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Immunology I cquired immunity

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					Immunology I                                    IB Topic 6.3 and 11.1
The vertebrate body possesses two mechanisms which protect it from potentially dangerous
viruses, bacteria, other pathogens, and abnormal cells which could develop into cancer.

   One of these mechanisms is nonspecific, that is, it does not distinguish between infective
    agents.

   The second mechanism is specific in that it responds in a very specific manner (production
    of antibodies) to the particular type of infective agent.

I   Nonspecific mechanisms

        An invading microbe must cross the external barrier formed by the skin and mucous
        membranes.
       If the external barrier is penetrated, the microbe encounters a second line of defense:
        interacting mechanisms of phagocytic white blood cells, antimicrobial proteins, and the
        inflammatory response.
6.6.3
    A. The Skin and Mucous Membranes

        The skin and mucous membranes act as physical barriers preventing entry of pathogens

        Pathogen = disease causing organism; bacteria, virus, protest, fungi, animals like worms

           In humans, oil and sweat gland secretions acidify the skin (pH 3 – 5) which
            discourages microbial growth.
           The normal bacterial flora of the skin (adapted to the acidity) may release acids and
            other metabolic wastes to further inhibit pathogen growth.
           Saliva, tears and mucus secretions also wash away potential invading microbes in
            addition to containing antimicrobial proteins.
           An enzyme (lysozyme) in perspiration, tears, and saliva attacks the cell walls of
            many bacteria and destroys other microbes entering the respiratory system and eyes.
           In the respiratory tract, nostril hairs filter inhaled particles and mucus traps
            microorganisms that are then swept out of the upper respiratory tract by cilia.
           In digestive tract, stomach acid kills many bacteria.

6.3.4
    B. Phagocytic White Cells and Natural Killer Cells

        Neutrophils (kamikazes) are cells that become phagocytic in infected tissue.

           Comprise 60% - 70% of total white cells.
           Attracted by chemical signals, they enter infected tissues by amoeboid movement,
            only live a few days as they destroy themselves when destroying pathogens.

        Macrophages are large amoeboid cells that use pseudopodia to phagocytize (eat)
microbes.
                  Fixed macrophages are especially numerous in the lymph nodes and spleen. This is
                   why lymph nodes swell when you are fighting off a cold or flu virus.


Nice to know

           Natural killer cells destroy the body’s own infected cells, especially those harboring
viruses.
                  Also assault aberrant cells that could form tumors.
                  Are not phagocytic.

6.6.11
     C. The Inflammatory Response

            A localized inflammatory response occurs when there is damage to a tissue due to
            physical injury or entry of microorganisms.

                 Vasodilation (increase in size of blood vessel) of arterioles near the injury increases
                  the blood supply to the area which produces the characteristic redness.
                 The dilated (increased diameter) vessels become more permeable allowing fluids to
                  move into surrounding tissues resulting in localized edema.
                 Histamine is released from injured cells.
                 Histamine causes the swelling and redness


            Migration of phagocytic cells into the injured area is also a result of increased blood
            flow and increased leakage from the capillaries.

II.          Specific invaders

             The immune system is the body’s third line of defense and is very specific in its
             response.

                  Distinguished from nonspecific defenses by: specificity, diversity, self/nonself
                   recognition, and memory.

                Specificity refers to this system’s ability to recognize and eliminate particular
                microorganisms and foreign molecules.

                Antigen = A foreign substance that elicits an immune response.

                Antibody = An antigen-binding immunoglobulin (protein), produced by B cells.

Antigens may be molecules exhibited on the surface of, produced by, or released from bacteria,
viruses, fungi, protozoans, parasitic worms, pollen, insect venom, f

          Self/nonself recognition is the ability of the immune system to distinguish between the
      body’s own molecules and foreign molecules (antigens), i.e. how do cell’s “see” if they c
      can’t “see?”
11.1.3
     D. Active Versus Passive Acquired Immunity amrik is cool

         Active immunity is the immunity conferred by recovery from an infectious disease,

                May be acquired naturally from an infection to the body or artificially by
                 vaccination.
                Vaccines may be inactivated bacterial toxins, killed microorganisms, or weakened
                 living microorganisms.

                 = In all cases the vaccine can no longer cause the disease but can provide antigens
                   To stimulate an immune response.

           Passive immunity = immunity which has been transferred from one individual to
          another by the transfer of antibodies.

                      Natural occurrence when antibodies cross the placenta from a pregnant
                       woman’s system to her fetus.
                      Passive immunity provides temporary protection to newborns whose immune
                       systems are not fully operational at birth.
                      Some antibodies are transferred to nursing infants through the milk.
                      Persists for only a few weeks or months after which the infant’s own system
                       defends its body.
                      May also be transferred artificially from an animal or human already immune to
                       the disease.

