Case #4 SLE Flashcards

Question

What is the mechanism of Type I Hypersensitivity?

Answer 1

Production of IgE antibody --\> immediate release of vasoconstrictive amines and other mediators from mast cells. Mast cells release mediators that act on vessels and smooth muscles and proinflammatory cytokines. Later recruitement of inflammatory cells

Answer 2

Production of IgG, IgM --\> binds to antigen on target cell or tissue --\> phagocytosis or lysis of target cell by activated compleemnt or Fc receptors; The deposited anibodies activate complement generating by-producs including chemotactic agents (mainly C5a) which direct the migration of pmn leukocytes and monocytes and anaphylatoxins. A-Opsonization and phagocytosis B- Complement and Fc receptor mediated inflammation C - Antibody-mediated cellular dysfunction

Answer 3

Deposition of antigen-antibody complexes --\> complement activation --\> recruitment of leukocytes by complement products and Fc receptors --\> release of enzymes and other toxic molecules

Answer 4

activated T lymphocytes --\> release of cytokines(IL2, IFN gamma) by CD4+, inflammation and macrophage activation Tcell (CD8+) mediated cytotoxicity

Answer 5

Hay Fever Insect venom sensitivity anaphylaxis to drugs atopic dermatitis some food allergies allergies to animals and animal products asthma

Answer 6

Cytotoxic HDNB (erythroblastosis fetalis - Rh- mother with Rh+ child) Goodpasture disease rheumatic fever Autoimmune or drug induced hemolytic anemia transfusion reactions NonCytotoxic Myasthenia Gravis (2 mice in a grave) Graves disease Type II Diabetes Mellitus

Answer 7

SLE Poststreptococcal glomerulonephritis polyarteritis nodosa Arthus reaction Serum sickness

Answer 8

**Ms. Tuberculosis** has **Contact dermatitis.** **MS** **T**uberculin test/Tuberculosis **Has**himoto thyroiditis Contact dermatitis (poison ivy) GVHD RA Crohn disease leprosy acute graft rejection

Answer 9

[Off label use] Rituximab and other anti-CD20 monoclonal antibodies (eg, ocrelizumab, ofatumumab, epratuzumab) Rituximab is a B-cell targeted therapy. This anti-CD20 antibody is a chimeric murine/human monoclonal antibody which causes cell lysis when the Fab domain binds to CD20. Rituximab binds to the antigen on the cell surface, activating **complement-dependent B-cell cytotoxicity**; and to human Fc receptors, mediating cell killing through an **antibody-dependent cellular toxicity.** Reducing B-cell response reduces autoimmune response.

Answer 10

BLyS Blockers - The B-cell survival molecule B-lymphocyte stimulator (BLyS) also known as B-cell activation factor of the TNF family (BAFF) plays a key role in the activation and differentiation of B cells. High serum levels of soluble BLyS, and its homolog APRIL (a proliferation inducing ligand), are found in SLE patients and in murine lupus. Selective blockade of BLyS reduces transitional type 2 follicular and marginal-zone B cells and significantly attenuates immune activation. Belimumab (Benlysta) - Belimumab is an IgG1-lambda monoclonal antibody that prevents the survival of B lymphocytes by blocking the binding of soluble human B lymphocyte stimulator protein (BLyS) to receptors on B lymphocytes. This reduces the activity of B-cell mediated immunity and the autoimmune response.

Answer 11

c. Atacicept - Atacicept (also known as TACI-Ig) is a soluble transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) receptor, which binds both BAFF and APRIL (Figure 1). Atacicept is of interest in SLE because of its profound effects on plasma cells, but its use leads to significant decrease in IgM and IgG immunoglobulin levels and increased infection.

Answer 12

T-cell target Costimulatory molecules provide the necessary second signal for T-cell activation by antigen-presenting cells. An antigen-independent signal for T-cell activation is the CD28:B7 costimulatory interaction. CD28 is expressed on T cells, whereas the ligands B7-1 and B7-2 (CD80 and CD86) are found on antigen-presenting cells.. CTLA4 inhibits T-cell activation by binding to B7-1 and B7-2 (CD80 and CD86) expressed on antigen-presenting cells. Therefore CTLA4 interacts with B7 but inhibits T-cell activation, by preventing the costimulatory signal CD28-B7 interaction necessary for T-cell activation. d. Abatacept - Abatacept is a soluble receptor or fusion protein encoded by fusion of CTLA-4 with the Fc portion of IgG1. Abatacept blocks CD28-B7 interaction and subsequent T-cell-dependent B-cell function.

Answer 13

Cytokines such as tumor necrosis factor alpha (TNF-α), interferon alpha and gamma (IFN-α/-γ) and interleukins (IL) 1, 6, 10, 15, and 18 are upregulated in SLE and play important roles in the inflammatory processes that leads to tissue and organ damage. These cytokines have been considered potential targets for the reduction of chronic inflammation in SLE. TNF-alpha - Infliximab, **A**dalimumab, **GOL**imumab, certolizumab pegol and a fusion protein that acts as a “decoy receptor” for TNF-α **E**tanercept IL-1 - Anakinra (A is #1) IL-6 - Tocilizumab (toll is $6)

Case #4 SLE Flashcards

(37 cards)