9282398
Description
Flashcards by Marissa Alvarez, updated more than 1 year ago
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Created by Marissa Alvarez
almost 7 years ago
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| Question | Answer |
| IMMUNE EVASION 1) Molecular Mimicry: | mimics the immune response in order to INVADE the immune response |
| IMMUNE EVASION: Protein Modifications | Glycosylation: key immune proteins, such as TCR, MHC, TLR and antibodies are glycosylated **when pathogen is glycosylated, it sterically blocks the action of proteases and can ESCAPE |
| IMMUNE INVASION: Down-Regulate HLA | TUMORS & VIRUSES target the HLA and wants to down regulate it so that the immune system cannot detect them |
| BRIDGING THE GAP B/W Innate and Adaptive Immunity | Innate immune response drive adaptive immune responses -recognition of PRR drives inflammation and recruitment of neutrophils, macrophages, and dendritic cells -Macrophages and dendritic cells and B cells are all APC's (professional) APC's stimulate adaptive immunity (T cells) |
| HLA HUMAN LEUKOCYTE ANTIGENS | Polymorphic Multiple loci Multiple alleles at loci Codominantly expressed Haplotypes (inherit 1/2 from mom and 1/2 from dad) Linkage disequilibrium (certain genes are found at a more than random frequency) Evolved to accommodate immune responses to enormous variety of foreign antigens (pathogens) “Self Ags” = Potent inducers of humoral and cell mediated immune responses = primary stimulus for HVG and GVH responses |
| CONCEPT FOR MHC CLASSES | MHC CLASS ONE = ONE LETTER ABBREVIATIONS MHC CLASS TWO = TWO LETTER ABBREVIATIONS |
| ANTIGEN PRESENTATION TO T CELLS: MHC CLASS ONE | INTRACELLULARLY derived peptides (8-10 aa) anchored at ends Expressed on ALL NUCLEATED CELLS except RBC's (phagocytes, etc.) Presents to CD8+ T cells (1*8 = 8) Ligand for KIR |
| ANTIGEN PRESENTATION TO T CELLS: MHC CLASS II | EXTRACELLULARLY derived peptides (>13 aa) bound by peptide side chains protruding into pockets in binding groove Expressed on APC (professionals-macrophages, dendritic, and B cells) Presents to CD4+ T cells (2 * 8 = 8) |
| PATHWAYS OF ANTIGEN PROCESSING | MHC Class I: Protein antigen in cytoplasm (INTRACELLULAR) -EX: VIRUS MHC Class II: Protein antigen in vesicles (ECTRACELLULAR) |
| Hypervariable Regions (HLA = responsible for enormous variety of response) | MHC Class I: alpha 1, 2, and 3 MHC Class II: Beta 1 and 2 -variability on Amino Acid position |
| MHC RESTRICTION | T cells are RESTRICTED to what they can recognize! MHC Class I: CD8+ T cytotoxic cells, intracellular (one letter abbreviations) MHC Class II: CD4+ T helper cells, extracellular (two-letter abbreviations) |
| Thymic Education: POSITIVE SELECTION | Postive selection: will live if LOW AFFINITY (based on signaling/binding) for SELF |
| Thymic Education: NEGATIVE SELECTION | Negative selection: if you bind with HIGH AFFINITY to SELF then you DIE (do NOT want MHC to recognize self peptides) |
| IMPORTANCE OF HLA IN BONE MARROW TRANSPLANT | HLA molecules from a donor are recognized by the recipient's immune system -By direct and indirect methods of allorecognition triggering an alloimmune response *WANT it to be INDIRECT |
| INDIRECT ALLORECOGNITION (in bone marrow transplantation) | the recipient APC takes up the donor peptide and presents it to T cell / MHC -BETTER because it takes more time for rejection to occur |
| DIRECT ALLORECOGNITION (in bone marrow transplantation) | the recipient T cell and MHC DIRECTLY recognize donor peptide -WORSE b/c it immediately rejects |
| HLA MATCHING AND HSC OUTCOME (stem cell transplant) | KEY CONCEPT: The better HLA MATCHED, the better stem cell transplant OUTCOME will be EX: using family members |
| CELIAC DISEASE (pathogenesis) | AUTOIMMUNE LIKE DISORDER of small intestine resulting from immune response to GLIADIN Deamidation of glutamine residues (by tissue transglutaminase or TTG) in gliadin peptides generate epitopes that bind to HLA-DQ2 and DQ8 eliciting T cell responses >95% of patients possess HLA-DQ2 or DQ8 - DQ2 = strongest genetic element (increases risk fro Celiac disease) -30% of Caucasian population carry DQ2, most eat wheat but only 1 in 100 develop celiac disease - other genetic and environmental factors contribute to susceptibility GWAS studies: IL21, IL2, TENR, KIAA1109 + 7 others with known immunologic function **HLA explains 35% of heritability; other genes about 4% |
| IMMUNOPATHOGENESIS OF CELIAC DISEASE | *Process DRIVEN by WHERE the protein came from! -in this case = EXTRACELLULAR b/c GLIADIN came from outside the cell (CD4+ T helper cells / MHC Class II) |
| Drug Hypersensitivity Reactions: ABACAVIR | HLA-B*57:01 anti-HIV drug |
| Abacavir hypersensitivity = Multisystem disease | Fever, constitutional symptoms, N/V/D, rash 4 – 8% of treated patients Possible Mechanisms: The hapten/prohapten model The p-i model The altered repertoire model |
| ABACAVIR HYPERSENSITIVITY (if (+) for HLA-B57:01, need to take another anti-HIV drug instead) | Abacavir demonstrated to bind to floor of B*57:01 groove **Alters self-peptide repertoire LEADS TO POLYCLONAL T CELL RESPONSE Mediated by CD8+ T cells releasing pro-inflammatory cytokines -In vitro – IFN gamma production -Ex vivo TNF in patient cells abrogated by CD8 depletion CD8 T cells PROLIFERATE Bx of patch test/skin from AHR show CD8 T cells HLA-B*57:01 screening has 100% negative predictive value (55% PPV) |
| Drug Hypersensitivity Reactions: ALLOPURINOL | HLA-B*58:01 |
| Drug Hypersensitivity Reactions: CARBAMAZEPINE | HLA-B*15:02 |
| NATURAL KILLER (NK) CELLS (innate) {MHC Class I} | -lymphocytes -recognize infected or stressed cells UNIQUE: b/c they can recognize your own cells if infected or have become cancerous -kill by poking a hole and releasing an enzyme to trigger APOPTOSIS SECRETE INF-GAMMA /TNF to ACTIVATE MACROPHAGES and DENDRITIC CELLS |
| NK (natural killer) CELL ACTIVATION | Innate because it is one of the ways to further fine-tune the recognition of self and non-self -KILLS if the MHC Class I is MISSING or if there are TOO MANY stimulatory ligands |
| ANTIGEN PROCESSING AND PRESENTATION | 1) PATHOGEN, PAMP, TLR (depending on the pathogen) 2) Particular APC depends on where the pathogen comes from: A) MHC Class I: intracellular B) MHC Class II: extracellular 3) T cell response/activation depending on corresponding MHC Class molecule A) MHC Class I = CD8+ T cytotoxic (kill) B) MHC Class II = CD4+ T helper (mediate killing, alert other T cells, etc.) |
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