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IMMUNE SYSTEM

•Specific and nonspecific response
       •Humoral immunity
IMMUNE SYSTEM
 Pathogen    (disease-causing     organism)     can    be
 bacteria, fungus, virus, or multicellular parasite.

 Pathogen   infects   animal    because   the     internal
 environment of animal offer a suitable habitat.

 The animal body is the ideal habitat for the pathogen

 to grow, reproduce, and medium for transportation
 to the new environments.
 Thus, a defense system must be made up in order to

 ward off the invasion of pathogen into the animal
 body.

 Immune system recognizes the pathogen as foreign

 body and respond by producing immune cells and
 protein.
IMMUNITY
 Immunity is defined as an ability of the body to resist

  invasion of pathogen or disease.

 A study of how the immune system of animal works is

  called immunology.

 Immunity are divided into nonspecific immunity and

  specific immunity.
Pathogens
                                      (microorganisms
                                        and viruses)


 INNATE IMMUNITY          Barrier defenses:
Recognition of traits     Skin
shared by broad ranges    Mucous membranes
of pathogens, using a     Secretions
small set of receptors
                          Internal defenses:
                          Phagocytic cells
 Rapid response           Antimicrobial proteins
                          Inflammatory response
                          Natural killer cells

ACQUIRED IMMUNITY          Humoral response:
Recognition of traits      Antibodies defend against
specific to particular     infection in body fluids.
pathogens, using a vast
array of receptors         Cell-mediated response:
                           Cytotoxic lymphocytes defend
 Slower response           against infection in body cells.
NONSPECIFIC IMMUNITY
 Also known as innate immunity.

 Present before any exposure to pathogens.

 Act immediately upon infection.

 Divided into surface barrier and internal defenses.
SURFACE BARRIER
 Skin is an outer covering of an animal body which act

 as primary defense system.

 Possess keratinized epithelial membrane that function

 as a barrier and prevent the pathogen that swarm on
 the skin.

 Keratin is resistant to most weak acids and bases

 and to bacterial enzymes and toxins.
 Mucous membranes line all body cavities that open

 to the exterior; the digestive, respiratory, urinary, and
 reproductive tracts.

 Epithelial membranes produce a variety of protective

 chemicals.
 The acidity of skin secretions (pH 3 to 5) inhibits

  bacterial growth. Sebum contains chemical that are
  toxic to bacteria.

 Vaginal secretion of adult females are very acidic.

 The stomach mucosa, secretes a concentrated

  hydrochloric acid solution and protein-digesting
  enzymes.
 Saliva, which cleanses the oral cavity and teeth.

 Lacrimal fluid of eye contains lysozyme, an enzyme
  that destroys the bacteria.
 Sticky mucus traps many microorganisms that enter
  the digestive and respiratory passageways.
 Tiny mucus-coated hairs inside the nose traps the
  pathogen, preventing it from entering the lower
  respiratory passages.
INTERNAL DEFENSES:CELLS AND
            CHEMICALS
 Internal defenses involve phagocytic cells, natural
 killer   cells,    antimicrobial    proteins,    and
 inflammatory response.
 The inflammatory response enlists macrophages,
 mast cells, all types of white blood cells, and other
 chemicals that kill pathogen.
 The phagocytic cells are the cells that functions in
 engulfing the pathogen.
PHAGOCYTIC CELLS
 If the pathogens succeed to get through the skin, then

  the phagocytic cells will combat the pathogens.

 Phagocytic     cells    consist    of    monocytes,
  macrophages, neutrophils and eosinophils.

 Pathogens are recognized by surface cell receptors

  which are also known as TLR (Toll-like receptors).
EXTRACELLULAR     Lipopolysaccharide
FLUID
        Helper
                         TLR4   Flagellin
        protein

WHITE
BLOOD
CELL
                                  TLR5


   VESICLE        TLR9

                   TLR3 Inflammatory
                        responses
      ds RNA
 Macrophages     derived   from   white   blood   cells,
 monocytes which leave and enter the tissues, and
 develop into macrophages.

 Neutrophils, the most abundant type of white blood

 cells.

 Eosinophils, white blood cells that weakly phagocyte

 the pathogens.
HUMAN LYMPHATIC SYSTEM
                            Interstitial fluid
       Adenoid

       Tonsil




            Lymph                                Blood
            nodes                                capillary

            Spleen         Tissue Lymphatic
                           cells  vessel
       Peyer’s patches
       (small intestine)
            Appendix


        Lymphatic
        vessels
                  Lymph                  Masses of
                  node                   defensive cells
MECHANISM OF PHAGOCYTOSIS
 Phagocytic cell engulfs the particulate matter.

 Cytoplasmic extension of phagocyte cell bind to the

  particulate matter and pull it into vacuole.

 Phagosome is formed.

 Phagosome      fuses    with   lysosome,       forming   a
  phagolysosome.
Microbes



PHAGOCYTIC CELL



Vacuole
                  Lysosome
                  containing
                  enzymes
NATURAL KILLER CELLS
 Function in lysing and killing the cancer cells and

  virus-infected body cells.

 Natural killer cells act before the specific immune

  system is activated.

