Brainscape's Knowledge GenomeTM

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


See full index

Immuno > 2: Tolerance & Autoimmunity > Flashcards

2: Tolerance & Autoimmunity Flashcards

1
Q

What is autoimmunity

A

Adaptive immune response with specificity for self antigens (autoantigens)

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

Criteria for disease to be autoimmune?

A
  1. Evidence of disease-specific adaptive immune response in affecetd tissue/organ/blood
  2. Passive transfer of autoreactive cells/antibodies replicates the disease
  3. Elimination of auto-immune response modifies disease
  4. History of autoimmune diseases and/or MHC associations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Genetic/environmental factors that can lead to autoimmune disease

A

Genes: identical twins and family
Sex: women more susceptible (9:1 in SLE)
Infections: inflammatory environment
Diet: obesity, high fat, effects on gut microbiome
Stress: physical or psychological - stress-related hormones
Microbiome: Gut/oral microbiome important in immunity
Dysbiosis may trigger autoimmune diseases

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

Mechanisms of autoimmunity

A
  1. All involve adaptive immune response against self
  2. Same mechanisms as used against pathogens
  3. T-cell tolerance BROKEN
  4. Autoimmune diseases are CHRONIC since self-tissue always present
  5. Effector mechanisms resemble Type 2/3/4 hypersensitivity reactions

BOTH B cell (antibodies) and T cells are involved in autoimmune disease

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

Examples of important autoimmune diseases

A 
Graves (Type 2)
SLE (Type 3)
Rheumatoid arthritis(Type 4)
T1DM (Type 4)
MS (Type 4)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How do you describe/classify autoimmune diseases

A

Organs affected (specific or systemic)
Involvement of specific antigens
Types of immune responses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Mechanism of autoimmune haemolytic anaemia?

A

Autoantibodies against RBCs

Result in clearance or complement-mediated lysis of autologous erythrocytes

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

Types of immune reactions in autoimmune diseases?

A

Type 2 hypersensitivity = Antibody response to antigen (intra/extracellular)

Type 3 hypersensitivity = Immune complex formed by antibody against antigen

Type 4 hypersensitivity = T-cell mediated delayed reaction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Mechanism of Graves?

A

anti-TSHreceptor antibody stimulates release of thyroid hormones, independent of feedback loop

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Mechanism of SLE?

A

Immune complex deposition in glomerulus leading to glomerulonephritis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Difference between Type 2 and 3?

A

Type 2 = LOCALISED tissue injury

Type 3 = Immune complexes in CIRCULATION leading to vasculitis

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

What is the dominant class of MHC genes for autoimmune disease?

A 
MHC class 2
HLA-DR genes associated with increased risk
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How is the T-cell response to antigens mediated?

A

MHC1 presents antigen to CD8 T-cell receptors

MHC2 presents antigen to CD4 T-cell receptors

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

Evidence for tolerance

A

Freemartin cattle are non-identical twins with different blood antigens
BUT adult cattle can tolerate skin grafts/blood transfusions from non-identical twin

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

Evidence for importance of timing in tolerance

A

Spleen/bone marrow cells were transferred to newborn and adult mice
Neonate mouse tolerated donor cells as they developed into adult

Adult mouse DID NOT tolerate donor cells

Suggests we develop tolerance early on

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Evidence for specificity in tolerance

A

Mouse cannot accept any strain of cells
Tolerance is ANTIGEN-SPECIFIC
(i.e. if neonate mouse given donor cells and develops tolerance, skin graft when it becomes adult MUST have same antigens as original donor cells)

17
Q

Explain the concept of immunological tolerance

A

Acquired INABILITY to respond to antigenic stimulus
3A’s:

Acquired - involves cells from acquired immune system which are ‘learned’

Antigen specific

Active process in neonates - effects are maintained throughout life

18
Q

Explain the mechanisms underlying tolerance

A

Central + Peripheral tolerance

Failure in one or more of these will result in autoimmune disease

19
Q

Explain central T-cell tolerance

A

Stem cells from bone marrow -> T-cell precursors -> Go to Thymus
In the thymus, T-cells recognise peptides on MHC
95% deleted, only 5% survive in the thymus

Useful thymocytes are the ones that see MHC WEAKLY which receive signal to survive

Useless (cant see MHC) or Dangerous (see self strongly) thymocytes die by apoptosis

20
Q

Explain central B-cell tolerance

A

Occurs in bone marrow
No self reaction -> go to periphery

Soluble self-molecule (moderate reaction) -> go to periphery as ANERGIC (non-functioning) B cell

Very weak self reaction -> IGNORANT B cells
They have receptors for self but haven’t been deleted because they haven’t seen antigen in bone marrow
Can potentially cause autoimmune disease

21
Q

Explain how defects in tolerance lead to autoimmune diseases

A

Failure in Central tolerance

APECED = rare autoimmune disease affecting many endocrine glands

Results from failure to delete T-cells in thymus

Caused by mutation in AIRE transcription factor gene
AIRE important for expression of tissue-specific genes/peptides. Expression of these ensure self-binding T-cells are detected and deleted
Mutation -> Autoreactive T-cells NOT DELETED

22
Q

What kind of genetic defects can lead to autoimmune disease?

A 
B-lymphocyte activation (producing autoantibodies)
Failure in apoptosis
Clearance of (self) antigens like complements (more likely to produce autoimmune response)
23
Q

Explain peripheral tolerance

A

Not all self-antigens are expressed in thymus
Hence mechanisms required to prevent mature lymphocytes from becoming autoreactive

ANERGY: Naive T-cells require co-stimulation for full activation (other than MHC presenting the antigen)
Without co-stimulation, T-cell doesn’t proliferate
Puts T-cell in REFRACTORY state (non-responsive)

Immunological IGNORANCE
Occurs when antigen conc. too LOW in periphery for T-cell to detect OR antigen-presenting molecules (MHC) are low
Occurs at immunologically PRIVELEGED sites

Suppression by regulatory T-cells

24
Q

Example of failure of ignorance?

A

Sympathetic Opthalmia
Physical damage to eye releases eye-specific antigens into draining lymph node
Activates T-cells specific to eye antigens
T-cells go to eyes and cause damage

25
Q

Example of failure of regulation of peripheral tolerance?

A

IPEX
Mutation in FOXP3 which codes for TF important in development of regulatory T-cells
Results in accumulation of auto-reactive T-cells

26
Q

How can infections affect tolerance?

A
  1. Mimic self-molecules - causing activation of self-reactive T-cell resulting in autoimmune disease
  2. Microbe binding to APC presenting a self-antigen induces expression of co-stimulatory molecules, T-cell can bind and become activated, forming self-reactive T-cells resulting in autoimmune disease

Other mechanisms:

Induce changes in expression/recognition of self proteins
Inappropriate MHC class 2 expression
Affect regulatory T-cells directly

Immuno (5 decks)

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