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Immunology - Leukocytes (Lymphatic System (Lymph Nodes and Lymphocyte…

- - - - T cell Development
        
        Notes:
        
        T cells are made in the bone marrow initially
        
        they migrate to the thymus in 1st trimester gestation of fetus
        
        T cells are double negative for both CD 4 and 8 at the thymus
        
        also TCR = toll cell receptor negative
        
        they develop from the outside in
        --> cortex to medulla
        
        cortex --> positive selection for TCR that works and CD4 8 +
        
        medulla = negative selection
        --> they lose one of their CD4 or CD8
        
        Cases
        
        T cell maturation
        
        Notes:
        
        note that both T cells and B cell are made in the bone marrow
        --> T cells then migrate and mature in the thymus and B cells remain in the bone marrow to mature
        --> reason why T cells are called thymocytes
        
        T cells go from
        --> Pro - T cells (double negative, arrive at the thymus)
        --> immature T cells (double positive = CD4 and CD8)
        --> they then go from cortex (positive selection) to the medulla (negative selection)
        --> mature T cells with either CD4 or CD8
        
        Clinical Case
        
        T cell maturation case 2
        
        Notes:
        
        note
        
        Clinical Case
    - - Lymph Node Follicles
        
        either Primary lymph follicles
        --> dormant B cells
        
        Secondary follicles
        --> formation of germ centres
        --> active proliferation of activated plasma B cells
        
        Primary Lymph Follicles = Dormant
        
        Plasma B Cells waiting to be activated
        
        Clinical Cases
        
        Clinical Case
        
        Notes:
        
        note that
        
        Clinical Case
        
        Secondary Lymph Follicles with Germ centres
        
        Activated Plasma B Cells in Lymph Nodes
        
        form germ cells within follicles
        
        Notes:
        
        note that there are two parts of releasing activated plasma B cells into the plasma for giving off antibodies in primary response
        
        these two parts have switched % of plasma cells,
        
        first part has little bit, most migrate to lymph nodes to form germ centres
        --> most initial response are IgM
        
        second part in the germ centres, only few become dormant long term memroy cells for that antigen, majority will class switch in the germinal centre and release as different isotypes for that antigen as plasma cells
        --> most second response are IgG
        
        Part 1 = initial activation of naive B cells in the lymph organs or peripheral tissues
        
        few become activated initial response IgM plasma cells that go out right away
        
        majority migrate to the lymph nodes to form germinal centres
        
        Part 2 = Germinal centre dormant memory cells and isotype class switch + release second wave of troops
        
        few become memory cells and lay dormant in the germ centres
        
        most go through CD40 class switching from T cells to GAMED isotypes
        
        most become IgG = second wave of antibodies
      - Primary Development
        In Bone Marrow
- - - - 3 groups to MYeloid progeninator cell lines...
        "ME, MY uncle BEN, and the OMEGA"
        ME = Mast cells and Erythrocytes are one group
        MY uncle BEN = myeloblasts make the biggest group
        --> Basophils, Eosinophils, Neutrophils and Monocytes
        OMEGA = megakaryocytes are their own group
        --> they form platets
      - Myeloblasts
        
        ME and MY uncle BEN and the OMEGA
        
        *Macrophages
        
        Specialized
        Macrophages
        
        Langerhan's Cells
        
        specialized macrophages of the dermal layers of skin
        
        Example:
        
        Notes:
        
        Langerhans cells are specialized macrophages in the dermal layers of the skin
        --> Langerhans cells are "longer hands"
        
        Kupffer cells are specialized macrophages in the venous system of the liver
        --> Kupffer cells cuff "alcoholics" = found in the liver
        
        *Granulocytes
        
        My Uncle BEN...
        
        basophils, Eosinophils, neutrophils
        
        *Eosinophils
        
        it's EAZY eatin parasites when you're PAACN alot of MBP
        
        helminths = parasites
        
        it's EAZY eatin parasites when you're PAACN alot of MBP = major basic protein
        
        P = parasites
        
        A = asthma
        
        A = allergic
        --> Ellergic IgE and IL-4
        
        C = chronic adrenal insufficiency
        
        N = neoplasms
        
        *DRESS Syndrome
        
        DRESS = Drug Reaction Eosinophilia / SYSTEMIC symptoms
        
        from a drug 2-8 weeks after starting it
        
        very common with certain AEDs
        --> similar to Steve Johson syndorme?
        