 Able to detect and eliminate the virus infected cell and

  cancerous cell (virus infected cell and cancerous cell
  do not express class I MHC protein).
 The natural killer cells detect the cell which is lack of

  self cell surface receptors (class I MHC protein).

 Natural killer cells also promote the target cells to

  undergo apoptosis (programmed cell death).
INFLAMMATORY RESPONSE
 The benefits of inflammatory response:

1. Prevent the spread of damaging agents to nearby

   tissues.

2. Disposes of cell debris and pathogen.

3. Set the stage for repair (blood clotting).
INFLAMMATORY RESPONSE
 Factors which elicit inflammatory response:
1. Physical trauma ( a blow)
2. Intense heat
3. Irritating chemicals
4. Infection by viruses, fungi, and bacteria


The four cardinal signs of accute inflammation:
1. Pain
2. Redness
3. Heat
4. Swelling
Tissue
                                injured


                         Histamine (released by
                          basophils),chemical
                        mediators, prostaglandin,
                            complement kinin



     Vasodilation of           Increased             Attract neutrophils,
        arterioles              capillary             monocytes, and
•Local hyperemia              permeability             lymphocytes to
(increased blood flow     •Capillaries leak               injured area
to injured area           fluid (exudate)                (chemotaxis)
                                                    •Pus formation
 Mast   cells-   key   components   of   inflammatory
 response., release histamine.

 Pus- break down tissue, die or dying neutrophils,

 dead or living pathogen, accumulate in the wound.

 Hyperemia (congestion of blood)- causes redness

 and heat of an inflammed region.
 Inflammation can be divided into local inflammation

 and systemic inflammation.

 Fever is an example of systemic inflammation. It is

 triggered by pyrogens. The high body temperature
 inhibits the microbial multiplication and enhances
 body repair.
 Exudates- fluid containing antibodies and clotting

 factors.

 Secretion of exudate causes local edema (swelling)

 and contributes to the sensation of pain.
Splinter




          Chemical Macrophage                    Fluid
Mast cell signals

                    Capillary                                    Phagocytosis

Red blood cells Phagocytic cell




                Major events in a local inflammatory responses
INFLAMMATORY CHEMICALS
CHEMICAL          SOURCE                                            PHYSIOLOGICAL
                                                                    EFFECTS
Histamine         Granules of basophils and mast cells, released    Promotes vasodilation of local
                  in response to mechanical injury, presence of     arterioles, increases permeability of
                  certain microorganisms, and chemicals             local capillaries, promoting exudate
                  released by neutrophils.                          formation.
Kinins            A plasma protein, kininogen is cleaved by the     Same as for histamine, also induce
                  enzyme kallikrein found in plasma, urine,         chemotaxis of leukocytes and
                  saliva, and lysosomes of neutrophils, and other   prompt neutrophils to release
                  types of cells, cleavage releases active kinin    lysosomal enzymes, thereby
                  peptides.                                         enhancing generation of of more
                                                                    kinin, induce pain.
Prostaglandins    Fatty   acid    molecules     produced   from     Sensitize blood vessels to effects
                  arachidonic acid-found in all cell membranes;     of other inflammatory mediators,
                  generated by enzymes of neutrophils,              one of the intermediate steps of
                  basophils, mast cells and others.                 prostaglandin generation produces
                                                                    free radicals, which can cause
                                                                    inflammation; induce pain.
ADAPTIVE/ SPECIFIC IMMUNITY
 Specific; recognizes and respond to specific pathogens

 or foreign substances.

 Systemic; Immunity not only involve to the initial

 infection site.

 Possess ‘memory’; Able to mount stronger attacks on

 the pathogens which encounter the body previously.
 Adaptive   immunity   are   divided    into   humoral
 response and cell-mediated response.

 Humoral    response   involves   the   production   of
 antibody.

 Cell-mediated immunity involves cytotoxic cells.
HUMORAL RESPONSE
 Antibody-mediated immunity.

 Production of antibodies by lymphocytes.

 Antibodies present in the body’s “humors,” or fluids

  (blood, lymph).

 Involve antigen recognition, antigen presenting, and B

  cell proliferation.
B cells undergo maturity (antigen
     binds to its surface receptor, Tcells
     nearby)


        B cells undergo clonal
        selection (reproduce
        asexually by mitosis)



              Plasma cells



Antibodies                     Long-lived memory
                               cells
Humoral (antibody-mediated) immune response
                              Antigen (1st exposure)
   Stimulates                    Engulfed by
   Gives rise to
                                   Antigen-
                                presenting cell


            B cell                Helper T cell



                                   Memory
                                 Helper T cells



                            Antigen (2nd exposure)
        Plasma cells      Memory
                          B cells

                   Secreted
                  antibodies
Defend against extracellular pathogens
Antigen-
                presenting
                cell                    Peptide antigen


                Bacterium

                                     Class II MHC molecule

                                      CD4
                                     TCR (T cell receptor)
   Humoral              Cytokines       Helper T cell
  immunity
                                                             Cell-mediated
(secretion of
                                                                immunity
antibodies by
                                                               (attack on
plasma cells
                                                             infected cells)
                            B cell        Cytotoxic T cell
LYMPHOCYTES
           (B CELLS AND T CELLS)
 B cells and T cells are lymphocytes.

 Involve in the humoral immune response.

