Immunology

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Section I

• Immunology

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Nonspecific Mechanisms To Fight Infection

• Skin Mucous Membranes
• Sweat gland secretions (acidic)
• Bacterial flora release acids
• Saliva, tears and mucous secretion
• Lysozyme in tears and perspiration
• Nostril hairs
• Stomach acid

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Phagocytic White Cells and Natural Killer Cells

• Neutrophils ( majority of wbcs)
• - Released from bone marrow
• Enter by amoeboid movt live only a few days
• Attracted by a chemical signal (i.e., pus)
• Capable of phagocytosis
• or cell lysis (engulf)
• Arrive first, eliminate
• microorganisms die

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Phagocyte ingesting polystyrene beads

• These phagosomes deliver their contents to
  lysosomes

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Phagocytic White Cells and Natural Killer Cells
(cont.)

• Monocytes migrate to the tissues (organ
  connective) where they enlarge and become
  macrophages
• From bone marrow
• Use pseudopodia to phagocytize cells (e.g.
  bacteria, viruses, cell debris)
• Secrete lysozyme and interferon
• Expose molecules of digested bodies to more
  specialized calls, such as B and Th lymphocytes

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Phagocytic White Cells (cont.)

• Eosinophils Understanding The Immune System -
  Phagocytes and Granulocytes
• Have digestive enzymes in granules which are
  discharged against pathogen or parasitic worms
  and Phagocyte antigen - antibody complexes

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Cells within the tissues of the Immune System
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Natural Killer Cells or NK

• To attack, cytotoxic T cells need to
• recognize a specific antigen,
• whereas natural killer or NK cells
• do not. Both types contain
• granules filled with potent
• chemicals, and both types
• kill on contact. The killer binds
• to its target, aims its weapons,
• and delivers a burst of lethal chemicals.

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Mature T cell Macrophages

• Bind to receptor on
• target cells
• Recruit other cells
• Can serve as interleukins
• in that they serve as a
• messenger between
• leukocytes or wbcs

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Antimicrobial Proteins

• Complement System
• 20 proteins which interact
• Attract phagocytes (call chemotaxis) to foreign
  cells and help destroy by promoting cell lysis

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Antimicrobial Proteins (cont.)

• Interferons
• Secreted produced by virus-infected cells
• Types alpha, beta, and gamma
• Stimulate production of proteins that inhibit
  viral replication (including neighboring cells)
• Not a virus-specific defense
• Works best against short-term infections such as
  colds and influenza
• Activates phagocytes which enhances their ability
  to ingest and kill microorganisms
• Can be mass produced to be tested as treatments
  for viral infections and cancer

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Inflammatory Response

• Occurs when there is damage to tissue due to
  physical injury or entry of microorganism
• Vasodilation of small vessels increases the blood
  supply to the area (redness)
• Dilated vessels become more permeable, allowing
  fluids to move in, resulting in a localized edema

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Inflammatory Response (cont.)

• Chemical signals initiate the inflammatory
  response
• Histamine released from cells called Basophils
  and mast cells in connective tissue
• Prostaglandins released from white blood cells
  and damaged tissue (cause increased blood flow)
• The increased blood flow delivers clotting
  elements which help block the spread of
  pathogenic microbes and begins the repair process

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Inflammatory Response (cont.)

• Macrophages destroy pathogens and clean up area
• Pus may develop before absorbed by the body
• Bone marrow may release more leukocytes
• Fever develops due to toxins produced or due to
  pyrogens released by leukocytes
• Fever can inhibit growth of some micros

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Complement System

• These complement proteins
• help the antibodies destroy
• bacteria
• The diagram shows the C1
• encountering an antibody bound
• to an antigen
• The end product punctures the
• cell membrane of the target cell

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Complements illustrated
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Section II

• Immune System Defends the Body Against Specific
  Invaders

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Antigen /Antibody Connection

• Foreign molecules, or antigens, carry
• distinctive markers, characteristic shapes
• called epitopes that protrude from their
  surfaces.
• Our Immune system has the ability to
• recognize many millions of distinctive
• non-self molecules, and to respond by
• producing molecules, or antibodies
• - also cells - that can match and counteract
• each one of the non-self molecules.

