1. List compnents of immune system :
    • *Hematopoiesis
    • *Red Blood Cells
    • *Platelets
    • *White blood cells
  2. What is hematopoiesis?
    • Formation and development of blood cells.
    • Blood cells originate from hematopoietic stem cells found in the bone marrow.
  3. Describe Red Blood Cells:
    • Also known as erythrocytes
    • carry oxygen in blood
  4. Describe platelets
    • Fragments of megakaryocytes
    • important component in blood clotting
  5. Describe White blood cells:
    • Also known as leukocytes
    • important in host defenses
    • divided into four categories(granulocytes, mononuclear phagocytes, lymphocytes, dendrititc cells)
  6. Whats are granulocytes?
    • 1.) Neutrophils (55%-65%)
    • 2.) Eosinophils (2%-4%)
    • 3.) Bsophils (0%-1%), mast cells
  7. Location and Function of neutrophils ?
    • Location : Account for most of the ciculating leukocytes: few in tissues except furing inflammation .
    • Functions: Phagocytize and digest engulfed materials.
  8. Location and Function of Eosinophils?
    • Location: Few in tissues except in certain types of inflammation and allergies.
    • Functions: Participate in inflammatory reaction and immunity to some parasites
  9. Location and function of Basophils ?
    • Location: Basophils in circulation; mast cells present in most tissues.
    • functions Release histamine and other inflammation inducing chemicals from the granules
  10. What are Mononuclear Phagocytes ?
    • Monocytes (3%-8%)
    • Macrophages
  11. Location and function of Monocytes ?
    • Location : in circulation; they differentiate into either macrophages or dendritic cells when they migrate into tissue.
    • Function: Phagocytize and digest engulfed materials.
  12. Location and function of Macrophages?
    • Location: Present in virtually all tissues; given various names based on the tissue in which they are found.
    • Functions: Phagocytize and digest engulfed materials
  13. Location and functions of Dendritic cells and Lymphocytes
    • Location: initially in tissues, but they migrate to secondary lymphoid organs (such as lymph node, spleen, thymus, appendix, tonsils)
    • Functions: Gather antigen from the tissues and then bring it to lymphocytes that congregate in the secondary lymphoid organs.
  14. Modes of phagocyte intracellular killing
    Pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterms (PAMPs) thus signaling the presence of foreign invaders or tissue damage.
  15. What are the three pathways of activation :
    • 1.) Classical pathway
    • 2.) Alternative pathway
    • 3.) Lectin pathway
  16. What is Alternative pathway initiated by:
    Binding of C3b to cell surfaces (regulatory proteins protect host cell surfaces)
  17. What is Lectin pathway initiated by :
    Binding of mannan-binding lectins to cell surfaces
  18. What is classical pathway initiated by :
    Antigen-antibody complexes.
  19. Alternative pathway
    • Provides a means of non-specific resistance against infection without the participation of antibodies.
    • Requires preformed C3b along with factors B and D .
    • Properdin helps to stabilize complex.
    • Initiates activation of other complement proteins.
    • -Short half-life (100us) in fluid phase.
    • -Regulation of C3 by serum proteins (DAF, Factor I, factor H)
  20. Lectin pathway:
    • –Initiated
    • by three proteins: a mannan-binding lectin (MBL), also known as mannan-binding
    • protein (MBP) which interacts with
    • two mannan-binding lectin-associated serine proteases (MASP and MADSP2),
    • analogous to C1r and C1s. This interaction generates a complex analogous to
    • C1qrs and leads to antibody -independent activation of the classical pathway.


    • •Pattern
    • recognition molecule

    •Detects mannan found on microbial cells
  21. Classical pathway:
    • Antigen–Antibody dependent (IgG or IgM)
    • –Part
    • of adaptive response

    • •Antibodies
    • interact complement C1 (C1qrs)

    • –Activates
    • protein

    • »Leads
    • to activation of all complex proteins

    • –Activity
    • limited by C1-esterase inhibitor (C1INH)

    • »Other
    • inhibitors of complement pathway to prevent inappropriate activation of
    • complement
  22. Complement Cascade:
    Membrane Attack Complex (MAC)
    • •Lysis of foreign cells
    • –Complexes
    • of C5b, C6, C7, C8 and multiple C9 spontaneously assemble
    • •Forms
    • donut-shaped structure called membrane attack complex (MAC)
    • •Creates pores in membrane
    • •Most effective on Gram-negative cells
    • –Little
    • effect on Gram+ bacteria, due to
    • their thick peptidoglycan wall – the MAC cannot get to the membrane
  23. Complement Cascade
    • •Activation of complement leads to major protective outcomes
    • •Inflammation
    • •Lysis
    • of foreign cells (MAC)
    • •Opsonization

