Microbiology - Autoimmunity Flashcards Preview

MS 2 - Unit 2 > Microbiology - Autoimmunity > Flashcards

Flashcards in Microbiology - Autoimmunity Deck (26):

What is Myasthenia gravis? What drug would treat this?

Anti-acetylcholine receptor (antagonist) Ig binding results in receptor endocytosis and degradation

fewer receptors lead to decreased sensitivity to stimulation and progressive muscle weakening.

Treat with AChE inhibitor - e.g. Neostigmine


What is graves disease?

Normally, thyroid-stimulating hormone (TSH) induces the breakdown of iodinated thyroglobulin, releasing tri-iodothyronine (T3) and thyroxine (T4 ) signaling the pituitary to stop releasing TSH.

In graves disease autoantibodies bind to the TSH receptor of thyroid cells, mimicking the action of TSH so more thyroid hormones are released


What do auto- I-antigen IgG antibodies cause?

autoimmune hemolytic anemia


What causes autoimmune thrombocytic purpura?

auto antibodies against platelet integrin GPIIb/IIIA


What is goodpastures syndrome? what causes it?

autoimmune disease associated with glomerulonephritis and pulmonary hemorrhage

auto-antibodies against non-collagenous domain of basement membrane collagen type IV


What is pemphigus vulgaris? What causes it?

autoimmune dissease associated with blistering of the skin

auto-antibodies against epidermal cadherin


What causes acute rheumatic fever? What are the symptoms?

antibodies against streptococcal cell wall antigens that cross react with cardiac muscle

leads to arthritis, myocarditis, late scarring of heart valves


Defects/certain isoforms of these can affect susceptibility to autoimmunity

AIRE, Fas, FasL, bcl-2, TNF, FoxP3 complotypes, cytokines, signaling molecules (eg.SHP-1)


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

HLAs (human leukocyte antigens - human version of MHCs)


What are major factors that contribute to development of autoimmunity?

1)Breakdown in central T cell tolerance

2)Breakdown in peripheral T cell tolerance

3) Breakdown in B cell tolerance

4) antigen molecular mimicry leading to detection of self antigen as foreign
5)T-regulatory cell supression

6) Release of self antigens from immonologically privileged tissues (e.g. CNS) due to trauma -


What factors/mechanisms can lead to a breakdown in peripheral T cell tolerance?

Insufficient control of T-cell costimulation

Activation of naïve T cells requires both antigen presentation and costimulation (B-7/CD28)

Self cells don't express co-stimulatory molecules so self antigens don't activate T-cells

If T cell is activated against self antigen it will stimulate B cells to produce auto-antibodies against self-antigen presenting cells

-Autoreactive T cells may have lower threshold for activation
-Allelic variants of CTLA-4 (soluble and membrane CTLA-4 compete for binding to B-7)
-CD40, CD40L variants


What factors/mechanisms can lead to breakdown in central T cell tolerance?

- Normally T cells that bind to self peptides presented by MHC on the thymic cells are deleted through negative selection

- Defects in AIRE lead to the production of a variety of autoimmune B and T cell responses, and autoimmune polyglandular diseases (thryroid, adrenal, pancreatic etc)

**AIRE = auto-immune regulating element (AIRE gene allows thymic endothelial cells to express many tissue specific antigens. It functions to desensitize auto-reactive T-cells during development and in doing so is the major facilitator of negative selection. If you pollute the AIRE, you can't tell who is who)


Even if negative selection works properly, some autoreactive cells do escape - why prevents these cells from becoming activated by self antigens?

peripheral tolerance (lack of co-stimulatory signal on peripheral tissue cells prevents T-cell activation)

Auto-reactive T cells also undergo induced tolerance from T regulatory cells


What is central B cell tolerance?

Peripheral B cell tolerance?

Clonal deletion of self-reactive B cells in the bone marrow (but not all are deleted!)

-Without cognate T cell help, antigen-activated B cells in the T cell zone of a lymph node die by apoptosis
-B cells may also become anergic after encounter with soluble antigen, and then will be eliminated by antigen-specific T cell through Fas signaling.


