Immunology Week 5 Review

Immunology Week 5 Review  OBJECTIVES 9.16 ◼ State where you would expect to find receptors of the adaptive immune system within the context of the cell and correlate the ligands and receptors of the two types of immune cells with their signaling outcomes (more on this later too, but tod...

Immunology Week 5 Review  OBJECTIVES 9.16 ◼ State where you would expect to find receptors of the adaptive immune system within the context of the cell and correlate the ligands and receptors of the two types of immune cells with their signaling outcomes (more on this later too, but today it’s KIR & KAR) ◼ Compare and contrast NK & NKT cells ◼ Describe how NK cells can work with macrophages & dendritic cells to bring about an immune response ◼ Outline the movement of lymphocytes throughout the body and key anatomical features ◼ Describe how adaptive immune system differs from innate & unique features of the adaptive immune system ◼ Recognize & describe the microenvironments where adaptive immune cells mature & the adaptive immune response develops ◼ Identify the primary & secondary immune organs in vertebrates & describe their function in relation to the adaptive immune system  REVIEW OF LAST CLASS ◼ State where you would expect to find receptors of the adaptive immune system within the context of the cell and correlate the ligands and receptors of the two types of immune cells with their signaling outcomes (more on this later too, but today it’s KIR & KAR) ◼ KAR & KIR are the receptors found on NK cells 1. KAR binds to MICA & MICB 2. KIR binds MHC class I ◼ NKT cells do not have KAR & KIR, but they have a TCR of limited repertoire  REVIEW OF LAST CLASS ◼ Compare and contrast NK & NKT cells ◼ Both come from CLP ◼ NK come from Common ILC Precursor, NKT probably come from T Cell precursor since they have a TCR ◼ NK cells have KAR & KIR as receptors, NKT have TCRs ◼ NK cells kill virally infected cells, cancerous cells, cells covered in antibody, and cells without normal levels of MHC without prior sensitization, NKT respond to lipids, glycolipids, or hydrophobic peptides presented by nonclassical MHC (aka they need prior sensitization)  REVIEW OF LAST CLASS ◼ Describe how NK cells can work with macrophages & dendritic cells to bring about an immune response  REVIEW OF LAST CLASS ◼ Outline the movement of lymphocytes throughout the body and key anatomical features  REVIEW OF LAST CLASS ◼ Describe how adaptive immune system differs from innate & unique features of the adaptive immune system  REVIEW OF LAST CLASS ◼ Recognize & describe microenvironments where adaptive immune cells mature & adaptive response develops ◼ DITKI is useful!!!!! ◼ Identify primary & secondary immune organs & describe their function in relation to the adaptive immune system ◼ Primary- where immune cells develop, Secondary- where immune response is initiated  OBJECTIVES 9.18 ◼ Compare & contrast how adaptive immune system differs from innate immune system ◼ List unique features of the adaptive immune system (specifically immune cells) ◼ Describe the function & role of each common lymphoid progenitor descended cell (& various subtypes) & be able to identify them based on generalized picture, description of function, or histology (if applicable) ◼ List known inducing cytokine and key effector cytokines ◼ State where you would expect to find receptors of the adaptive immune system within the context of the cell and correlate the ligands and receptors of the two main lymphocytes with their signaling outcomes; e.g. TCR, BCR (we’ll also talk more about this later!) ◼ Compare and contrast the subtypes of T cells (αβ T cells, CD4+ (& 5 subtypes), CD8+ (Tc & Ts), γδ T cells) REVIEW OF LAST CLASS ◼ Compare & contrast how adaptive immune system differs from innate immune system ◼ On-going theme, good