Introduction to Immunology
What is immunity?
 We are surronded by             Function of immune
  bacteria,viruses, and fungi,     system
  swarms on our skin and
  invades our inner               Defends body against these
  passageways!!!                   small foreign invaders
 Immunity: is the ability        To distinguish between self
  of organism to resist            (normal component of the
  infection by any foreign         body) and non-self (foreign
  (non-self) invaders              component)s
       The Immune System
     The immune system is the body's defense against infectious
      organisms and other invaders.
     Each exposure (to the same pathogen) increases the effectivity
      of the response
     Primary Lymphoid organs of the immune system
       I. Thymus
       II. Bone marrow
       Secondary lymphoid organs
       I. Lymph nodes
       II. Spleen
       III. Skin
       IV. liver
       V. Tonsils
3      VI. Small intestine
The Immune System
Immune system is divided into:
 innate Immune system         Acquired Immune system
 There is immediate maximal     There is a lag time between
           response           exposure and maximal response
        Non-specific                      specific
   Exposure results in no     Exposure results in immunologic
   immunologic memory                    memory
Non-specific immune System       Specific immune System
     (innate or natural)          (adaptive or acquired)
                             Immune system
                   Acquired                       Innate
                 immune system                 immune system
      Humoral              Cellular      1st line of   2nd line of
(antibody mediated)    (Cell mediated)   defense       defense
  immune response      immune response
                                           Skin        Inflammation
 B-lymphocytes        T-lymphocytes       Mucous        Phagocytosis
                                         membrane       Complement
                                                       Natural killers
                                                          Cytokines
Defense Against Disease
             Nonspecific External Barriers
             skin, mucous membranes
              If these barriers are penetrated,
              the body responds with
             Innate Immune Response
             phagocytic and natural killer cells,
             inflammation, fever
        If the innate immune response is insufficient,
        the body responds with
         Adaptive Immune Response
         cell-mediated immunity, humoral immunity
INNATE IMMUN SYSTEM
                               Is consists of:
 Innate immunity refers to     Anatomic Barriers (skin and
                                   mucous membrane)
  nonspecific defense             Stomach acid and
  mechanisms that come into        enzymes(lyzozymes)
  play immediately or within      Tear & saliva
  hours of an antigen's           Phagocytosis (phagocytes)
                                   Interferon
  appearance in the body.         Complement system
 These mechanisms include        NK (natural killer)
  physical barriers               mast cells
                                  Inflammatory reaction
                                  innate immune System(Natural)
The first lines of defense (Anatomical barriers ):
      The natural barriers
  1- the skin                               2- mucous membranes
That protect organ system open to the external environment such as the digestive, respiratory, reproductive system and
urinary system
First line of defense
  Non-specific defenses are designed to prevent infections
   by viruses and bacteria. These include:
    Intact skin
    Mucus and Cilia
  Role of skin
 Dead skin cells are constantly
  sloughed off, making it hard for
  invading bacteria to colonize.
 Sweat and oils contain anti-
  microbial chemicals, including
  some antibiotics.
   Role of mucus and cilia
 Mucus contains lysozymes, enzymes
  that destroy bacterial cell walls.
 The normal flow of mucus washes
  bacteria and viruses off of mucus
  membranes.
 Cilia in the respiratory tract move
  mucus out of the lungs to keep
  bacteria and viruses out.
 Second Line defences
 Role of phagocytes
 Phagocytes are several types of white
  blood cells (including macrophages and
  neutrophils) that seek and destroy
  invaders. Some also destroy damaged
  body cells.
 Phagocytes are attracted by an
  inflammatory response of damaged
  cells.
Role of inflammation
  Inflammation is signaled by mast cells, which release
   histamine.
  Histamine causes fluids to collect around an injury to
   dilute toxins. This causes swelling.
  The temperature of the tissues may rise, which can kill
   temperature-sensitive microbes.
Role of fever
  Fever is a defense mechanism that can destroy many types
   of microbes.
  Fever also helps fight viral infections by increasing
   interferon production.
  While high fevers can be dangerous, some doctors
   recommend letting low fevers run their course without
   taking aspirin or ibuprofen.
