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2013-09-08 02:11:15

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  1. Define immunology and describe its goal
    • Immunology: the study of the body's defense against infection (immunity)
    • Study (at a cellular/molecular level)
    • 1. How our body recognizes an invader but not our own cells (specificity)
    • 2. How our body eliminates the invader, and cures itself
    • 3. How our body develops long-lasting immunity to many infectious diseases
  2. Describe Edward Jenner's contribution
    • The "father" of immunology
    • Demonstrated that cowpox pus gives immunity to smallpox
    • Smallpox is now completely eradicated (1979)
    • Knew nothing of the infections agents that cause disease
  3. Describe Robert Koch's contribution
    • "Proved" that infections diseases are caused by microorganisms (germ theory of disease)
    • Koch's postulates: A method to show that a specific pathogen causes a specific disease
    • 1. Suspected pathogen present in ALL causes of the disease and absent in healthy individuals
    • 2. Suspected organism grown in pure culture
    • 3. Cells from pure culture should cause disease in healthy individual
    • 4. Organism should be re-isolated from the newly-diseased individual
  4. Describe Louis Pasteur's contribution
    • First to artificially generate weakened agents!
    • Discovered that weakened (old) cholera bacteria caused chickens to become immune to the disease
    • Applied immunization method to anthrax (exposed bacilli to O2) and rabies (dried nerve tissue in affected rabbits)
  5. Describe Emil von Behring and Shibasaburo Kitasato's contribution
    • Discovery of antibodies
    • Discovered that broth cultures of diphtheria or tetanus bacilli caused production of "antitoxins" in guinea pigs
    • Showed that antitoxins produced by one animal could cure an animal showing symptoms
  6. What are the two types of immune responses? (general overview from beginning of class)
    • Innate immunity: the body's built-in ability to recognize and destroy pathogens and their products
    • Does not lead to long-lasting immunity
    • Is not specific
    • Includes physical barriers (skin), chemical barriers (stomach acid), and the relatively non-specific cellular responses (phagocytes)
    • Adaptive immunity: acquired ability of an individual as an adaptation to pathogens
    • Activated by exposure to specific antigens
    • Results in immunological memory (lifelong protection from reinfection)
  7. Describe Elie Metchnikoff's contribution
    Discovered that microorganisms could be engulfed/digested by phagocytic cells (macrophages)
  8. What is the "general overview" of an infection that involves innate and adaptive? (beginning of class, think of the handout picture)
    • Phagocytic WBCs (macrophages/neutrophils) recognize/target pathogens
    • If overwhelmed, they release cytokines/chemokines which cause inflammation of nearby blood vessels and trigger recruitment
    • Dendritic cells engulf infection and present antigen on surface to activate T cells (Tcyto, TFH, TH1)
    • TFH cells are then involved in B cell development/activation
    • Tcyto: destroys infected body cells
    • B cells produce antibodies and confer immunological memory
  9. What are the four main tasks of an immune system?
    • Immunological recognition: presence of infection must be detected
    • Carried out by innate WBCs and adaptive lymphocytes
    • Immune effector functions: contain and eliminate infection
    • Carried out by destructive capacities of WBCs, complement system, and antibodies
    • Immune regulation: must not damage the body
    • Failure will cause allergy/autoimmune disorder
    • Immunological memory: protect against recurring pathogen
  10. Describe the phases of the immune response
    • 1. Initial defenses against infection are physical (skin) and chemical (mucosa, stomach acids) barriers
    • 2. Innate immune system and complement system can immediately destroy foreign organisms
    • 3. Adaptive immune system takes days to develop, but can eliminate infections more efficiently due to specific recognition functions.
  11. Describe formation of the blood cells
    • Originate from pluripotent hematopoietic stem cells in bone marrow
    • Two types of stem cells...