 B cells are originated from the bone marrow.

 T cells are also originated from the bone marrow but it

  migrated to the thymus.
ANTIGEN
 Antigens are foreign substances which elicits adaptive

  immune response.

 Antigens are either natural or synthetic.

 Nonself; antigens are normally not parts of the body.

 Most antigens are large and complex molecules.
 To elicit adaptive immunity, antigen recognition must

  occur.

 Antigen recognition- the B cell and T cell bind to the

  antigen.

 The antigen binding- via antigen receptor which

  attached to the surface of B cell and T cell plasma
  membranes.
B CELL RECEPTOR
                                                Antigen-
              Antigen-                          binding site
              binding              Disulfide
              site                 bridge
                             V
                         V                           Variable
                                                     regions



                             Light C C          Constant
                             chain              regions
                                                  Transmembrane
                                                  region
                                                Plasma
                                 Heavy chains   membrane
     B cell
(a) B cell receptor
T CELL RECEPTOR
                      Antigen-
                      binding
                      site

   Variable
   regions             V V

    Constant
    regions            C C
Transmembrane
region
Plasma
membrane
                  Disulfide bridge
              Cytoplasm of T cell      T cell
                 (b) T cell receptor
B CELLS ANTIGEN RECEPTORS
Y-shaped.


Consist four polypeptide chains. Two identical light chains
and two identical heavy chains.



Have constant region (C) and variable region (V).


When the antigen receptors bind to an antigen, B cell
activation occurs.
 The antigen receptor bind to the epitope.

 Epitope- Also known as antigenic determinant, a

  small, accesible portion of an antigen that binds to an
  antigen receptor.
 An antigen possesses several different epitopes.

 All the antigen receptors which are located at a single

  lymphocyte only bind to the same epitope.

 When the antigen bind to the antigen receptor, B cell

  activates and give rise to plasma cells.

 Plasma cells produce antibodies.
Epitopes
                                                            (antigenic
                                                            determinants)

Antigen-binding sites

                                     Antigen
                        Antibody A
                                               Antibody C


 C              C

       C C                   Antibody B
ANTIBODIES
 Also known as immunoglobulins.

 Similar structure with B cell antigen receptors, but

 antibodies   do   not   attach   to   the   surface   cell
 membranes.
ANTIBODY CLASSES
 Antibodies are divided into five major classes.

 Polyclonal antibodies- products of many different

  clones of B cells following exposure to a microbial
  agent.

 Monoclonal antibodies- prepared a single clone of B

  cells grown in culture.
Class of Immuno-         Distribution           Function
globulin (Antibody
     IgM             First Ig class        Promotes neutraliza-
  (pentamer)         produced after        tion and cross-
                     initial exposure to   linking of antigens;
                     antigen; then its     very effective in
                     concentration in      complement system
                     the blood             activation
                                declines

       IgG                                  Promotes
    (monomer)        Most abundant Ig                 opsoniz
                     class in blood;                  a-
                     also present in        tion,
                     tissue fluids                    neutraliz
                                                      ation,
                                            and cross-linking
                                                      of
                                           crosses placenta,
                                            antigens; less
                                           thus conferring
                                                      effec-
                                           passive immunity
                                           on fetusactivation
                                            tive in
                                                      of
        IgA          Present in             Provides localized
                                            complement
      (dimer)        secretions such        defense of mucous
                                                      system
                     as tears, saliva,      membranes by
                                            than IgM
                     mucus, and             cross-linking and
                     breast milk            neutralization of
                                            antigens



                                           Triggers release from
       IgE           Present in blood      mast cells and
    (monomer)        at low concen-        basophils of hista-
                     trations              mine and other
                                           chemicals that cause
                                           allergic reactions

        IgD
     (monomer)        Present              Acts as antigen
                                primari    receptor in the
                                ly         antigen-
                      on surface of                   stimulat
                      B cells that have               ed
                      not been             proliferation and
                                expos      differentiation of
                                ed         B cells (clonal
                      to antigens          selection
Class of Immuno-
                          Distribution           Function
globulin (Antibody)


     IgM               First Ig class        Promotes neutraliza-
  (pentamer)           produced after        tion and cross-
                       initial exposure to   linking of antigens;
                       antigen; then its     very effective in
                       concentration in      complement system
                       the blood declines    activation
             J chain
Class of Immuno-
                        Distribution          Function
globulin (Antibody)

        IgG
     (monomer)        Most abundant Ig   Promotes opsoniza-
                      class in blood;    tion, neutralization,
                      also present in    and cross-linking of
                      tissue fluids      antigens; less effec-
                                         tive in activation of
                                         complement system
                                         than IgM
                                         Only Ig class that
                                         crosses placenta,
                                         thus conferring
                                         passive immunity
                                         on fetus
Class of Immuno-
                         Distribution          Function
 globulin (Antibody)

        IgA
      (dimer)          Present in          Provides localized
                       secretions such     defense of mucous
                       as tears, saliva,   membranes by
                       mucus, and          cross-linking and
             J chain   breast milk         neutralization of
                                           antigens

                                           Presence in breast
                                           milk confers
Secretory                                  passive immunity
component                                  on nursing infant
Class of Immuno-
globulin (Antibody)    Distribution        Function


