Immunology of Autoimmunity Flashcards

1
Q

when do autoimmune diseases occur

A

when components of the human immune system become perturbed
- some factors involved in this are known

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2
Q

how do biologics used to treat autoimmune diseases work

A
  1. work by interacting and modulating with components of the innate and adaptive immune system
    - so autoimmune diseases can be treated by either dampening down these adaptive immune responses (mostly auto reactive B and T cells)
    - or innate responses (mostly proinflammatory cytokines)
  2. based on antibodies- work by blocking receptors or binding to and inactivating their ligands
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3
Q

what do many autoimmune diseases manifest as

A

chronic inflammatory diseases

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4
Q

what are the characteristics of innate immunity

A
  • present at all times
  • reacts immediately
  • activates the adaptive system
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5
Q

what are the characteristics of adaptive immunity

A
  • develops in response to infection and is protective against specific pathogens
  • leverages components of the innate response and develops memory
  • both innate and adaptive are required for normal function
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6
Q

what is inflammation

A

the reaction of vascularised living tissue to local injury
- it is a series of vascular and cellular reactions, aiming to protect the body against the injurious agent

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7
Q

what are the cardinal signs of inflammation

A
  1. heat
  2. redness
  3. swelling
  4. pain
  5. loss of function
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8
Q

what are the types of inflammation

A
  1. acute- sudden onset and short duration
  2. chronic- gradual onset and long duration
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9
Q

give examples of innate immune cells

A
  1. neutrophils
  2. macrophages
  3. dendritic cells
  4. natural killer cells
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10
Q

where are monocytes derived

A

derived from hematopoietic stem cells in bone marrow
- blood= 1-6% leukocyte

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11
Q

what is the function of monocytes

A
  1. migrate into tissues and differentiate into macrophages
  2. they phagocytose microorganisms and present antigens to T cells
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12
Q

what does the name of monocyte derived cells depend on

A

depends on the tissue they reside in:
1. liver= Kupffer cells
2. lung- alveolar Mf
3. CNS- microglial cells
4. bone- osteoclasts

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13
Q

where are polymorphonuclear neutrophils derived

A
  • 50-70% of circulating white blood cells
  • infection activates cytokines that stimulate the bone marrow to produce neutrophils
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14
Q

what is the function of neutrophils

A
  1. they are active phagocytic cells
  2. they circulate in peripheral blood for 7-10 hours and migrate by extravasation into tissues, where they have a lifespan of a few days
  3. they are attracted to tissues by chemotactic factors
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15
Q

give examples of soluble mediators

A

cytokines and chemokines

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16
Q

how does the balance and level of cytokines and chemokines secreted affect the outcome of the response

A
  1. alert to infection
  2. recruit cells to site
  3. activate further immune response
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17
Q

what effect do cytokines have on endothelial cells

A

change the morphology, adhesive properties and permeability of endothelial cells

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18
Q

give examples of cytokines

A

IL1, IL6, TNFa

19
Q

describe the permeability of post endothelial cells

A

impermeable to cells and plasma

20
Q

what is autoimmunity

A

the responses to self antigens or antigens associated with the microbiota that leads to tissue damage and disease

21
Q

when does autoimmunity occur

A

when adaptive cells break self tolerance
-host cells recognised as foreign and adaptive immune cells target them for destruction

22
Q

how is auto inflammation caused

A

when innate immune cells become activated
- due to dysregulated secretion of pro inflammatory cytokines and consequent damage to host tissues

23
Q

what is the critical function of the immune system

A

to discriminate self from non self

24
Q

what do autoimmune responses resemble

A

resemble normal immune responses to pathogens, in that T and B lymphocytes are activated by antigens (autoantigens)

25
Q

describe the result of the effects of autoantigens

A
  1. gives rise to auto reactive effector (T) cells and autoantibodies (from B cells) against the self antigen
  2. regulatory T cells may also fail to do their job of keeping the immune system in line
  3. such dysregulated immune responses to self tissues lead to chronic syndromes
    - autoimmune diseases
26
Q

what is CD4 lineage

A

antigen presenting cells see antigen which present it as peptides with MHC II to naive CD4+ T helper cells, which become effector T cells of 4 basic types

