Exam questions 11, 16, 17 Flashcards
Macrophage functions:
Phagocytosis, antigen presentation, cytokine production.
TLR structure:
Extracellular LRRs for ligand binding, transmembrane domain, cytoplasmic TIR domain for signaling.
TLR MyD88 signaling:
TLR binds PAMPs, recruits MyD88, activates IRAKs, TRAF6, TAK1, IKK, releases NF-κB to initiate cytokine transcription.
IL-1b secretion regulation:
Pro-IL-1b cleaved by caspase-1 into mature IL-1b by inflammasome activation.
Complement activation pathways:
Classical (C1q binding to antibodies), Lectin (MBL binding to carbohydrates), Alternative (spontaneous C3 hydrolysis).
Complement functions:
MAC formation, opsonization, inflammation via anaphylatoxins.
MAC assembly:
C5b binds C6, C7, C8, C9 to form a pore in pathogen membrane.
Complement deficiency disease:
Hereditary angioedema, C1 inhibitor deficiency, causing excessive bradykinin release.
Antigens:
Molecules recognized by the immune system, triggering an immune response.
Antigen presentation:
Displaying antigen-MHC complexes on cell surfaces for T-cell recognition.
MHCI pathway:
Intracellular antigens degraded by proteasome, loaded onto MHCI, recognized by CD8+ T cells.
MHCII pathway:
Extracellular antigens endocytosed, processed, and loaded onto MHCII, recognized by CD4+ T cells.
Naïve CD8+ T-cell priming:
Dendritic cells present antigen via MHCI, CD4+ T cells “license” dendritic cells.
Primary foci vs germinal centers:
Primary foci produce low-affinity antibodies quickly, germinal centers undergo somatic hypermutation and class switching for high-affinity antibodies.
Germinal center processes:
Somatic hypermutation (SHM) improves antigen binding, class-switch recombination (CSR) changes antibody isotype.
Antibody effector functions:
Fc region mediates neutralization, complement activation, opsonization, ADCC.
ADCC vs T-cell-mediated cytotoxicity:
ADCC: NK cells, antibodies bind to infected cells. T-cell: CD8+ T cells recognize antigens via MHCI.
Monoclonal vs polyclonal antibodies:
Monoclonal: One epitope, high specificity. Polyclonal: Multiple epitopes, broader detection.
Linear vs conformational determinants:
Linear: Recognized by amino acid sequence. Conformational: Recognized by 3D protein structure.
Leukocyte types and functions:
Neutrophils: Phagocytosis, first responders. Basophils: Release histamine, allergies. Eosinophils: Combat parasites. Monocytes: Differentiate into macrophages or dendritic cells.
Physical and chemical barriers:
Skin, mucous membranes prevent pathogen entry
Monoclonal and polyclonal antibody definitions:
Monoclonal: One epitope, high specificity. Polyclonal: Multiple epitopes, broader detection.
Pros/Cons of monoclonal antibodies:
Pros: Specific, reproducible. Cons: Expensive, may miss heterogeneity.
Enzyme-Linked ImmunoSorbent Assay (ELISA):
Detects antigens/antibodies using enzyme-linked antibodies for color change. Clinical use: HIV antibody detection, pregnancy tests.
MHC molecule display:
MHCI: Intracellular peptides, recognized by CD8+ T-cells. MHCII: Extracellular peptides, recognized by CD4+ T-cells. CD1: Lipid-based antigens, recognized by specific T-cells.
MHCI/MHCII antigen presentation:
MHCI: Intracellular antigen processing via proteasome, ER transport. MHCII: Extracellular antigen processing in endosomes.
Cross-priming:
Dendritic cells present extracellular antigens on MHCI, activating CD8+ T-cells.
Naïve T-cell activation:
Signal 1: TCR binding, Signal 2: Co-stimulation (CD28/B7), Signal 3: Cytokines for differentiation.
T-cell subsets and cytokines:
Th1: IFN-γ, macrophage activation. Th2: IL-4, IL-13, B-cell activation. Th17: IL-17, inflammation. Treg: IL-10, TGF-β, immune suppression. CD8+ T-cells: Kill infected cells via perforin/granzymes.
Cancer hallmarks:
Sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling immortality, inducing angiogenesis, activating invasion/metastasis, avoiding immune destruction.
Proto-oncogenes vs tumor suppressor genes:
Proto-oncogenes promote growth
Tumor-specific vs tumor-associated antigens:
Tumor-specific: Unique to tumor cells. Tumor-associated: Overexpressed in tumors but also present in normal cells.
B-cell activation by thymus-dependent antigens:
Antigen binding activates B-cells, interaction with CD4+ T-cells for proliferation, SHM, and CSR, forming plasma and memory cells.
Apoptosis:
Programmed cell death, intrinsic pathway activates caspases, apoptotic debris cleared by phagocytes.
Phagocytosis process:
Binding, uptake into phagosomes, fusion with lysosomes, degradation and presentation.
Importance of phagocytosis:
Removes pathogens, processes antigens for T-cell presentation.
Phagocytosing cells:
Macrophages, neutrophils, dendritic cells, monocytes.
Direct vs indirect phagocytosis activation:
Direct: PRRs bind microbes. Indirect: Opsonins mark microbes for phagocytosis.
Antigen presentation and adaptive immunity:
Antigen presentation activates T-cells, initiating immune responses.
MHCII expression and recognition:
MHCII on dendritic cells, macrophages, B-cells
Cytosolic antigen processing:
Degraded by proteasomes, loaded onto MHCI, presented to CD8+ T-cells.
CD8+ T-cell priming:
Cross-presentation by dendritic cells using MHCI.
CD4+ T-cell activation signals:
TCR recognition, co-stimulation, cytokines for differentiation.
Cytotoxic T cells and NK cells killing mechanism:
Perforin-granzyme pathway, Fas-FasL interaction (CTL only), NK cells also mediate ADCC.
Cytotoxic T cells vs NK cells target identification:
CTLs recognize MHCI-presented antigens, NK cells detect absence of MHCI or antibody-coated targets.
CD4+ T helper subsets:
Th1, Th2, Th17, Tfh, Treg.
Th1 and Th2 cytokine roles:
Th1: IFN-γ for macrophage activation. Th2: IL-4, IL-5 for B-cell activation.
Mature naïve B-2 cell characteristics:
Surface IgD, IgM, recirculates between blood and lymphoid organs, expresses CD19, CD21, CD40.
Antibody structure:
Y-shaped glycoproteins with heavy and light chains, variable region for antigen binding, constant region for effector function.
T-dependent B-2 cell response:
Antigen binding, presentation to CD4+ T-cells, proliferation, SHM, CSR, differentiation into plasma and memory cells.
IgM and IgG complement activation:
Both recruit C1q, IgM is more effective due to pentamer structure.
B-1 vs T-dependent B-2 cell antibodies:
B-1: IgM, low affinity. B-2: High-affinity, isotype-switched, SHM, and CSR.
BCR structure:
Immunoglobulin with hydrophilic spacer, hydrophobic transmembrane region, cytoplasmic tail.
Igα/Igβ signaling from BCR:
Phosphorylation of ITAM motifs, recruitment of adaptor proteins.
Phospholipid modification leading to Ca²⁺ increase:
PLCγ cleaves PIP2, producing DAG and IP3, which increase cytosolic Ca²⁺.
Increased Ca²⁺ and NFAT activation:
Ca²⁺ binds calmodulin, activating calcineurin, dephosphorylates NFAT for nuclear translocation.
