NONSPECIFIC HOST DEFENSE MECHANISMS

( outlined by Algerico F. Baiño, Jr., RN )

I. INTRODUCTION

 In this lesson, we will learn how our bodies combat pathogens in an attempt to prevent the infectious
diseases they cause
 Host defense mechanisms is the way in which the body protects itself from pathogens, it can be thought
of as an army consisting of three lines of defense
 The First ( skin and mucous membranes ) and the Second line ( Inflammation and Phagocytosis ) of
defense are called NON-SPECIFIC defense mechanisms
 The Third line of defense is called the SPECIFIC defense mechanism which comprise of our Immune
response
 ANTIBODIES - are special proteins produced in the body by the third line of defense, in response to the
presence of foreign substances ( Antigens ). Antibodies are very specific, in that they can only recognize
and attach to the antigen that stimulated their production
 ANTIGENS - are also called foreign substances. They stimulate the production of specific antibodies and
are also called “ Antibody-Generating” substances

II. NON-SPECIFIC HOST DEFENSE MECHANISMS

 Are general and serve to protect the body against harmful substances
 Includes mechanical and physical barriers to invasions, chemical factors, microbial antagonism by our
indigenous microbiota, fever, inflammatory response ( inflammation ) and phagocytic white blood cells
( phagocytes )

FIRST LINE OF DEFENSE

EXAMPLE DESCRIPTION
Skin and Mucous  Intact and unbroken skin covering our body serves as a physical and mechanical
Membranes as barrier
Physical Barriers  It is only when the skin is cut, abraded (scratched ), or burned that pathogens gain
entrance or when they are injected through the skin
 Mucous membranes, which are composed of a only a single layer of cells, also serv
as a physical or mechanical barrier to pathogens
Cellular and Chemical  Dryness of most areas of the skin inhibits colonization by many pathogens
Factors  Acidity and Temperature of the skin also inhibit the growth of pathogens.
 Oily sebum produced by the sebaceous glands are toxic to some pathogens
 Perspiration flushes organisms by pores and the surface of the skin and also
contains lysozyme enzyme that degrades
 Lysozyme, lactoferrin and lactoperoxidase kills bacteria or inhibit their growth
1. Lysozyme destroys bacterial cell wall by degrading peptidoglycan
2. Lactoferrin is a protein that binds iron which is a chemical required by all
pathogens and pathogen are unable to compete with lactoferrin
3. Lactoperoxidase is an enzyme that produces superoxide radicals and highly
reactive forms of oxygen that are toxic to bacteria
 Hair, mucous membranes and irregular chambers of the nose serves to trap
much of the inhaled debris
 Cilia from the posterior nasal membranes, nasal sinuses , bronchi and trachea
sweep the trapped dust and microbes upward toward the throat and is expelled
by swallowing or sneezing and coughing
 Phagocytes in the mucous membranes may also be involved in the mucociliary
clearance mechanism
 Swallowing of the saliva can be thought of as a nonspecific host defense mechanism
 The following factors protects the GI tract :
1. Digestive Enzymes - Bile, lowers the surface tension and causes chemical
changes in bacterial cell walls and membranes that make bacteria easier to
digest.
2. Acidity of the Stomach ( pH 1.5 ) - Acid and Bile combination makes the small
intestine free of bacteria
3. Alkalinity of the intestines
 Peristalsis and urination serve to remove pathogens from the GI tract and urinary
tract respectively
 Infrequent urination, benigh prostatic hyperplasea and failure to urinate after sex,
increases the chances of developing urinary bladder infections
 The low pH of the vagina( acid ) usually inhibits the colonization of pathogens but
oral contraceptives increases the pH of the vagina, thus, making it susceptible to
colonization
Microbial Antagonism  A condition wherein the resident microbes of the indegenous microbiota prevent
colonization by arriving pathogens
 Factors that are attributed to the inhibitory capability of the Indigenous microbiota
1. Competition for colonization sites
2. Competition for nutrients
3. Production of substances that kill other bacteria
 The effectiveness of microbial antagonism is frequently decreased after prolonged
administration of broad spectrum antibiotics, leading to overgrowth of bacteria or
fungi that are resistant to antibiotics (s) being administered and it leads to
Superinfection, which is an “overgrowth” or “population explosion”
 Example of superinfections are : Yeasts Vaginitis ( Candida albicans ), Antibiotic-
associated diarrhea and Pseudomembranous colitis ( CLostridium difficile ) in the
colon
 Bacteriocins are proteins proteins that kill other bacteria and they are ore potent
than antibiotics. An example is Colicin, produced by E. coli
SECOND LINE OF DEFENSE
Transferrin  A glycoprotein synthesized by the liver which has a high affinity for Iron
 Functions to store and deliver iron to host cells
 Since pathogens loves Iron, Transferrin sequesters ( take ) Iron away from the
pathogens and depriving them, eventually killing them.
Fever  Characterized by a a body temperature greater than 37.8 degrees Celcius
( Normal : 36.2-37.5 )
 Pyrogens / Pyrogenic Substances are the substances that stimulate the production
of fever, and they ( pyrogens ) may originate inside or outside of the cell. An
example of endogenous pyrogen is Interleukin 1 ( IL-1) produced by the WBCs
 How does fever help in the host’s defenses ?
1. Stimulates WBCs to destroy invaders
2. Reduces free plasma Iron, thereby limiting the growth of pathogens
3. Produces IL-1 which in turns causes the proliferation, maturatio and activation
of lymphocytes in the immunologic response
4. Slows down the growth rate of certain pathogens and also kills fastidious
pathogens
Interferons  Are small, antiviral proteins produced by virus infected cells wherein they
“interfere” with viral replication
 3 types of interferons
1. Alpha - produced by B lymphocytes( B cells ), monocytes and Macrophages
2. Beta - produced by fibroblasts and virus infected cells
3. Gamma - activated by T lymphocytes ( T cells ) and Natural Killer Cells ( NK
cells )
 Once interferons are released from the cells, they attach to the membranes of the
surrounding cells and prevent viral replication from occurring in those cells, thus,
spread of infection is inhibited allowing other body defenses to fight the disease
more effectively that is why viral diseases are limited in duration.
 Interferons are “Species - Specific”. Hence, they are effective only in the species of
animal that produced them
 Interferons are also “Non-virus Specific”, which means that they are effective
against a variety of viruses and not just the particular type of virus that stimulated
their production.
 Human interferons are industrially produced by Genitically -Engineered Bacteria
and are used experimentally to treat certain viral infections
 Aside from interfering with viral multiplication, interferons also activate cerain
lymphocytes ( NK cells ) to kill virus infected cells