                       = Rabies is treated by injecting antibodies from people vaccinated against
                                                       rabies; produces an IMMEDIATE immunity
                                                important to quickly progressing infections.
                                                Is this ACTIVE OR PASSIVE IMMUNITY?
11.1.2
C.        Humoral Immunity and Cell-Mediated Immunity

          The body will mount either a humoral response or a cell-mediated response depending
          on the antigen which stimulates the system.

          Humoral immunity (AKA plasma-mediated immunity) produces antibodies in response
          to toxins, free bacteria, and viruses present in the body fluids.

          Cell-mediated immunity is the response to intracellular bacteria and viruses, fungi,
          protozoans, worms, transplanted tissues and cancer cells.


D.        Cells of the Immune System

                    Early B and T cells (as well as other WBCs) develop from stem cells in the bone
                     marrow. They only differentiate after reaching their site of maturation.
               B cells (B lymphocytes) are responsible for the humoral immune response.

                = B cells form in the bone marrow and remain there to complete their maturation.

               T cells (T lymphocytes) are responsible for the cell-mediated immune response.

                = T cells also form in the bone marrow, then migrate to the thymus gland to
                mature.

           Mature B cells and T cells are concentrated in the lymph nodes, spleen and other
           lymph organs.

           Plasma cells are the cell, which actually defend the body during an immune
           response.

                Activated B become plasma cells which secrete antibodies (humoral response)
                 that “handcuff” the antigen and/or pathogen.
                Activated T cells may produce two types of cells: cytotoxic T cells which destroy
                 infected cells and cancer cells; and helper T cells which secrete cytokines.

           Cytokine = Molecules secreted by one cell to activate other cells.

                Cytokines help regulate both B and T cells and thus are involved in both the
                 humoral and cell-mediated responses.


III.   Clonal selection

                Each B and T cell will recognize and respond to only one antigen.
                When an antigen enters the body and binds to receptors on the specific B or T
                 cell, the cells are activated and begin to divide.

                 = The divisions produce a large number of clones, which bind to the antigen

                 = If, for example, a B cell is activated, it will proliferate (reproduce) by
                 mitosis to produce a large number of plasma cells that will each secrete an
                 antibody which functions as an antigen receptor for the specific antigen that
                 activated the original B cell.

                The activated B or T cells proliferate to produce a clone of millions of effector
                 cells, which are specific for the original antigen (clonal selection).

           Clonal selection = Antigen-specific selection of a lymphocyte that activates it to
               produce clones of B or T cells dedicated to eliminating the antigen that
               provoked the initial immune response.



 IV.           Memory cells
             The primary immune response is the increase in number of B and T cells to form
             clones of specific to an antigen during the body’s FIRSTt exposure to the
             antigen.

                       There is a 5 to 10 day lag period between exposure and maximum
                        production of antibodies
                       The B or T cells selected by the antigen are differentiating into killer T cells
                        and plasma B cells during the lag period.

          A secondary immune response occurs when the body is exposed to a previously
          encountered antigen.

                      The response is faster (3 to 5 days) and more prolonged than a primary
                       response.
                      The antibodies produced are also more effective at binding the antigen.
                      When the same antigen that caused a primary immune response again enters
                       the body, the memory cells are activated and rapidly proliferate to form a new
                       clone of effector cells and memory cells.
                      These new clones of effector and memory cells are the secondary immune
                       response.

V.     Self/nonself recognition

       Self-tolerance = The lack of a destructive immune response to the body’s own cells.
             Any lymphocytes with receptors for molecules present in the body are
                 destroyed in utero; the body contains no lymphocytes with antigen receptor for
                 its own molecules, only for foreign molecules.

       The major histocompatibility complex (MHC) is a group of glycoproteins embedded in
       the plasma membranes of cells.
            Important “self-makers”
            The probability that two individuals will have matching MHC sets is virtually zero
              unless they are identical twins.

VI.    The humoral response

       The humoral response occurs when an antigen binds to B cell receptors
       The B cells differentiate into a clone of plasma cells, which begin to secrete antibodies.
        These antibodies are most effective against pathogens circulating in the blood or
          lymph.


      A. The Activation of B cells

      Often a two- step process.

           One step is the binding of the antigen to a specific antigen-receptors on the surface of
            the B cell.

      The other step in B cell activation involves macrophages and helper T cells;
          After macrophages phagocytize pathogens, pieces of the partially digested antigen
           molecules are bound to the surface of the macrophage. Like in the old days when
           attackers had their heads cut off and put on pikes.
          These presented antigen molecules result in the macrophage functioning as an
           antigen-presenting cell.(a pike with a head on it)
          A T cell with a receptor specific for presented antigen recognizes the antigen (head)
          The T cell is “activated” to form helper T cells
          These helper T cells secrete cytokines (chemicals) which stimulate B cells.
          Each plasma cell (=effector cell) then secretes antibodies specific for the antigen.


