Perturbations in the System Flashcards

1
Q

What are ways the immune system can become hijacked?

A
  • superantigens produced by bacteria and viruses
  • genetic polymorphisms, exploited by viruses
  • immune evasion by viruses
  • autoimmune diseases
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2
Q

Define superantigen. What do they lead to?

A
  • do not require uptake and processing
  • bind to the side of the MHC Class II and CD4+ TCR
  • causes overactivation of TCR => cytokine storm
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3
Q

List examples of superantigens.

A
  • TSST-1 (Toxic Shock Syndrome Toxin-1)

- SE (Staphylococcal enterotoxin)

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4
Q

Describe the mechanism of pathology in Toxic Shock Syndrome.

A
  1. TSST-1 causes activation of T cells => Th1 => IFNg
  2. IFNg activates macrophages to produce IL-1, IL-6, and TNFa
  3. TNFa causes increased capillary permeability => hypotension; also causes disseminated intravascular coagulation
  4. IL-1 and IL-6 cause fever, rash
  5. Altogether, this can lead to coma and death
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5
Q

Describe the importance of MHC Class II polymorphism in TSS.

A
  • MHC Class II polymorphism dictates intensity of response
    ==> some people may die from TSS and other have no clinical symptoms
  • the polymorphism dictates the binding to TCR, activation of T cells, and cytokine production
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6
Q

List clinical symptoms of TSS.

A
  • fever
  • hypotension
  • rash
  • desquamation of the palms and soles (shedding)
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7
Q

Define DIC.

A

Disseminating Intravascular Coagulation (DIC)

  • occurs in TSS
  • creates clots in the blood
  • depletes clotting factors in other places
  • leads to bleeding
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8
Q

What causes TSS? Who does it affect?

A
  • staphylococcus aureus strains release TSST-1
  • typically associated with tampon use (can cause skin abrasions, providing entry for S. aureus)
  • can also occur in men and children (all you need is point of entry)
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9
Q

Describe the relationship between genetic polymorphisms and disease susceptibility.

A
  • TSS is exacerbated by certain MHC II polymorphisms

- can increase susceptibility OR resistance to certain immune disorders

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10
Q

What is the relationship between CCR5 genetic polymorphisms and disease?

A

If you have a defect or nonfunctioning CCR5 gene…

  • increases resistance to HIV (yay!)
  • increases susceptibility (decreases resistance) to west nile virus (boo!)
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11
Q

Why is CCR5 defect protective against HIV?

A

HIV requires costimulation by CD4 and CCR5 to be able to gain entry to the host cell
- no CCR5 = no HIV

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12
Q

Define CCR5.

A
  • chemokine receptor
  • expressed on immune effector cells
  • activation of CCR5 allows migration of T cell to site of infection
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13
Q

Describe how hetero vs homozygous CCR5 genetic defects present.

A
  • homozygous for CCR5 defect = completely protective

- heterozygous for CCR5 defect = slow progression of disease

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14
Q

How does the CCR5 defect affect west nile virus resistance?

A

Decreased Resistance

  • normally, WNV causes chemokines to bind to T cells and recruit them to the CNS to fight off the infection
  • without CCR5, the T cells cannot be recruited => infection persists => fatal viral encephalitis
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15
Q

List ways of viral immune evasion.

A
  1. induce production of IL-10 => immune suppression
  2. produce viral IL-10 => immune suppression
  3. produce or induce chemokines => recruit cells to infect
  4. express chemokine receptors => migration of infected cells into other areas to spread virus
  5. alter activity of host chemokine receptors => inhibit immune response or migration
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16
Q

Describe the mechanism by which IL-10 aids in viral immune evasion.

A

Typically, infection leads to production of IFNg => macrophages, DCs, Th1

  • some viruses also induce production of IL-10
  • lowers activation of macrophages and DCs
  • increases Th2 response, which inhibits Th1 and antibody formation
  • viral IL-10 orthologs do the same thing
17
Q

Describe the mechanism by which chemokine production/chemokine receptor modulation aids in viral immune evasion.

A
  1. chemokine secretion attracts susceptible cells
  2. chemokine gradient attracts infected cells to other tissues
  3. inhibition of chemokine receptor prevents immune activation
18
Q

What key factors play a role in the development of autoimmune diseases?

A
  • genetics
  • gender (females have stronger Th1 and antibody response => more likely to develop)
    ==> problems occur after puberty => sex hormones play a role
19
Q

What causes autoimmunity?

A

loss of tolerance

20
Q

Peripheral tolerance is enforced by…?

