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stork kau edu sa Files files ImmuneS

VIEWS: 6 PAGES: 44

									Chapter six:
The Immune System




       Dr. Sanaa Tork
In this chapter you will learn about :
1. What Is the Immune System and what does It do? The immune
   system is the body's defense against infectious organisms and
   other invaders.
2. The immune system is made up of a network of cells, tissues,
   and organs that work together to protect the body.
3. Distinguish between internal defense mechanisms of
   invertebrates and vertebrates
4. Distinguish between specific and nonspecific immune responses
5. The cells that are part of this defense system are white blood
   cells, or leukocytes.
6. Leukocytes are produced or stored in many locations throughout
   the body, including the thymus, spleen, and bone marrow. For
   this reason, they are called the lymphoid organs. There are also
   clumps of lymphoid tissue throughout the body, primarily in the
   form of lymph nodes, that house the leukocytes. The leukocytes
   circulate through the body between the organs and nodes by
   means of the lymphatic vessels.

                                Dr. Sanaa Tork
7. Two basic types of leukocytes combine to seek out and destroy the
   organisms or substances that cause disease. The phagocytes: are cells
   that chew up invading organisms. The most common type is the
   neutrophils which primarily fight bacteria. The lymphocytes: are
   cells that allow the body to remember and recognize previous invaders.
8. There are two kinds of lymphocytes: the B lymphocytes and the T
   lymphocytes. Lymphocytes start out in the bone marrow and either
   stay there and mature into B cells, or they leave for the thymus gland,
   where they mature into T cells.
9. B lymphocytes and T lymphocytes have separate jobs to do: B
   lymphocytes are like the body's military intelligence system, seeking
   out their targets and sending defenses to lock onto them. T cells are
   like the soldiers, destroying the invaders that the intelligence system
   has identified.
10.Explain the meaning of antigen (a foreign substance that invades the
   body and can detect by several types of cells work together to
   recognize and respond to it. These cells trigger the B lymphocytes to
   produce antibodies)
11.Antibodies are specialized proteins that lock onto specific antigens.
12.Compare active and passive immune system

                                 Dr. Sanaa Tork
13. Disorders of the immune system can be broken down into four
    main categories: immunodeficiency disorders (primary or
    acquired) , autoimmune disorders (in which the body's own
    immune system attacks its own tissue as foreign matter),
    allergic disorders (in which the immune system overreacts in
    response to an antigen), cancers of the immune system




                            Dr. Sanaa Tork
                   Foreign invaders - viruses, bacteria, allergens
                                Immunity
                   parasites- constantly bombard our body.
Pathogens
-Bactria
-Virus
-Parasite
-Fungi                       Foreign invaders
                                (Non-self)
 Transplantation


 Vaccination
                                         Immunity
    The ability of organism to resist infection by any forgein invaders (non-self)

                                 The Immune System

Is an interacting set of specialized cells and proteins designed to identify and destroy foreign
invaders and abnormal substances befor they can damage the body.

Function of immune system:
Defends body against foreign invaders
Can distinguish between self (normal component of the body) and non-self (foreign component)

                                                Dr. Sanaa Tork
Immune system divided into:


Non-specific immune System                Specific immune System
     (innate or natural)                   (adaptive or acquired)




         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 memory               immunologic memory

                                 Dr. Sanaa Tork
                 Innate defense against infection
• All animals have some form of innate immunity (first line of defense)
• Innate immune response are defenses that act the same whether or not an invader has
  been encountered.
1.Invertebrate immune system:
Invertebrates rely only on the innate immunity for example:
Insects :
a)have an exoskeleton, which is a dry barrier that keeps out of bacteria and viruses.
b)Pathogens that breach that external defense confront a set of internal defense like: low
  pH and secretion of lysozyme (digest cell wall of many bacteria)
c)Circulating insect immune cells are capable of phagocytosis, engulfing and destroying
  foreign invaders
d)Insects innate immune system also includes recognition proteins that bind to molecules
  found only on the outside of the bacteria, fungi and other pathogens
e)Recognition of the invading microbes triggers the production of antimicrobial peptides
  that bring about the destruction of the invaders.
2- Vertebrate immune system
In vertebrates, innate immune system coexists with the more recently evolved system of
  acquired immune system
                                        Dr. Sanaa Tork
In mammals: innate immune System (natural) consists of:

A- Anatomic Barriers (skin and mucous
   membrane)
B- Cellular response
      - Phagocytosis (phagocytes): Ingestion and destruction of foreign particles
        by microphages and macrophages (type of white blood cells
      - Complement system
      - NK (natural killer) (another types of WBC, are not phagocytes, they attack
        cancer cells and virus –infected cells by releasing chemicals that promote
         programmed cell death)
       -mast cells
       - inflammatory reaction

C- Soluble factors
       include proteins that either attack microbes directly or impede their reproduction. like
   interferons which are proteins produced by virus-infected cells that help other cells to
   resist viruses (stimulating the production of antiviral proteins that block viral
   reproduction)
A-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




                                          Dr. Sanaa Tork
               Component                                                            Functions

                                         Skin and mucous membranes – mechanical factors

             Intact skin                 Forms a physical barrier to the entrance of microbes.
        Mucous membranes                 Inhibit the entrance of many microbes, but not as effective as intact skin.
               Mucus                     Traps microbes in respiratory and digestive tracts.
        Hairs (nostril hairs)            Filter incoming air from microbes and dust in nose.
Cilia (on cells lining the respiratory   Together with mucus, trap and remove microbes and dust from upper
                 tract)                  respiratory tract.
             Tear ducts                  Tears dilute and wash away irritating substances and microbes.
               Saliva                    Washes microbes from surfaces of teeth and mucous membranes of mouth.
             Epiglottis                  Prevents microbes and dust from entering trachea.
                Urine                    Washes microbes from urethra.
                                          Skin and mucous membranes – chemical factors

            Gastric juice                Destroys bacteria and most toxins in stomach.
          Acid pH of skin                Discourages growth of many microbes.
     Unsaturated fatty acids             Antibacterial substance in sebum (sweat).
 Defensins (low molecular weight         found in the lung and gastrointestinal tract have antimicrobial activity.
            proteins)
                                         in the lung (substances that promote phagocytosis of particles by phagocytic
            Surfactants
                                         cells).
                                         found in tears, saliva and nasal secretions can breakdown the cell wall of
   Lysozyme and phospholipase
                                         bacteria and destabilize bacterial membranes (Antimicrobial substance)
                                         Skin and mucous membranes – biological factors

                                         On the skin and in the gastrointestinal tract can prevent the colonization of
         The normal flora                pathogenic bacteria by secreting toxic substances or by competing with
                                                      Dr. Sanaa Tork
                                         pathogenic bacteria for nutrients or attachment to cell surfaces.
      2. Second line of defense (Cellular barrirs)
• Microbes that breach a mammal’s external barriers are confronted by innate defense
  cells (second line of defense or cellular response).
• These are classified as white blood cells (Phagocytes).
• They are found in the interstitial fluid as well as blood vessels