to review slide 7 above, and which cell types fall under innate vs. adaptive (& which ones bridge, & HOW)  REVIEW OF LAST CLASS ◼ List unique features of the adaptive immune system (specifically immune cells) ◼ Innate has myeloid cells (e.g. monocytes, neutrophils, eosinophils, basophils, etc.) ◼ Adaptive has lymphoid cells (e.g., B & T cells) ◼ NK cells are more adaptive and from the lymphoid line, but can bridge innate and adaptive as they are the first line defense against viral infections ◼ ILCs & LTis are descended from lymphoid lineage, but function in an innate capacity ◼ Dendritic cells are considered the bridge between innate and adaptive as they are the cells that present antigen to T cells in secondary lymphoid tissues (LNs)  REVIEW OF LAST CLASS ◼ Describe the function & role of each common lymphoid progenitor descended cell (& various subtypes) & be able to identify them based on generalized picture, description of function, or histology (if applicable) These are all the adaptive cells we’ve learned. Fill in their definitions, unique markers for discriminating them from the generic small lymphocyte picture, etc. ◼ B cell ◼ B1 ◼ B2 ◼ T cell ◼ αβ T cells ◼ CD4+ ◼ TH1 ◼ TH2 ◼ TH17 ◼ TFH ◼ TRED ◼ CD8+ ◼ Tc ◼ TS ◼ γδ T cells ◼ NK ◼ NKT ◼ ILCs ◼ ILC1 ◼ ILC2 ◼ ILC3 ◼ LTi  REVIEW OF LAST CLASS ◼ List known inducing cytokine and key effector cytokines ◼ IL-7 drives lymphocytes ◼ IL-12 → ILC1 → IFNγ ◼ IL-25, IL-33 → ILC2 → IL-4, IL-5, IL-13 ◼ IL-1β, IL-23 → ILC3 → IL-17, IL-22 ◼ Type 1 Immunity → IFNγ ◼ Type 2 Immunity → IL-4, IL-5, IL-13 ◼ Type 3 Immunity → IL-17, IL-22 ◼ NKT secrete large amounts of cytokines, especially IL-4 ◼ Before acquiring capacity to kill aberrant cells, cytotoxic T cells must usually receive help (cytokine IL-2)  REVIEW OF LAST CLASS ◼ State where you would expect to find receptors of the adaptive immune system within the context of the cell and correlate the ligands and receptors of the two types of immune cells with their signaling outcomes; e.g. TCR, BCR (we’ll also talk more about this later!) ◼ T cells have T cell receptors (TCRs, a type of immunoglobulin) ◼ B cells have B cell receptors (BCRs, a type of immunoglobulin) ◼ NK cells have KAR & KIR ◼ NKT cells do NOT have KAR & KIR, they have a rearranged TCR of extremely limited repertoire  REVIEW OF LAST CLASS ◼ Compare and contrast the subtypes of T cells (αβ T cells, CD4+ (& 5 subtypes), CD8+ (Tc & Ts), γδ T cells) ◼ αβ T cells- majority of T cells, which express an antigen receptor (TCR) composed of an α chain & a β chain Dependent on antigen presentation by MHC I & MHC II. ◼ CD4+ T cells (helper)- required for most humoral or cell-mediated immune responses ◼ T helper Type 1 (TH1)- activate macrophages, fight intracellular pathogens ◼ T helper Type 2 (TH2)- fight extracellular infections, activate B cells, involved in allergy ◼ T helper Type 17 (TH17)- protects against infection & maintains mucosal barrier, recruit neutrophils, autoimmune? ◼ T follicular helper (TFH)- provide help to B cells for forming germinal centers & maturation ◼ Regulatory T cell (TREG)- required to maintain peripheral self-tolerance ◼ CD8+ T cells (cytotoxic) ◼ Tc cells- identify body cells that are infected with intracellular organisms & eliminate the cells harboring these organisms ◼ Ts cells- downregulate & thus control adaptive immune responses ◼ γδ T cells- minority of circulating T cells that expresses an antigen receptor (TCR) composed of an γ chain & a δ chain. Recognize different types of antigen that αβ T cells & are NOT dependent on antigen presentation by MHC I & MHC II ◼ Most do not have CD4+ or CD8+, in small exceptions do you have CD4+ or CD8+ γδ T cells  OBJECTIVES 9.20 ◼ Identify & explain antigen processing & presentation (basics- why is it important?) ◼ Differentiate professional APCs