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66 Cards in this Set
- Front
- Back
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Which type of cell mediates cellular rejection?
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T-cell:
CTLs cause destruction. Th cause delayed hypersensitivity reaction. |
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What is the "direct pathway"?
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Dendritic cells from the donor express HLA I&II, AND costimulatory signals.
CD8: kill those cells. CD4: Activate macrophages. ACUTE REJECTION. |
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What is the "indirect pathway"?
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Our own APC present donor antigens, just like any foreign peptide.
Causes only delayed-type hypersensitivity using Th and Macrophages, since CTLs aren't activated by this (because they only see OUR APC's, and not the donor's, so they have no one to kill). CHRONIC REJECTION. |
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Morphology- hyperacute:
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Infiltration of neutrophiles after deposition of immunoglobulin-complement complexes.
Thrombotic occlusion in glomeruli. Fibrinoid necrosis at arterial walls. |
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Morphology- acute:
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Mononuclear infiltrate, edems, hemmorage- both CD4 and CD8.
Damage to blood vessels d/t AB, necrotizing vasculitis, neutrophlic infiltrate. |
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Morphology- chronic rejection:
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Obliterative intimal fibrosis
Glomerular loss Interstitial fibrosis Tubular atrophy Mononuclear cell infiltrate (&eosinophiles). |
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In which type of rejection do you see fibrosis?
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Chronic.
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Who is the most common immunosuppression drug?
What does it do? |
Cyclosporin- blocks activation of "nuclear fsactors", transcription factor for cytokines (mainly IL-2).
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What is Azathioprine?
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Immunosuppresion drug. Inhibits leukocyte development from bone marrow.
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What do you use streoids for?
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Immunosuppression.
Block inflammation. |
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What do you use Rapamycin for?
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Immunosuppression.
Inhibits lymphocyte proliferation. |
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What are monoclonal anti t-cell antibodies?
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Immunosuppressive treatment.
Anti-CD3 and anti IL-2alphachain. Block T-cell activation. |
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What is "mixed chimerism"?
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Recipient learns to live with injected donor cells- tolerance to donor alloantigens.
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What causes GVH?
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When immuno-competent cells go in immuno-crippled recipient.
Not just bone marrow- any lymphoid organs, like liver or un-radiated blood. |
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Why can GVH happen even after HLA-matching?
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Subtle differences between HLAs we didn't pick up on.
Minor histocompatability differences. |
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What are the symptoms of acute GVH?
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Rash -> Desquamation.
Jaundice. Bloody diarrhea. |
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What infection is common in GVH?
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CMV.
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what are the symptoms of chronic GVH?
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Extensive cutaneous injury- fibrosis of dermis.
Jaundice- chronic liver disease. Depletion of lymphocytes inlymph nodes. Autoimmunity. |
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What causes rejection of allogenic bone marrow?
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NK & T cells that survived the radiation (grafted precursors lack MHC class I).
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Are autoantibodies rare?
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No, they can be found in apparantely normal people, especially older.
Can be formed after damage to tissue- help clean tissue breakdown products. |
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What happens in diabetic mellitus I?
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T cells and antibodies react against beta-cells in islets.
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What is Goodpasture syndrome?
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antibodies to basement membranes of lung and kidney.
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What is Central Immunologic Tolerance?
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Death of self-reactive lymphocytes in thymus (T) or bone marrow (B).
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What is the AIRE protein?
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AutoImmune REgulator: stimulates expression of peripheral self-antigens in thymus, to teach T-cells.
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What happens to T-cells that meat self-antigens they recognize?
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Die or turn into Treg.
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What is Peripheral Tolerance?
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Silencing of T-cells that have escaped intrathymic negative selection.
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What is anergy?
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Lymphocytes that cannot be activated, even if they meet their antigen + costimulatory signals.
Happens to T-cells that meet antigen without costimulatory signals. |
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Means of peripheral tolerance?
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1. Anergy (self-antigen usually comes without costimulatory signals). Requires CTLA4.
2. Suppression by Treg 3. Clonal deletion: constant stimulation, eventually will lead to death by FasL. 4. Antigen sequesteration- the self-antigens are usually hidden ("immunoprivileged tissues"). |
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What are susceptibility genes?
(autoimmune) |
Presence of particulr MHC alleles- affects negative selection/Treg.
Related to specific AAB creation, not generalized predisposition. |
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What is the role of infection in autoimmune diseases?
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1. Upregulate expression of co-stimulatory molecules on APC- and if they were to present self-antigens..
2. Molecular mimcry. 3. Tissue injury may release self-antigens/alter them. 4. Induce production of cytokines. |
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What is Epitope Spread?
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Infectino may release/damage self-antigens- expose epitopes that are usually concealed, and that lymphocytes haven't developed a tolerance for.
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What ANAs are indicative of SLE?