    1. Phagocytes:
•     They are produced throughout life by the bone marrow. They are stored there before
      being distributed around the body in the blood.
• Neutrophils
      are a kind of phagocyte and form about 60% of the white cells in the blood. They
      travel throughout the body often leaving the blood by squeezing through the walls of
      capillaries to the tissues. During an infection they are releases in large numbers from
      their stores but they are short-lived cells.
• Macrophages
      are also phagocytes but are larger than neutrophils and tend to be found in organs, such
      as the lungs, liver, spleen, kidney and lymph-nodes and through the interstitial fluid
      rather than remaining in the blood. they leave the bone marrow and travel in the blood
      as monocytes, which develop into macrophages once they leave the blood and settle in
      the organs, removing any foreign matter found there (eating any bacteria and virus -
      infected cells they encounter).
• Macrophages are long-lived cells and play a crucial role initiating immune
     responses since they do not destroy pathogens completely, but cut them up to
     display antigens that can be recognized by lymphocytes.
• Conclusion
  Macrophages : very large white cells that can move around body, or remain in certain
    tissues. Long lived, act as scavengers
•    ingest bacteria, viruses, dead cells, dust
•    most circulate in the blood, lymph and extracellular fluid
•    they are attracted to the site of infection by chemicals given off by dying cells
•    after ingesting a foreign invader, they “wear” pieces of it called antigens on their cell
     membrane receptors – this tells other types of immune system cells what to look for




                                             Dr. Sanaa Tork
Phases of phagocytosis:
1. Chemotaxis and adherence of microbe to phagocyte:
   when pathogens invade the body and cause an infection, some of the cells under
   attack respond by releasing chemicals such as histamine. These with any chemicals
   released by the pathogens themselves, attract passin phagocytes to the site. The
   phagocytes destroy the pathogens by phagocytosis .
2. Attachments and uptake (Ingestion of microbes by phagocyte):
   The phagocytes move towards the pathogens, which may be clustered together and
   covered in antibodies. This further stimulates the phagocytes to attack them. This is
   because phagocytes have receptor proteins on their surfaces that recognize antibody
   molecules and attach to them.
3. Digestion:
   formation of phagosome, fusion of phagosome with lysosyme to form
   phagolysosome, digestion of the ingested microbes and the formation of residual
   body.
4. After ingesting a foreign invader,
   they “wear” pieces of it called antigens (antigenic determinant) on their cell
   membrane receptors (Major Histocompatibility Complex (MHC)– in this case it
   named Antigen Presenting Cell (APC) this tells other types of immune system
   cells what to look for


                                     Dr. Sanaa Tork
Dr. Sanaa Tork
2. Second line of innate defence cont.

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: Substances on the surfaces of many microbes trigger a cascade
    of steps that activate the complement system, leading to the lyses (bursting) of the
    invaders, 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



                                       Dr. Sanaa Tork
Dr. Sanaa Tork
    Natural killer cells (NK 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, because water
    rushing inside the cell will induce osmotic
    swelling, and an influx of calcium may trigger
    apoptosis.




                                         Dr. Sanaa Tork
     Mast cells
•    found in tissues (connective tissues and mucous
     membranes) like the skin, near blood vessels.
•    are activated after antigen binds to a specific type of
     antibody called IgE that is attached to receptors on the mast
     cell.
•    activated mast cells release substances that contribute to
     inflammation, such as histamine.
•    mast cells are important in allergic responses but are also
     part of the innate immune response, helping to protect from
     infection.

    Soluble factors
• Interferon
     Interferon is a protein produced by virus-infected cells that inhibits the
     synthesis of viral proteins, leading to decreased viral replication. It also can
     cause apoptosis of virus-infected cells.
Acute phase proteins
      – proteins in the plasma that increase during infection and inflammation
      – can be used diagnostically to give an indication of acute inflammation
      – An example of an acute phase protein is C-reactive protein, which fixes
        complement.
                            INNATE IMMUNE SYSTEM
                                 Cellular response
1- Inflammatory response:
1- Is a major component of our innate immune system
2- any damage to tissue, whether caused by microorganisms or by physical injury
   triggers this response
3- the injury area become red, worm and swollen this reaction is inflammation

Inflammation
The damage cells release chemical alarm signals such as histamine, which is a vasodilator.
This causes localised swelling, redness, heat, pain. Can also cause high temperature, brings
white cells to the area of infection