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Antigen/Antibody Continued (2)

• An antigen can be a bacterium or a virus, or even
  a portion or product of one of these organisms.
  Tissues or cells from another individual also act
  as antigens that's why transplanted tissues are
  rejected as foreign.
• How Antibodies are Produced

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Third Line of Defense

• Specificity recognize and eliminate
  microorganisms and foreign molecules
• Antigen foreign substances that elicit an
  immune response
• Can be molecules exhibited on the surface of,
  produced by, or released from bacteria, viruses,
  fungi, protozoans, parasitic worms, pollen,
  insect venom, transplanted organs, or worn-out
  cells
• Each has a unique molecular shape
• Stimulates production of an antibody that defends
  specifically against the particular antigen

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Third Line of Defense (cont.)

• Antibody antigen-binding
• immunoglobulin (protein),
• produced by B cells
• functions as the effector
• in an immune response.

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Third Line of Defense Continued

• Diversity ability to respond to invaders which
  are recognized by their antigenic markers
• Based on a variety of lymphocyte pops
• Each antibody-producing lymphocyte is stimulated
  by a specific antigen lymphocytes synthesize and
  secrete the appropriate antibody

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Third Line of Defense (cont.)

• Memory your immune system can recognize
  previously encountered antigens and react faster
• Acquired immunity is a resistance to some
  infection encountered earlier in life (e.g.
  chicken pox)
• Self/nonself recognition the ability to
  distinguish between the bodys own molecules
  versus foreign molecules
• Failure leads to autoimmune disorders which
  destroy bodys own tissue

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Active Versus Passive Acquired Immunity

• Active Immunity conferred by recovery from an
  infectious disease
• Depends on each persons immune system
• Acquired naturally from an infection or
  artificially by vaccination
• Vaccines can be inactivated bacterial toxins,
  killed microorganisms, or weakened living
  microorganisms
• Can no longer cause the disease
• Can act as antigens and stimulate immune response

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Active Versus Passive Acquired Immunity (cont.)

• Passive immunity can be transferred from one
  person to another by the transfer of antibodies
• Antibodies can cross the placenta to the fetus
• Some from nursing infants through milk
• Persists a few weeks or months until infants own
  system defends its body
• Can be transferred artificially from an animal or
  human already immune to the disease
• Rabies is treated by injecting antibodies from
  people vaccinated against rabies
• Short in duration, but permits your body to begin
  to produce antibodies against the virus

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Humoral Immunity and Cell-Mediated Immunity

• Humoral Immunity produces antibodies in response
  to toxins, free bacteria, and viruses
• Synthesized by certain lymphocytes and circulate
  in blood plasma and lymph
• Cell-mediated Immunity the response to
  intracellular bacteria and viruses, fungi,
  protozoans, worms, transplanted tissues, and
  cancer

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Cells of the Immune System

• Lymphocytes
• Responsible for both humoral and cell-mediated
  immunity in that there are two main classes B
  cells and T cells
• Develop from multipotent stem cells in bone
  marrow, differentiate when they reach the site of
  maturation
• B cells (B lymphocytes) the humoral immune and
  in the bone marrow until maturation
• T cells (T lymphocytes) the cell-mediated immune
  response migrate to the thymus gland to mature

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Types of cells B Cells

• B cells (B lymphocytes) the humoral immune and
  in the bone marrow until maturation

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Cells of the Immune System (cont.)

• Mature cells (B and T) are concentrated in the
  lymph nodes, spleen, and other lymphatic organs
• They are there to contact antigens
• Antigen receptors are on the membranes of both
• The receptors on a B cell are membrane-bound
  antibody molecules which will recognize specific
  antigens
• The T cell antigen receptors are proteins (not
  antibodies) embedded in the membrane which
  recognize specific antigens

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Cells of the Immune System (cont.)

• Effector Cells
• Actually defend the body during an immune
  response
• Result from a division of lymphocytes when the
  binding of antigens to their antigen receptors
• Activated Bs give rise to effector cells called
  plasma cells which secrete antibodies that
  eliminate the activating antigen
• Activated T cells produce two types
• Helper T cells secrete cytokines
• Cytotoxic T cells destroy infected and cancer
  cells

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Cells of the Immune System (cont.)