Complement System  These are a group of approximately 30 different proteins that are found in normal
blood plasma because it is complemetary to the action of the immune system
 The proteins of the compliment system interact with each other in a stepwise manner
known as the compliment cascade that assists in the destruction of many pathogens
 What happens during complement activation ?
1. Initiation and amplification of inflammation
2. Attraction of phagocytes to sites where they are needed
3. Activation of leukocytes
4. Lysis of bacteria and other foreign cells
5. Increased phagocytosis by phagocytic cells ( opsonization )
 Opsonization is a process by which phagocytosis is facilitated by the deposition of
opsonins, such as antibodies of certain complement fragments, onto the surface of
particles or cells.
Acute - Phase Proteins They increase rapidly in response to infection, inflammation and tissue injury. Hence,
( plasma level of they enhance resistance to infection and promoting the repair of damaged tissue.
molecules )  It includes C reactive protein ( a marker used in the laboratory for the indication of
inflammation ), serum amyloid A protein, protease inhibitors and coagulation
proteins.
Cytokines  Are chemical mediators released by different types of cells in the human body and
enables cells to communicate with one another, acting as a chemical messengers
both within the immune system and between the immune system and other systems
of the human body
Inflammation /  A collective series of events when a body normally responds to any local injury,
inflammatory response irritation, microbial invasion or bacterial toxin
3 MAJOR EVENTS OF INFLAMMATION ARE AS FOLLOWS :
1. Vasodilation - increased diameter of the capillaries to allow increase blood flow to
the site
2. Increased permeability of the capillaries allowing plasma and plasma proteins to
escape
3. Escape of leukocytes from the capillaries so that they can accumulate at the site of
the injury
PRIMARY PURPOSES OF THE INFLAMMATORY RESPONSE
1. Localize an infection
2. Prevent the spread of microbial invaders
3. Neutralize any toxins being produced at the site
4. Aid in the repair of damaged tissue
SEQUENCE OF EVENTS IN INFLAMMATION
1. Tissue Injury - which is triggered by either physical, chemical or biological agents
2. Vasodilation
 Increased blood flow to the area resulting to redness and heat
 Mediated by vasoactive agents like histamine and prostaglandins released from
damaged cells
3. Increased permeability
 Results when vasodilation causes the endothelial cells that line the capillaries to
stretch and separate, leading to plasma escape from the capillaries causing the
site to become edematous ( swollen )
 protein rich exudate with immunoglobulins and complement moves into injured
area
4. Emigration of Leukocytes (Neutrophils and Macrophages ) adhere to endothelial
cells of capillaries
5. Chemostaxis- Neutrophils and macrophages move to site of the injury in response to
gradient of chemotactic mediators released by injured tissue
6. Phagocytosis - phagocyte attaches to bacterium and engulfs it by endocytosis and
bacteria are degraed by oxygen radicals and digestive enzymes.
4 CARDINAL ( MAIN ) SIGNS AND SYMPTOMS OF INFLAMMATION
1. Redness
2. Heat
3. Swelling ( edema )
4. Pain
FREQUENTLY ASKED QUESTIONS

