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Immunity Week 3 > ICL 6.1: Autoimmunity > Flashcards

ICL 6.1: Autoimmunity Flashcards

1
Q

what is the significance of immunological tolerance?

A

all individuals are tolerant of their own antigens (self-tolerance); breakdown of self-tolerance results in autoimmunity

therapeutic potential: inducing tolerance may be exploited to prevent graft rejection, treat autoimmune and allergic diseases, and prevent immune responses in gene therapy

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2
Q

what is the pathology behind autoimmunity?

A
  1. susceptibility genes –> failure of self-tolerance –> persistence of functional self-reactive lymphocytes –> activation of self-reactive lymphocytes –> immune responses against self tissues
  2. environmental triggers like infections or tissue injury –> activation of self-reactive lymphocytes –> immune responses against self tissues
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3
Q

what environmental factors can induce autoimmune diseases?

A
  1. virus clustering (RA, Sjögren’s s., SLE, MS)
  2. infectious microorganisms (molecular mimicry)
  3. sun exposure (SLE)
  4. exogenous estrogens, sex hormones in general
  5. obesity
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4
Q

which gender is more prone to autoimmune diseases?

A

women are WAY more prone to like every single autoimmune disease

however, this doesn’t eliminate the possibility that a male will have an autoimmune disease!

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5
Q

what are the characteristics of autoimmunity?

A
  1. existence of self antibodies
  2. it is potentially reversible!!
  3. higher incidence in older people
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6
Q

why is autoimmunity higher in older populations?

A

when a cell dies, it releases the contents of the nucleus which can stimulate the immune system to produce antibodies

so everybody has a small amount of auto-antibodies in their body

as you get older, more neutrophils and cells die and you generate more auto-antibodies

autoimmunity is not a problem, it’s a normal process!

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7
Q

what are the characteristics of autoimmune disease?

A

there is severe 1. tissue damage!***

  1. there are clinical symptoms associated with the tissue damage
  2. protracted course but usually fatal
  3. familial clustering
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8
Q

what are the two categories of autoimmune diseases?

A
  1. organ specific

2. non-organ specific

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9
Q

what are the characteristics of organ-specific autoimmune diseases?

A
  1. autoimmune attack vs. self-antigens of given organ
  2. it results in a damage of organ structure and function
  3. treatment is focused on the replacement of organ function
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10
Q

what are the characteristics of non organ-specific autoimmune diseases?

A
  1. widespread self-antigens are targets for autoimmune attack
  2. damage affects such structures as blood vessels, cell nuclei etc.
  3. treatment is aimed to inhibit activation of the immune system
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11
Q

which diseases are examples of organ-specific autoimmune disease?

A
  1. type I diabetes
  2. goodpasture’s syndrome
  3. multiple sclerosis
  4. grave’s disease
  5. Hashimoto’s thyroiditis
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12
Q

what are examples of non organ-specific disease?

A
  1. rheumatoid arthritis
  2. scleroderma
  3. SLE
  4. primary Sjogren syndrome
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13
Q

what kind of autoimmune disease is SLE?

A

non organ specific

it effects your skin, heart, kidney, joints; it’s systemic!

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14
Q

what mediates autoimmune diseases?

A

autoimmune diseases caused by IgG mediated mechanisms require T cell help in order to produce antibodies

since IgG is involved, hypersensitivity reactions II, III and IV are involved

transfer of T cells from an animal with autoimmune disease to a healthy animal can transfer disease!!

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15
Q

autoimmune diseases are often linked to what?

A

specific MHC genes

MHC genes regulate T cells!

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16
Q

when do autoimmune diseases happen?

A

when auto-reactive T cells or auto-antibodies cause tissue damage through hypersensitivity reaction types II, III and IV

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17
Q

what is a type II hypersensitivity reaction?

A

IgG and IgM antibodies bind to antigens on human cells/tissue

this leads to lysis by complement or phagocytosis

18
Q

which autoimmune diseases are type II hypersensitivity reactions?

A
  1. autoimmune hemolytic anemia
  2. autoimmune thrombocytopenia purpura
  3. goodpasture’s syndrome
  4. pemphigus vulgaris
  5. acute rheumatic fever
  6. grave’s disease
  7. myasthenia gravis
  8. insulin-resistant diabetes
  9. hypoglycemia
19
Q

how are type II hypersensitivity reactions related to autoimmune disease?

A

antibodies that cause disease are most often autoantibodies against self antigen of human cells or tissues

Ab may modify the function of cells by binding onto receptors that cause disease by stimulating or blocking receptor function

human cells = autoimmune hemolytic anemia

tissues = good pasture’s syndrome, acute rheumatic fever

20
Q

what can cause autoimmune hemolytic anemia?

A

after administration of certain drugs (like penicillin)

drug molecules bind to surface components of human cells and create new epitopes to which the immune system is not tolerant

these epitopes stimulate the formation of IgM and IgG antibodies that are specific for the conjugate of drug and cell surface component

21
Q

what is type III hypersensitivity reaction?