• Helper T cells
• secrete cytokines carry the
• T4 marker essential
• for turning on antibody
• production activate
• cytotoxic T cells
• Cytotoxic T cells
• destroy cells infected by
• viruses or cancer subset of
• T cells

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Cytokines

• Cytokine lymphokines can be produced by
  lymphocytes monokines by monocytes
  macrophages

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Section III

• Clonal Selection of Lymphocytes Basis for
  Immunological Specificity and Diversity

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Response Due to Diversity of Antigen-Specific
Lymphocytes

• Each lymphocyte will respond to only one antigen
• Determined during embryonic development before
  antigen are encountered
• Clonal Selection antigenic-specific selection
  of a lymphocyte that activates clones of effector
  cells that eliminate the antigen that provoked
  the initial immune response

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Response Due to Diversity of Antigen-Specific
Lymphocytes (cont.)

• When an antigen enters the body, it binds to
  receptors on specific lymphocytes those
  lymphocytes are activated and begin dividing
• These divisions make identical effector cells or
  clones that bind to the antigen that stimulated
  the response
• e.g., a B cell when activated, will proliferate
  to make plasma cells that secrete an antibody
  which acts as a antigen receptor for the specific
  antigen that activated the original B cell

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Section IV

• Memory Cells Action in a Secondary Immune Response

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Primary Immune Response

• Primary Immune Response the making of
  lymphocytes to form clones of effector cells
  specific to antigen
• 5 to 10 day lag between exposure and effector
  cells
• Lymphocytes to effector T cells plasma cells
  during this time period

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B cell/Helper T cell/Plasma cell
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2nd Immune Response

• 2nd immune response when the body is exposed to
  previously encountered antigens
• Response is faster and more prolonged
• Antibodies more effective at binding to antigen

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2nd Immune Response (cont)

• This is called immunological memory
• Based on memory cells produced during clonal
  selection
• Not active during primary response
• New clones of effector and memory cells are the
  2nd response

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Section V

• Self/nonself Recognition with Molecular Markers

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Surface of Lymphocytes

• Surfaces have antigen receptors that detect
  foreign molecules that enter the body
• No lymphocytes reactive against the bodys own
  molecules under normal conditions

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Surface of Lymphocytes (cont.)

• Self-tolerance lack of a destructive immune
  response to the bodys won cells
• Develops (before birth) when T B lymphocytes
  begin to mature in the thymus and bone marrow
• Any lymphocytes with receptors for molecules
  present in the body at that time are destroyed
• Only has antigen receptors for foreign molecules

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Surface of Lymphocytes (cont.)

• Mayor histocompatibility complex (MHC or HLA) are
  glycoproteins within the plasma membrane
  Histocompatibility Molecules
• Self-markers coded by a family of genes
• 20 MHC genes 100 alleles for each gene
• No one has the same markers except identical
  twins
• Two main classes of MHC molecules
• Class 1 MHC molecules on nucleated cells (fig.
  43.16)
• Class 2 MHC molecules on specialized cells like
  (fig. 43.17) macrophages, B, and active T cells

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Section VI

• The Humoral Response B Cells Defend against
  Pathogens by Generating Specific Antibodies

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Background Facts

• B cells differentiate into a clone of plasma
  cells that secrete antibodies (fig. 43.17)
• Most effective against pathogen is blood or lymph
• Memory cells produce and form the basis for 2nd
  immune response

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Activation of B Cells

• First step binding of the antigen to specific
  antigen-receptors on the surface of B cells
• 2nd step is the B cell activation involving
  macrophages helper T cells ends with the
  production of plasma cells (p. 909 fig 43.14 p.
  911, fig 43.17)
• Macrophage phagocytes pathogens

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Activation of B cells (cont.)

• Pieces of digested antigen bind to class 2 MHC
  molecules that are moved and present on the
  surface of macrophage
• This is called an antigen-presenting cell
• Helper T cell specific of the presented antigen
  binds to self/nonself MHC complex
• T cell is activated and forms a clone of helper T
  cells

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Activation of B cells (cont.)

• These T cells secrete cytokines which elicit
  other B cells with the same antigen
  (Fig. 43.17)
• T cell contact activates these B cells to form a
  clone of plasma cells
• Each plasma cell (effector cell) then secretes
  antibodies specific for the antigen

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Antibody and cell mediated Responses
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Activation of B cells (cont.)

• Each macrophage can display a of different
  antigens depending on the type of pathogen
  phagocytized
• B cells again are specific and can bind to and
  display only one type of antigen
• Macrophages are nonspecific can enhance
  specific defense by selectively activating helper
  T cells which in turn activate B cells specific
  for the antigen
• Helper T cells are antigen-specific

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T-dependent T-independent Antigens

• T-dependent antigens antigens that evolve the
  cooperative response involving macros, helper
  Ts, B cells
• T-independent antigens antigens that trigger
  humoral immune responses without macrophage or T
  cell involvement
• Stimulated by the antigen which binds to several
  antigen receptors on the B cells surface

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T-dependent T-independent Antigens (cont.)