Complement:
•   Complement is not a cell but a group of proteins
•   set of about 30 different kinds of proteins that circulate in an inactive form in the blood
•   These proteins can act together (in complement) with other defense mechanisms
•   made in the liver
•   Activated by infection,
•   activated complements:
     – help to recruit phagocytes to site of inflammation and activate them
     – bind to receptors on phagocytes, helping to remove agent of infection
     – form pores in the invader or infected cell’s membrane (like the NKs do)
     – activate mast cells to release histamine and other factors
     – Certain complement proteins also help trigger the inflammatory responses
Natural killer cells (NK cells)
NK Cells, known as Natural Killer Cells, target virus infections
and tumors. They usually take 3 days to become active. When
active they will destroy the infected cells.
 instead of attacking the invaders, they attack the body’s own
   cells that have become infected by viruses
 they also attack potential cancer cells, often before they form
   tumors
 they bind to cells using an antibody “bridge”, then kill it by
   secreting a chemical (perforin) that makes holes in the cell
   membrane of the target cell. With enough holes, the cell will
   die.
Cytokines
 Chemical messengers
 Cytokines are small secreted proteins released by cells have a specific
  effect on the interactions and communications between cells.
 Cytokine is a general name; other names include lymphokine
  (cytokines made by lymphocytes), monokine (cytokines made by
  monocytes), chemokine (cytokines with chemotactic activities), and
  interleukin (cytokines made by one leukocyte and acting on other
  leukocytes).
Cytokines
 Cytokines may act on the cells that secrete them (autocrine
  action), on nearby cells (paracrine action), or in some instances on
  distant cells (endocrine action)
Specific defenses
  Specific defenses are those that give us immunity to
   certain diseases.
  In specific defenses, the immune system forms a chemical
   “memory” of the invading microbe. If the microbe is
   encountered again, the body reacts so quickly that few or
   no symptoms are felt.
Major players
  The major players in the immune system include:
    Macrophage
    T cells (helper, cytotoxic, memory)
    B cells (plasma, memory)
    Antibodies
Dual Nature of Adaptive Immunity
 T and B cells develop from stem cells in red bone marrow
                                                            Figure 17.8
Dual Nature of Adaptive Immunity
 Red bone marrow stem cells produce lymphocytes
 1. B cells -Humoral immunity
 Some lymphocytes that mature in redbone marrow become B cells.
 Antibody production
 Antibodies are found in serum and lymph.
 2. T cells - Cell-mediated immunity
 Some lymphocytes migrate through the thymus become T cells (T-
  lymphocytes)
 Activation of macrophages, natural killer cells (NK)
 Antigen-specific cytotoxic T-lymphocytes
 Release of various cytokines in response to an antigen.
The Nature of Antigens
 Antigen (Ag): A substance that causes the body to produce specific
  antibodies or sensitized T cells
   Antibodies (Ab) interact with epitopes or antigenic determinants
 Hapten: Antigen is combined with carrier molecules
Antigens
           Figure 17.1
Hapten: a small molecule that is antigenic but incapable by itself
of inducing a specific immune response.
                                                            Figure 17.2
      Antibodies
 Antibody is a large Y-shaped protein an
  immunoglobulin (Ig)
 They are secreted form of the B-cell
  receptor
 The antibody recognizes a unique part
  of the antigen       – epitope( a
  portion of a molecule to which an
  antibody binds) or antigenic
  determinants.
 Antibody Structure
The Ig monomer consists
of four paired polypeptide
chains connected by
disulfide bonds.
Two identical heavy chains
Two identical light chains
Each chain has two
domains: one constant
domain (C) and
one variable domain (V)
The type of heavy chain
present defines the class
of antibody (IgA, IgD, IgE,
IgG, and IgM)
                              Figure 17.3a,b
Antibodies
             Figure 17.3c
IgG Antibodies
 Monomer
 80% of serum Ab
 Fix complement
 In blood, lymph, and intestine
 Cross placenta
 Enhance phagocytosis; neutralize toxins and viruses; protects fetus
  and newborn
 Half-life = 23 days
IgM Antibodies
 Pentamer
 5–10% of serum Abs
 Fix complement
 In blood, in lymph, and on B cells
 Agglutinates microbes; first Ab produced in
  response to infection
 Half-life = 5 days
IgA Antibodies
 Dimer
 10–15% of serum Abs
 In secretions, (mucus, salvia, tears, and breast milk)
 Mucosal protection
 Half-life = 6 days
IgD Antibodies
 Monomer
 0.2% of serum Abs
 In blood, in lymph, and on B cells
 On the surface of B cells, initiate immune response
 Half-life = 3 days
IgE Antibodies
 Monomer
 0.002% of serum Abs
 On mast cells, on basophils, and in blood
 Allergic reactions; lysis of parasitic worms
 Half-life = 2 days
Antibodies as Receptors
 Antibodies can attach to
  B cells, and serve to
  recognize foreign
  antigens.