    • Unattended activation of complement proteins
    • regulated by short
    • half-life of some complement
    • proteins and specific
    • host proteins that inactivate complement proteins
  24. Inflammation :
    • inflammation occurs in response to tissue damage.
    • There are 4 cardinal signs.
    • 1.) Heat(calor)
    • 2.) Pain(dolor)
    • 3.) Redness (rubor)
    • 4.) Swelling (tumor)
    • sometimes Loss of function (functio laesa)
  25. Fever :
    • A major difference in the biological
    • outcome of inducing apoptosis, necrosis, or pyroptosis is the ensuing
    • inflammatory response. Apoptosis is
    • generally immunologically silent, while necrosis and pyroptosis are accompanied by secretion of proinflammatory cytokines and the
    • extracellular release of the cytosolic content.
  26. Strategy of humoral immune response :
    •Overview of humoral immunity

    –Mediated by B lymphocytes

    •a.k.a B cells

    –Develops in bone marrow

    B cells carry multiple B cell receptors (BCRs)

    • Membrane-bound
    • derivative of the Ab it is programmed to
    • make

    • –B cells may be triggered to proliferate into
    • plasma cells

    • Plasma cells produce
    • antibodies

    –Antibodies are produced when antigen binds BCR

    –Some B cells produce memory cells
  27. Cell-mediated immune response:
    • •Overview of cellular
    • immunity

    –Mediated by T lymphocytes

    •a.k.a T cells

    –Matures in thymus

    –Two predominant subsets

    •Cytotoxic (CD8+) T cells

    •Helper (CD4+) T cells

    • –T cell receptors (TCR) help with antigen
    • recognition
  28. Anatomy of the lymphoid system :
    •Primary lymphoid organs

    • Bone marrow and thymus are primary lymphoid
    • organs

    • •Location where stem
    • cells destined to become B and T cells mature (pick up their BCRs or TCRs)

    • –B cells mature in bone
    • marrow (prior to birth in fetal liver)

    • –T cells mature in
    • thymus

    • •Once mature, cells
    • leave primary lymphoid organs and migrate to secondary lymphoid organs where
    • they wait to encounter antigen
  29. Antigens
    • •Word comes from
    • compounds that elicit antibody production

    –Antibody generator

    • •Includes an enormous
    • variety of materials

    • •Today, term used to
    • describe any compound that reacts specifically with an Ab or an Ag receptor on a lymphocyte

    –Ag may not elicit an immune response (immunogens elicits IRs)

    • –Substances w/ MW < 10,000 da typically not
    • immunogenic

    • •Proteins and
    • polysaccharides induce strong responses

    –Lipids and nucleic acids often do not

    • •Recognition of antigen
    • directed at antigenic determinant or epitope
  30. Antibody isotype classes :
    •Five classes of Ab


    • •First Ab to respond to
    • infection

    •5 – 13% of Ab in circulation

    •Structure: pentamer

    • –Five monomer units
    • joined together at the constant region

    • –Primarily involved in
    • control of bloodstream infections

    • •Found on the surface
    • of B lymphocytes as a monomer

    • •Most efficient at
    • eliciting “classical” complement cascade (highest affinity for complement)

    • •Effective in
    • agglutination and precipitation reactions

    • •Only class produced
    • during immune responses to T-independent Ags

    • •Only Ab that can be formed by
    • the fetus if infected in utero (IgM production gen. begins after birth)
  31. Clonal selection of B cells
    •Clonal Selection Theory

    • –Antigen bind to only one of a multitude of
    • preformed lymphocytes

    • •Initiates multiplication of specific
    • antigen-specific lymphocytes

    Process called clonal selection

    • –Repeated cycles of cell division generates
    • population of copied antibodies

    »Termed clonal expansion

    • •Without sustained
    • stimulation, cells undergo apoptosis curtailing the immune response
  32. Clonal selection of lymphocytes :
    • •Lymphocyte
    • characteristics include


    • •Have not fully developed their antigen specific
    • receptor


    • •Have antigen receptor but have not encountered
    • antigen


    •Able to proliferate

    •Have bound antigen


    •Descendents of activated lymphocytes

    •Able to produce specific cytokines

    •Plasma cells, T helper and cytotoxic T cells effector cells

    –Memory lymphocytes

    •Long-lived descendents of activated lymphocytes

    • •Memory cells responsible for speed and
    • effectiveness of secondary response

    • –Remembers antigen on
    • subsequent exposure
  33. B lymphocyte and antibody response :
    • •In many cases B cell
    • needs confirmation from T helper cells

    •Co-stimulatory or second signal

    • •TH cell releases cytokines that activates B cells to divide and
    • differentiate

    –Produce plasma cells and memory B cells

    • If the T cell does not
    • recognize the Ag the immune response may become “tolerant” to that antigen
  34. Antibody diversity: not enough DNA for separate genes encoding each antibody.
    •Diversity involves

    –Gene Rearrangement

    • •Maturing B cell
    • selects 3 segments


    –Imprecise Joining

    • •Nucleotides deleted or
    • added

    –Combinatorial Associations

    • •Specific groupings of
    • light and heavy chains
  35. T lymphocytes antigen recognition and response: consist of ... .
    Alpha chain, Beta chain, Antigen: MHC-binding site
  36. T Lymphocytes Antigen Recognition and response : General Characteristics.
    • –During antigen
    • presentation, antigen cradled in grove of major histocompatability complex molecule (MHC molecule)