        1 more item...
        
        *Neutrophils
        
        granulocyte
        
        part of
        --> My Uncle BEN...
        --> basophils, Eosinophils, neutrophils
        
        NADPH oxidase killing by Neutrophils
        
        NADPH is the main enzyme that starts off the reaction
        --> NADPH makes superoxide, then superoxide, then bleach finally = OHCl
        
        2 more items...
        
        Different types of Neutrophils
        
        left shift = band cells
        
        1 more item...
      - *Mast Cells
        
        ME and MY uncle BEN and the OMEGA
        
        IgE - Independent Mast Cell Degranulation
        
        Notes:
        
        IgE independent Mast cell degranulation happens from very specific drugs
        --> most common are oppioids
        
        works NOT through activating IgE antibodies, but through cAMP path of PKA and through Gq PI3 kinase path (=Tyrosin kinase reccptors)
        
        extreme itching of the arms, legs and back
        --> does this get worse on more exposure like in allergic reactions?
        
        Clinical Cases
        
        Clinical Case
        
        3 more items...
        
        Mastocytosis
        
        Mast cells mainly release Histamine
        
        thus mastocytosis presents with anything with H1 and H2 receptors
        
        H2 in the stomach --> high gastric acid and ulcers
      - *Megakaryocytes
        
        ME and MY uncle BEN and the OMEGA
      - *RBCs = Erythrocytes
        
        ME and MY uncle BEN and the OMEGA
        
        Different types of RBC inclusion bodies
        
        splenectomy = Howell- Jolly bodies
        
        *Basophillic Stipplin
        
        stippling = means ribosomes collecting up
        
        this means there are abnormal proteins or something wrong with protein synthesis
        
        in RBCs this means usually problem with HEME synthesis
        --> Thal, sideroblastic, lead poisioning, etc.
    - - Small lymphocytes
        
        *Lymphocytes
        
        *Activation of B cells and T cells
        
        T cell Co stimulation / regulation
        --> Th cell rule of 7 x 4 = 28
        --> B7 on APC binds
        --> CD28 on Th cell = co STIMULATE
        --> CTLA-4 on Th cell = co REGULATE
        --> separate PD-1 on Th cell = co REGULATE
        
        B cell class switching = CD40 Ligand and CD40
        --> "CD40 is 4 Different classes"
        
        *B cells
        VDJ Rearrangement
        
        how B cells make many different kinds of antibodies
        
        3 more items...
        
        *Activation of T cells
        
        T cell Co stimulation / regulation
        --> Th cell rule of 7 x 4 = 28
        --> B7 on APC binds
        --> CD28 on Th cell = co STIMULATE
        --> CTLA-4 on Th cell = co REGULATE
        --> separate PD-1 on Th cell = co REGULATE
        
        1 more item...
        
        *NK = Natural Killer Cells
        
        lymphoid cells, BUT for the innate immunity
        --> cytoctoxic = kill virally infected cells and tumor cells
        
        NO COUNTRY FOR OLD MEN - NATURAL KILLER
        --> air compressor = perforins poke holes
        --> granzymes go through the perforins holes and cause apoptosis
        
        Granulocyte that kills cells that have no MHC1 antigen on their surface
        --> NK only kills them if they get the coin flip wrong
        
        express special CD 16 and CD56
        --> think of NK travelling in texas on Route 16 + Route 56
        
        *T cells
        
        3 types of T cells
        --> CD4/MHC2 = Th helper cells
        --> CD8/MHC1 = Tc cytotoxic Tcells
        --> CD3(general) = regulatory T cells
        --> CD25 + FOX = specific regulatory markers
        
        CD 8+ T cells = Killer Cytotoxic T cells
        
        T cell Development
        
        see lymph nodes
        
        CD 4+ T cells = Helper T cells
        
        sub classes TH1 and TH2
        
        1 more item...
        
        Infectious Mononucleosis (Mono) and Reactive Lymphocytes
        
        secondary to EBV usually
        
        reactive macrophages release perforin and granzymes
        
        granzymes = granular enzymes = grandiose apoptosis
        
        Clinical Case
        
        Notes:
        
        note that Infectious mononucleosis from EBV are reactive cytotoxic lymphocyte = mostly natural killer cells and t cells
        
        they have cytotoxic granuoles = perforin and granzymes