The major results of inflammatory response are :
1- to disinfect and clean injury area
2- also helps prevent the spread of infection to surrounding tissues
3- Clotting proteins present in blood plasma pass into the interstitial fluid during
  inflammation, along with platelets form local clots that help seal off the infected
  region and allow healing to begin.
Events that make up the inflammatory response in case where a pin
 has broken the skin, allowing infection by bacteria:
1- the damage cells soon release chemical alarm signals like histamine and prostaglandin
2- the chemicals spark the mobilization of various defenses, histamine and prostaglandin
  induces neighboring blood vessels to dilate and become leakier. Blood flow to the
  damage area increases and blood plasma pass out of the leaky vessels into the
  interstitial fluid of the affected tissues. Other chemicals (some of complement system)
  attract phagocyte to the affected area. The phagocytes squeeze between the cells of the
  blood vessels wall. The local increase in blood flow, fluid and cells produces the
  redness, heat, and swelling characteristic of inflammation.
3- the phagocytes engulf bacteria and the remains of damage body cells, many blood cells
  die in the process, their remains are also engulfed and digested. The pus that often
  accumulates at the site of an infection consists mainly of dead white cells and fluid that
  has leaked from the capillaries during the inflammatory response.
4- the inflammatory response may be localized or widespread (systemic), some bacteria
  or protozoans get into the blood or release toxins that carried throughout the body in the
  bloodstream. Another response to systemic infection is fever, an abnormally high body
  temperature.




                                        Dr. Sanaa Tork
Dr. Sanaa Tork
The release of histamine and prostaglandin causes local vessel dilation resulting in:
         • increased capillary permeability
         • increased blood flow  more WBCs to site  redness and warmth
         • phagocytes move out of vessels into intracellular fluid (ICF)
         • edema (swelling) due to fluids seeping from capillaries

Fevers have both positive and negative effects on infection and body functions
 POSITIVE (moderate fever)                     NEGATIVE
 • indicate a reaction to infection           • extreme heat  enzyme denaturation
 • stimulate phagocytosis and hasten tissue     and interruption of normal biochemical
   repair                                       reactions

 • slow bacterial growth                           > 39° C (103°F) is dangerous

    – increases body temperature beyond            > 41°C (105°F) could be fatal and
      the tolerance of some bacteria                 requires medical attention, leading
                                                     to a condition called septic shock
    – decreases blood iron levels                    which characterized by very high
       (Lactoferrin and Transferrin)                 fever and low blood pressure
                           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
                                                            Interferons
                                                           Natural killers


                                 Dr. Sanaa Tork
                        The acquired immune system
1. When the innate immune response fails to ward off a pathogen, the acquired immune
   response provides a second line of defenses.

2. Acquired immunity found only on vertebrates, is a set of defenses that are activated only
   after exposure to pathogens.

3. Once activated , the acquired immune response provides a strong defense against
   pathogens that is highly specific (acts against one infectious agent but not another)

4. Acquired immune response has a remarkable memory (it can remember antigen it has
   encountered before and react against them)

5. Can amplify certain innate responses such as inflammation and the complement system

6. acquired immunity is usually obtained by natural exposure to antigens but it can also be
   achieved by vaccination (vaccine is composed of a harmless variant or part of a disease-
   causing microbe such as an inactived bacterial toxin, a dead or weakened microbe, or a
   pieces of a microbe)

7. Vaccination also known as immunization, because vaccine stimulates the immune
   system to mount specific defense against this harmless antigen, if it is exposed to the
   actual microbe, our immune system will respond quickly and effectively

8. For this reason the widespread of vaccination of children has virtually eliminated some
   viral diseases such as polio, smallpox and measles.
                       Induced Immunity (acquired immune response)