      IgE
                      Present in blood   Triggers release from
   (monomer)
                      at low concen-     mast cells and
                      trations           basophils of hista-
                                         mine and other
                                         chemicals that cause
                                         allergic reactions
Class of Immuno-
                         Distribution          Function
 globulin (Antibody)


       IgD             Present primarily   Acts as antigen
    (monomer)          on surface of       receptor in the
                       B cells that have   antigen-stimulated
                       not been exposed    proliferation and
                       to antigens         differentiation of
                                           B cells (clonal
                                           selection)
Trans-
membrane
region
ANTIBODY TARGETS AND
            FUNCTIONS
 Neutralization- antibodies block specific sites on

 viruses   or   bacterial   exotoxins   (toxin   chemicals
 secreted by bacteria).

 The virus or exotoxin cannot bind to the receptors on

 tissue cells to cause injury.
 Agglutination-   Antibodies bind to the antigenic
 determinant on more on one antigen at a time.

 Forming antigen-antibody complexes which causes

 clumping of the foreign cells.
 Precipitation- Soluble molucles are cross-linked into

 large complexes that settle out of solution.
 Complement fixation and activation- Antibodies bind

 to cells, cause the antibodies to change its shapes.

 The antibodies expose the transmembrane regions.

 Complement fixation into the antigenic cell’s surface

 is triggered, followed by the cell lysis.
Viral neutralization   Opsonization        Activation of complement system and pore formation

                           Bacterium
                                                                  Complement proteins
              Virus


                                                                              Formation of
                                                                              membrane
                                                                              attack complex
                              Macrophage
                                                                                        Flow of water
                                                                                        and ions

                                                                                                 Pore



                                              Foreign
                                              cell
ANTIGEN RECOGNITION
 B cell antigen receptors – bind to the epitopes of

 antigens.

 T cell antigen receptor – bind to the fragments of

 antigens that are presented on the surface of host
 cells.
MHC
 Major Histocompatibility Complex molecule.

 Encodes    a group of glycoproteins called MHC
 proteins.

 MHC proteins are divided into two groups, Class I

 MHC proteins and Class II MHC proteins.
Class I MHC protein                  Class II MHC protein
Found on virtually all body cells.   Found only on certain cells that acts
                                     on immune system.
Involves in the cell-mediated        Involves in the humoral immunity.
immunity.
RECOGNITION OF PROTEIN
         ANTIGENS BY T CELLS
 The antigen is engulf by the cell. The antigen is

 cleaved by host cell’s enzyme into antigen fragment.

 Antigen fragment binds to MHC molecule.

 Antigen fragment-MHC complex is brought to the

 surface of the cell.

 T cell recognizes the antigen fragment-MHC complex.
THE ROLE OF THE MHC
 Bind to antigen fragment.

 Transport the antigen fragment to the surface of the

  cell.

 Lead to antigen presentation, the display of the

  antigen fragment on the cell surface.
HELPER T CELLS
 Activates the adaptive immune response.

 Antigen fragment is presented by class MHC proteins

 on the host cell.

 The host cell which displays the antigen fragment is

 called antigen-presenting cell.
 In the cell mediated immunity, the Class I MHC
  protein formed a complex with the antigen fragment.
 In the humoral immunity, the antigen fragment forms a
  complex with the Class II MHC protein.
Top view: binding surface
                               exposed to antigen receptors




         Antigen


Class I MHC                                         Antigen
molecule
                   Plasma
                   membrane of
                   infected cell
Antigen-
Infected cell                      Microbe     presenting
                        1.                     cell
Antigen                 Antigen
fragment                associat
                        es with                   Antigen
                        MHC                       fragment
Class I MHC             molecul
molecule                e
                                             Class II
 T cell                                          MHC
 receptor                                    molecule
                       2. Tcell
                                              T cell
                       recognize              receptor
                       s
                       combinati
       a) Cytotoxic T cell
                       on
                                             b) Helper T cell
B CELL AND T CELL DEVELOPMENT
 The antigen presenting leads to B cell and T cell

  activation.

 B     cell    is    activated    (stimulated   to   undergo
  differentiation).

 B cell proliferates to form clones.

 The     clones      bear   the    same    antigen-specific
  receptors, similar to the activated B lymphocyte cell.
 Some cells from the clones form effector cells.The

 effector cells which form from the B cells are plasma
 cells.
 T cell is activated and proliferates to form clones.

  Some of the clones become effector cells.

 The effector cells which arise from T cells are divided

  into helper T cells and cytotoxic T cells.
CLONAL SELECTION
 The proliferation of B cells is the example of clonal

  selection process.

 B cells form clones, a group of cell which are identical

  to the original cell.
MONOCLONAL ANTIBODY
 Providing passive immunity.

 Are made by fusing tumor cells and B lymphocytes.

 The resulting cell are called hybridomas.

 Hybridomas proliferates in culture, and produce a

  single type of antibody.

 Used to diagnose pregnancy, sexually transmitted

  diseases, hepatitis and rabies.
CELL MEDIATED IMMUNITY
 Involve the cytotoxic T cells.

