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Hematopoietic stem cell (HSC), Exhausted T cell, Function: IELs have a…

- - - - Effector T cells/αβ T cells TCR + POSITVE become the subsets
        
        Th1
        
        Strong TCR
        
        Signal inducers: IFN-y, IL-12
        
        Effector molecules/Cytokines: IFN-y, TNF-a, GM-CSF, IL-2
        
        TF: T-bet
        
        Phenotype/Surface markers: CD183 (CXCR3), CD4 +, CCR6 −
        
        Characteristics: Increases MHC-1, Supports macrophages, Against IC pathogens
        
        Th2
        
        Weak TCR
        
        Phenotype/Surface marker:CD194 (CCR4)
        
        Signal inducers: IL-4, IL-2
        
        TF: GATA3
        
        Effector molecules/Cytokines: IL-4, IL5, IL-10, IL-13, TGF-B
        
        Characteristics: Activates eosinophils, against EC parasites, supports mast cells, eosinophils, basophils, B cells
        
        Th9
        
        Phenotype/Surface marker: CCR3, CCR6, CXCR3
        
        Signal inducers: IL-4, IL-2, TGF-B
        
        Effector molecules/Cytokines: IL-9 (growth & activation mast cells)
        
        Characteristics: Mucosal immunity, against EC parasites, cancer regulation
        
        TF: PU-1
        
        Th17
        
        Phenotype/Surface marker: CCR6
        
        CD4+, CXCR3 −, CCR4 +
        
        Signal inducers: IL-6, IL-21 (induces production IFN-y & perforin NK cells), IL-23 (enhance Th17 expansion), TGF-B
        
        TF: RORyt
        
        Effector molecules/Cytokines: IL-17 (neutrophil recruitment & prod. of IL-1, TNF-a), IL-21, IL-22, IL-26
        
        Characteristics: Pro-inflammatory, activates the epithelium, activates neutrophils, against EC pathogens.
        
        Treg
        
        Phenotype/Surface marker:CD25, IL2Ra
        
        TF: FOXp3
        
        Signal inducers: IL-2 (support Tregs), TGF-b
        
        Effector molecules/Cytokines: IL-35 (inhibitory, limits inflammatory responses, IL-10, TGF-b
        
        Characteristics: Supports other immune cells, promotes cancer, prevent autoimmunity, regulates T cell priming and T cell function. Tregs are very important for peripheral tolerance.
        
        Location: a lot are in the gut
        
        Tfh
        
        tonsils, spleen, lymph nodes Tfh cells reside in B cell follicles within secondary lymphoid organs such as the lymph nodes, spleen, and Peyer’s patches.
        
        Phenotype/Surface marker: CXCR5, CD40L
        
        TF: BCL-6
        
        Signal inducers: IL-16,(?) IL-23, TGF-b
        
        Effector molecules/Cytokines: IL-4, IL-21, IFN-y
        
        Characteristics: Support B cells in increasing antibody affinity, B cell activation, isotype switching
        
        CD4+
        
        Central Memory T cells : CD45RA(-) , CCR7 (+): same like naive T cells, !! CD127 (-)
      - γδ T cells 5%(subgroup IEL)
        
        Intraepithelial lymphocytes (IEL) mucosa epithelial level; primarily the gut
        
        Characteristics: no priming needed, generated from naive T cells, elevated IEL is associated with mucosal inflammation
        
        IELs HAVE a TCRs!! Their TCRs allow them to recognize stress signals or non-peptide antigens directly, without the need for antigen presentation by MHC molecules.
        
        Characteristics: They recognize a broad range of antigens including non-peptide antigens, critical for surveillance, fast response, reside in epithelial tissue or other lymphoid tissue i.e., the spleen Promote tissue repair and cell healing.
        
        The majority of γδ T cells are activated in an MHC-independent manner
        
        γδ T cells are unique in their ability to influence both innate and adaptive arms
        
        various tissues, peripheral tissues. The gut, skin, and lungs mainly. They are not limited to epithelial tissue like IELs are
        
        Produce: IFN-y (activate macrophages and enhance APC), IL-17 (Neutrophil recruitment, and stimulate TNF-a and IL-1 production), TNF-a (resistance to infection and cancers) also they can produce IL-10, IL-21
        
        Stimulated by: certain stress or heat shock proteins. - Butyrophilins (BTNs) help γδ T cells recognize these proteins
      - Marker: CD3
      - naive T cells: CD45RA(+), also CD27 (+), CCR7 (+)
      - all T cells, except for the memory T cells will be CD45RA (+) positive
    - - TF: T-bet
      - Responds to : intracellular viruses, tumors, bacteria, parasites TNF-alpha
      - Activated by: lack of MHC-1, activitory signals
      - ADCC!!!
        
