Overview of the Immune System

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Overview of the Immune System

• Historical Perspective, Innate and Adaptive
  Immunity, Comparative Immunity, and Immune System
  Dysfunction
• Reading Chapter 1

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• Introduction to the Immune System
• Defense system evolved to protect against
  infectious agents and cancerous cells
• Functional activities of the Immune System
• Recognition
• Response
• Effector
• Memory
• Arms of the Immune System
• Innate/Natural
• Adaptive/Acquired

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• Historical Perspective
• Early accounts of disease and pestilence
• Thucydides and the term immunity
• Early attempts to induce immunity
• 15th Century Chinese and Turks develop
  variolation
• Edward Jenner, 1798
• Louis Pasteur (1870s)- the beginning of
  Immunology as a discipline and origins of the
  term vaccine
• First human vaccination (1885) attenuated rabis
  virus

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Identification of the Two Arms of the Immune
System

• 1883 Metchnikoff and Ehrlich demonstrate
  Cell-Mediated Immunity
• First evidence of cellular phagocytosis
• 1890 Behring and Kitasato demonstrate Humoral
  Immunity
• Demonstrated that the noncellular component of
  blood could transfer immunity to diptheria from
  one organism to another
• The great debate cellular or humoral immunity
• Supporters gather evidence, ex.
• Bruce Glick and identification of T and B
  lymphocytes
• Elvin Kabat and identification of antibodies in
  serum
• Demonstration of autoimmune disease and
  contradiction of Ehrlichs horror autotaxicus

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Two Theories on the Mechanism of Specificity of
the Immune System

• Selective Theory
• Paul Ehrlich (1900) side- chain receptors and
  the lock and key mechanism specificity is
  predetermined
• Porter and Eldeman (1972) determined antibody
  structure (receptors are both soluble and
  membrane bound)
• Instructional Theory
• Linus Pauling, Friedrich Breinl and Felix
  Harwrowitz (1930s and 1940s) Antigen is
  important for determining specificity of the
  antibody (disproved)

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Modern Theory of Specificity

• Clonal-Selection Theory
• Underlying paradigm of modern immunology
• Niels Jerne, David Talmadge, F MacFarlane Burnet
• An individual lymphocyte expresses a membrane
  receptor specific for a distinct antigen
• Receptor specificity is determined before
  lymphocyte is exposed to the antigen
• Binding of antigen to the receptor activates the
  lymphocyte causing it to proliferate into a clone
  of cells with similar immunologic specificity

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• Innate and Adaptive Immunity

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Innate Immunity

• First defense against infection
• Components present before infection
• Mechanism of protection is not specific for
  infectious agent
• Important components and types of defensive
  barriers

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• Innate Immunity and its defensive barriers
• Types of barriers
• Anatomical Physiologic Phagocytic Inflammatory
• Anatomical barriers and the prevention of entry
• Skin
• Epidermis
• Dermis

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• Skin
• Dermis
• Connective tissue, blood vessels, hair follicles,
  sebaceous glands, sweat glands
• Sebaceous glands and the production of sebum
• Lactic acid and fatty acid
• Maintenance of acidic pH of skin
• Vulnerability of skin as a barrier

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• Innate Immunity
• Anatomical barriers
• Mucous membranes

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• Toll and Toll-like receptors (TLRs)
• Function
• Identification
• Examples
• TLR2
• TLR4
• TLR3
• Limited specificity of the innate immune system

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• Phagocytic Barriers
• Phagocytosis
• Cell types
• Monocytes, neutrophils, tissue macrophages
• Phagocytic process

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• Phagocytosis

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• Inflammatory barriers
• Five Characteristic signs
• Redness, swelling, heat, pain, loss of function
• Causative events
• Vasodilation, increased capillary permeability,
  emigration of phagocytes
• Role of chemical mediators

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Adaptive Immunity

• Characteristic Features
• Antigenic specificity
• Diversity
• Immunologic memory
• Self/non-self recognition

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• Humoral and Cellular branches of Adaptive
  (Specific) Immunity
• Antigen Recognition by Lymphocytes
• WBCs produced in the bone marrow
• Circulate in blood and lymph
• Reside in lymph nodes
• Produce and display receptors that recognize
  foreign particles

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• Functional Cell Types of Adaptive Immunity
• Lymphocytes
• B Lymphocytes
• Memory and Plasma B cells
• T Lymphocytes
• T helper (TH) and T cytotoxic (TC) cells
• Expression of membrane associated proteins CD4
  and CD8
• Antigen Presenting Cells
• Macrophages
• Lymphocytes
• Dendritic cells

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• Major Histocompatibility Complex (MHC)
• Large genetic complex with multiple loci encoding
  membrane bound glycoproteins
• Class I and Class II MHC molecules
• Recognition by CD8 and CD4 cells
• Presentation of antigenic peptides to T
  lymphocytes

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• Antigen-presenting cells (APC)
• Function- internalize antigen by phagocytosis or
  endocytosis and display antigenic peptide on MHC
• Express co-stimulatory molecules to activate T
  cells
• Cell types
• Macrophages, lymphocytes, dendritic cells

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Exogenous
Endogenous

• MHC molecules and the processing of antigens
• Antigen presentation to T lymphocytes
• Exogenous foreign particle endocytosis or
  phagocytosis Class II MHC CD4 T helper
  cells
• Endogenous foreign particle degraded into
  peptides Class I MHC CD8 T cytotoxic
  cells

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• Antigen selection and clonal expansion

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• Humoral Response
• Immunologic memory
• First exposure Primary response lag of
  5-7 days and peaks at 10-17 days while TH cells
  activate B cells
• Second exposure Induction of a rapid response
  lag of 1-2 days lasts months to years due to
  clonal expansion and activation of memory B cells

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• Cell-mediated immune response
• Collaboration of innate and adaptive immune
  responses yields strong defense against infection
  (Table 1.3)

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Innate and Adaptive Immunity
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• Immune Dysfunction