 Cytotoxic cells- destroy any cells in the body that

  harbor anything foreign.
Released cytotoxic T cell
 Cytotoxic T cell

                      Perforin


   CD8                                                                 Dying target cell
Class I             Granzymes
     MHC                                                Pore
molecule             TCR


Targe
     t
cell


                                 The killing action
                                 of cytotoxic T cells
CYTOTOXIC T CELL
 T cells which undergo proliferation will form effector
  cells.
 The effector cells are helper T cells and cytotoxic T
  cells.
 The surface of the cytotoxic T cells have glycoproteins
   called CD8 (different from the helper T cells which
  possess CD4).
 All body cells display class I MHC antigens, so all
  infected cells or abnormal cells can be destroyed by
  cytotoxic T cells.
Humoral (antibody-mediated) immune response                            Cell-mediated immune response
                                                Antigen (1st exposure)
                                                                                                               Stimulates
                                                    Engulfed by                                                Gives rise to
                                                      Antigen-
                                                   presenting cell




             B cell                                 Helper T cell                             Cytotoxic T cell




                                                                                                                               Overview
                                                     Memory
                                                   Helper T cells                                                              of
                                                                                                                               acquired/
                                                                                                                               adaptive
                                                Antigen (2nd exposure)

          Plasma cells            Memory B cells                     Memory                        Active                      immune
                                                                                              Cytotoxic T cells
                                                                     Cytotoxic T
                                                                             cells
                                                                                                                               system
            Secreted
           antibodies

Defend against extracellular pathogens by binding to antigens,            Defend against intracellular pathogens
thereby neutralizing pathogens or making them better targets              and cancer by binding to and lysing the
for phagocytes and complement proteins   .                                infected cells or cancer cells   .