        The immune system use antibodies to help destroy harmful cells. When antibodies stick to a harmful cell, they flag it as a target. NK cells, recognize these cells and kill it.
      - Effector molecules/Cytokines: IFN-y, granzymes, perforin
      - When NK cells recognize normal MHC-1 levels, this is an inhibitory signal, preventing the destruction of healthy cells.
      - Marker: CD56, but negative for CD127!, and CD16(+)
      - IL-12 stimulates NK cells to produce IFN-y
      - IL-15 is crucial for a cell to become an NK cell!
  - - - TF: (determines their products), T-bet (same as Th1)
      - Responds to : intracellular viruses, tumors, bacteria, parasites
      - Effector molecules/Cytokines: IFN-y (--> Cell stress)
      - Characteristics:Provide an immediate response that stops/limits the spread of infection until
        NKs arrive from the blood, and activate macrophages like Th1
      - Inducing signals: (same cytokines as they produce, but amplified!
      - Marker: CD127, CD49a, TRAIL, NKp44
    - - Effector molecules/Cytokines: IL-4, IL-5, IL-13
      - mucosal surfaces, farther away from B cells
      - Characteristics: Activate neutrophils and there is a role in tissue repair like in Th2 cells
      - Responds to: large EC parasites
      - TF: BCL11B and ROR-alpha (different than Th2: GATA3), GATA3, GFI
      - Marker: CD161 (high!)
    - - TF: ROR-y-t (same as Th17)
      - Responds to: EC bacteria and fungi
      - Effector molecules/Cytokines: IL-22, IL-17
      - abundant mucosal tissue
      - Characteristics: Helps in Th17 activation (Type 3 immunity) & they stimulate barrier function; anti microbial peptides, mucus.
      - Antigen presenting cell!!!
        
        APCs need co-stimulatory signals. If the co-stim signal is missing --> anergy (the body fails to respond to an antigen). ILC3 are more like 'peacekeepers' to keep the immune system balanced
        
        ILC3s produce GM-CSF and IL-22, enhancing DC activation and migration to lymph nodes where they present antigens to T cells.
      - Marker: NKp44 (Natural killer cell protein 44 + help NK cells detect stressed, infected, transformed cells)
    - - mucosal surfaces gut, lung. Primarily in secondary lymphoid organs.
      - They can contribute to autoimmune diseases by promoting formation of Tertiary Lymphoid Structures (TLS), that drive antigen-specific immune responses at chronic inflammation sites - Crypto patches.
      - Marker: CD127, CD117, TOX
      - Induced by: TOX (Specific!!!)
- - - - Erythrocyte
    - - Platelets
  - - - Respiratory burst, ROS, TNF-a
      - Marker: CD15, CD16 (+)
    - - Monocyte
        
        --> ?
        
        Macrophage
        
        Characteristics: Have Fc receptors! They can participate in ADCC, promotes Th1 development
        
        Stimulated by: bacterial products, IL-3, IL-4, IL10, IL-13, IFN-y, TNF-b (lymphoid tissue development, inflammatory responses,cytotoxicity)
        
        Effector molecules/Cytokines: TNF-a, IL-1B, IL-6 (promotes B cell differentiation), IL-12, IL-23 (enhance expansion of Th17), GM-CSF (also secreted by macrophages, promotes DC differentiation and promotes myeloid cell development)
        
        TF: STAT6
        
        Marker: CD16 (+)! but also CD14, CD68, CD163
        
        Marker: CD14, CD16 (+)!
      - Dendritic cell
        
        cDC1
        
        Marker: CD141 (BDCA3), CD33, CD13, low CD11c, low CD11b
        
        Responds to: IC pathogens (virus, tumor), TLR 3/9/10
        
        Effector cells/Cytokines: TNF-a, CXCL9/10, IL-12 (bridges innate & adaptive system, defense IC pathogens, for naive T cell -> Th1, stimulates NK to produce IFN-y, enhances CD8+ function),
        
        TNF-a, CXCL9/10, Il-12
        
        Characteristics: Cross presentation via MHC-I, activates CD8+ cells, initiating cytotoxic responses, activates NK cells, Th1 cells
        
        Location: primarily in lymph nodes, spleen, skin
        
        cDC2
        
        Marker: CD11b, CD11c, CD1
        
        Responds to: IC pathogen, EC bacteria and fungi, parasites/allergens, TLR 4, 5 2 &6
        
        Effector cells/Cytokines: TNF-a (responsible for several signaling events within the cell leading to necrosis/apoptosis), IL-10, IL-12, IL-23
        
        Location: Primarily in the lymph nodes, spleen, skin and mucosal tissues (gut, lungs)
        
        cDC2 specialize in presenting antigens to CD4+ T cells and Regulating Helper T cell Responses!!!
        
        cDC2 also play a role in maintaining tolerance to self-antigens and regulating immune homeostasis in tissues, preventing inappropriate immune responses.
        
        pDC (plasmacytoid)
        
        Marker: CD123, low CD11c, CD303 (BDCA2), CD304 (BDCA4)
        
        Responds to: viruses, tumors, TLR 7, TLR 9
        
        Effector cells/Cytokines: TNF-a, IFN-a, IL-6 , GrzB
        
        ! Present in blood & specifically anti-viral
        
        ! All negative for CD3, and positive for IRF4/8 (are TFs that are important for DC development