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Immune Tolerance and Autoimmune Disease Flashcards

1
Q

Normally microbes are _____ and self antigens are _____

A

immunogenic, tolerogenic

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2
Q

Normal immune response +microbe=

A

proliferation and differentiation

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3
Q

Self-tolerance + self antigen =

A
  • Anergy- functional unresponsiveness
  • Deletion- Cell death
  • Change in specificity- receptor editing
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4
Q

Immune Tolerance

A
  • Tolerance is a lack of response to an antigen that is induced by previous exposure of lymphocytes
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5
Q

Normal indiv are tolerant to

A

self Antigens

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6
Q

failure of self-tolerance results in

A

autoimmunity

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7
Q

immune tolerance can be use therapeutic for

A
  • Organ transplantaion
  • Autoimmune disease
  • Allergic diseases
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8
Q

Central tolerance

A
  • Immunological tolerance to self antnigens induced in immature lymphocytes in bone marrow and thymus
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9
Q

central tolerance mechanisms

A
  • Deletion ( cell death)
  • Receptor editing (change in BCR)
  • Devlopment of TRegs
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10
Q

deficiency of ____ shown in many autoimmune diseases in humans

A

TRegs

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11
Q

Central tolerance for T lymphocytes

Positive selection in Thymus

A
  • low-affinity interaction of TCR with self MHC molecule positively selects and rescues thymocytes from programmed cell death
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12
Q

Central tolerance for T lymphocytes

negative selection in Thymus

A

apoptoic death

deletion of self-reactive t cells devlops central tolerance

(prevents future autoimmune diseases)

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13
Q

Perpheral Tolerance

A
  • Immune tolerance to self antigens in peripheral tissues encounterd by mature lymphocytes
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14
Q

Peripheral Tolerance Mechanisms

A
  • Clonal Anergy: (B7:CD28)
  • Deletion: cell death
  • Suppression via
    • Tregs
    • Il-10
    • TGF-Beta
    • block macrophage activation
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15
Q

Mucosal Tolerance

3 independent mechanisms

A
  • Ignorance
    • of antigen by the immune system (anergy)
  • Deletion
    • of T cells
  • Generation of regulatory T cells
    • controls inflammatory response
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16
Q

Safeguard against autoimmunity

A
  • Tolerance to self Ag is learned/acquired
  • lymphocytes recognize self-Ag and become autoreactive
  • autoreactive lymphocytes absent due to central and peropheral tolerance
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17
Q

Autoimmune Diseases

A
  • failure of self-tolerance
  • adaptive immune responses against self antigens
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18
Q

autoimmune diseases genteic factors

A

HLA association

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19
Q

Autoimmune disease generation of

A
  • autoreactive B cells
  • autoreactive T cells
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20
Q

auto-abs or autoreactive T cells attack

A

body’s own cells, tissues and organs

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21
Q

attack on the body’s own cells, tissue, and organs causing

A

inflammation and tissue damage through

  • Hypersensitivity reactions II, III, IV
  • Compliment activation
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22
Q

autoimmune diseases are

A

very common, often chronic and long lasting

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23
Q

complement activation leads to

(autoimmune disease development )

A
  • inflammaiton
  • deficiency in complement proteins (C1q, C2, C4)
  • Result: no clearance of immune complexes & apoptotic cells
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24
Q

Antibody-dependent cytotoxic

Hypersensitivity (Type II)

A
  • Ag-Ab binding activates cytotoxic cells, killing antigenic target cells

(Type II- IgM and IgG Abs binding to Ags)