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Immune system

  • 1. IMMUNE SYSTEM •Specific and nonspecific response •Humoral immunity
  • 2. IMMUNE SYSTEM  Pathogen (disease-causing organism) can be bacteria, fungus, virus, or multicellular parasite.  Pathogen infects animal because the internal environment of animal offer a suitable habitat.  The animal body is the ideal habitat for the pathogen to grow, reproduce, and medium for transportation to the new environments.
  • 3.  Thus, a defense system must be made up in order to ward off the invasion of pathogen into the animal body.  Immune system recognizes the pathogen as foreign body and respond by producing immune cells and protein.
  • 4. IMMUNITY  Immunity is defined as an ability of the body to resist invasion of pathogen or disease.  A study of how the immune system of animal works is called immunology.  Immunity are divided into nonspecific immunity and specific immunity.
  • 5. Pathogens (microorganisms and viruses) INNATE IMMUNITY Barrier defenses: Recognition of traits Skin shared by broad ranges Mucous membranes of pathogens, using a Secretions small set of receptors Internal defenses: Phagocytic cells Rapid response Antimicrobial proteins Inflammatory response Natural killer cells ACQUIRED IMMUNITY Humoral response: Recognition of traits Antibodies defend against specific to particular infection in body fluids. pathogens, using a vast array of receptors Cell-mediated response: Cytotoxic lymphocytes defend Slower response against infection in body cells.
  • 6. NONSPECIFIC IMMUNITY  Also known as innate immunity.  Present before any exposure to pathogens.  Act immediately upon infection.  Divided into surface barrier and internal defenses.
  • 7. SURFACE BARRIER  Skin is an outer covering of an animal body which act as primary defense system.  Possess keratinized epithelial membrane that function as a barrier and prevent the pathogen that swarm on the skin.  Keratin is resistant to most weak acids and bases and to bacterial enzymes and toxins.
  • 8.  Mucous membranes line all body cavities that open to the exterior; the digestive, respiratory, urinary, and reproductive tracts.  Epithelial membranes produce a variety of protective chemicals.
  • 9.  The acidity of skin secretions (pH 3 to 5) inhibits bacterial growth. Sebum contains chemical that are toxic to bacteria.  Vaginal secretion of adult females are very acidic.  The stomach mucosa, secretes a concentrated hydrochloric acid solution and protein-digesting enzymes.
  • 10.  Saliva, which cleanses the oral cavity and teeth.  Lacrimal fluid of eye contains lysozyme, an enzyme that destroys the bacteria.  Sticky mucus traps many microorganisms that enter the digestive and respiratory passageways.  Tiny mucus-coated hairs inside the nose traps the pathogen, preventing it from entering the lower respiratory passages.
  • 11. INTERNAL DEFENSES:CELLS AND CHEMICALS  Internal defenses involve phagocytic cells, natural killer cells, antimicrobial proteins, and inflammatory response.  The inflammatory response enlists macrophages, mast cells, all types of white blood cells, and other chemicals that kill pathogen.  The phagocytic cells are the cells that functions in engulfing the pathogen.
  • 12. PHAGOCYTIC CELLS  If the pathogens succeed to get through the skin, then the phagocytic cells will combat the pathogens.  Phagocytic cells consist of monocytes, macrophages, neutrophils and eosinophils.  Pathogens are recognized by surface cell receptors which are also known as TLR (Toll-like receptors).
  • 13. EXTRACELLULAR Lipopolysaccharide FLUID Helper TLR4 Flagellin protein WHITE BLOOD CELL TLR5 VESICLE TLR9 TLR3 Inflammatory responses ds RNA
  • 14.  Macrophages derived from white blood cells, monocytes which leave and enter the tissues, and develop into macrophages.  Neutrophils, the most abundant type of white blood cells.  Eosinophils, white blood cells that weakly phagocyte the pathogens.
  • 15. HUMAN LYMPHATIC SYSTEM Interstitial fluid Adenoid Tonsil Lymph Blood nodes capillary Spleen Tissue Lymphatic cells vessel Peyer’s patches (small intestine) Appendix Lymphatic vessels Lymph Masses of node defensive cells
  • 16. MECHANISM OF PHAGOCYTOSIS  Phagocytic cell engulfs the particulate matter.  Cytoplasmic extension of phagocyte cell bind to the particulate matter and pull it into vacuole.  Phagosome is formed.  Phagosome fuses with lysosome, forming a phagolysosome.
  • 17. Microbes PHAGOCYTIC CELL Vacuole Lysosome containing enzymes
  • 18. NATURAL KILLER CELLS  Function in lysing and killing the cancer cells and virus-infected body cells.  Natural killer cells act before the specific immune system is activated.  Able to detect and eliminate the virus infected cell and cancerous cell (virus infected cell and cancerous cell do not express class I MHC protein).
  • 19.  The natural killer cells detect the cell which is lack of self cell surface receptors (class I MHC protein).  Natural killer cells also promote the target cells to undergo apoptosis (programmed cell death).
  • 20. INFLAMMATORY RESPONSE  The benefits of inflammatory response: 1. Prevent the spread of damaging agents to nearby tissues. 2. Disposes of cell debris and pathogen. 3. Set the stage for repair (blood clotting).
  • 21. INFLAMMATORY RESPONSE  Factors which elicit inflammatory response: 1. Physical trauma ( a blow) 2. Intense heat 3. Irritating chemicals 4. Infection by viruses, fungi, and bacteria The four cardinal signs of accute inflammation: 1. Pain 2. Redness 3. Heat 4. Swelling
  • 22. Tissue injured Histamine (released by basophils),chemical mediators, prostaglandin, complement kinin Vasodilation of Increased Attract neutrophils, arterioles capillary monocytes, and •Local hyperemia permeability lymphocytes to (increased blood flow •Capillaries leak injured area to injured area fluid (exudate) (chemotaxis) •Pus formation
  • 23.  Mast cells- key components of inflammatory response., release histamine.  Pus- break down tissue, die or dying neutrophils, dead or living pathogen, accumulate in the wound.  Hyperemia (congestion of blood)- causes redness and heat of an inflammed region.
  • 24.  Inflammation can be divided into local inflammation and systemic inflammation.  Fever is an example of systemic inflammation. It is triggered by pyrogens. The high body temperature inhibits the microbial multiplication and enhances body repair.
  • 25.  Exudates- fluid containing antibodies and clotting factors.  Secretion of exudate causes local edema (swelling) and contributes to the sensation of pain.