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Smith.
dsDNA. |
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What does Anti-phospholipid AB syndrome cause in blood?
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Hypercoagulability.
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What regulates the expression of autoimmune diseases?
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While the genetic makeup regulates the formatino of AAB, the expression of disease is influenced by non-genetic factors, like environment.
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What can lack of complement proteins cause?
(happens in lupus) |
Impair removal of circulating immune complexes by MNP, thus favoring tissue deposition.
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How does UV light exacerbate SLE?
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Induces keratinocytes to produce IL-1.
Alter the DNA and make it immunogenic. |
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Why are pregnant women more prone to outbursts of SLE?
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More sex hormones.
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What type of response is SLE?
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Antigen specific Th induce cell-dependent B-cell response.
Also contribute: defective clearance of apoptotic cells. Dysregulation of cytokines (IFN). |
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What do you see in the skin of SLE?
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Liquefactive degeneration of basal layer.
Edema at dermal junction. Mononuclear infiltrate of dermis. |
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What happens to the joints in SLE?
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Nonerosive synovities, little deformity.
(distinguishes from RA). |
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What are the symptoms of SLE?
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Lupus nephritis (mainly in glomeruli).
Erythemia in skin (rash). Joints. Pericarditis. Mitral & aortic valve thickening. Enlarged spleen. CAD (especially if treated with corticosteroids). |
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MCC death in SLE?
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Renal failure.
Intercurrent infections. CAD. |
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What is Chronic Discoid Lupus Erythematosus?
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Skin manifestations like SLE, without the systemic.
Some show positive ANAs, but NOT dsDNA. |
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What is Subacute Cutaneous Lupus Erythematosus?
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Skin involvement.
Mild systemic symptoms. |
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What id Drug-induced LE?
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Drugs cause ANAs- usually anti-Histone.
Similar to SLE, but without renal/CNS involvement. The disease remits after withdrawal of the drug. |
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What is Sjogren Sx?
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Chronic disease- dry eyes & mouth d/t immunologic destruction of lacrimal and salivary glands.
Can be primary (isolated) or secondary (mainly with RA). |
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What does Sjogren Sx usually come with?
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RA.
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What AAB do you see in Sjogren syndrome?
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Ribonucleoproteins- Ro, La
RO/LA AAB ARE SEROLOGIC MARKERS OF THIS DISEASE. |
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What causes the symptoms of Sjogren?
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Not the AAB, but the Th response.
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What infections might initiate Sjogren?
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EBV
HCV HTLV1 |
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Who is most commonly affected by Sjogren Sx?
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older women- show parotid gland enlargement.
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What type of cancer do Sjogrens develop?
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Non-Jodgkin lymphomas (B-cell), d/t polyclonal B-cell activation in lymph nodes.
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What is Scleroderma?
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Chronic disease.
Abnormal accumulation of fibrous tissue in skin and organs. |
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What are the two types of Scleroderma?
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1. Diffuse- widespread skin involvement, rapid progression.
2. Limited-skin involvement confined to fingers, forearms and face. Visceral involvement occurs late. Comes with CREST. |
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What is the trigger for extensive fibrosis in Scleroderma?
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Abnormal immune response to vascular damage -> local accumulation of GF and induce fibroblasts to produce collagen.
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What do you see in the arteries of patients with systemic Scleroderma?
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Intimal thickening.
Microvasculr disease presents early- capillary dilation with leaking, as well as destruction. Eventually, you get ischemic injury and scarring. |
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What types of cells are involved in Scleroderma?
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Th.
Hyperresponsive fibroblasts. |
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What ANAs do you see in Scleroderma?
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Topoisomerase I (diffuse).
Anti-centromer (limited, comes with CREST). |
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What are the symptoms of systemic Scleroderma?
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1. Skin: atrophy, from distal (fingers) to proximal.
2. Reflux, Barret's metaplasia. 3. Inflammation in joints, but NO destruction! 4. Kidneys- intimal thickening of vessel walls. 5. Hypertension. |
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Who is most affected by Scleroderma?
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Woman, 50-60.
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What is Mixed Connective Tissue Disease?
ANAs? Treatment? |
Co-existence of features suggestive of many AA.
AB to RNP particles that contain U1-RNP. Responds well to steroids. |
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What is Polyarthritis Nodues?
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Necrotizing inflammation of blood vessels (NON-infectious!).
Immunologic pathogenetic mechanism. |
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What does RA primarily attack?
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Joints- destruction of the articular catilage.
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Who is most affected by RA?
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Woman, age 40-70.
There is a genetic susceptibility. |
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What cells react in RA?
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Th and B cells.
Th stimulate secretion of TNF and IL-1 from other cells in the joint. TNF and IL-1 cause production of prostaglandins, MMP, RANK-L. |
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Which joints are first affected by RA?
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Small joints- usually MCP & PIP.
Causes deformation of joints! |