What is the two hit hypothesis?

susecptability + trigger (infection/trauma/inflammation)


What is universal to all autoimmune disease?

breakdown of T and B cell tolerance and the production of autoantibody and/or inflammatory autoreactive T cells


Type 1 diabetes is associated with what HLAs and infections?

Coxsackie A,B



How does molecular mimicry contribute to autoimmune infections?

Pathogen-derived peptides structurally similar to a self antigen can stimulate a T cell response directed against the self-antigen leading B cell activation and auto-antibody production


How can infection lead to autoimmunity?

During infection, Class I and Class II MHC expression may be induced or increased due to interferon- gama production

e.g. Hashimoto’s disease- normally thryroid cells don't express MHC II but infection or non-specific inflammation can lead to exposure of thyroid cells to interferon gamma, which results in expression of MHC II. T cells then recognize thyroid peptides presented on newly expressed MHC II molecules and induce autoimmune thyroid disease.

The thyroid gland in hashimotos resembles secondary lymphoid tissue, with B and T cells present.


What is sympathetic opthalmia?

normally entry of naïve lymphocytes is prevented to certain sites of immune privilage such as the eye but self antigens may be exposed to circulation by wound or infection, and effector cells can gain access

Eye trauma releases antigen into surrounding tissue - makes its way to lymph node, is detected as foreign antigen, immune system is primed and effector T cells return through circulation and cause bilateral autoimmune inflammatory dissease


Can autoimmune diseases be maternally transmitted to fetus? If so which ones?

IgG mediated yes b/c it can cross placenta - Hemolytic anemia, Myasthenia gravis, Thrombocytopenia purpura, Neonatal lupus

T-cell mediated autoimmune disorders are not transmitted b/c lymphocytes don't cross placenta


What markers are diagnostic for Systemic lupus erythematosus?

What is classic clinical sign?

Immune complexes contain anti-DNA, anti-nucleosome antibodies, among others
Anti-dsDNA titer is diagnostic
Specificity of response broadens over time- epitope spreading

Symptoms may include butterfly-shaped rash on face, fatigue, headaches, and glomerular damage due to immunoglobulin deposits


What is Juvenile diabetes?

Type I diabetes or insulin-dependent diabetes

Beta-cells in the pancreas produce little or no insulin due to destruction by inflammatory cytotoxic CD8+ T cells.

A target antigen is glutamic acid decarboxylase (GAD)

Symptoms include increased thirst and urination, weight loss, nausea, fatigue, diabetic pancreas with insulitis (lymphocytic infiltrate)


What causes RA?

Production of antibodies that react with the constant regions of other antibodies (rheumatoid factor - IgM complexes with Fc from IgG) and infiltration of the joint synovium by inflammatory CD4+ and CD8+ T cells


What causes MS?

Myelin sheath covering cells of spinal cord and brain destroyed due to TH1 CD4+ T cells which secrete IFNγ and activate macrophages, also mast cell and complement activation

Autoantibodies to myelin basic protein, proteolipid protein, myelin oligodendrocyte glycoprotein

Symptoms may disappear and recur over time and include weakness, tremors or paralysis of one or more extremities, numbness, decreased memory and attention span


What are some treatments for autoimmune diseases?

Physical removal of antigen, antibody or immune complexes-splenectomy (plasmapheresis)

Intravenous IgG (ivIg)- FcR effects, Ig suppression, anti-idiotype, regulatory antibodies, decrease presentation, C’ (compliment?) activation

Anti-inflammatory drugs to reduce the inflammatory response (NSAIDS, steroids)

Depletion of immune cells (azathioprine, methotraxate, cyclophosphamide; LJP394; anti-CD20-Rituximab)

Blocking interaction and/or activation of immune cells – e.g., bind to cytokines, block second signals (Enbrel-TNFα antagonist; anti-TNF-infliximab; soluble CTLA-4), BlyS, BAFF

Replacement therapy– e.g., insulin for diabetes, synthroid (Hashimoto’s)

Hormones, diet, exercise