  • 26. Splinter Chemical Macrophage Fluid Mast cell signals Capillary Phagocytosis Red blood cells Phagocytic cell Major events in a local inflammatory responses
  • 27. INFLAMMATORY CHEMICALS CHEMICAL SOURCE PHYSIOLOGICAL EFFECTS Histamine Granules of basophils and mast cells, released Promotes vasodilation of local in response to mechanical injury, presence of arterioles, increases permeability of certain microorganisms, and chemicals local capillaries, promoting exudate released by neutrophils. formation. Kinins A plasma protein, kininogen is cleaved by the Same as for histamine, also induce enzyme kallikrein found in plasma, urine, chemotaxis of leukocytes and saliva, and lysosomes of neutrophils, and other prompt neutrophils to release types of cells, cleavage releases active kinin lysosomal enzymes, thereby peptides. enhancing generation of of more kinin, induce pain. Prostaglandins Fatty acid molecules produced from Sensitize blood vessels to effects arachidonic acid-found in all cell membranes; of other inflammatory mediators, generated by enzymes of neutrophils, one of the intermediate steps of basophils, mast cells and others. prostaglandin generation produces free radicals, which can cause inflammation; induce pain.
  • 28. ADAPTIVE/ SPECIFIC IMMUNITY  Specific; recognizes and respond to specific pathogens or foreign substances.  Systemic; Immunity not only involve to the initial infection site.  Possess ‘memory’; Able to mount stronger attacks on the pathogens which encounter the body previously.
  • 29.  Adaptive immunity are divided into humoral response and cell-mediated response.  Humoral response involves the production of antibody.  Cell-mediated immunity involves cytotoxic cells.
  • 30. HUMORAL RESPONSE  Antibody-mediated immunity.  Production of antibodies by lymphocytes.  Antibodies present in the body’s “humors,” or fluids (blood, lymph).  Involve antigen recognition, antigen presenting, and B cell proliferation.
  • 31. B cells undergo maturity (antigen binds to its surface receptor, Tcells nearby) B cells undergo clonal selection (reproduce asexually by mitosis) Plasma cells Antibodies Long-lived memory cells
  • 32. Humoral (antibody-mediated) immune response Antigen (1st exposure) Stimulates Engulfed by Gives rise to Antigen- presenting cell B cell Helper T cell Memory Helper T cells Antigen (2nd exposure) Plasma cells Memory B cells Secreted antibodies Defend against extracellular pathogens
  • 33. Antigen- presenting cell Peptide antigen Bacterium Class II MHC molecule CD4 TCR (T cell receptor) Humoral Cytokines Helper T cell immunity Cell-mediated (secretion of immunity antibodies by (attack on plasma cells infected cells) B cell Cytotoxic T cell
  • 34. LYMPHOCYTES (B CELLS AND T CELLS)  B cells and T cells are lymphocytes.  Involve in the humoral immune response.  B cells are originated from the bone marrow.  T cells are also originated from the bone marrow but it migrated to the thymus.
  • 35. ANTIGEN  Antigens are foreign substances which elicits adaptive immune response.  Antigens are either natural or synthetic.  Nonself; antigens are normally not parts of the body.  Most antigens are large and complex molecules.
  • 36.  To elicit adaptive immunity, antigen recognition must occur.  Antigen recognition- the B cell and T cell bind to the antigen.  The antigen binding- via antigen receptor which attached to the surface of B cell and T cell plasma membranes.
  • 37. B CELL RECEPTOR Antigen- Antigen- binding site binding Disulfide site bridge V V Variable regions Light C C Constant chain regions Transmembrane region Plasma Heavy chains membrane B cell (a) B cell receptor
  • 38. T CELL RECEPTOR Antigen- binding site Variable regions V V Constant regions C C Transmembrane region Plasma membrane Disulfide bridge Cytoplasm of T cell T cell (b) T cell receptor
  • 39. B CELLS ANTIGEN RECEPTORS Y-shaped. Consist four polypeptide chains. Two identical light chains and two identical heavy chains. Have constant region (C) and variable region (V). When the antigen receptors bind to an antigen, B cell activation occurs.
  • 40.  The antigen receptor bind to the epitope.  Epitope- Also known as antigenic determinant, a small, accesible portion of an antigen that binds to an antigen receptor.
  • 41.  An antigen possesses several different epitopes.  All the antigen receptors which are located at a single lymphocyte only bind to the same epitope.  When the antigen bind to the antigen receptor, B cell activates and give rise to plasma cells.  Plasma cells produce antibodies.
  • 42. Epitopes (antigenic determinants) Antigen-binding sites Antigen Antibody A Antibody C C C C C Antibody B
  • 43. ANTIBODIES  Also known as immunoglobulins.  Similar structure with B cell antigen receptors, but antibodies do not attach to the surface cell membranes.
  • 44. ANTIBODY CLASSES  Antibodies are divided into five major classes.  Polyclonal antibodies- products of many different clones of B cells following exposure to a microbial agent.  Monoclonal antibodies- prepared a single clone of B cells grown in culture.
  • 45. Class of Immuno- Distribution Function globulin (Antibody IgM First Ig class Promotes neutraliza- (pentamer) produced after tion and cross- initial exposure to linking of antigens; antigen; then its very effective in concentration in complement system the blood activation declines IgG Promotes (monomer) Most abundant Ig opsoniz class in blood; a- also present in tion, tissue fluids neutraliz ation, and cross-linking of crosses placenta, antigens; less thus conferring effec- passive immunity on fetusactivation tive in of IgA Present in Provides localized complement (dimer) secretions such defense of mucous system as tears, saliva, membranes by than IgM mucus, and cross-linking and breast milk neutralization of antigens Triggers release from IgE Present in blood mast cells and (monomer) at low concen- basophils of hista- trations mine and other chemicals that cause allergic reactions IgD (monomer) Present Acts as antigen primari receptor in the ly antigen- on surface of stimulat B cells that have ed not been proliferation and expos differentiation of ed B cells (clonal to antigens selection
  • 46. Class of Immuno- Distribution Function globulin (Antibody) IgM First Ig class Promotes neutraliza- (pentamer) produced after tion and cross- initial exposure to linking of antigens; antigen; then its very effective in concentration in complement system the blood declines activation J chain
