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Black Chapter 16 - Innate Host Defenses

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					                              Chapter 16
                             Innate Host defense

IMMUNOLOGY AND IMMUNITY
Immunology is the study of Immunity, which refers to the capacity to recognize and
defend against infections agents and other foreign substance.

Susceptibility is vulnerability to infectious agents.
The immune system is the body system that provides the host with specific immunity to
particular infectious agents.

TYPES OF IMMUNITY
The body’s three lines of defense against infection:

1).Surface defense; skin and mucous membranes ( thin layer cells that secrete mucus).
act as physical barriers to penetration and secrete chemicals inhospitable to pathogens.

2).Innate Immunity, genetic immunity provides nonspecific, hereditary defense and
protection against many pathogens without prior exposure.

3).Adaptive Defenses respond to particular invading agents; provided by the immune
system, they form a second line of defense against pathogens.

Both the innate and adaptive immune system depend on leukocytes and proteins in
plasma.
There are about 10 kinds of leukocytes, all are formed in bone marrow. They are
distinguished by size, morphology and function.

(A). Skin and Mucous Membranes

(B). Phagocytosis
       Defense cells include Granulocytes (Basophils, Mast cells, Eosinophils and
       neutrophils ) and agranulicytes ( monocytes and Lymphocytes).

       The first response of the innate immune system is activation of complement.
       The first response on invading microorganism is phagocytosis.

       Phagocytes is a cell that ingests and digests foreign substances.
       Phagotic cells include neutrophils in the blood and in injured tissues, monocytes
       in the blood , and fixed and wandering macrophages.
       Macrophages are long-lived nature forms of monocytes that are located in
       tissues.

       The process of Phagocytosis:
       1). Invading organisms and damaged tissues release chemicals are attracted by
       phagocytes – chemotaxis. Phagocytes also can secrete cytokines to attract more
       phagocytes at site.
       2). Ingestion occurs as the phagocyte, phagocytes extend pseudopods,
       surrounds and ingests a microbe or other foreign substance into a phagosome.
       3). Digestion occurs as lysomoes surround a vacuole and release the enzymes into
       it, forming a phagolysosome. in neutrophils they fuse with intracellular granules.
       Both contribute chemicals that digest and kill most pathogens.
       Debris from digested bacteria is expelled from the phagocyte as the phagosome
       fuses with the cell membrane.

       Some microbes resist phagocytosis by producing capsules or specific proteins,
       preventing release of lysosomal enzymes, and by producinh toxins (lekocidin and
       streptolysin)

       Extracellular Killing
       Eosinophils defend against parasitic worm infections by secreting cytotoxic
       enzymes.

       Nature killer (NK) cells secrete products that kill virus-infected cells and certain
       cancer cells.

Type             Class name     Role                                           Participate in
                                                                               innate immune
                                                                               system
Macrophage       Phagocyte   Traps invading organisms by                       yes
                             phagocytosis, kills them when phagosome
                             fuses with lysosome initiate inflammation.
Neutrophil       Phagocyte   Traps invading organisms by                       yes
                 and         phagocytosis, most mumerous
                 granulocyte phagocytes,kills them with toxic agents in
                             its granule.
Monocyte                     Circulate in blood and give rise to               yes
                             macrophage, agranular
Eosinophil       Granulocyte Protect against parasites such as
                             helminthic worms, releases in allergic
                             response
Basophil         Granulocyte Unknown, release histamine
Mast cell        Granulocyte Protect against parasites such as
                             helminthic worm, release histamine
Nature Killer                Kills host cells that contain intracellular       yes
cell                         pathogens and virus-infected cells.
B cell           Small       When activated, differentiate into plasma
                 lymphocyte cells
Plasma cell      Lymphocyte Makes antibodies
T cells          Small       Some kill infected host cells, others
                 lymphocytes regulate adaptive immune system
Dendritic cell               Stimulate B cell to differentiate

       Thrombocytes: platelets, form clots which in turn increase vascular permeability,
       chemotaxis of leukocytes, and fix complement proteins.

(C).Inflammation
Inflammation is the body’s response to tissue damage. It is characterized by localized
increased temperature, redness, swelling, and pain.

       The Acute Inflammation process
       1). Acute inflammation is initiated by histamine released by damaged tissues,
       which dilates and increases permeability of blood vessels (vasodialtion).
       2).Activation of cytokines also contributes to initiation of inflammation.
       3). Dilation of blood vessels accounts for redness and increased tissue
       temperature; increased permeability accounts for edema (swelling).
       4). Tissue injury also initiates the blood-clotting mechanism.
       5). Bradykinin stimulates pain receptors; prostaglandins intensify its effect.
       6).Inflammed tissues also stimulate an increase in the number of leukocytes in the
       blood (leukocytosis) by releasing cytokines that trigger leukocytes production.
       7). Neutrophils and macrophages migrate from the blood to the site of injury
       (diapedesis).
       8). Leukocytes and macrophages phagocytized microbes and tissue debris.

       Repair and Regeneration
       Repair and regeneration occur as capillaries grow into the site of injury and
       fibroblasts replace the dissolving blood clot. The resulting granulation tissue is
       strengthened by connective tissue fibers (from fibroblasts) and the overgrowth of
       epithelial cells.
       Macrophages consume dead microorganisms, host cells, and foreign particles in a
       wound.
       After the debris has been cleared, the affected tissues regenerate and finally heal.
       Nerve tissues cannot regenerate.