                Active immunity                                         Passive immunity
      Production of a person’s own antibodies.           1.An individual is given antibodies by another
                    Long lasting                           (received of premade antibodies)
                                                         2.Short-term resistance (weeks- 6months)
                                                         3.Passive immunity is temporary because
  Natural Active            Artificial Active              the recipient’s immune system is not
When pathogen enters     • Vaccination – usually           stimulated by antigen
body in the normal         contains a safe antigen
way, we make               from the pathogen.
antibodies               • Person makes antibodies         Natural Passive            Artificial Passive
                           without becoming ill         •Fetus obtains            • Gamma globulin
                                                        antibodies from its         injection
                                                        mother’s bloodstream.     • extremely fast, but short
                                                        •Baby receives              lived
                                                        antibodies in breast milk • (e.g. snake venom, which
                                                                                    controlled by injecting
                                                                                    the victim with
                                                                                    antivenin)

                                                 Dr. Sanaa Tork
•Antigens (antibody generating) – foreign molecules that stimulate an acquired immune
response which responds with an increase in the number cells that either attack the invader
directly or produce immune proteins called antibody

•Most antigens are proteins or large polysaccharides on the surface of foreign invaders such
as protein coat molecules of viruses, parts of the capsules and cell walls of bacteria and ;
macromolecules on the surface cells of other kinds of organisms such as protozoan and
parasitic worms or antigenic molecules on blood cells or tissue cells from other individuals
or found dissolved in body fluids like bacterial toxins and bee venom.

•Antibodies (immunoglogulins) – proteins found in the blood plasma that attached to one
particular kind of antigen and helps counter its effects It produced by lymphocytes in
response to antigens

•Antibody usually recognizes and binds to a small surface-exposed region of an antigen that
binds to antigen-binding site of antibody called antigenic determinant or epitope

•Paratope or antigen-binding site: a specific region on the antibody molecule, recognize
an antigenic determinant by the fact that the binding site and antigenic determinant have
complementary shapes (like lock and key)
                                                  Paratope
• An antigen usually has several different determinants, so different antibodies can bind
  to the same antigen

• The immune system’s ability to defend against an enormous variety of antigens depends
  on a process known as clonal selection:
  (one particular antigen interacts only with the tiny fraction of lymphocytes bearing
  receptors specific to that antigen, once activated by the antigen, these few selected cell
  proliferate, forming a clone (genetically identical population) of thousands of cells all
  specific for the stimulating antigen)

this antigen-driven cloning of lymphocytes- clonal selection is the vital step in the
   acquired immune response against infection
                              • Steps of clonal selection
1- The first time an antigen enters the body and is
swept into the lymph node
2- antigenic determinants on its surface bind to the
few B cells that have complementary receptors


3-the selected cell is activated , grow,
divided and differentiates into two distinct
types of cells (memory cell and plasma cell
(effector cell))

4- each plasma cell secrets antibody
molecules (as many as 2000 copies of its
antibody per second) each plasma cell
require large amounts of endoplasmic
reticulum, the secreted antibodies circulate
in the blood and lymphatic fluid,
contributing to the humoral immune
response. Each effector cell lasts only 4-5
days before dying off
                                          Dr. Sanaa Tork
•Two groups of cells produced by the activated B cells:
1. Plasma cell which are highly effective and combating infection, it lasts only 4-5 days
 (short lived)
2. Memory cell which differ from effector cells in both appearance and function, it lasts
 for decades in the lymph nodes, activated by a second exposure to the antigen
These steps show the primary immune response this phase occurs when lymphocytes are
 exposed to an antigen for the first time.

When the produced memory cells activated by the second exposure to the same antigen,
 they initiate the secondary immune response, this response is faster and stronger than the
 first, the selected memory cells multiply quickly, producing a large second clone of
 lymphocytes, produces very high levels of antibodies than the first response, effector
 cells are often more effective against antigen than those produced during the primary
 response




                                        Dr. Sanaa Tork
                                Antibody Molecules
1. Antibodies are the weapons of the humoral immune response
2. Each antibody molecule is made of four peptide chains, two identical heavy chains (give
   the molecule its Y shape) and two identical light chains, each light chain bounded to one
   of the heavy chain, at the fork of the Y bonds the two heavy chains
3. Each of the four chains of the molecule has a c (constant) region and a V (variant) region.
   At the tip of each arm of the Y, a pair of V regions forms an antigen-binding site (a region
   of a molecule responsible for the antibody’s recognition and binding function)
4. A huge variety in the three-dimensional shapes of the binding sites of different antibody
   molecules arises from a similarly large variety in the amino acid sequences in the V
   regions . This structural variety account for the diversity of lymphocytes and given the
   humoral immune system the ability to react to any kind of antigen.