A

Tregs

- prevent attacks by autoreactive T cells

21
Q

What can cause a loss of central tolerance?

A

mutations in AIRE

– self-reactive T cells are not negatively selected b/c not exposed to the self peptides

22
Q

What can cause a loss of B cell tolerance?

A
  • not exposed to peptide in bone marrow

- during somatic hypermutation, can produce auto-antibodies (typically checked by Tregs)

23
Q

List organ-specific autoimmune diseases.

A
  1. IDDM (pancreas)
  2. Graves (thyroid)
  3. Goodpasture’s (lung and kidney
  4. Myasthenia Gravis (neuromuscular)
  5. Multiple Sclerosis (brain)
24
Q

List systemic autoimmune diseases.

A
  1. Systemic Lupus Erythematosus

2. Rheumatoid Arthritis

25
Q

Which autoimmune disorders are Type II Hypersensitivity?

A

Mediated by antibodies

  • Graves
  • Goodpasture
  • Myasthenia Gravis
26
Q

Which autoimmune disorders are Type III Hypersensitivity?

A

Immune complex deposition

- SLE

27
Q

Which autoimmune disorders are Type IV Hypersensitivity?

A

T cell Mediated

  • IDDM
  • RA
  • MS
28
Q

Describe the cause, mechanism, and clinical symptoms of Graves’ Disease.

A
  • Cause: antibodies against TSH receptor
  • Mechanism: overstimulation of thyroid => hyperthyroidism, loss of negative feedback
  • Sx: goiter, hyperthyroidism, bulging eyes
29
Q

Describe the cause, mechanism, and clinical symptoms of Goodpasture’s Syndrome.

A
  • Cause: antibodies against alveolar and glomerular basement membranes
  • Sx: glomerulonephritis, pulmonary hemorrhage
30
Q

Describe the cause, mechanism, and clinical symptoms of Myasthenia Gravis.

A
  • Cause: antibodies against ACh receptor (causes internalization and blocks ACh effects)
  • Sx: blocks neuromuscular transmission, defects in brain function, defects in muscular function
31
Q

Describe the cause, mechanism, and clinical symptoms of Systemic Lupus Erythematosus.

A
  • Cause: antibodies against ds-DNA (most common)
  • Mechanism: complement activation causes immune complex deposition on basement membranes and inflammation
  • Sx: dermatological (butterfly rash), musculoskeletal (joint, muscle pain), renal (glomerulonephritis)
  • exacerbated by stress, drugs, sunlight
32
Q

How do you diagnose SLE?

A
  • test for anti-nuclear antibody (ANA)
  • anti-dsDNA antibody
  • decreased levels of C3
33
Q

Describe the cause, mechanism, and clinical symptoms of IDDM.

A
  • cause: antibodies against islet beta cells and CD8+ activation
  • Mechanism: CD8 T cells recognize MHC:self peptide on the surface of beta cells and kill them => no insulin
    => can be damaged by toxins, infectious agents (mumps, rubella, coxsackie B)
  • Sx: Type 1 Diabetes
  • equally affects males and females
34
Q

Describe the cause, mechanism, and clinical symptoms of Rheumatoid Arthritis.

A
  • cause: CD4 T cells activate B cells, macrophages, and plasma cells; rheumatoid factor, immune complex,
  • Mechanism: inflammation in synovial joints attracts immune cells => autoreactive CD4 T cells activate macrophages => cytokines induce production of MMP and RANKL => activate osteoclasts to destroy cartilage tissue
  • Sx: inflammation of synovial membranes of joints, cartilage, and bone
35
Q

Define Rheumatoid Factor.

A
  • antibodies (IgA, IgM, and IgG) against IgG
  • 85% of RA patients have this
  • “exception” to RA being characterized as Type IV (T cell)
36
Q

Describe the cause, mechanism, and clinical symptoms of Multiple Sclerosis.

A
  • Cause: CD4 T cells activate attack against Myosin Basic Protein (MBP) of myelin
  • Mechanism: inflammation in brain recruits immune cells => microglia present MBP antigen => CD4 T cells that were activated in the periphery activate the cell => mast cells, complement, antibodies, and cytokines activated => inflammation => demyelination
  • Sx: impaired coordination, tremor, etc.
  • high prevalence in northern hemisphere
37
Q

List the risk factors for autoimmune diseases.

A
  • genetic (MHC types, CCR5 polymorphisms)
  • gender (female)
  • environmental (smoking => RA)
  • infection (viral evasion, IDDM)