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Immunology (Clusters of Differentiation = *CD antigens (CD 18+ = adhesion…

- - - - Notes:
        
        note that LAD is due to absent CD18+ on leukocyte cell surfaces
        
        people with LAD present as young kids who get many recurrent infections, especially skin infections and wounds take longer to heal
        
        one example is late separation of the umbilical cord > 21 days after birth
        
        this all happens, especially in the peripheral skin infections, since the leukocytes can't properly migrate away from the blood and into the tissues
        
        this causes non-purulent infections = means they do not produce pus --> since there are no neutrophils present
        --> which produce puss when they die
      - Clinical Case
  - - - Clinical Case
      - Notes:
        -
- - - - Immunoglobulin Structure
        
        light chain and are constant
        
        heavy chain is variable = G A M E D
        
        variable ends on both the light and heavy chains
        --> where the Fab is located, Fab = fragment antigen binding site
        --> note the variable end can be present on any of the 5 types
        
        Compliment and Phagocytic Attachment Sites
        
        FAGS don't Fc their compliment
        
        Compliment binding site on Immunoglobulins
        
        Notes:
        
        the Ci compliment binds to the Fc portion of the antibody on ONLY IgM and IgG
        --> recall these are the only 2 antibodies that can activate the compliment system
        
        example:
        
        Gamma Immunoglubulins
        
        note that globulins in general as a protein class can be grouped by their molecular weight by gel electro
        
        GAM of immunoglobulins are gamma globulins
        
        Heavy Chain
        
        defines the 5 subtypes of antibodies
        
        coded for by different exons and mRNA splicing
      - 5 Immunoglobulins
        
        IgG
        
        IgG is the major opsonin
        --> helps phagocytes eat bacteria
        
        Notes:
        
        both IgM and IgG are first responders to any pathogen and good activators of the complement system
        --> IgM since it is the first antibody present on B cells before class switching
        --> IgG since it is the most abundant antibody in the serum
        
        IgM valence = 2
        
        IgG only antibody that can cross the placenta barrier
        --> IgG gives neonates immunity for first 6 months of life
        
        IgM
        
        IgM "makes" all other antibodies
        
        Notes:
        
        both IgM and IgG are first responders to any pathogen
        --> IgM since it is the first antibody present on B cells before class switching
        --> IgG since it is the most abundant antibody in the serum
        
        IgM as B Cell receptor
        --> valence = 2
        
        IgM as in serum = pentamer
        --> valence = 10
        
        IgD
        
        IgD tells B cells they are "DONE" maturing in bone marrow
        
        Notes:
        
        IgD valence = 2
        
        very low serum count
        
        IgD exist with IgM on the Bcells as B cell receptors when they are in the bone marrow
        
        IgD cells tell the B cells they are "DONE" maturing and to leave the bone marrow
        
        think of IgD = B cell driver's liscence
        --> once they express IgD they can leave the bone marrow and DRIVE around the body's lymphatic system
        --> they are amture at this point, but NAIVE
        
        IgA
        
        IgA "Airways and mucosA surface Area"
        
        Notes:
        
        IgA valence = 2
        
        in serum forms dimers --> valence = 4
        
        since IgA is important for surface Area mucosa and airway immunity against infection
        
        babies have IgG from mother for first 6 months through placenta transport
        
        but babies need respiratory protection
        --> they get IgA from mother's breast milk
        --> protection fro RTIs
        
        IgA deficiency
        
        body either doesn't produce IgA or build IgE antibodies against your own IgA
        
        1 more item...
        
        IgA migration through enterocytes to gut lumen
        
        IgE
        
        IgE = "Elergic reactions"
        
        Notes:
        
        IgE valence = 2
        
        in serum very low amount, mostly are attached firmly to granulocytes by Fc receptors
        
        granulocytes
        --> mast cells
        --> basophils
        --> eosinophils
        
        IgE good for complex pathogens like parasites and worms
        
        also for ELlergic reactions
        
        2 Functions of IgE
        
        Ellergic Reactions
        --> antibody mediated degranulation
        
        Parasitic cell-mediated cytotoxicity
        
        IgE Parasitic cell-mediated cytotoxicity example
        
        Case presentation:
        
        Notes:
        
        note that
      - B cell Receptors
        
        are essentially antibodies attached to B cells with a transmembrane part to them
        
        their variable region is called the Fab region
        
        Fab = fragment antigen binding
        --> think that only FRAGMENTS of antigen are needed to BIND
        --> Valence refers to the amount of Fab or binding availability different antibodies have
        
        As B cells mature they release their B cell receptors as antibodies
  - - - T cells
        