    • common lymphoid progenitor: gives rise to the lymphoid lineage of leukocytes (lymphocytes)
    • B lymphocytes, T lymphocytes, Natural Killer (NK) cells
    • common myeloid progenitor: gives rise to the myeloid lineage of leukocytes
    • Erythrocytes, megakaryocytes (platelets), neutrophil, eosinophil, basophil, monocyte, mast cell, dendritic cell
  12. How are T and B lymphocytes different from other leukocytes? From each other?
    • Only leukocytes with possession of specific antigen receptors.
    • T lymphocytes: differentiate in the thymus
    • differentiate into effector T cells (variety of functions) after antigen exposure.
    • B lymphocytes: differentiate in the bone marrow
    • differentiate into antibody-secreting plasma cells after antigen exposure.
  13. Describe the myeloid lineage of leukocytes in detail (3 "types")
    • 1. Neutrophils, eosinophils, and basophils
    • Circulate in blood
    • Called "Granulocytes" or "polymorphonuclear leukocytes"
    • 2. Immature dendritic cells
    • Phagocytic cells that enter the tissue and mature after they encounter a potential pathogen
    • Present antigen on surface for adaptive immune cells
    • 3. Monocytes
    • Enter tissues where they differentiate into macrophages
    • 4. Mast cells
    • The precursor is still unknown
    • Mature in tissues
  14. Describe macrophages in detail
    • Reside in almost all tissues
    • Differentiate from monocytes when the monocytes leave the bloodstream
    • Functions...
    • 1. Engulf and kill invading microorganisms
    • first defense in innate immunity
    • 2. Opsonization
    • Dispose of pathogens and infected cells target by an adaptive immune response
    • 3. Help induce inflammation
    • by secreting signaling proteins that activate/recruit other immune-system cells
    • Prerequisite for successful immune response
    • 4. Act as general scavenger cells in the body
    • Clearing dead cells and cell debris
  15. What are the 3 types of phagocytes?
    • 1. Monocytes/macrophages: because most infections occur int he tissues, macrophages are the primary protector
    • 2. Granulocytes: neutrophils, eosinophils, and basophils
    • 3. Dendritic cells: present antigen for adaptive response
  16. Basic granulocyte information
    • Differentiated by staining properties of granules
    • Short-lived (only a few days)
    • Production increased during immune responses
    • Neutrophils:
    • Most numerous and most important cell in the innate immune response
    • Work with macrophages
    • Basophils and Eosinophils:
    • Less abundant than neutrophils
    • Mainly function against parasites
    • Contribute to allergic inflammatory reactions
  17. Describe clonal deletion/selection
    • Clonal deletion: the removal of naïve lymphocytes that would recognize "self" cells as antigens
    • Clonal selection: the proliferation/development of naïve lymphocytes after being exposed to their corresponding antigen
  18. Describe the development of the different types of lymphocytes
    • 1. Bone Marrow Stem cell
    • 2. B cell development in bone marrow
    • 2. T Cell development in thymus
    • 3. wait in secondary lymphoid tissues (lymph nodes, spleen, mucosal tissues) until antigen exposure
    • 4. Become effector B cells (plasma cells OR memory cells)
    • 4. Become effector T cells Tcyto, TFH, TH1)
    • Tcyto: killers
    • TFH: activate B cells
    • TH1: help macrophage
  19. Basic dendritic cell information
    • Dendritic cells have long fingerlike processes, like the dendrites of nerve cells
    • Immature dendritic cells migrate through the bloodstream (normal) from the bone marrow to enter the tissues (infection)
    • Perform phagocytosis and macropinocytosis in the tissues and degrade particulate matter
    • Encounter with a pathogen stimulates maturation and the display of antigens from the pathogen
    • This activates  the antigen receptor of T lymphocytes
    • Thus they form a crucial link between the innate and adaptive immunity
  20. Describe the lymphoid lineage of leukocytes (types, names)
    • Antigen-nonspecific lymphocytes: Natural Killer cells (innate immune system)
    • Antigen-specific lymphocytes: B and T lymphocytes (adaptive immune system)
  21. Describe natural killer cells
    • Large granular lymphoid-like cells
    • Recognize and kill intracellular infections (tumor cells and virus-infected cells) before the adaptive immune response kicks in
    • Function by looking for a LACK of MHC I and II receptors on infected cells
  22. Describe the antigen-specific lymphocytes before, during, and after exposure to infection
    • Before: 108 different receptors which can mount response against almost any kind of pathogen
    • Most circulate as small, featureless cells with few organelles and inactive nuclear chromatin
    • During: after meeting their antigen they become activated and differentiated into effector lymphocytes
    • effector T cells- cytotoxic, helper, and regulatory
    • effector B cells- antibody-producing plasma cells
    • After: Some activated effector lymphocytes differentiate into memory cells
    • memory cells are more sensitive and respond rapidly on reexposure to their specific antigen
  23. T lymphocytes activation in detail
    • T cell is activated by the by the interaction between the antigen on a dendritic cell and the TCR (T-cell antigen receptor)
    • It proliferates/differentiates into 3 effector T-lymphocytes...
