Class #10 - Autoimmune/immunodeficiency Flashcards
Gene associated with Autoimmune diseases (AD) regarging immune signaling?
PTPN22
Microbial role in AD (2)?
1-Induction of costimulants
2-Molecular mimicry
Sx of Systemic Lupus Erythematosis (SLE)?
Butterfly rash hair loss swollen joints light sensitivity glomerulonephritis
SLE autoantibodies attaches to?
dissolved nuclear content like DNA (Hypersensitivity type 4)
Pathogenesis of SLE?
Susceptibility genes + External triggers (UV light) ->apoptotic bodies -> Ig against apoptotic bodies ->
Rheumatoid Arthritis (RA) pathogenesis?
{Susceptibility genes (HLA)} + {Envir. Factors that may trigger the conversion of arginine to citrulline (citrullination)} -> creation of anti-citrullinated protein ab (antibody) and other autoantibodies (all of them called rheumatoid factor)
Panus?
Infiltration of immune cells and hyperplasia of synovial cells.
RA and bones?
RANKL and expressed on T cells stimulating bone resorption by osteoclast.
Multiple sclerosis (MS) pathogenesis?
T cells/monocyte cross the BBB by expressing the right combination of integrins -> Diapedisis -> They then attack oligodendrocytes (making myelin sheath) -> Discoloration of white matter in the brain
MS course (4)?
1-Relapsing-remitting MS (most common type)
2-Primary progressive
3-Secondary progressive
4-Progressive-relapsing
Inflammatory Bowel Disease (IBD) types?
Crohn’s: throughout GIT in discontinuous matter, lesion into musc. layer
Ulcerative colitis: Only colon, only mucosal layer
T cell association in IBD?
Crohn = Th1
Ulcera.: Th2
Genes involved in Crohn?
NOD2: Encode p+ that binds to intracellular bacteria and then activate NF-kB ->prod. cytokines -> promote barrier function of epithelial cells.
NOD2 - defective = defective epi. barrier
Ulcerative Colitis autoantibodies?
A) Perinuclear anti-neutrophil cytoplasmic antibodies (pANCA)
B) Molecular mimicry
“Transplant”, 2 types of reactions?
1-Direct alloantigen recognition: Host recognize MHC on graft as non-sefl. Scene of battle vasculature.
2-Indirect alloantigen recognition: Graft cells react. Scene of battle = skin,GIT,liver
3 types of Direct alloantigen recognition
1-Hyperacute: type 2 hypersensitivity. Preformed Ig. Blood incompatibilities.
2-Acute:
2.1 Type 4 hypersensitivity. Involve T cells. CD4+ recruiting macrophage that will cause damage to parenchymal cells. Result in wavy appearance of basement membrane.
2.2 Type 2 hypersensitivity. Ig form within the capillaries and induce complement activation.
3. Chronic rejection: Slow inflammation of vessel walls (type 4 hypersensitivity). Manifesting in hyperplasia of smooth musc. resulting in occlusion of blood vessels
Indirect alloantigen recognition also called. Reasons?
Graft vs Host Disease (GVHD).
1-Immunocompetent tissues in immunocompromised host.
2-T cell from transplant recognize the host as non-self and attack.
Primary vs 2nd immunodeficiency?
1-genes
2-infections, cancer, drugs, malnutrition
Primary immunodeficiency types?
Specific: Ig deficiency, cell-mediated
Non specific: complement, neutrophils defect
Primary immunodeficiency : What is X-linked severe combined immunod.?
Pro-T cell -> gamma chain not expressed, cannot become Immature T-cell.
Primary immunodeficiency: What is X linked gamma globulemia (BTK)?
Pro-B cell -> Pre B cell -> Defect in tyrosine kinase, cannot become Immature B cell.
Primary immunodeficiency: Severe Combined Immunod. (scid)?
Absence functional T-cell
Secondary immunodeficiency : AIDS pathogenesis?
gp120 (HIV) -> CD4 ->gp120 -> CCR5/CXCR4 coreceptors (t-cell) ->gp41(HIV) allows it to enter cytoplasm
Proliferation of HIV?
RNA converted to DNA by reverse transcriptase then enter nucleus and binds to DNA of cell. Cell needs to be undrergoing proliferation.
Ways HIV kill CD4+ T-cells?
1) Direct killing: membrane permeability defect
2) Killed by CD8+ by MHC 1 HIV antigen recognition
3) Infected CD4+ can trigger apoptosis of uninfected CD4+
Treatment of AIDS
Drug combination: Anti-Retroviral Therapy (ART)