       Chronic Inflammation
       Chronic inflammation is a persist inflammation in which the inflammation agent
       continues to cause tissue injury as host defenses fail to overcome the agent
       completely.

       Granulomatous inflammation is a chronic inflammation in which monocytes,
       lymphocytes, and macrophages surround necrotic tissue to form a granuloma.

       Chronic granulomatous disease (CGD): defective phagocytes, can not kill
       microorganisms. Suffer frequent bacterial infection.

(D).Fever
       Fever is an increase in body temperature caused by pyrogens, which increase the
       setting (thermostst) of the temperature-regulating center in the hypothalamus.

       Exogenous pyrogens (usually pathogens ands their toxins) come from outside the
       body and stimulates a cytokine that acts as an endogenous pyrogen.

       Fever and the chemicals associated with it augment the immune response and
       inhibit the growth of microorganisms by lowering plasma iron concentrations.
       Fever also increases the rate of chemical reactions, raises the temperature above
       the optimum growth rate for some pathogens, and makes the patient feel ill.
       Antipyretics are recommended only for high fevers and for patients with disorders
       that would be exacerbated by fever.

(E). Antimicrobial Substances
       Complement system and interferons (antiviral proteins).
       The innate system has two defenses against viral infections: interferons and
       nature killer cells.

       Interferons:
              Proteins that act nonspecifically to cause cell killing or to stimulate cells to
              produce antiviral proteins.
              Interferons are potent.
              Interferon can be made by recombinantDNA technology and has proved to
              be therapeutic for certain malignancies; other theraoeutic applications are
              being studies.

              There are three kinds of interferons: alpha, beta and gamma.
              Virus-infected cells produce interferons that cause neighboring cells to
              produce antiviral proteins (AVP), which interfere with viral protein
              synthesis.
              Some bacteria, some protozoa, double-stranded RNA, and endotoxin
              stimulate cells to make interferons.
              Interferons are useful fighting certain leukemias.
              Interferons are regulate cell functions, including motility, cell division,
              activation of macrophages, and transplant tissue rejection.

       Nature Killer cells
             Nature killer cells fight viral infection by killing infected host cells.
             Nature killer cells are attracted to infected tissues and activated by
             cytokines.
             Viral infection causes host cells to lose major histocompatibility complex
             (MHC) class I, allowing natural killer cells to bind.
             Lethal compounds are released from intracellular lytic granules when
             nature killer cells bind to virus-infected cells.
             Patients who lack natural killer cells suffer repeated viral infection even if
             their adaptive immune system is normal.
              they also kill antibody-coated pathogens. They cannot distinguish among
              antibodies.

       Complement
            Complement refers to a set of blood proteins that, when activated,
            produce a cascade of protein reactions.
            The complement system can be activated by
            Classical pathway : antibodies bind to antigens and involves complement
            proteins C1, C4 and C2.
            Alternative pathway: is activated by contact between complement
            proteins and polysaccharides at the pathogen surface.

              Activation of complement:
              Activation of complement system is rapid and nonspecific.
              It promotes opsonization, inflammation, and immune cytolysis through
              the formation of membrane attack complexes (MACs).
              In opsonization, invading agents are coated with opsonins (antibodies)
              and C3b complement protein, making the invaders recognizable to
              phagoctes.
              In immune cytolysis, complement proteins produce lesions on invaders’s
              plasma membranes that cause cell lysis.

               General process, facilitated by binding of Complement (C3) to bacterial
              cell walls
              Lysosomal enzymes destroy pathogen by lysis of component molecules –
              left with pieces
              in a series of reactions, C3 is converted to C3b, but only if invading
              microorganisms are present.
              Normally C3b is unstable, but when bound to microbial cells it interacts
              with other complement component to form C3 convertase, which
              catalyzes the formation of much more C3.
              C3b has three critical roles: It enters the terminal complement pathway,
              which leads to the formation of the membrane attack complex, it acts as
              opsonin; and participates in forming C5a.

SECRETED PROTEINS OF IMMUNE SYSTEM
    Antibody – produced by plasma B to neutralize one specific antigen
    Complement – circulating proteins: lysis bacterial walls, facilitate phagocytosis
                   (opsonization)
    Interleukins – secreted by leukocytes and act between them to activate other cells
    Histamine – vasodilator
    Heparin – anticoagulant
    Interferons – inhibit viral transcription/translation
    Perforin – makes hole in bacterial wall
    Tumor necrosis Factor – kills cancer cells, unknown mechanism of action
    Lymphotoxin – destroys DNA of infected cells
The Lymphatic System
The lymphatic system consists of s network of lymphatic vessels, lymph nodes and
lymphatic nodules (uncapsulated), and the thymus gland, the spleen, and lymph.
Spleen is the largest lymph organ.

All lymphatic tissues that filter blood and lymph are susceptible to infections by
pathogens they filter when the pathogens overwhelm defenses.
Nonspecific defenses consist of the actions of phagocytic cells.
Molecular Defenses

				
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