A

antibodies may cause tissue injury and disease by forming
immune complexes that deposit in blood vessels or tissues

smaller immune complexes are less efficient at fixing complement, they tend to circulate in the blood and become deposited in blood vessel walls

when these complexes accumulate at such sites, they become capable of fixing complement and initiating tissue-damaging inflammatory reactions

Ag-Ab complexes activate complement

22
Q

what type of hypersensitivity reaction is SLE?

A

type III

SLE is mediated by antibodies against DNA and other nuclear components

23
Q

what lab results would be diagnostic of SLE?

A

immunoflurescence shows her blood contains an anti-nuclear antibody

skin biopsy shows to contain IgG and complement deposits

24
Q

which parts of the body are commonly effected in immune complex disease?

A

joint, skin and kidney involvement are very typical of immune complex disease

25
Q

what is type IV hypersensitivity reactions?

A

they are caused by T cells (CD4) specific for the sensitizing antigen, that release cytokines which leads to macrophage activation

type IV hypersensitivity reactions may also include killing of sensitized targets by cytotoxic T cells (CD8)

26
Q

which autoimmune diseases are classified as type IV hypersensitivity reactions?

A
  1. insulin-dependent diabetes mellitus
  2. rheumatoid arthritis
  3. multiple sclerosis
  4. Celiac disease
27
Q

what is insulin-dependent diabetes mellitus?

A

it’s a type IV hypersensitivity reaction

there is an auto-antigen against pancreatic β-cell antigen

this leads to β-cell destruction

28
Q

what is rheumatoid arthritis?

A

there is an auto-antigen against an unknown synovial joint antigen

leads to joint inflammation and destruction

29
Q

what is multiple sclerosis?

A

auto antigen against myelin basic protein, proteolipid protein

leads to brain degeneration and paralysis

30
Q

what is Celiac disease?

A

auto antigen against gluten modified by tissue transglutaminase

leads to malabsorption of nutrients and atrophy of intestinal villi

31
Q

what isn’t being produced when someone has insulin-dependent diabetes mellitus? why?

A

the islets of Langerhans contain several cell types secreting distinct hormones; each cell expresses different tissue-specific proteins

β cells secrete insulin

in insulin-dependent diabetes an effector T cell recognizes peptides from a β cell-specific protein and kills the β cell

someone officially has type I diabetes once there are insufficient b cells to provide the insulin necessary to control the level of glucose in the blood

glucagon and somatostatin are still produced by the α and δ cells but insulin can’t eb made without the β cells

32
Q

what would a tissue biopsy of someone with insulin-dependent diabetes mellitus?

A

brown!!

the brown is from the destruction of insulin secreting β cells of the pancreas

33
Q

what’s the difference between insulin dependent and insulin independent diabetes?

A

T cells kill the pancreas β cell so not enough insulin is not produced = type I diabetes

insulin independent diabetes is when you have enough insulin released but the problem is that there’s an antibody that recognizes the insulin receptor and destroys it = type II diabetes

34
Q

what do the α, β and δ cells of the pancreas make?

A

α = glucagon

β = insulin

δ = somatostatin

35
Q

what are the characteristics of type I diabetes?

A

type I diabetes is characterized by loss of the insulin-producing beta cells of the pancreas

the majority of typeI diabetes is of the immune-mediated nature, in which beta cell loss is a T-cell-mediated autoimmune attack

**low level of serum insulin is indicative of type I diabetes

36
Q

what are the characteristics of type II diabetes?

A

typeII diabetes mellitus is characterized by insulin resistance

the defective responsiveness of body tissues to insulin is believed to involve the antibodies against insulin receptor that reduce insulin sensitivity = type II hypersensitivity reaction

**serum insulin levels are normal/high because it’s a problem with the insulin receptor, not insulin itself

the most dangerous complications of obesity are type II diabetes and vessel disease

37
Q

is IDDM effected by genetics?

A

yup. if an identical twin develops IDDM, there is a 35% chance his or her twin will also do so

IDDM often occurs in people who inherit the HLA alleles DQ2

38
Q

which gene is related to IDDM?

A

DQ2 HLA alleles

in most HLA-DQ alleles, position 57 in the HLA-DQ β chain is occupied by an aspartic acid residue

with HLA-DQ2, this position is replaced by another amino acid residue, and this change has reduced binding for a pancreatic islet cell antigen

autoreactive T cells cannot be deleted in the thymus and the potential for autoimmunity to increased

39
Q

what is Hashimoto’s disease?

A

the thyroid loses the capacity to make thyroid hormone

Hashimoto’s disease seems to involve a CD4 T cell response, and both T cells and antibodies specific for thyroid antigens are produced

lymphocytes infiltrate the thyroid, causing a progressive destruction of the normal thyroid tissue

patients with Hashimoto’s disease become hypothyroid, and eventually are unable to make thyroid hormone

40
Q

what is the treatment for Hashimoto’s disease?

A

replacement therapy with thyroid hormone

Immunity Week 3 (14 decks)

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