Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Year 2 MCD Immunology > 4: Tolerance and Auto-Immunity > Flashcards

4: Tolerance and Auto-Immunity Flashcards

1
Q

Explain the overall concepts how auto-immune diseases may develop

A

Autoimmunity is a adaptive immune response to self-antigens

–> Person lost sel-tolerance!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Whar are the different factors that are needed to qualify a diseae as auto-immune?

A
  • Evidence of disease-specific adaptive immune response in the affected target tissue, organ or blood
  • Passive transfer of autoreactive cells or antibodies replicates the disease
  • Elimination of the autoimmune response modifies disease
  • Makes it more likely: History of autoimmune disease (personal or family), and/or MHC associations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the different genetic and environmental factors that might contribute to the development of auto-immune diseases?

A
  • Genetics: many loci/ very complex (often MHC II) –> proofe in twin and family studies
  • Sex: women more susceptible (e.g. 9:1 in SLE)
  • Infections: inflammatory environment makes it more likely to break self-tolerance
  • Diet: obesity, high fat, effects on gut microbiome: diet modification may relieve autoimmune symptoms
  • Stress: physical and psychological, stress-related hormones
  • Microbiome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Explain the overall concept of auto-immune diseases

A

Overall: the same mechanisms as normal immune responses are used (Type II-IV) just to self

  • involved with breaking T-cell tolerance –> T-cells do play a role
  • Chronic conditions (self is always present) , often with episods of better/worse control
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Explain the hygiene hypothesis

A

It states that the decreasing number of exposure to antigens in childhood leads to an increase in

  • autoimmune diseases
  • ashmah
  • allergies and hypersensitivities

–> due to the fact that the immune sysetem is not trained correctly/does not learn tolerance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

List important auto-immune diseases

A
  • Rheumatoid Arthritis:
  • Type I diabetes
  • Multiple Sclerosis:
  • Systemic Lupus Erythematosus (SLE):
  • Autoimmune thyroid disease (ATD): including Hashimoto’s and Graves’ disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How can autoimmune diseases be described according to the organ they affect?

A

The diseases can be ogan specific (e.g. graves where antibodies are produced against organ-specific antigens)

Multi-systemic

e.g. SLE where immune-complexes in the blood cause symptoms –> many tissues affected

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Explain how involvement of specific antibodies can lead to a classification of an auto-immune disease

A

Tissue specific auto-antigens might be presentative /characterisic of specific disease

  • E.g. neonatal Graves (where mother has graves and antibodies against thyroid cross placenta)
  • against RBC
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the different immune-reactions that are known to play a part in auto-immune disease

A

Type II - IV

  • •Antibody response to cellular or extracellular matrix antigen (Type II)
  • •Immune complex formed by antibody against soluble antigen (Type III)
  • •T-cell mediated disease (Delayed type hypersensitivity reaction, Type IV)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Name examples of type II mediated auto-immune diseases

A
  1. Graves
  2. Autoimmune haemolytic anaemia
  3. Myasthenia Gravis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Name example of a Type III hypersensitivity mediated autoimmune diease

A

SLE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Name example of Type IV mediated auto-immune diseases

A
  1. DMT1
  2. Rheumathoid ARthritis
  3. MS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the dominant genetic factor affecting susceptibility to autoimmune disease?

A

HLA (MHC) Class II

–> most genetic predispositions/loci are involved in regulation / expression of MHC class II

–> Show the strong association and involvement of CD4+ T-cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is immunological tolerance?

A

•Defined as the acquired inability to respond to an antigenic stimulus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the main characteristics of immunological tolerance?