    • Cytotoxic: kill cells that are infected with viruses or other intracellular pathogens
    • Helper: provide essential additional signals
    • to antigen-stimulated B cells to influence antibody production
    • to macrophages for more efficient killing of engulfed pathogens
    • Regulatory: suppress the activity of other lymphocytes
    • Control immune response
  24. Describe the TCR
    • each T cell has thousands of identical TCR on its surface
    • TCR consists of α and β polypeptides
    • TCR is quite different from BCR in its structure and properties
  25. Describe B lymphocyte activation in detail
    • Free antigen binds to BCR
    • Antigen is taken up by receptor-mediated endocytosis when the activated B cell is stimulated by TFH cell
    • Plasma cell produces antibodies which are a secreted form of the BCR (identical specificity)
    • Antibody molecules  are also known as immunoglobulins (Ig), BCR are also known as membrane immunoglobulin (mIg) or surface immunoglobulin (sIg)
  26. What are the two groups of lymphoid organs?
    • Primary lymphoid organs: bone marrow and thymus
    • where lymphocytes are generated
    • Secondary lymphoid organs: lymph nodes, spleen, mucosal lymphoid tissues (gut, nasal, respiratory tract, urogenital tract, etc)
    • Where mature naïve lymphocytes are maintained and adaptive immune responses are initiated
  27. What are the two parts of the lymphatic system and their purpose?
    • Network of lymphatic vessels: transport system for fluids that have escaped from the blood vascular system and returns them to the bloodstream
    • starts in lymph capillaries (near blood capillaries)
    • Interstitial fluid in the lymphatic = lymph (recycled blood plasma)
    • Various lymphoid tissues and organs: house phagocytic cells and lymphocytes
  28. What is the first defense against invading pathogens?  What happens if these are breached?
    • Physical, chemical, and anatomical barriers (skin, mucosal epithelium)
    • If these are breached they are met by cells that mount an innate immune response and inflammation
  29. Describe the Macrophage/inflammation response in detail
    • Machrophages in the tissue recognize pathogens through specific receptors
    • Engagement of receptors triggers the macrophage to engulf/degrade the pathogen and to secrete cytokines/chemokines
    • Cytokines/chemokines initiate inflammation
    • Cytokines: increase permeability of blood vessels (heat, redness, swelling)
    • allows fluid/proteins from blood into the tissues which help to directly destroy the pathogen
    • Also increases the flow of lymph carrying the pathogen and APCs to nearby lymphoid tissues to imitate the adaptive immune response
    • Activation of complement system leads to coating of microbes with complement fragments which aids phagocytosis by macrophages
    • change adhesive properties of endothelial cells allowing the leukocytes to migrate into tissues 
    • Chemokines: recruit neutrophils in large numbers which engulf/destroy pathogens
    • influx of neutrophils followed by increased entry of monocytes which differentiate into macrophages