  • 47. Class of Immuno- Distribution Function globulin (Antibody) IgG (monomer) Most abundant Ig Promotes opsoniza- class in blood; tion, neutralization, also present in and cross-linking of tissue fluids antigens; less effec- tive in activation of complement system than IgM Only Ig class that crosses placenta, thus conferring passive immunity on fetus
  • 48. Class of Immuno- Distribution Function globulin (Antibody) IgA (dimer) Present in Provides localized secretions such defense of mucous as tears, saliva, membranes by mucus, and cross-linking and J chain breast milk neutralization of antigens Presence in breast milk confers Secretory passive immunity component on nursing infant
  • 49. Class of Immuno- globulin (Antibody) Distribution Function IgE Present in blood Triggers release from (monomer) at low concen- mast cells and trations basophils of hista- mine and other chemicals that cause allergic reactions
  • 50. Class of Immuno- Distribution Function globulin (Antibody) IgD Present primarily Acts as antigen (monomer) on surface of receptor in the B cells that have antigen-stimulated not been exposed proliferation and to antigens differentiation of B cells (clonal selection) Trans- membrane region
  • 51. ANTIBODY TARGETS AND FUNCTIONS  Neutralization- antibodies block specific sites on viruses or bacterial exotoxins (toxin chemicals secreted by bacteria).  The virus or exotoxin cannot bind to the receptors on tissue cells to cause injury.
  • 52.  Agglutination- Antibodies bind to the antigenic determinant on more on one antigen at a time.  Forming antigen-antibody complexes which causes clumping of the foreign cells.
  • 53.  Precipitation- Soluble molucles are cross-linked into large complexes that settle out of solution.
  • 54.  Complement fixation and activation- Antibodies bind to cells, cause the antibodies to change its shapes.  The antibodies expose the transmembrane regions.  Complement fixation into the antigenic cell’s surface is triggered, followed by the cell lysis.
  • 55. Viral neutralization Opsonization Activation of complement system and pore formation Bacterium Complement proteins Virus Formation of membrane attack complex Macrophage Flow of water and ions Pore Foreign cell
  • 56. ANTIGEN RECOGNITION  B cell antigen receptors – bind to the epitopes of antigens.  T cell antigen receptor – bind to the fragments of antigens that are presented on the surface of host cells.
  • 57. MHC  Major Histocompatibility Complex molecule.  Encodes a group of glycoproteins called MHC proteins.  MHC proteins are divided into two groups, Class I MHC proteins and Class II MHC proteins.
  • 58. Class I MHC protein Class II MHC protein Found on virtually all body cells. Found only on certain cells that acts on immune system. Involves in the cell-mediated Involves in the humoral immunity. immunity.
  • 59. RECOGNITION OF PROTEIN ANTIGENS BY T CELLS  The antigen is engulf by the cell. The antigen is cleaved by host cell’s enzyme into antigen fragment.  Antigen fragment binds to MHC molecule.  Antigen fragment-MHC complex is brought to the surface of the cell.  T cell recognizes the antigen fragment-MHC complex.
  • 60. THE ROLE OF THE MHC  Bind to antigen fragment.  Transport the antigen fragment to the surface of the cell.  Lead to antigen presentation, the display of the antigen fragment on the cell surface.
  • 61. HELPER T CELLS  Activates the adaptive immune response.  Antigen fragment is presented by class MHC proteins on the host cell.  The host cell which displays the antigen fragment is called antigen-presenting cell.
  • 62.  In the cell mediated immunity, the Class I MHC protein formed a complex with the antigen fragment.  In the humoral immunity, the antigen fragment forms a complex with the Class II MHC protein.
  • 63. Top view: binding surface exposed to antigen receptors Antigen Class I MHC Antigen molecule Plasma membrane of infected cell
  • 64. Antigen- Infected cell Microbe presenting 1. cell Antigen Antigen fragment associat es with Antigen MHC fragment Class I MHC molecul molecule e Class II T cell MHC receptor molecule 2. Tcell T cell recognize receptor s combinati a) Cytotoxic T cell on b) Helper T cell
  • 65. B CELL AND T CELL DEVELOPMENT  The antigen presenting leads to B cell and T cell activation.  B cell is activated (stimulated to undergo differentiation).  B cell proliferates to form clones.  The clones bear the same antigen-specific receptors, similar to the activated B lymphocyte cell.
  • 66.  Some cells from the clones form effector cells.The effector cells which form from the B cells are plasma cells.
  • 67.  T cell is activated and proliferates to form clones. Some of the clones become effector cells.  The effector cells which arise from T cells are divided into helper T cells and cytotoxic T cells.
  • 68. CLONAL SELECTION  The proliferation of B cells is the example of clonal selection process.  B cells form clones, a group of cell which are identical to the original cell.
  • 69. MONOCLONAL ANTIBODY  Providing passive immunity.  Are made by fusing tumor cells and B lymphocytes.  The resulting cell are called hybridomas.  Hybridomas proliferates in culture, and produce a single type of antibody.  Used to diagnose pregnancy, sexually transmitted diseases, hepatitis and rabies.
  • 70. CELL MEDIATED IMMUNITY  Involve the cytotoxic T cells.  Cytotoxic cells- destroy any cells in the body that harbor anything foreign.
  • 71. Released cytotoxic T cell Cytotoxic T cell Perforin CD8 Dying target cell Class I Granzymes MHC Pore molecule TCR Targe t cell The killing action of cytotoxic T cells
  • 72. CYTOTOXIC T CELL  T cells which undergo proliferation will form effector cells.  The effector cells are helper T cells and cytotoxic T cells.  The surface of the cytotoxic T cells have glycoproteins called CD8 (different from the helper T cells which possess CD4).  All body cells display class I MHC antigens, so all infected cells or abnormal cells can be destroyed by cytotoxic T cells.
  • 73. Humoral (antibody-mediated) immune response Cell-mediated immune response Antigen (1st exposure) Stimulates Engulfed by Gives rise to Antigen- presenting cell B cell Helper T cell Cytotoxic T cell Overview Memory Helper T cells of acquired/ adaptive Antigen (2nd exposure) Plasma cells Memory B cells Memory Active immune Cytotoxic T cells Cytotoxic T cells system Secreted antibodies Defend against extracellular pathogens by binding to antigens, Defend against intracellular pathogens thereby neutralizing pathogens or making them better targets and cancer by binding to and lysing the for phagocytes and complement proteins . infected cells or cancer cells .