                                  Region binds to Complement

                              Region binds to Macrophage
•   The tail of the antibody molecule, formed by the constant regions of the heavy
    chains, helps mediate the disposal of the bound antigen.
•   Antibodies with different kinds of heavy chains C regions are grouped into
    different classes.
•   Human and other mammals have five major classes of antibodies called : IgA, IgD,
    IgE, IgG, IgM

Antibodies inactive antigen by:

1.agglutination of microbes :makes pathogens
  clump together, enfances phagocytosis.
2. Neutralization (antitoxins) neutralize the toxins
  produced by bacteria, blocks viral binding sites,
  coats bacteria.
3.Activation of complement system (leads to cell
  lysis) digests the bacterial membrane, killing
  the bacterium
4.opsonisation (precipitation of dissolved
  antigens) coats the pathogen in protein that
  identifies them as foreign cells

                                         Dr. Sanaa Tork
                                       Lymphocytes:

• Lymphocytes are white blood cells, smaller than phagocytes. They have a large nucleus
   that fills most of the cell., like all blood cells, lymphocytes originate from stem cells
   before birth in bone marrow, there are two types of lymphocyte
1. B lymphocytes (B cells) continue developing in the bone marrow until they are mature
   and then spread throughout the body concentrating in lymph nodes and the spleen.
2. T lymphocytes ( T cells ) leave the bone marrow and collect in the thymus where they
   mature. Only mature lymphocytes can carry out immune responses. Both types of
   lymphocytes are responsible for the acquired immune system




                                          Dr. Sanaa Tork
During the maturation process :

• many different types of B and T lymphocyte develop, Perhaps many millions, certain
  genes in the lymphocyte cell are turn on , this leads the cell to synthesize molecules of
  specific protein, incorporated into the plasma membrane. The molecules are antigen
  receptors, capable of binding one specific type of antigen, each type is specialized to
  respond to one antigen, giving the immune system as a whole the ability to respond to
  almost any type of pathogen that enters the body.

• Each T and B cells has about 100 000 antigen receptors on a single cell and all the
  receptors on a single cell are identical- they all recognize the same antigen
• In case of B cells , the receptors are almost identical to the particular antibody that the B
  cell will secrete.

• When mature, both B and T cells circulate between the blood and the lymph. This
  ensures that they are distributed throughout the body so that they come into contact with
  any pathogens and with each other.
• Acquired immune responses depend on B and T cells interacting with each other to give
  an effective defense.

• When a B and T cell within a lymphatic organ first confronts the specific antigen it is
  programmed to recognize, it differentiates further and becomes a fully mature component
  of the immune system.
                                         Dr. Sanaa Tork
Two types of acquired immune response:

1- The humoral immune response:
- involves the secretion of antibodies by B cell into the blood and lymph,
- the humoral defense defends primary against bacteria and viruses present in body fluids
- this defense can be passively transferred by injecting blood plasma (containing
antibodies) from an immune individual into a non immune individual

 2- The cell- mediated immune response:
- produced by T cells
- this defensive system results from the action of defensive cells rather than the
  defensive proteins of the humoral response
-certain T cells attack body cells that are infected with bacteria or viruses, others
  function indirectly by promoting phagocytosis by other blood cells and by
  stimulating B cells to produce antibodies

Thus T cells play a part in both the cell- mediated and humoral immune response


                                          Dr. Sanaa Tork
• Briefly, some Tcells (TH) coordinate the immune response, stimulating B
  cells to divide and then secrete antibodies into the blood; these antibodies
  destroy the antigenic pathogens. Other Tcells (NK) seek out and kill any of
  the body’s own cells that are infected with pathogens. To do this they must
  make direct contact with infected cells.




