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Innate Immunity Nonspecific Defenses of the Host (DOC)

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					Chapter 16 Innate Immunity: Nonspecific
Defenses of the Host
Immunity or resistance is the body’s ability to ward off disease from microbes and
protect our selves from environmental agents(pollens, drugs, foods and chemicals).

Susceptibility is the body’s vulnerability to diseases and lack of immunity.

Overview of the Body’s Defenses
First Line of Defense (Innate/Nonspecific Immunity)

      Skin
      Mucus membrane
      Microbiota

Second Line of Defense (Innate/Nonspecific Immunity)

      Natural Killer Cells
      White Blood Cells (Phagocytic)
      Inflammation
      Fever
      Antimicrobial substances
       a. complement
       b. interferon

Third Line of Defense (Adaptive/Acquired Immunity)

      T cells
      B cells
      Antibodies

The Concept of Immunity
Innate (nonspecific) immunity refers to the defenses present at birth such as skin and
mucus membrane

Adaptive (specific) immunity refers to the defenses that have specific microbial
recognition that acts against the microbes when the first line of defense is breached, such
as T and B cells and antibodies.

First Line of Defense
Physical Factors
1. Skin (Intact)
     Epidermis is the outer, thinner portion directly in contact with the external
        environment.
            o Top layer sheds periodically to remove microbes
            o Contains keratin as protective protein.
     Dermis is the inner and thicker portion consisting of connective tissues.
     Keratin is the protective protein of the epidermis layer.

2. Mucous Membranes and other physical factors

      Consist of epithelial and underlying connective tissue layers such as respiratory
       and gastrointestinal tracts.
      Less protection than skin but nonetheless inhibit microbial entrance
      Mucus is a thick viscous fluid secreted by mucous membrane to lubricate tracts.
      Treponema pallidum survives in mucus and can penetrate the membranes.
      Lacrimal apparatus (lacrimal glands, tears, canals, ducts) wash away keep
       microorganisms from settling on the eyes.
      Saliva produce by salivary glands dilutes microorganism, wash them away from
       teeths and mucous membranes of the mouth
      Nose hairs filters inhaled microorganisms
      Cillia in the lower respiratory tract help propels out toward the throat (ciliary
       escalator) microorganisms that have become trapped.
      Epiglottis that covers the larynx (voice box) during swallowing prevents
       microorganisms from entering the lower respiratory tract.
      Urine cleanse urethra
      Vaginal secretions move microorganisms out.
      Defecation and vomiting expel microbes

3. Normal Microbiota

      Normal Microbiota are opportunistic microorganisms that inhabit the body and
       helps ward off and do not cause disease under normal conditions.
      Normal microbiota in the vagina secrete acidic substance to prevent Candida
       albicans from causing vaginitis
      Escherichia coli secretes bacteriocins that inhibit the growth of Salmonella and
       Shigella.

Chemical Factors
1. Sebum
     Oily substance produce by sebaceous glands of the skin to form protective film on
       the skin surface and to prevent hair from drying and becoming brittle.
2. Low pH (3 and 5)
     Caused by secretions of lactic acid and fatty acid prevents growth of many
       microorganisms.

3. Lysozyme
     Contains in the perspiration breaks down cells walls of gram-positive bacteria and
       to lesser extent gram-negative bacteria.

4. Gastric Juice (pH 1.2-3.0)
     Gastric juice which is a mixture of hydrochloric acid, enzymes and mucus
        produced by stomach glands destroy bacteria and their toxins.
     Exception is Clostridium botulinum and Staphylococcus aureus.
     Helicobacter pylori neutralizes stomach acid and grow to cause ulcers and
        gastritis.