        CD 4+ T cells = Helper T cells
        
        sub classes TH1 and TH2
        
        TH1 and TH2 Case example
        
        Clinical Case
        
        Notes:
        
        note that T helper cells = CD4+ are first naive t helper cells
        --> they are then activated by APCs to either go into TH1 or TH2 cells
        --> this depends on the type of cell that activates them and hence the cytokines that are released from the APC
        
        think IL-4 are again "for helping" --> they activate the secondary measure = TH2
        --> TH2 then secretes many interleukins for stimulaing the B cell antibody response
        
        for macrophage activation from TH cells, this requires the t cell to be activated itself by a macrophage
        
        if the APC is a macrophage, it release IL-12 or IFN-gamma
        --> IL-12 and IFN - gamma differentiate the naive Th cell into TH1
        
        TH1 then activates direct cell madiate immunity
        --> macrophages and CD8 killer t cells
        
        CD 8+ T cells = Killer Cytotoxic T cells
        
        T cell Development
        
        see lymph nodes
      - Infectious Mononucleosis (Mono) and Reactive Lymphocytes
        
        secondary to EBV usually
        
        reactive macrophages release perforin and granzymes
        
        granzymes = granular enzymes = grandiose apoptosis
        
        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
        
        Clinical Case
      - B cells
        
        B Cell Activation
        
        require dimerization of B cell receptors
        
        tyrosine protein of the receptors come together and release cascade that makes NF-kappa-B
        
        NF-kappaB = is pro-inflammatory gene regulator
        --> makes the initial pro-inflammatory chemokines
        = IL 1, 6 + TNF-Alpha
        
        also makes IL - 2 = B cell autocrine/paracrine proliferator
        
        makes BCL-2 = antiapoptosis factor
        --> is a fail safe to prevent the IL2 proliferation from being stopped
        
        Default Plasma cells = B cells begin as IgM Plasma Cells
        
        CD 40 Class Switching of B cells
        
        B cells have CD 40 used for class switching
        
        CD40L on T h cells activates the B cell to class switch to a different antibody
        
        CD40 = "4D = 4 Different classes"
        
        think of B cells as NAIVE and STUPID
        
        they Th cell once binds CD40L to CD40 for class switch
        
        also send cytokines to the B cell to tell it what kind of antibodies to make
        
        Cytokines and Class Switch
        
        Exon Splicing for Class Switch
        
        VDJ region
        
        AIDs
        
        2 more items...
        
        2 more items...
        
        IgM Plasma cells
        
        can be class switched to other IGs
        
        done by activated Th cells
        once a plasma b cell is class switched from IgM
        --> it can NEVER reverse back to IgM class
        
        Secondary CD21 B cell activation
        
        Bcells can also be activated through the secondary CD21 pathway
        --> complement system pathway
        
        Notes:
        6 and 6 rule for B cells
        
        6 month rule
        --> most mature B cells will never be activated and will live for 6 months before they are degraded and new B cells are made
        
        6 week rule
        --> if a B cell is activated into a plasma cell
        --> thus producing antibodies
        --> regardless of the class type, this plasma cell will survive for ONLY 6 weeks before degraded
        --> it will also not proliferate during this time
        
        VDJ Rearrangement
        
        how B cells make many different kinds of antibodies
        
        B cell Receptors
        
        are essentially antibodies attached to B cells with a transmembrane part to them
        
        their variable region is called the Fab region
        
        Fab = fragment antigen binding site
        --> Valence refers to the amount of Fab or binding availability different antibodies have
        
        As B cells mature they release their B cell receptors as antibodies
    - - Macrophages
        
        Specialized
        Macrophages
        
        Langerhan's Cells
        
        specialized macrophages of the dermal layers of skin
        
        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
        
        Example:
- - - - Notes:
        
        note
      - Case presentation:
- - - - 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
    - - Primary Development
        In Bone Marrow
      - Lymph Node Follicles
        
        either Primary lymph follicles
        --> dormant B cells
        
        Secondary follicles
        --> formation of germ centres
        --> active proliferation of activated plasma B cells
        
        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 Lymph Follicles = Dormant
        
        Plasma B Cells waiting to be activated
        
        Clinical Cases
        
        Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that
- - - - Allergic Reaction example
        
        Clinical Case
        
        Notes:
        
        note that in an allergic reaction, the first exposure ever to the antigen has a class switch from IgM to IgE antibodies that bind to the specific antigen
        
        these IgE are now ready in B cells to be released if the antigen = allergen ever enters again
        
        second exposure --> these IgE antibodies bind to basophils and mast cells = granulocytes
        --> cause them to release granules, cytokines, and interleukins
        --> histamine, leukotrienes, proteases, prostaglandins, etc.
      - Allergic Reaction example 2
        
        Clinical Case
        
        Notes:
        
        note that the IgE that are produced for people who have allergies, these are not just free floating antibodies in the tissues or blood,
        
        they are mostly IgE antibodies that are surface bound to granulocytes like basophils and mast cells
        
        once the antgien or allergen enters the tissue it binds to IgE on these granulocytes and they release histamine, etc.
    - - Henoch-Schonlein Purpura
        
        IgA complexes --> systemic vasculitis
        
        remember the "HENOCH PAAAPacy" = pope Henoch-Schonlein German pope fictional
        
        "HENOCH PAAAPacy" = pope Henoch-Schonlein German pope fictional
        
        PAAAP = purpura
        
        A = IgA complexes cause vasculitis systemicall
        
        arthralgia = from the IgA complexes collecting in joints
        
        Abdominal pain = again from the IgA
        
        Henoch-Schonlein Purpura case
        
        Notes:
        
        note that HS purpura present with PAAAP as in this case
        
        Case presentation:
      - Acute Serum Sickness = ASS Type reaction
        
        FAP symptoms = fever arthralgias, Pruritic rash
        
        1-2 wks post Mabs or Abx or venom
        
        ASS example
        
        Case presentation:
        
        Notes:
        
        note that ASS = acute serum sickness is a common way people who are allergic to certain medications or venom
        --> happens 1 wk - 2wks after being given them
        
        type 3 hypersensitivity reaction
        
        immune complexes of IgM and IgG and also complement cytokine = C3 get depositied in tissues and cause pruritic rashes and fever and
        
        FAP symptoms = fever arthralgias, Pruritic rash
        
        note that because you get these depositions int he issue of the Imune complexes and the C3, you have less c3 total circulating in the blood
    - - *Poison ivy Dermatitis
        
        Type 4 Hypersensitivity Reaction
        
        Clinical Cases
        
        Clinical Case
        
        Notes:
        
        note that
        
        Clinical Case
        
        Posion Ivy Dermatitis
        
        Case presentation:
        
        Notes:
        
        note that Poison Ivy Dermatitis is a type 4 hypersensitivity reaction
        --> think that it usually takes a few days for poison ivy dermatitis to actually appear
      - *Reactive skin testing (Tuberculin TB)
        
        Type 4 Hypersensitivity Reaction
        
        also candida injection for general CD8 testing
        
        Clinical Cases
        
        Clinical Case
        
        Notes:
        
        note that
        
        Clinical Case
- - - - Notes:
        
        Margination / Capture = activation of endothelial cells
        --> selectins on the endothelial cells are expressed in the blood stream, they are activated by cytokines from the affected tissue
        --> selectins "select" the leukocytes passing by
        --> selectin binds to Syaliated glycoproteins
        --> think "Silly leukocytes" --> NEVER had any idea what they were being selected for
        --> think of them like young soldiers in a draft being selected --> "silly leukocytes being selected"
        
        Rolling
        --> still with P and E selectin bing to syaliated glycoproteins
        
        Activation of Leukocytes
        --> cytokines activate the WBC
        --> their integrin receptors go into the active state
        
        Adhesion
        --> integrin of WBC binds to ICAM = intercellular / Integrin Adhesion Molecule
        
        Crawling
        --> still ICAM but the cell "crawls" until it finds an opening to enter the tissue
        
        Transmigration
        --> Platelet endothelial cell adhesion molecule (PECAM-1) also known as cluster of differentiation 31 (CD31)
      - Case presentation:
    - - CD 18+ and LAD genetic disorder
        
        LAD = leukocyte adhesion disorder
        
        LAD is an autosomal recessive disorder
        
        Notes:
        
        note that LAD is due to absent CD18+ on leukocyte cell surfaces
        
        people with LAD present as young kids who get many recurrent infections, especially skin infections and wounds take longer to heal
        
        one example is late separation of the umbilical cord > 21 days after birth
        
        this all happens, especially in the peripheral skin infections, since the leukocytes can't properly migrate away from the blood and into the tissues
        
        this causes non-purulent infections = means they do not produce pus --> since there are no neutrophils present
        --> which produce puss when they die
        
        Clinical Case
- - - - Clinical Cases
        
        Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that
        
        Notes:
        
        note our cells have CD 55 and CD 59 to protect our cells from the compliment system attacking us
        
        think of 59 next to the Fc region of the antibody
        --> this is only to remember CD59
- - - - IMMUNE RESPONSE order