrome' be treated?

Back 76

repeated use of antibiotics, drugs to stimulate the bone marrow

Front 77

What is it called when kittens are born without a thymus (no T-lymphocyte development)? Seen in Birman cats with an autosomal recessive inheritance pattern.

Back 77

Hypotrichosis with thymic aplasia in cats

Front 78

What are some important viruses that destroy lymphoid tissues?

Back 78

retroviruses, herpes, feline leukemia virus, canine distemper virus, feline parvovirus, canine parvovirus, bovine viral diarrhea virus

Front 79

recurring infections
poorly developed thymus, decreased T cells, IgG. No IgA, but normal quantities of IgM,
– Often die following vaccination with a modified live distemper virus vaccine which, in these dogs causes disease.

Back 79

Signs of X-linked SCID in Dogs

Front 80

X-linked SCID is seen in what breeds of dogs?

Back 80

basset hounds and welsh corgis, males only

Front 81

Autosomal recessive SCID is seen in what breed of dogs?

Back 81

Jack russell terriers

• Defect is DNA-protein kinase catalytic subunit. Thus, similar to SCID in Arabian horses. Different genetic defect leading to the same lack of function of this important enzyme.

Front 82

THIS CAUSE OF ?
Defect in the DNA-dependent protein kinase catalytic subunit leads to lack of rejoining of DNA for genes that code for TCR and BCR proteins

Back 82

SCID (severe combined immune deficiency) in arabian foals

complete inability of the adaptive immune system to respond.
* Absence of functional T and B lymphocytes!!!