A

The 3 As

  1. Acquired -involves cells of the acquired immune system and is ‘learned’
  2. Antigen specific
  3. Active process in neonates, the effects of which are maintained throughout life
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Explain the process of establishing central tolerance for T-cells

A

T-cell maturation and selection takes place in the thmus

  • If cells are too self reacting (bind too much to MHC) (or not reacting/binding to MHC at all) than they will be killed
  • Only Useful (see MHC weakly): receive signal to survive. “Positive selection”
17
Q

Explain the development of central B-cell tolerance

A

Part of B-cell maturation, takes place in Bone Marrow

  • If B cell binds to multivalent self-molecule –> clonar deletion of cell or receptor editing
  • If reacting to soluble self-molecule –> might go into periphery but don’t mediate a response (because no maturation in BM took place)
  • Low-affinity for MHC migrate into body and act as active B-cells
18
Q

Name examples how defects in central tolerance may lead to autoimmune disease

A

E.g. APECED (Symptomgruppe Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy)

results from a failure to delete T-cells in the thymus due to

  • mutation in the Transcription Factor AIRE (involved in tissue-specific antigen Presentation)
19
Q

What is AIRE?

Explain its role and function in autoimmune diseases

A

AIRE is a transcription factor in the thymus

  • expresses the tissue specific antigens in the thymus (that the T-cell can be tested for)
  • If defect: tissue-specific antigens can’t be tested and self-reactive t-cells are release into the circulation
20
Q

Explain the role of genetics in the development of auto-immune disesase

A

Most autoimmune diseases are associated with multiple defects and genetic traits

  • e.g. might affect multiple pathways leading to a failure of tolerance e.g. via
    • induction of tolerance (B lymphocyte activation: CD22, SHP-1): autoantibody production
    • apoptosis (Fas, Fas-ligand): failure in cell death
    • clearance of antigen (Complement proteins C1q, C1r and C1s): abundance/persistence of autoantigen
21
Q

Why is peripheral tolerance necessary?

A

•Some antigens may not be expressed in the thymus or bone marrow, and may be expressed only after the immune system has matured

–> prevent mature lymphocytes to become self-reactant

22
Q

What are the overall systems by which peripheral tolerance can be achieved?

A
  1. Anergy
  2. Suppression by regulatory T cells
  3. (Ignorance of antigen)
23
Q

Explain the process of anergy in the development of peripheral tolerance

A

For naïve T-cell to be activated: it required co-stimmulation

  • often via co-stimmulatory molecules
  • normally these molecules are absent on most body cells
  • Without costimulation then cell proliferation and/or factor production does not procee
  • Subsequent stimulation leads to a refractory state termed ‘ANERGY’
24
Q

Explain the concept of immunological ignorance in the development of peripheral tolerance

A

Occurs

  • when antigen-concentrations are too low
  • when relevant APC are absent –> most cells are MHC II negative
  • at immunologically privileged sites where immune cells cannot normally penetrate
25
Q

Name an example where a failure of immunological ignorance can lead to an auto-immune disease

A

E.g. at immunologically privileged sites where immune cells cannot normally penetrate: for example in the eye, central and peripheral nervous system and testes. In this case, cells have never been tolerised against the auto-antigens

–> SO If antigens from there come into the blood stream: there will be a reaction!

Example: sympathetic ophthalmia

26
Q

Explain the role of Suppression/ Regulation in the concept of peripheral tolerance

A

Regulatory T cells (Treg) actively supress autoreactive T-cells and inhibit a response

  1. Treg cells are charecterised by many Factors but one main one
    1. FOXP3
27
Q

Explain how failure of failure in the regulation of peripheral rolerance may lead to autoimmunity

A

E.g. IPEX

  • fatal recessive disorder with mutation in FOXP3 gene of Tregs
    • no supression of auto-reactive T-cells lead to severe + fatal symptoms
      • early onset insulin dependent diabetes mellitus
      • severe enteropathy
      • eczema
      • variable autoimmune phenomena
      • severe infections
28
Q

Explain the inflence of infections on immunoligical tolerance

A

There is some evidence, that infections might break self tolerance and induce auto-immunity via

  • molecular mimicy of self-molecules
    • organism produce something that looks like self-antigen
  • Produce a pro-inflammatory environment
    • increase in MHC II expression
    • increase cytokines lead to co-stimmulation of T-cells
  • Change in the expression and recognition of self-molecules
  • Might cause Tissue damage at immunological-priviledged site
  • Failure in regulation : effects on regulatory T-cells
  • Immune deviation: shift in type of immune response e.g. Th1-Th2

Year 2 MCD Immunology (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions