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Immunology (Immune systems protect us from pathogens (Viruses (cannot self…

- - - - Internal
        
        Response is apoptosis
        
        cancer cells avoid apoptosis leading to uncontrolled growth
      - External
  - - - phagocytes
      - lympocytes
      - blood cells derived from hemapoeitic stems cells (multipotent) in bone marrow
        
        Stem cells
        
        Myeloid progenitor cells
        
        phagocytes
        
        nuetrophils
        
        immature dendritic cells
        
        Monocytes
        
        Blood monocytes
        
        macrophages (in tissue)
        
        lymphoid progenitor cells
        
        lymphocytes
    - - acute phase (compement proteins)
      - antibodies
- - - - immediate
      - short-term
      - Maternal
        
        placenta
        
        breast milk
        
        newborns lack adaptive immunity
      - Artificial: donor antibodies/"immunoglobulin therapy"
    - - immunoglobins
      - 2 identical
      - constant heavy chains
      - variable light chains
        
        bind antigens
  - - - intracellular bacteria
      - viruses
    - - only bind protein antigens
        
        peptides (epitope)
        
        result of protein degradation
      - cannot bind directly
        
        requires MHC molecule
        
        "presents" TCR w/ peptide
        
        has epitope specificity
    - - only mature dendritic cells can activate T-cells
  - - - generate effector cells and memory cells
        
        susequent exposer
        
        more effective response
        
        more memory cells
  - - - bone marrow
        
        haemapoietic stem cell
        
        lymphoid progenitor cells
        
        naive B cells (circulation)
        
        Thymyus: thymocytes (express both CD8 and CD4)
        
        circulation
        
        naive helper T-cells (CD4)
        
        naive cytotoxic T cells (CD8)
  - - - site where B and T cells meet lymph-born pathogen
      - Lymphatic system
        
        plasma enters tissues via capillaries = interstitial tissue
        
        interstitial tissue enters lymphatic vessels = lymph
        
        lymph filters through lymph nodes
        
        removes waste products from tissues and initiates adaptive immunity
    - - where blood-borne pathogens are met
    - - M (microfold) cells transport pathogens into malt)
  - - - variable regions of BCRs and TCRs bind
      - specificity arises from random arrangement of variable region genes
- - - - Interfering with chain prevents transmission
        
        Can control infectious disease by eliminating the resevoir
    - - Very young & old
      - genetic defects
      - compromised immune system
      - vaccines protect the immunodeficient through herd immunity
- - - - keeps up with pathogen replication
  - - - Modes of pathogen entry
        
        Respiration
        
        cilia
        
        sneezing
        
        coughing
        
        mucuus
        
        secreted by goblet cells
        
        Skin
        
        karitinized
        
        Ingestion
        
        Mucous
        
        Urinary Tract
      - Epithelial Cells
        
        thick layers
        
        classified by shape
        
        squamous
        
        cuboiodal
        
        columnar
        
        simple or stratified
        
        Properties
        
        tight junctions
        
        leaky gut syndrome
        
        rapidly renewable
        
        desquamation
        
        secrete antimicrobial peptides
        
        defensins
        
        block virus binding and inhibit replication
        
        form pores in bacteria
      - Barrier types
        
        Mechanical (expel/flush out)
        
        urinating
        
        blinking
        
        spit
        
        sweat
        
        vomitting
        
        peristalsis
        
        coughing/sneezing
        
        Chemical
        
        fatty acids (skin)
        
        enzymes: lysozyme, pepsin
        
        low pH
        
        antibacterial peptides; cryptidins
        
        Microbiological: microbiota
        
        opportunistic pathogens
    - - initiate adaptive immunity
      - Phagocytes: digest extracellular pathogens by phagocytosis
        
        Types
        
        macrophages
        
        tissues (below/within epithelial cell layer)
        
        arise from blood monocytes that enter tissues
        
        role in adaptive immunity
        
        immature dendritc cells
        
        circulation & tissues
        
        maturation-dependent function
        
        neutrophils
        
        in circulation
        
        rapidly enter infected tissue
        
        come from myeloid progenitor cells
        
        infection results in production of more
        
        short-lived
        
        Neutropenia = low neutrophil count
        
        septic shock/neutropenic sepsis
        
        triggered by binding of pathogen (PRR-PAMP)
        
        cell membrane internalizes pathogen in phagosome
        
        phagosome fuses with lysosome
        
        lysosome secrete acids and enzymes that kill pathogens
        
        Acids
        
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        Enzymes
        
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        Phagocytes use PRR which bind to PAMPS expressed on microbes
        
        PAMPS
        
        only expressed by microbes
        
        low mutation rate; critical for survival
        
        integrity
        
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        pathogenicity
        
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        PRRs can bind many PAMPs
        
        binding triggers cytokine release see cytokines
        
        intracellular bacteria avoid phagocytosis
        
        require T-cell immunity
        
        escape phagocytosis
        
        inhibit lysosome fusing
        
        resistant to acids and enzymes
      - Lymphocytes
        
        natural killers
        
        in cirulation
        
        recruited by type I interferons secreted by virus infected cells see proteins > cytokines > INF-1
        
        kill intracellular viruses
        
        early response to viral infection
        
        induce apoptosis
        
        cytoplasmic granules
        
        perforin: forms pores
        
        granzyme: degrades nucleic acids
        
        apoptosis
  - - - including plants and invertebrates
  - - - secreted by all activated nucleated cells
        
        many types simultaneously
      - cell communication
        
        activate or suppress most cell behaviors
        
        proliferation
        
        growth
        
        maturation
        
        survival
      - innate and adaptive immunity
      - Include
        
        Chemokines
        
        type 1 INF (interferon)
        
        alpha
        
        beta
        
        important anti-virals
        
        only anti-viral suppresses immune response to intracellular bacteria
        
        released by virus-infected cells in response to internal PRR-PAMP binding
        
        "tell" NK cells to kill infected cell
        
        rapid process
        
        "tell" infected cells to produce antiviral enzymes
        
        inhibit viral replication
        
        limit viral speed
        
        no innate immunity against viruses that block IFN production
        
        Pro-inflammatory = TNF (tumor necrosis factor), IL-1, IL-6 (interleukins)
        
        growth factors/colony stimulating factors
        
        regulate hematopeisis
      - Production triggered by PAMP-PRR binding
        
        TNF, IL-1, IL-6
        
        activate endothelial cells (surround blood vessels)
        
        vasodilate; increase permeability
        
        circulating immune cells enter; enhance pathogen clearance
        
        release inflammatory mediators that stimulate nerves (pain)
        
        includes T-cells (adaptive>T-cell)
        
        Inflammation
        
        Chemokines
        
        attract cells to infected tissue
        
        leave tissue and enter circulation
        
        activate hypothalamus
        
        produce prostaglandins
        
        fever
        
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        secrete acute phase proteins (C3) see complement proteins
    - - cleaves into C3a+C3b in presence of pathogen
        
        phagocytes express C3b receptors
        
        provides additional binding interaction to trigger phagocytes
      - secreted by hepatocytes
      - C3a Maintains inflammation
        
        activates endothelial cells (maintains vasodilaiton; permeability)
        
        attracts circulating phagocytes to infected tissue