Saturday, August 21, 2021

Physical and chemical barrier .Defence of innate resistance

     - potential microbial pathogen invading a human host immediately confronts a vast array of innate defense mechanisms.
     -  Although the effectiveness of an individual mechanism may not be great, collectively they are formidable.

         Many direct factors (age, nutrition, physiology, fever, genetics) and indirect factors (personal hygiene, socioeconomic status, living condition) contribute in some degree to all host-microbe relationships.
- At times, they favor the establishment of the microorganism; at other times, they provide the host some measure of general defense.





 Physical and mechanical barriers along with host secretions are the host's first line of defense against pathogens. e.g.,
1. Skin
2. Mucous membranes
3. Epithelia of the respiratory
4. Gastrointestinal, and
5. Genitourinary systems

1. SKIN

- Intact skin contributes greatly to innate host resistance because it is a
very effective mechanical barrier to microbial invasion.
- Its outer LAyer consists of thick, closely packed cells called Keratinocytes, which produce Keratins- Scleraproteins (insoluble proteins) that are the main components of hair, nails, and the outer skin cells.
- These outer skin cells shed continuously, removing microorganisms that manage to adhere to their surface.
- The skin is slightly acidic (around pH 5 to 6) due to sebum, secretions from sweat glands, and organic acids produced by commensal staphylococci & high concentration of sodium chloride and is subject toperiodic drying.

2. MUCOUS MEMBRANES

- The mucous membranes of the eye (conjunctiva) and the respiratory, digestive, and urogenital systems withstand microbial invasion because the intact stratified epithelium and mucus form a protective covering that resists penetration and traps microorganisms.
- Many mucosal surfaces are bathed in specific antimicrobial secretions. For example, cervical mucus, prostatic fluid, and tears are toxic to many bacteria.
- The conjunctiva that lines the interior surface of each eyelid and the expose surface of the eyeball is a good example of how a mucous membrane functions to provide chemical as well as physical protection from microorganisms.
- It is kept moist by the continuous flushing action of tears from the lacrimal glands.
- Tears contain large amounts of lysozyme, lactoferrin, and other antimicrobial chemicals.

Lysozyme:

lyses bacteria by hydrolyzing the β(1-4) bond connecting N-acetylmuramic acid(NAG) and N-acetylglucosamine
(NAM) of the bacterial cell wall peptidoglycan especially inGram-positive bacteria.


Lactoferrin:

- Tears and other mucous secretions also contain significant amounts of the iron-binding protein lactoferrin.
- Lactoferrin is released by activated phagocytic cells called macrophages and polymorphonuclearleukocytes (PMNs).
- It sequesters iron from the blood plasma, reducing the amount of iron available to invading microbial pathogens thereby limiting their ability to multiply.


Lactoperoxidase:

- mucous membranes produce lactoperoxidase,
- catalyzes the production of superoxide radicals, a reactive oxygen species that is toxic to many microorganisms.


3. Respiratory System

- The average person inhales at least eight microorganisms a minute, or 10,000 each day.
- Once inhaled, microorganism must first survive and penetrate the air- filtration system of the upper and lower respiratory tracts.
- Airflow in these tracts is very turbulent, microorganisms are deposited on the moist, sticky mucosal surfaces. Microbes lArger tHAn 10 µm usually are trapped by hairs and cilia lining the nasal cavity.
- The cilia in the nasal cavity beat toward the pharynx, so that mucus with its trapped microorganisms is moved toward the mouth to be expelled
 - Humidification of the air within the nasal cavity causes many microorganisms to swell, and this aids phagocytosis.
- Microbes sMAller THAn 10 µm (i.e., most bacterial cells) pass through nasal cavity and trapped by the mucociliary blanket that coats the mucosal surfaces of lower respiratory system.
- The trapped microbes are transported by ciliary action the
mucociliary escalator-that moves them away from the lungs.
- Coughing and sneezing reflexes clear the respiratory system of microorganisms by expelling air forcefully from the lungs through the mouth and nose, respectively.
- SAlivAtion also washes microorganisms from the mouth and nasopharyngeal areas into the stomach.
- Microorganisms that succeed in reaching the alveoli of the lungs encounter a population of specialized cells called alveolar macrophages that ingest and kill most inhaled microorganisms by phagocytosis.




4. Gastrointestinal Tract

- Most microorganisms that reach the stomach are killed by the acidic gastric juice (pH 2-3): mixture of
hydrochloric acid + proteolytic enzymes + mucus.
- However, some microorganisms and their products
(e.g., protozoan cysts, HeliCOBACTER pylori, Clostridium spp., and staphylococcal toxins) can survive the stomach acidity.
- Organisms embedded in food particles may be protected from gastric juice and reach the small intestine and damaged by pancreatic enzymes, bile, enzymes in intestinal secretions, and the GALT( Gut associated lymphoid tissue) system.
  Peristalsis and the normal shedding of columnar epithelial cells act in concert to purge intestinal microorganisms.
- In addition, the normal micro biota of large intestine is extremely important in preventing the establishment of pathogenic organisms.
- E.g., metabolic products (e.g., fatty acids) of many normal microbiota in the intestinal tract prevent unwanted microorganisms from becoming established.
- Other normal microbiota outcompete potential pathogens for attachment sites and nutrients.
-       The mucous membranes of the intestinal tract contain cells called Paneth cells - produce lysozyme , peptides called cryptidins- are toxic for some bacteria, as they form membrane channels that result in cell lysis.



5. Genitourinary Tract

- Kidneys, ureters, and urinary bladder of mammals are sterile in normal condition.
- Urine within the urinary bladder also is sterile.
- However, in both males and females, a few bacteria are usually
present in the distal portion of the urethra.
- The factors responsible for this sterility are complex. In addition to removing microbes by flushing action, urine kills some bacteria due to its low pH and the presence of urea and other metabolic end products (e.g., uric acid, fatty acids, mucin, enzymes).
- Portions of the kidney are so hypertonic that few organisms can
survive there.
- In males, the anatomical length of the urethra (20 cm) provides distance barrier that excludes microorganisms from the urinary bladder.
- In females, short urethra (5 cm) is more readily traversed by
microorganisms;
- This explains why urinary tract infections are 14 times more
common in females than in males.
- The vagina has another unique defense.
- Under the influence of ESTROGENS,
- Vaginal epithelium produces increased amounts of glycogen that is degrade to form lactic acid by acid- tolerant LACTOBACIllus ACIdophilus bacteria.
- Normal vaginal secretions contain up to 108 of these bacteria per ml.
- Thus an acidic environment (pH 3-5) unfavorable to most other organisms for establishment.
- Cervical mucus also has some antibacterial activity.











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