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Immunology Y2 > Tolerance and Autoimmunity > Flashcards

Tolerance and Autoimmunity Flashcards

1
Q

4 criteria for an autoimmune disease?

A

Evidence of disease specific adaptive immune response in the affected target tissue/organ/blood

Passive transfer of auto reactive cells or antibodies replaces the disease

elimination of the autoimmune response eliminates the disease

history of autoimmune disease/MHC associations

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2
Q

factors for autoimmune disease? (6)

A 
Microbiome
Stress
Diet
Sex
Infections
Genes
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3
Q

effector mechanism of autoimmunity resembles which HS reactions?

A

mechanisms resemble those of hypersensitivity reactions, types II, III, and IV

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4
Q

What is the hygiene hypothesis? What evidence supports this?

A

that if the immune system isn’t fighting infection it may begin to fight self

  • Incidence of autoimmune disease (and hypersensitivity) is increasing
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5
Q

During pregnancy what happens to autoimmune diseases and why?

A
  • During pregnancy there is a shift away from inflammatory responses to help protect the fetus, so often diseases go away during pregnancy then come back (e.g. arthritis)
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6
Q

Some important autoimmune diseases? (5)

A 
RA
T1DM
MS
SLE
Autoimmune thyroid disease
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7
Q

Example of a specific target autoimmune disease? (3)

A

Graves’
T1DM
Pernicious anaemia

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8
Q

Example of a nonspecific target autoimmune disease? (3)

A

SLE/RA/Vasculitis

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9
Q

What is a t2 HS reaction

A
  • Antibody response to cell surface or insoluble extracellular matrix antigen (against insuluble antigen
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10
Q

What is a t3 HS reaction

A
  • Immune complex formed by antibody against soluble antigen that go into circulation
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11
Q

What is a t4 HS reaction

A
  • T-cell mediated disease (Delayed type hypersensitivity reaction,
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12
Q

What is Goodpastures syndrome

A

antibody binds to basement membranes in kidney- leads to complement activation and inflammation

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13
Q

Summarise Graves disease

A

antibodies against TSH receptor cause release of thyroid hormone w/o negative feedback

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14
Q

Example of a T3 HS disease

A

SLE

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15
Q

3 examples of T4 HS diseases?

A

Insulin dependent diabetes mellitus
RA
MS

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16
Q

Autoantigen and pathology and HS reaction type of:

RA

A

T4
unknown synovial joint antigen
Joint inflammation and destruction

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17
Q

Autoantigen and pathology and HS reaction type of:

MS

A

Myelin basic protein, proteolipid protein

T4

Brain degeneration (demyelination) weakness and paralysis

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18
Q

What do CD8+ cells recognise

A

MHC Class I

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19
Q

What do CD4+ cells recognise

A

MHC Class II

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20
Q

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

A

MHC class II

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21
Q

What is tolerance defined as

A

ACQUIRED INABILITY TO RESPOND TO AN ANTIGENIC STIMULUS

22
Q

2 types of tolerance?

A

Central and peripheral

23
Q

What is central tolerance?

A

The elimination of self-reactive lymphocytes during lymphocyte development

24
Q

What is peripheral tolerance

A

Anergy, active suppression (by regulatory T cells), ignorance of antigen (non-exposure/ignorance to antigen)

25
Q

Where does central tolerance occur (2)

A

THYMIC EPITHELIAL CELLS (TECs) and DENDRITIC CELLS (DCs)

26
Q

What 3 categories does the thymus separate lymphocytes into

A
  1. Useless (can’t see MHC) die by apoptosis
  2. Useful (see MHC weakly) receive signal to survive- “Positive selection”
  3. Dangerous (see self strongly) receive signal to die by apoptosis- “Negative selection”
27
Q

What % of thymocytes survive thymus selection

A

5

28
Q

Which type of immune cell goes to the thymus

A

pre T-cells

29
Q

Which type of immune cell matures in the bone marrow

A

B cells

30
Q

What happens to a B cell that has no self reaction in the bone marrow

A

Migrates to periphery and matures

31
Q

What happens to a B cell that has a reaction to a multivalent self molecule in the bone marrow

A

Clonal deletion or receptor editing leading to apoptosis

32
Q

What happens to a B cell that has a reaction to a soluble self molecule in the bone marrow

A

Migrates to periphery and becomes anergic

33
Q

What happens to a B cell that has a reaction to a low-affinity-non-crosslinking self molecule in the bone marrow

A

Migrates to periphery and becomes a mature clonal ignorant B cell

34
Q

What is apeced and what does it effect? (6)

A 
-	APECED is a rare autoimmune disease which affects the endocrine glands:
 Thyroid
 Kidneys
 Chronic mucocutaneous candidiasis
 Gonadal failure
 DM
 Pernicious anaemia
35
Q

What does failure of central tolerance result in

A
  • APECED
36
Q

What causes Apeced

A

mutations in the transcription factor AIRE (autoimmune regulator) gene

37
Q

What is AIRE important in

A
  • AIRE is important for the expression of ‘tissue-specific’ genes in the thymus
38
Q

Many of the genes that are implicated in genetic susceptibility to autoimmune diseases are involved in… (3)

A
  1. induction of tolerance
  2. apoptosis
  3. clearance of antigen
39
Q

3 mechanisms for inducing and maintaining tolerance in the periphery?

A
  1. Anergy
  2. Suppression by regulatory T cells
  3. (Ignorance of antigen)
40
Q

What do naive T cells need for full activation? Examples of what they need? (3)

A

co-stimulation for full activation: CD80, CD86 and CD40 are examples of costimulatory molecules expressed on APC

41
Q

What does stimulation without a co-stimulatory molecule lead to

A

Anergy

42
Q

How does anergy occur

A

stimulation without a co-stimulatory molecule lead to

43
Q

When does immunological ignorance occur (2)

A

when antigen concentration is too low in the periphery

and when relevant antigen presenting molecule is absent:

44
Q

Which MHC class are most cells in the periphery

A

class I

45
Q

Where does immunological ignorance occur (3)

A

immunologically privileged sites such as eye, testes and PNS

46
Q

Why might cells at immunologically privileged sites react against autoantigens

A

They have never been tolerised

47
Q

What transcription factor is required for Treg development

A

FOX P3

48
Q

FOXP3 is required for what

A

Treg development

49
Q

IPEX stands for what

A

Immune dysregulation, Polyendocrinopathy, Enteropathy and X-linked inheritance syndrome

50
Q

Symptoms of IPEX? (5)

A
  • Early onset insulin dependent diabetes mellitus
  • Severe enteropathy
  • Eczema
  • Variable autoimmune phenomena
  • Severe infections
51
Q

Symptoms of IPEX? (5)

A
  • Early onset insulin dependent diabetes mellitus
  • Severe enteropathy
  • Eczema
  • Variable autoimmune phenomena
  • Severe infections
52
Q

Ways in which infections can cause autoimmunity? (5)

A
  • Infections may carry out molecular mimicry of self-molecules
  • Induce changes in the expression and recognition of self-proteins
  • Induction of co-stimulatory molecules or inappropriate MHC class II expression: pro-inflammatory environment
  • Failure in regulation by effecting/infecting regulatory T-cells
  • Immune deviation shift in type of immune response e.g. Th1-Th2
  • Tissue damage at immunologically privileged sites

Immunology Y2 (5 decks)

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