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Inflammation block > Overview of autoimmunity development & autoimmune disease > Flashcards

Overview of autoimmunity development & autoimmune disease Flashcards

1
Q

What controls Autoreactive T & B cells ?

A

Peripheral tolerance mechanisms

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2
Q

What can result when peripheral tolerance fails?

A

Autoimmune diseases may result

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3
Q

What is the purpose of positive selection of T cells ?

A
  • If TCRs are incapable of binding, the T cell will undergo a type of cell death celled apoptosis( so low affinity lacks cytoplasmic signalling domains)
  • If a T cell’s TCR successfully binds to the MHC complexes on the thymic cells, the T cell receives survival signals and is positively selected.
  • Also determines whether the T cell will be CD4 or CD8
  • If binds to MHC class 1= CD8
  • MHC class II = CD4
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4
Q

What is the purpose of negative selection of T cells ?

A
  • With negative selection we are eliminating T cells that recognize and attack our own cells i.e self reactive T cells
  • TCRs that bind TOO strongly to the MHC complexes lead to apoptosis
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5
Q

How is diversity introduced to TCRs

A
  • Precursor T cells (thymocytes) rearrange their TCR genes in the thymus
  • Cutting and splicing of the chains occurs at random
  • 3 regions involved ( V,D,J)
  • D to J rearrangement
  • V to DJ rearrangement
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6
Q

What is central tolerance and what is important to note about it?

A
  • Central tolerance is the process of thymic selection involving positive and negative selection
  • It is important to note that central tolerance does not delete all potentially dangerous lymphocytes
  • So some escape and are self- reactive
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7
Q

What is central tolerance?

A
  • Needed as thymic selection is not complete
  • Self-reactive (autoreactive) CD4 t cells can be detected in the peripheral blood of healthy humans
  • Looks for T cells that react with myelin basic protein (MBP)
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8
Q

What is the significance of MBP in multiple slcerosis

A

-Patients with MS have autoreactive T cells that react with MBP; they are specific to be able to attack and destroy the myelin sheath leading to nerve disruption & paralysis
-MBP is part of the myelin sheath
-

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9
Q

Why do only a small proportion of the developing T cells come out as successive naive T cells that are fully formed?

A

-Because there are 2 selection processes that result in apoptosis for some of them.

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10
Q

Outline the different layers of self tolerance, their mechanism and their site of action

A

Type: Central tolerance
Mechanism: Deletion, editing
Site of action: Thymus, bone marrow

Type: Antigen segregation
Mechanism: Physical barrier to self-antigen access to lymphoid system
Site of action: peripheral organs eg thyroid, pancreas

Type: Peripheral anergy
Mechanism: cellular inactivation by weak signalling without co-stimulus
Site of action: Secondary lymphoid tissue

Type: Regulatory cells
Mechanism: Suppression by cytokines, intercellular signals
Site of action: secondary lymphoid tissue and sites of inflammation

Type:Cytokine deviation
Mechanism: Differentiation to TH2 cells, limiting inflammatory cytokine secretion
Site of action: Secondary lymphoid tissue & sites of inflammation

Type: Clonal exhaustion
Mechanism: apoptosis post activation
Site of action: secondary lymphoid tissue & sits of inflammation

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11
Q

What is secondary lymphoid tissue

A
  • Sites where lymphocytes interact with each other and non-lymphoid cells to generate immune responses to antigens
  • These include the spleen, lymph nodes, and mucosa-associated lymphoid tissues (MALT).
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12
Q

What is ankylosing spondylitis ?

A

-A chronic condition in which the spine & other areas of the body become inflammed

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13
Q

What is Goodpastures syndrome?

A
  • Aka anti-glomerular basement membrane disease
  • rare autoimmune disease in which antibodies attach to the basement membrane in lungs & kidneys, leading to bleeding from the lungs and kidney failure
  • patients have autoabs to type IV collagen i.e type II hypersensitivity reaction
  • Present in basement membranes throughout the body including lungs, kidney and inner ear
  • All patients get glomerulonephritis; only 40% get lung hemorrhage; none get ear problems
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14
Q

How does autoantigen availability explain the disease pattern exhibited by goodpastures syndrome?

A
  • Glomeruli filter plasma so the BM is accessible
  • Cochlear BM not accessible to autoabs ( eq of antigen sequestration-immunological ignorance)
  • In lung, Bm separates alveolar epithelium from capillary endothelium- so 40% lung disease caused by damage due to smoking
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15
Q

State the different mechanisms used for activation of autoreactive T & B cells by infectious agents

A
  1. ) Molecular mimicry
  2. ) Viral & bacterial superantigens
  3. ) Enhanced processing and presentation of auto-Ags
  4. ) Bystander activation
  5. ) Lymphotrophic viruses eg B cells with Hep C> ABS> IC
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16
Q

Outline SLE including its type of hypersensitivity

A
  • Type III hypersensitivity reaction
  • Skin rash caused by complexes of DNA & anti-DNA antibodies becoming localized in the skin to cause inflammation
  • Butterfly rash= classic diagnostic feature
  • Capillaries of your face are very close the skin so inflammation occurs here
17
Q

State the type of hypersensitivity exhibited by type I diabetes Mellitus

A

-Type IV hypersensitivity

18
Q

What is the significance of the islet of Langerhans of the pancreas in type 1 diabetes

A

-They get destroyed

19
Q

State the type(s) of hypersensitivity exhibited by rheumatoid arthritis.

A

Type II, III & IV hypersensitivity reactions

20
Q

What are the mechanisms of maintenance or reinstatement of peripheral T cell tolerance ?

A
  • T cell deletion/apoptosis
  • Anergy
  • Immunological tolerance
  • Immune deviation
  • Suppression (immune regulation)
21
Q

What is Anergy ?

A
  • Involves deletion/apoptosis
  • This is a state of hyporesponsiveness of lymphocytes to 2nd encounter/challenge with the priming antigen
  • Sub-optimal antigen recognition inactivates naive T cells, inducing a state of anergy ( others are deleted)
22
Q

What is immune deviation?

A
  • As we know, there are subsets of CD4 T cells e.g Th1, Th2 Etc. These subsets produce different cytokines upon encounter with antigen and activate different cell types.
  • An eg of immune deviation is cross-regulation of Th1 & Th2
  • Th1 ( which is generally bad for autoimmune disease) deviates to Th2 (which is bad for allergy/asthma)
23
Q

Outline CD4+ CD25+ regulatory T cells and their importance

A

Generated in thymus & periphery

  • Thymus-derived CD4+CD25+ regulatory T cells: natural Tregs (nTregs)
  • Peripherally- generated CD4+ CD25 regulatory T cells: inducible Tregs( iTregs)

Help to maintain immune tolerance/prevent autoimmunity

Removal of thymus early after birth: spontaneous autoimmunity

Transfer of CD4+CD25+ Tregs prevents autoimmunity

Inflammation block (27 decks)

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