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25
Three mechanisms for Type II cytotoxicity
1. Lysis of cells 2. Cell injury by inflammatory cells 3. Phagocytosis of antobody coated cells
26
Immune complex-mediated hypersensitivity (type III)
* inflammation * Immune complex deposition-mediated diseases * immune complex formation in blood vessels:
27
immune complex formation despositon in blood vessels triggers (type III)
* Platelet aggregation * complement activation * microthrombi formation * C5a C3a recruitment of PMNs * damage to the blood vessel
28
type(IV)/DTH
* T cell mediated inflammatory response * antigen-specific TH1-type CD4 T cells
29
type IV/ DTH ( delayed-type hypersensitivity) diseases
* **Contact dermatitis (Haptens)** * **TB** * Granulomas (TB and leprosy) * allergic reactions to pathogens (bacteria, viruses, fungi) * **Rejection of transplants** * **Autoimmune disease**
30
type II hypersensituvity Ab-induced damage
* idiopathic thrombocytopenic purpura * autoimmune hemolytic anaemia
31
type II hypersensitivity Ab-induced receptor stimulation or blockade
* Grave's disease * Myasthenia gravis * Insulin receptor Ab syndrome
32
type III hypersensitivity
systemic lupus erythematosus Vasculitis
33
type IV hypersensitivity
* Insulin-dependent diabetes mellitus * Hasimoto's thyroiditis * Rheumatoid arthritis * Multiple Sclerosis
34
Anti- DNA antibody associated with which diseas ?
Lupus n
35
Complement-fixing autoantibodies associated with which autoimmune diseases
autoimmune anemias thrombocytopenia
36
37
tissue-specific autoantibodies associted with which diseases
systemic Lupus Erythematosus (SLE) Rheumatoid arthritis (RA) Type I Diabetes mellitus
38
autoantibodies to cell-surface receptors associated with which diseases
grave's disease myasthenia gravis
39
Autoimmune hemolytic anemia target antigen mechanisms of disease clinical manifestations
* RBC membrane proteins (Rh Ag) * opsonizaton and phagocytosis of erythrocytes * Hemoylsis anemia
40
Autoimmune thrombocytopenic purpura target antigen mechanisms of disease clinical manifestations
* platelet membrane proteins * opsonization and phagocytosis of platelts * Bleeding
41
Acute rheumatic fever target antigen mechanisms of disease clinical manifestations
* Streptococcal Ag specific Ab crossreacts myocardial Ag * inflammation macrophage activation * Myocarditis, Arthritis
42
myasthenia gravis target antigen mechanisms of disease clinical manifestations
* Acetylcholline (Ach) receptor * Antibody inhibits Ach binding * muscle weakness and paralysis
43
Graves' disease target antigen mechanisms of disease clinical manifestations
* TSH (thyroid stimulating hormone) receptor * Ab-mediated stimulation of TSH receptors * Hyperthyroidism
44
autoantibodies to receptors bind
to cell memebrane receptors and interfere with endogenous ligand binding to the receptor
45
Patient with graves' disease
* hyperthyroidism * exophthalmos * Blood tests * overactive thryroid * autoantibodies to thyroid peroxidase * increase of T3 and T4 levels
46
mechanisms of T cell-mediated tissue injury
* self Ag activate T cells causing tissue injury and autoimmune disease *
47
cell injury in type 1 diabetes, RA or MS is mediated by
Th cells via DTH
48
cell killind mediated by
CTLs
49
Tissue injury by Killing of target cells by
Th cells CTLs
50
T cell-mediated autoimmune diseases list
1. type 1 diabetes 2. rheumatoid arthritis 3. multiple sclerosis 4. hasimoto's thyroiditis
51
type 1 diabetes antigen clinical manifestations
* islet cell Ag * impaired glucose metabolism, vascular diseses
52
rheumatoid arthritis antigen clinical manifestations
* synovial fluid Ag * inflammation & erosion of joints & bones
53
multiple sclerosis antigen clinical manifestations
* myelin protein * demyelination of CNS, sensory and motor dysfunction
54
hasimoto's thyroiditis antigen clinical manifestations
* thyroglobulin * destruction of thyroid gland, hypothyroidism
55
Molecular Mimicry in rheumatic fever
* leads to inflammatory disease of the heart valves * carbohydrate Antigens on the group A streptococcal cell wall cross- react with a heart valve Atigens
56
Diseases of molecular mimicry autoimmune disease
* rheumatic * type I diabetes * Guillain-Barre syndrome
57
link btwn RA and \_\_\_\_\_\_established through\_\_\_\_
periodonitis, protein citrullinatoin
58
P.gingivalis infection and autoimmune disease due to
* heat shock proteins (HSP) 60 from P. gingivalis * causes periodontitis & autoimmune atherosclerosis * Genteic factors * inflammation * TNF-alpha production
59
treatment of P.gingivalis infection in RA patients
* anti-TNF-alpha treatment * Infliximab * Remicade * Humira * Omega-3 fatty acids * reduces swelling, helps tender joints * Dietary polyphenols
60
How does an autoimmune disease develop?
* not fully understood * self-Ag is not expressed in the thyms * genic predisposition
61
Diagnosis of autoimmune diseases
* tissue biopsies * Ab * complement proteins * determination of auto-Ab
62
treatment of autoimmune diseases that block inflammation
* NSAIDS * COX-2 inhibitors * Corticosteroids
63
treatment of autoimmune diseases cyclophosphamide
prevents proliferation B cells (reduces auto-Ab production used in SLE)
64
treatment of autoimmune diseases Infliximab (Remicade) Adalimumab(Humira)
* Anti-TNF- alpha mAb * control inflammation * used in crohn's disease * RA
65
treatment of autoimmune diseases Rituximab
* Anti-CD20 mAb * eliminates B cells used in RA SLE
66
central tolerance
* Apoptosis (deletion) * Receptor editing B cells * Development of regulatory T lymphocytes (CD4+ T cells only)
67
Peripheral tolerance
* Anergy * Apoptosis (deletion) * suppression
68
Molecular Mimicry
* presence of autoreactive B cells recognizes self-Ag and also cross-reactive to foreign Antigen * Cross-reactive foreign Antigen triggers Th cell activation and cytokine secretion
69
Cross-reactive foreign Antigen triggers Th cell activation and cytokine secretion
* B cell proliferate, differentiate, and secrete autoantibodies * The antibodies bind to the pathogenic structures and control infection * Residual auto-abs bind to self-Ag and may trigge autoimmune disease
70
Therapeutic Applications of Mucosal Tolerance in Autoimmune Diseases
* trails in patients with MS, RA, diabetes * T cell proliferative responses were affected and TGF-B secreting cells were present in treated patient

Mandal (7 decks)

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