    •Two types MHC

    • –MHC
    • class I

    »Bind endogenous antigen

    • –MHC
    • class II

    »Bind exogenous antigen
  37. T lymphocytes Antigen recognition and response : General characteristics contin.
    –Two major functional T cell populations

    •Cytotoxic T cells

    • –Proliferate and differentiate to destroy infected
    • or cancerous “self” cells and in graft rejection

    Have CD8 marker

    • –Recognize MHC
    • class I

    •Helper T cells (orchestrate immune response)

    • –Multiply and develop into cells that activate
    • cell mediated immune responses and macrophages (Th1-type) and humoral (B cells)
    • responses (Th2-type)

    –Stimulate other T cells

    Have CD4 marker

    –Recognize antigen displayed by MHC class II
  38. Functions of Tc (CD8) cells :
    • –Induce apoptosis in “self” cells and graft
    • rejection

    • •Cells infected with virus or intracellular
    • microbe

    •Destroys cancerous “self” cells

    •Foreign cells involved with graft rejection

    • –Nucleated target cells degrade portion of
    • proteins

    •Load peptides into groove of MHC class I molecule

    •MHC class I molecule recognized by circulating Tc cell

    –Cell destroyed by lethal effector function of Tc cell

    •Tc cells releases pre-formed cytotoxins (perforin and other proteases such as granzymes) that induces cell lysis or apoptosis

    • •Can induce apoptosis via binding of FasL (Fas Ligand) on activated CD8 T
    • cell to Fas on the target cell

    –Secretes cytokines
  39. Role of TH cells in macrophage activation:
    • –Macrophages routinely
    • engulf invading microbes resistant to lysosomal killing

    • –TH cells “activate” macrophages by delivering cytokines that
    • induce more potent destructive mechanisms

    • –If immune response can
    • not deal with the microbial infection, activated macrophages can fuse to form a
    • multinucleated giant cell and together with
    • other macrophages, PMNs, and T cells can contain the infection within a granuloma thus preventing dissemination of the infection
  40. Lymphocyte development :
    • •During lymphocyte development, B and T cells acquire ability to
    • recognize distinct epitopes

    • –Once committed to
    • specific antigen, cells “checked out” to ensure proper function and that they
    • do not respond to self antigens

    B cells undergo developmental stages in bone marrow

    T cells go through process in thymus
  41. Negative selection of "Self" Reactive B cells :
    •Negative Selection

    • –Process of eliminating lymphocytes that express
    • “self” antigens (clonal deletion)

    –Failure of clonal deletion leads to production of autoantibodies

    –B cell w/ BCR is exposed to Ags w/n bone marrow and all that bind “self” antigens undergo apoptosis

    • –Naïve B cells that recognize Ag in secondary lymphoid tissues are eliminated if they do not receive second
    • signal from T helper cell
  42. Negative selection of "self" reactive T cells continued :
    •Occurs in thymus

    •Positive Selection

    • –Only those T cells that recognized self MHC is
    • “positively” selected

    •TCR recognizes a peptide:MHC complex

    •Negative Selection

    • –T cells that recognize “self” antigens are
    • negatively selected
  43. Gamma/delta T cells :
    • •Very small part of T
    • cell population in the periphery (3-5% of T cells)

    • •Most evidence suggests
    • that they do not require either MHC processing or presentation of antigen in
    • context of MHC

    • –Present glycolipids, phospholipids, and some protein ags that are neither
    • processed or presented in the context of MHC

    More of a role in innate immunity

    –Role is similar to a PRR

    • –May kill infected cells or organisms using
    • mechanisms similar to those of CTLs (granulysin and perforin)

    –Secrete cytokines and chemokines
  44. Natural killer cells :
    •Natural killer cells descend from lymphoid stem cells

    They lack antigen specificity

    •No antigen receptors

    •Memory? (maybe)

    • –Mediate lysis of host cells altered
    • by stress, viral infection, or transformed into tumor cells (these cells
    • express less class I MHC)

    • –Killing is regulated
    • by the balance b/w positive signals generated by the engagement of activating
    • receptors and negative signals from inhibitory receptors

    • The expression of relatively high levels of class I MHC
    • molecules on normal cells protects them against NK-cell-mediated killing
  45. Natural killer T Cells continued:
    •Characteristics common to both T cells and NK cells

    T-cell receptor invariant

    • •TCRa and TCRb chains encoded by
    • specific gene segments

    • –TCR on NKT cells does not recognize MHC-bound peptides but rather a glycolipid presented by another
    • molecule (CD1d)

    NKT cells do not form memory cells

    • –Expresses a number of
    • markers that are characteristic of NK cells but not T cells

    •Involved in innate immunity

    –Antibacterial immunity

    • –Response to lipid
    • antigens specific to tumor cells
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