27
Q

where does CD4 lineage occur

A

in the adaptive immune system

28
Q

how does a lymphocyte distinguish between self and non self

A
  1. there are mechanisms that prevent autoimmunity like checkpoints
    - each partially effective in preventing anti self responses
    - together, acts synergistically to prevent autoimmunity without ablating protection against pathogens
  2. ultimate aim is immunological tolerance
29
Q

what is immunological tolerance

A

mechanisms hat prevent an immune response being mounted against the bodys own tissues
- this is manifested by immunological non reactivity of B and T cells to self antigens

30
Q

what are the 2 major groups of checkpoints

A
  1. central tolerance mechanisms in thymus and bone marrow
  2. peripheral tolerance mechanisms in secondary lymphoid tissue/sites of inflammation
31
Q

what are the functions of T regulatory cells

A
  1. protectors against autoimmunity
  2. express a transcription factor which alters the expression of many genes
  3. when activated, Tregs express large quantities of the cytokines TGFB and IL10
    - these are immunosuppressants that inhibit activity of NK cells and CD8 cells
  4. Tregs also have powerful destructive effects on APCs such as dendritic cells
  5. the antigenic peptides recognised by the TCRs of Tregs tend to be self peptides (autoantigens)
  6. so major function is to inhibit CD4+ Tn1, Tn2, Tn17, CD8 and CTLs from mounting an immune attack against self components to protect the body against autoimmunity
32
Q

what occurs when there is a lack of Tregs

A

severe autoimmune conditions arise

33
Q

what does inflammation due to hashimotos disease lead to

A

leads to underactive thyroid gland

34
Q

what is the diagnostic sign of Hashimotos disease

A

enlarged thyroid

35
Q

what are symptoms of Hashimotos disease

A
  1. enlarged thyroid
  2. front of neck looks swollen
  3. may make swallowing difficult
  4. weight gain
  5. fatigue
  6. paleness/puffiness in face
  7. joint/muscle pain
  8. constipation
  9. hair loss or thinning
  10. slowed heart rate
36
Q

what is the treatment of HD

A

daily use of synthetic thyroid hormone
- levothyroxine

37
Q

what does RA show characteristics of

A

both autoimmune and auto inflammatory disease

38
Q

describe the autoinflammatory responses in RA

A
  1. once RA is triggered, immune cells migrate into joints where they produce large quantities of immune mediators (cytokines/chemokines), leading to activation and recruitment of more immune cells into the tissue
39
Q

what do mutations in cells of the innate immune system lead to

A
  1. leads to elevated levels of proinflammatory cytokines, creating a positive feedback loop of exacerbating inflammation
    - by blocking these secreted cytokines, the systemic inflammatory symptoms are alleviated
40
Q

why were immunotherapies developed and what do they do

A
  1. were developed to decrease the amount of circulating TNFa, IL6 and IL1B
  2. these drugs (tocilizumab, etanercept) are able to bind to and sequester these cytokines or their receptors
41
Q

what is the mode of action of TNFa, IL1 and IL6

A

binding of an inflammatory cytokine to its receptor leads to the production of inflammatory effector molecules

42
Q

what is TNFa involved in

A

involved in systemic inflammation
- as TNF promotes the proinflammatory response, amplified and dysregulated production of TNF if associated with autoimmune disorders such as RA, ankylosing spondylitis, IBS and psoriasis
- these disorders can be treated using a TNF inhibitor

43
Q

what is TNFa secreted by

A

macrophages

44
Q

what is the role of IL6

A
  1. regulates many pathways that could contribute to its effect on inflammatory disease progression
  2. during CD4 T cell differentiation, IL6 promotes IL17 and IL21 production and suppresses Treg cell function
  3. IL6 promotes neutrophil and macrophage recruitment and survival through induction of IL17 production
  4. also acts on non immune cells, altering the function of fibroblasts and osteoclasts
  5. this all leads to deposition of matrix, antibody complexes and proteases in the targeted tissue, leading to tissue destruction