from atypical/amateur APCs, esp. how they present, and what types of antigens. What cell types are they found on? ◼ Identify & explain the locations & functions of MHC molecules ◼ Compare & Contrast MHC I & MHC II molecules including structure, formation, function, type of peptide, cells they present to, etc. ◼ Describe the importance of MHC restriction ◼ Describe the “Sweaty T-Shirt” Study (Your “Also A Scientist”)  REVIEW OF LAST CLASS ◼ Identify & explain antigen processing & presentation (basics- why is it important?) ◼ T cell activation must be tightly regulated- difficult to slow down cell-mediated immune response once started ◼ Therefore, it is NECESSARY for other cells to process & then present foreign antigens to T cells with additional signals required for recognition & full activation of the cell- mediated response  REVIEW OF LAST CLASS ◼ Differentiate professional APCs from atypical/amateur APCs, esp. how they present, and what types of antigens. What cell types are they found on? High avidity Low avidity  REVIEW OF LAST CLASS ◼ Identify & explain the locations & functions of MHC molecules ◼ MHC-I ◼ Co-dominantly expressed 45-kDa MHC class I molecules with β2 microglobulin (β2m) found on surface of ALL NUCLEATED cells ◼ MHC Class I three genetic loci, HLA-A, -B, & -C, are highly polymorphic with more than 100 alleles at each locus ◼ MHC class I molecules (HLA-A, HLA-B, or HLA-C) together with β2 microglobulin (β2m) form a closed peptide cleft between α1 & α2 domains that can noncovalently bind an 8-9 amino-acid peptide ◼ MHC-II ◼ Normally only expressed on surfaces of APCs, some activated T cells, & some specialized epithelial cells in thymus & intestine ◼ Co-dominantly expressed as noncovalent heterodimers, a 32-38 kDa α chain & a 29-32 kDa β chain form a binding groove (α1 & β1 domains) that can accommodate 18-20 amino acid peptide  REVIEW OF LAST CLASS ◼ Compare & Contrast MHC I & MHC II molecules including structure, formation, function, type of peptide, cells they present to, etc. ◼ MHC-I ◼ Co-dominantly expressed 45-kDa MHC class I molecules with β 2 microglobulin (β2m) found on surface of ALL NUCLEATED cells ◼ MHC Class I three genetic loci, HLA-A, -B, & -C, are highly polymorphic with more than 100 alleles at each locus ◼ MHC class I molecules (HLA-A, HLA-B, or HLA-C) together with β2 microglobulin (β2m) form a closed peptide cleft between α 1 & α2 domains that can noncovalently bind an 8-9 amino-acid peptide ◼ CD8+ T cells ◼ MHC-II ◼ Normally only expressed on surfaces of APCs, some activated T cells, & some specialized epithelial cells in thymus & intestine ◼ Co-dominantly expressed as noncovalent heterodimers, a 32-38 kDa α chain & a 29-32 kDa β chain form a binding groove (α 1 & β1 domains) that can accommodate 18-20 amino acid peptide ◼ CD4+ T cells  REVIEW OF LAST CLASS ◼ Describe the importance of MHC restriction ◼ T cell activation must be tightly regulated- difficult to slow down cell-mediated immune response once started ◼ Therefore, it is NECESSARY for other cells to process & then present foreign antigens to T cells with additional signals required for recognition & full activation of the cell- mediated response ◼ Left panel: ◼ CD8 co-receptor binds to α3 domain of MHC class I heavy chain, ensuring MHC class I molecules present peptides only to CD8+ T cells ◼ Right panel: ◼ CD4 co-receptor binds to β2 domain of MHC class II molecules, ensuring peptides bound by MHC class II REVIEW OF LAST CLASS ◼ Describe the “Sweaty T-Shirt” Study (Your “Also A Scientist”) ◼ Men wore Tshirts for 2 days and then heterosexual women blindly smelled them and then rated the scent ◼ Tshirts from males with MHC most different from the women were reported to smell the best ◼ Provides evidence that mate choice in humans MIGHT be MHC- Dependent? (Lots of variables)