• Usually weaker
• No memory cells are generated
• Whether dependent or independent, a B cell gives
  rise to a clone of plasma cells
• Each effector cell secretes up to 2000 antibodies
  / sec for 4 to 5 days

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Molecular Basis of Antigen-Antibody Specificity

• Antigens are proteins or large polysaccharides of
  the outer part of pathogens or transplanted cells
• Can be coats of viruses, capsules, and cell walls
  of bacteria
• Molecules of transplanted tissues and organ or
  blood cells are recognized as foreign
• Antibodies recognize the surface of an antigen or
  the epitope, not the entire antigen molecule (see
  fig. fig 43.10), sometimes call the antigenic
  determinant

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Molecular Basis of Antigen-Antibody Specificity
(cont)

• Antibodies are Proteins in a Class Called
  Immunoglobulins (lgs)
• See fig. 43.18
• Structure associated with its function
• Y-shaped with 4 polypeptide chains two identical
  light chains and two identical heavy chains
• All 4 chains have constant C regions that vary
  little in a.a. sequence

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Molecular Basis of Antigen-Antibody Specificity
(cont)

• At the tips of the Y are variable (V) regions
  show extensive variation from antibody to
  antibody
• Functions as antigen-binding sites that result in
  specific shapes that fit and bind to specific
  antigen epitopes
• This site is responsible for the antibodys
  ability to identify specific epitope and stem
  (constant) regions through which the antibody
  inactivates or destroys the antigenic invader

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Molecular Basis of Antigen-Antibody Specificity
(cont)

• 5 types of constant regions which are the five
  major classes of mammalian immunoglobins (table
  43.18)
• IgM 5 Y-shapes monomers appear in the initial
  exposure to an antigen
• IgG most abundant fights against bacteria,
  viruses, and toxins in blood
• IgA in mucous membranes prevent bacteria and
  viruses from attaching to epithelial surfaces in
  saliva, tears, perspiration
• IgD found on B cells initiates differentiation
  of B cells
• IgE stimulates basophils and mast cells to
  release histamine and cause allergic reaction
  when triggered by an antigen

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Section VII

• In the Cell-Mediated Response, T Cells defend
  Against Intracellular Pathogens

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The Cell-Mediated Immune Response

• It is the defense that combats pathogens that
  have already entered cells
• Key components are helper T cells (TH) and
  cytotoxic T cells (TC)
• T cells cannot detect free antigens in the body
  fluids
• The receptor of a helper T cell recognizes the
  molecular combination of an antigen fragment with
  a class 2 MHC

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The Cell-Mediated Immune Response (cont.)

• The receptor of a cytotoxic T cell recognizes the
  combination of an antigen fragment with a class 1
  MHC molecule
• The MHC-antigen complex displayed on an infected
  body cell stimulates T cells to multiply and form
  clones of TH and TC which recognized the pathogen

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The Cell-Mediated Immune Response (cont.)

• (TH) cells stimulate B cells to secrete
  antibodies against T-dependent antigens in a
  humoral response
• (TH) cells also activate other types of T cells
  to mount cell-mediated responses to antigens
• Helper T cells are able to stimulate other
  lymphocytes by receiving and sending cytokines
  such as interleuking-2. Increased levels of
  cytokines also increase the cell-mediated
  response by stimulating another class of T-cells
  into cytotoxic cells (effector cells)

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Section VIII

• Complement Proteins Participate in Both
  Nonspecific and Specific Defenses

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Complement Proteins circulate in the Blood in
Inactive Forms

• Complement protein attaches to, and bridges the
  gap between, two adjacent antibody molecules
• This antibody-complement activates proteins to
  from a membrane attack complex

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Complement Proteins circulate in the Blood in
Inactive Forms (cont.)

• This membrane attack complex lyses the pathogens
  membrane producing a lesion and the lyses of the
  cell
• There is also a nonspecific defense mechanism
• Complement and phagocytes work together two ways
• Opsonization where the proteins attach to a
  foreign cell and stimulate phagocytes to engulf
  the cell
• In immune adherence, where they coast a microbe
  which causes to adhere to blood vessel walls and
  sets it up for circulating phagocytes