                                 Dr. Sanaa Tork
     T helper cells stimulate humoral and cell-mediated immune
                               responses
•     Helper T cells interact with others white blood cells –including macrophages, B cells,
      and other types of immune cells-that function as antigen –presenting cells.
•     All the cell mediate immune response and much of the humoral immune response
      depend on the precise interaction of antigen-presenting cells and helper T cells.
•     The interaction activate other cells of the immune system
•     The antigen presenting cells presents a foreign antigen to helper T cell.
•     The ability of a helper T cell to recognize a unique self-nonself complex on an antigen
      – presenting cell depends on the receptors embedded in the T cell’s plasma membrane.
•     T cell receptor actually has two binding sites: one for antigen and one self protein. The
      two binding sites enable T cell receptor to recognize the overall shape of a self-nonself
      complex on an antigen –presenting cell.
•     The immune response is highly specific because the receptors on each helper T cell
      can bind only one kind of self – nonself complex on an antigen-presenting cell.
•     The binding of T cell receptor to self –nonself complex activates the helper T cell
•     Other kinds of the signals can enhance this activation such as interleukin-1 which
      diffuse to the T helper cell and stimulate it.
•     Activated helper T cell promote the immune response in several ways, being the
      secretion of addational stimulatory proteins such as:
    interleukin-2 which make T helper grow and divide, producing both memory cells and
      qdditional active helper T cells. It also activate B cells , thus stimulating the humoral
      immune response, and stimulates the activity of cytotoxic T cells
                                          Dr. Sanaa Tork
                                    B-lymphocytes

•      The antibody- producing B-cells of the humoral response make up one arm of the
       acquired immune response network
•      Humoral defense system identifies and helps destroy invaders that are in our blood,
       lymph or interstitial fluid (outside our body cell)
•      B cell respond to free antigens present on the surface of the body fluids, T cells
       respond only to antigens present on the surface of the body’s own cells
•      B lymphocytes make antibodies = immunoglobulins

    1000s of different B cells, each recognises a
    different antigen on the surface of a macrophage.
    Each antigen stimulates production of a single
    specific antibody

B cells (along with T cells) come in contact with antigen.
They are stimulated (by T cells) to produce many clones,
plasma cells, which make antibodies.


    Memory B cells – faster, more sensitive reaction
     = secondary response

                                           Dr. Sanaa Tork
                                  How B-cells work…

                    Pathogen (e.g. bacteria, virus)

                       B-cells             Plasma cells
                       Each recognise      Clones of the
                       a different         correct B-cell,
Macrophage             antigen. The        which produce
                       correct one         antibodies
                       develops into…




  Macrophage
  Phagocytoses pathogen
  and displays antigens on                                   1st meeting a pathogen, this
  surface                                                    process takes 10-14 days
                                         Dr. Sanaa Tork      Memory B cell= subesquent
                                                             meetings, takes about 5 days
                                   T lymphocytes
•   Mature T cells have specific cell surface receptors called T cell receptors.
•   T cells are activated when they encounter this antigen in contact with another host
    cell.
•   Sometimes this is a macrophage that has engulfed a pathogen and cut it up to expose
    the pathogen's surface molecules or it may be a body cell that has been invaded by a
    pathogen and is similarly displaying the antigen on its plasma membrane as a kind of
    “signal” . Those T cells that have matching receptors respond to the antigen by
    dividing.