1. Why is there Pain or Tenderness along with inflammation?

 Pain is the result of actual damage to nerve fibers due to injury, irritation of
microbial toxins, irritation by microbial toxins or other cellular secretions such as
prostaglandins or increased pressure on nerve endings due to edema.

2. Why is there an accumulation of fluids or cellular debris at the site of inflammation?

 This is referred to as an inflammatory exudate
 If the exudate is thick and greenish yellow color, it contains many live and dead
leukocytes, and it is known as Pus or Purulent exudate
 Pyogenic Microbes or Pus producing microbes such as staphylococci and
streptococci are present, additional pus is produced as a result of the killing
effect of bactrerial toxins on phagocytes and tissue cells.
 Bluish Green Pus is caused by Psuedomonas aeruginosa infection due to bluish -
green pigment pyocyanin produced by the organism

3. What is the role of the lymphatic system ?

 The primary function of the lymphatic system includes draining and circulating
intercellular fluids from tissues, transporting digested fats from the digestive
system to the blood, removing foreign matter and microbes from the lymph and
producing antibodies and other factors to aid in the destruction and
detoxification of any invading microbes.
Phagocytosis  Is the process by which phagocytes surround and engulf ( ingest ) foreign material
 The three major categories of leukocytes found in the blood are Monocytes,
Lymphocytes and Granulocytes
 The three types of granulocytes are Neutrophils, Eosinophils and Basophils.
 Phagocytic white blood cells are called Phagocytes
 The two most important groups of phagocytes in the human body are
Macrophages and Neutrophils and are sometimes called “ Professional
Phagocytes”
 Macrophages serve as the clean up crew to rid the body of unwanted and often
harmful substances such as dead cells, unused cellular secretions, debris and
microbes
 Phagocytic Granulocytes includes Neutrophils and Basophils
 Neurtophils are much more efficient at phagocytosis than eosinophils
 Eosinophilia is in abnormnally increased number of eosinophils caused by allergies
and helminth infections
 Basophils are involved in allergic and inflammatory reactions
 Macrophages develop from a type of leukocyte called monocytes during the
inflammatory response to infections and are considered to be effective phagocytes
 Wandering macrophages are those that leave the bloodstream and migrate to
infected areas
 Reticuloendothelial System ( RES ) - where the macrophages are found and it
includes all cells in the liver, spleen, lymph nodes and bone marrow, as well as the
lungs, blood vessels, intestines and brain and the main function of the RES is the
engulfment and removal of foreign and useless particles, living or dead ( excess
cellular secretions, dead and dying leukocytes, erythrocytes and tissue cells, foreign
debris and microbes that gain entrance to the body )
4 STEPS IN PHAGOCYTOSIS
Steps Description
1. Chemotaxis  Happens when the phagocytes are attracted by chemotactic
agents to the site where they are needed
 Chemotactic agents are “Chemical attractants” which are
produced by chemokines
 PHAGOCYTES move along a concentration gradient ( from
low to high ), wherein the highest concentration is at the site of
inflammation and also where chemotactic agents are being
made.
2. Attachment  Refer to the attachment of phagocyte to the object to be