Antigen-Antibody
Antibodies comprise a specific class of proteins called immunoglobulins (Igs)

               Antibodies are Y-shaped molecules
There are five types of constant regions: You don’t need to know these.
IgM: circulating antibodies which appear in response to an initial exposure to an antigen.
IgG: protects against bacteria, viruses, and toxins circulating in blood and lymph; triggers
complement system action.
IgA: prevents attachment of bacteria and viruses to epithelial surfaces
IgD: probably functions as an antigen-receptor which initiates differentiation of B cells.
IgE: stimulates mast cells and basophills, to release histamine and other chemicals

How Antibodies Work
         Antibodies do not directly destroy an antigenic pathogen. The antibody binds to the
         antigen to form an antigen-antibody complex which gets eaten by macrophages.

Monoclonal Antibody Technology
Monoclonal antibodies: Defensive proteins produced by cells descended from a single cell;
all antibodies produced b these cells are identical.
These monoclonal antibodies:
Can be used in diagnositc labs to detect pathogenic microbes in clinical samples. (ie. HIV
antibodies)
Form the basis for over-the-counter pregnancy tests (HCG in female urine)
Are used as therapeutic agents
Show promise in treating cancer
Monoclonal antibodies are produced by hybridoma cells from the fusion of certain cancer
cells (myelomas) with normal antibody-producing plasma cells.
They will produce a single type of antibody and can be cultured indefinitely to manufacture that
antibody on a larger scale.


Blood Groups
The human ABO blood groups provide a good example of nonself recognition
Individuals of blood type A have the A antigen and make anti-B antibodies
Individuals of blood type B have the B antigen and make anti-A antibodies
Individuals of blood type AB have the A and B antigen and make no antibodies
Individuals of blood type O have neither the A nor B antigen make anti-A and anti-B antibodies
Blood group antibodies can cause blood of a different antigenic type to agglutinate, a life-
threatening reaction.
Type O individuals are universal donors since their blood has neither antigen.
Type AB individuals are universal recipients since they produce neither antibody A or antibody B
Usually IgM class antibodies do not cross the placenta, thus they present no harm to a developing
fetus with a blood type different from the mother.

Tissue Grafts and Organ Transplants
The MHC is a biochemical fingerprint unique to each individual
The MHC complicates tissue grafts and organ transplants since foreign MHC molecules are
antigens and cause cytotoxic T cells to mount a cell-mediated response.

Skip this part unless you want to understand allergies.
Abnormal immune function leads to disease states
Autoimmune disease: the immune system reacts against self
Allergy: a hypersensitivity of the body’s defense system to an environmental antigen called
an allergen
Antibodies recognize poll as allergens
The mast cell cause release of histamine and other inflammatory agents.
Histamine cause dilation and increased permeability of small blood vessels which results in the
common symptoms of an allergy.
Anti-histamines are drugs used to treat allergies since they interfere with the action of histamine.
Anaphylactic shock is a life-threatening reaction to injected or ingested antigens
Death may occur in a few minutes
         This hypersensitivity may be associated with foods or insect venom.
         Epinephrine may be injected to counteract the allergic response.

Immunodeficiency
Immunodeficiency refers to a condition where an individual is inherently deficient in either
humoral or cell-mediated immune defense.
Not all cases of immunodeficiency are inborn conditions
Some viral infections cause depression of the immune system (AIDS)
         Acquired immunodeficiency syndrome is a severe immune system disorder caused by
         infection with the human immunodeficiency virus (HIV)
           Characterized by a reduction of T cells and the appearance of characteristic secondary
           infections
           Mortality rate approaches 100%
           HIV probably evolved from another virus in central Africa and may have gone
           unrecognized for many years.
           The immune system is devastated by HIV since the virus targets helper T cells which
           play a central role in both the humoral and cell-mediated responses.
           The HIV may also remain as a provirus in the infected cell genome for many years
           before becoming active.
         HIV is not eliminated from the body by antibodies for several reasons:
           The virus is invisible to the immune system
           The virus undergoes rapid mutational changes in antigens during replication which
           eventually overwhelms the immune system
           The population of helper T-cells eventually declines to the point where cell-mediated
           immunity collapses.
         AIDS is the late stage of HIV infection and is defined by a reduced T cell population
         and the appearance of secondary infections.
           Takes an average of about ten years to reach this stage of infection
           Individuals exposed to HIV have circulating antibodies that can be detected; displaying
           these antibodies designates an individual as HIV-positive
         HIV is only transmitted through the transfer of body fluid, blood or semen, containing
         infected cells.
           Most commonly transmitted in the US and Europe through unprotected sex between
           male homosexuals and unsterilized needles in intravenous drug users.
           In Africa and Asia, transmission through unprotected heterosexual sex is increasing
         AIDS is currently considered an incurable disease
           The best way to prevent additional infections is to educate people on how the disease is
           transmitted and how to protect themselves.

				
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Description: Immunology I cquired immunity