    Antigens as Effectors
 Free antibodies can bind
  to antigens, which “tags”
  the antigen for the
  immune system to attack
  and destroy.
Antigen recognition
 Cells of the immune system are “trained” to recognize “self ”
  proteins vs.
 If an antigen (“not self ”) protein is encountered by a
  macrophage, it will bring the protein to a helper        T-cell for
  identification.
 If the helper T-cell recognizes the protein as “not self,” it will
  launch an immune response.
Helper T cells
  Helper T-cells have receptors for recognizing antigens. If
   they are presented with an antigen, they release cytokines
   to stimulate B-cell division.
  The helper T-cell is the key cell to signal an immune
   response. If helper T-cells are disabled, as they are in
   people with AIDS, the immune system will not respond.
 B cells
 B-cells in general produce antibodies. Those with
  antibodies that bind with the invader’s antigen are
  stimulated to reproduce rapidly.
 B-cells differentiate into either plasma cells or memory B-
  cells.
 Plasma cells rapidly produce antibodies. Memory cells
  retain the “memory” of the invader and remain ready to
  divide rapidly if an invasion occurs again.
Clonal Selection
Role of antibodies
  Antibodies released into the blood stream will bind to the
   antigens that they are specific for.
  Antibodies may disable some microbes, or cause them to
   stick together (agglutinate). They “tag” microbes so that
   the microbes are quickly recognized by various white
   blood cells.
“Killer” T cells
  While B-cells divide and differentiate, so do T-cells.
  Some T-cells become cytotoxic, or “killer”     T-cells.
   These T-cells seek out and destroy any antigens in the
   system, and destroy microbes “tagged” by antibodies.
  Some cytotoxic T-cells can recognize and destroy
   cancer cells.
Calling a halt
  When the invader is destroyed, the helper          T-cell
   calls a halt to the immune response.
  Memory T-cells are formed, which can quickly divide and
   produce cytotoxic T-cells to quickly fight off the invader if
   it is encountered again in the future.
                          Induced Immunity (acquired immune response)
                  Active immunity                                           Passive immunity
      Production of a person’s own antibodies. Long        1. An individual is given antibodies by another (received
                          lasting                             of premade antibodies)
                                                           2. Short-term resistance (weeks- 6months)
                                                           3.Passive immunity is temporary because the
   Natural Active              Artificial Active             recipient’s immune system is not stimulated by
When pathogen enters       • Vaccination – usually           antigen
body in the normal way,      contains a safe antigen from
we make antibodies           the pathogen.
                           • Person makes antibodies          Natural Passive               Artificial Passive
                             without becoming ill         •Fetus obtains antibodies     • Gamma globulin injection
                                                          from its mother’s             • extremely fast, but short
                                                          bloodstream.                    lived
                                                          •Baby receives antibodies     • (e.g. snake venom, which
                                                          in breast milk                  controlled by injecting the
                                                                                          victim with antivenin)
Types of Acquired Immunity
 Naturally acquired active immunity
   Resulting from infection
 Artificially acquired active immunity
   Injection of Ag (vaccination)
 Naturally acquired passive immunity
   Transplacental or via colostrum
 Artificially acquired passive immunity
   Injection of Ab
      Two types of acquired immune
      response:           2- The cell- mediated immune response:
1- The humoral immune response:          -    produced by T cells
- involves the secretion of antibodies   -    this defensive system results from the
by B cell into the blood and lymph, -        action of defensive cells rather than the
the humoral defense defends primary           defensive proteins of the humoral
against bacteria and viruses present         response
in body fluids                              -certain T cells attack body cells that
 - this defense can be passively            are infected with bacteria or viruses,
   transferred by injecting blood            others
   plasma (containing antibodies)             function indirectly by promoting
   from an immune individual into a          phagocytosis by other blood cells and
   non immune individual                     by
                                              stimulating B cells to produce
                                             antibodies
The Results of Ag-Ab Binding
                               Figure 17.7
Agglutination
                Figure 17.7
Opsonization
               Figure 17.7
Complement Fixation
                      Figure 17.7
Antibody-Dependent Cell-Mediated Immunity
                                    Figure 17.7
Neutralization
     ANIMATION Humoral Immunity: Antibody Function
                                                     Figure 17.7