ingested.
 Opsonization is often necessary
3. Ingestion  Happens when the phagocyte surrounds the object with
pseudopodia, which fuse together, and the object is ingested
( Phagocytized or phagocytosed )
 During ingestion, the particle becomes surrounded by a
membrane. The membrane bound vesicle is called a
phagosome
4. Digestion  Happens when the phagosome fuses with a nearby lysosome
to form a digestive vacoule ( phagolysosome ), within which
killing and digestion occur.
 Digestive enzymes found in lysosomes includes lysozyme, B
Lysin, Lipases, Proteases, Peptidases, DNAes and RNAes,
wherein all of these degrade carbohydrates, lipids, proteins
and nucleic acids.
 Nicotinamide adenine dinucleotide phosphate oxidase, an
enzyme found in neutrophils, reduces oxygen to very
destructive products and thereby assist in the destruction of
the ingested microbes.
 Myeloperoxidase, an enzyme released after lysosome fusion,
produces hypochlorous acid which is a potent microbicidal
agent
MECHANISMS BY WHICH PATHOGENS ESCAPE DESTRUCTION BY PHAGOCYTES
1. Capsules  Serves as an Antiphagocytic function, protecting
encapsulated bacteria from being phagocytized
2. Leukocidin  An exoenzyme produced by bacteria which kills
phagocytes
3. Cell wall wax  Exemplified by Mycobacterium tuberculosis, which protects
them from digestion
 PATHOGENS THAT ARE ABLE TO SURVIVE WITHIN PHAGOCYTE
1. Rickettsia rickettsii
2. Legionella pneumophilia
3. Brucella abortus
4. Coxiella burnetii
5. Listeria monocytogenes
6. Salmonella spp
7. Toxoplasma gondii
8. Trypanosoma cruzi
9. Leishmania spp
PATHOGENS THAT ARE ABLE TO SURVIVE WITHIN LEUKOCYTES ( Intraleukocytic
Pathogens )
Obligate, Intracellular Gram ( - ) bacteria that causes tickborne diseases

1. Ehrlichia spp - causes human monocytic ehrlichiosis which infects monocytic phagocytes
2. Anaplasma spp - causes human anaplasmosis which infect granulocytes

DISORDERS AND CONDITIONS THAT ADVERSELY AFFECT PHAGOCYTIC AND

INFLAMMATORY PROCESSES
1. Leukopenia - low number of circulating leukocytes maybe due to bone marrow injury
as secondary to ionizing radiation or drugs, nutritional deficiencies or congenital stem
cell defects
DISORDERS AND CONDITIONS AFFECTING LEUKOCYTE MOTILITY AND
CHEMOSTAXIS
1. Defect in the production of Actin which is a structural protein associated with motility
2. CHS ( Chediak - Higashi Syndrome ) - an inherited childhood disease resulting to
decreased neutrophil chemotaxis, furthermore, abnormal lysosomes that does not
readily fuse with phagosomes leading to decreased bactericidal activity. CHS is
characterized by albinism, CNS abnormalities and recurrent bacterial infections
DISORDERS AND CONDITIONS AFFECTING INTRACELLULAR KILLING BY
PHAGOCYTES
1. CGD ( Chronic Granulomatous Disease ) - a fatal genetic disorder characterized by
repeated bacterial infections because the PMNs of individuals with CGD can ingest
bacteria but cannot kill certain species.
ADDITIONAL FACTORS THAT CAN IMPAIR HOST DEFENSE MECHANISMS
1. Nutritional status - Malnutrition decreases resistance to infection
2. Increased Iron Levels - Increased Iron is favorable to bacteria
3. Stress - stressful situations is susceptible to catch infections
4. Age - newborn and old people are susceptible
5. Cancer and Cancer chemotherapy AIDS - use of cancer chemotherapeutic agents kills
healthy cells
6. Drugs and Various Genetic defects - Steroids and alcohol, B and T cell Deficiencies