Second Line of Defense
Leukocytes (White Blood Cells)
Granulocytes

      Granulocytes have large granules in their cytoplasm that can be seen under a light
       microscope

1. Neutrophils
     Stains a pale lilac with a mixture of acidic and basic dyes and consist of 2 to 5
       lobes.
     Phagocytic, motile, active in the initial stages of infection.
     Have the ability to leave the blood, enter an infected tissue and destroy microbes
       and foreign particles.
2. Basophils
     Stains blue-purple with the basic dye methylene blue
     Phagocytic
     Release substances such as histamine that is important in inflammation and
       allergic response.
3. Eosinophils
     Stain orange or red with the basic dye eosin.
     Phagocytic and have the ability to leave the blood.
     Produce toxic proteins against certain parasites such as helminthes.

Agranulocytes

      Have granules but are not visible under a light microscope.
1. Monocytes
     Are not phagocytic until they leave the blood and mature into macrophage and
      become the best phagocyte in the tissue.

2. Lymphocytes
     3rd line of defense
     Play a key role in the adaptive immunity.
     Natural killer cells
     T cells
     B cells

Phagocytes
      Phagocytosis is the ingestion of microorganisms and other particles by a cell.
      Phagocytes are collective cells that perform phagocytosis.
      Phagocytes are activated by cytokines, lipid A and lipopolysaccharides (LPS).

The Mechanisms of Phagocytosis
1. Chemotaxis and adherence of microbe to phagocyte
     Microbe surface attaches to the plasma membrane of the phagocyte.
2. Ingestion of microbe by phagocyte
     Pseudopods engulf the microbe
3. Formation of a phagosome
     Phagosome surrounds the microbe.
4. Formation of phagolysosome
     Fusion of phagososome and lysosome.
5. Digestion of ingested microbe by enzymes.
6. Formation of residual body containing indigestible material.
7. Discharge of waste materials.

Inflammation
      Defensive response triggered by damage to the body’s tissue.
      It is characterized by redness, pain, heat, swelling and loss of function.
      Accute inflammation is an intense and short lasting inflammation. Example:
       response to boil.
      Chronic inflammation is a less intense but long lasting inflammation. Example:
       response to tuberculosis.

Process of Inflammation (3 Stages)
1. Vasodilation and increased permeability of blood vessels.
      Vasodilation is the dilation of blood vessels that increase blood flow to the
       damage tissue causing erythema (redness) and head associated inflammation.
      Increased permeability allows fluid to move from blood into tissue spaces causing
       edema (swelling).
      Histamine is a chemical substance released by damaged cells in response to injury
       and the causative agent of vasodilation and increased permeability.
      Abscess is the focus of infection consisting of localized collection of pus, dead
       cells and body fluids in a cavity as a cause of the breakdown of body tissues.

2. Phagocyte Migration and Phagocytosis.
     Margination is the sticking process of neutrophils and monocytes to the inner
       surface endothelium of blood vessels.

3. Tissue Repair
     Stroma is the supporting connective tissue that causes scar for example in the case
        of major tissue damage.
     Parenchyma is the functioning part of the tissue that can repair minor tissue
        damage with no visible signs.

Fever
      Fever is an abnormally high body temperature. (above 37 deg Cel or 98.6 deg F)
      Hypothalamus is the thermostat of the body (Microorganism releases LPS
       Phagocyte release interleukin-1hypothalamus releases prostaglandin 
       reset hypothalamus thermotat)
      Shivering and chill is a sign of that body temperature is increasing.
      Crisis is the phase of the fever when the body temperature is falling.

Antimicrobial Substances
1. The Complement System
     Complement system is a defensive system consisting of over 30 proteins
       produced by the liver and found circulating in the blood serum.
     Proteins of the complement system destroy microbes by cytolysis, inflammation,
       phagocytosis, and prevent excessive damage to host tissues.

2. Interferons
     Interferons (IFNs) are antiviral proteins and host-specific produced by certain
        cells such as lymphocytes and macrophages to prevent viral multiplication.

3. Transferrins
     Transferrins are iron-binding proteins found in the blood, milk, saliva, and tears
       that inhibit the growth of bacteria by reducing the available amount of iron.

4. Antimicrobial Peptides
   Consist of dozen amino acids produce my mucous membrane cells and
    phagocytes that binds to microbial plasma membranes to cause lysis.

				
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