• There are two main types of T cell:
1. T helper cells;
2. Killer T cells .
          when T helper cells are activated they release hormone – like cytokines that
   stimulate appropriate B cells to divide, develop into plasma cells and secrete
   antibodies. Some T helper cells secret cytokines that stimulate macrophges to carry
   out phagocytosis more vigorously. Killer T cells search the body for cells that have
   become invaded by pathogens and are displaying foreign antigens from the pathogens
   on their plasma membranes. Killer T cells recognise the antigens, attach themselves to
   the surface of infected cells and secrete toxic substances, killing the body cells and the
   pathogens inside.
    In addition to the helper cells and killer cells, memory T cells are produced which
   remain in the body and become active very quickly during the secondary response to
   antigens.
                                       Dr. Sanaa Tork
                                       T-lymphocytes
               Mature in Thymus, which is most active just before and after birth.
                          The thymus starts to shrink during puberty.


Helper T-Cells            Killer T-Cells               Suppressor T-Cells   Memory T-Cells
•Recognise antigens on    Also called cytotoxic        •Control the         •Can survive a long time
surface of leukocytes,    •Destroy abnormal body       immune system        and give lifelong
especially macrophages    cells, e.g. virus infected   when the antigen     immunity from
•Enlagre and form a       or cancer cells              /pathogen has        infection
clone of T-helper cells   •Stimulated by cytokines     been destroyed       •Can stimulate memory
•Secrete interferon and   (THcells)                    •Only recently       B-cells to produce
cytokines which           •Release perforin, which     discovered so        antibodies
stimulate B-cells and     forms pores in target        little is known      •Can trigger production
stimulate killer -cells   cells. This allows water     about them           of killer T cells
•Can be infected by HIV   and ions in = lysis




                                         Dr. Sanaa Tork
                             Killer T-cell         How T-cells work…
Abnormal cell e.g            recognises antigen
cancer cell, infected cell




Antigen
                                                             X
                                                                                    Killer T-cells release
                                                                                    perforin pores
                                                      Clones of killer T-cell
                                                      attach to antigen




                   X
     Normal cell




          Helper T-cell stimulates
          correct killer T-cell to
          multiply
                                                  X
                                 Helper T-cell also
                                                                                         Abnormal cell gains
                                                                                         water, swells and
                                 stimulates B-cells                                      bursts
                                 to make antibodies

                                                                         Memory T-
                                                                         cells stay in
 Suppressor T-cells
 turn off immune                                                         circulation
 response                                         Dr. Sanaa Tork
Dr. Sanaa Tork
Duration of immunity
Memory B-cells circulate for a long time. If the same pathogen infects the
body again, these B-cells can produce large amounts of specific antibody
very quickly. This is why you usually don’t suffer from the same infection
twice.
Memory T-cells survive a long time and trigger an immune response

Immune disorders
•Sometimes the body produces antibodies against its own tissues e.g. autoimmune
diseases e.g. rhumatoid arthritis, Crohn’s disease, SCID (bubble boy disease),
Asthma
In Lupus, for example, B cells make antibodies against a wide range of self molecules
such as histones and DNA released by the normal breakdown of body cells.
Lupus is characterized by skin rashes, fever, arthritis and kidney mal-function

In rheumatoid arthritis is another antibody-mediated autoimmune disease, it leads
to damage and painful inflammation of the cartilage and bone of joints

In multiple sclerosis, T cells react against the myelin sheath , peoples with MS has a
number of serious neurological abnormalities

•In Crohn disease, a chronic inflammation of the digestive tract, may be caused by
an autoimmune reaction against normal flora that inhabit the intestinal tract.

                                      Dr. Sanaa Tork
Immune deficiency diseases: here immune deficient people lack one or more of the
component of the immune system this makes them susceptible to frequent and
recurrent infections.
In rare congenital disease severe combined immunodeficiency (SCID) both T and B
cells are inactive or absent, people with SCID are sensitive to even minor infection.



•Allergies occur when the body reacts to antigens in our surrounding e.g.
peanut
•Antigens that cause allergies are called allergins


•Tumours – in most cases the body recognises tumours as being bad, because they
express abnormal molecules on the cell surface. However sometimes the body doesn’t
notice and cancers can develop




                                       Dr. Sanaa Tork

								
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