_NATURAL IMMUNITY
_ Innate immunity refers
to any inborn resistance to a pathogen. Action is immediate.
Response is not enhanced on repeated exposure to pathogen. It
is not acquired through contact with an antigen.
Innate immunity is nonspecific, i.e. it acts against many infectious agents and not to a particular agent, as for example,
surface barrier like skin will protect against different infectious agents, and phagocytes which can engulf a variety of infectious agents.
Components of the innate arm are preformed and thus can function immediately. Innate immunity may limit entry of microorganisms into the body and growth of microorganisms within the body.
Components and Mechanisms of Nonspecific Immunity
A. Barriers at the Portal of Entry. Anatomic and physiologic barriers against infection.
Anatomic Barriers: Skin and mucous membrane are mechanical barriers. They provide an effective barrier to the entry of most organisms.
Physiological Barriers. These include pH, various, chemical mediators like complement, interferon, lysozyme and temperature.
1. Skin : (a) Intact skin, (b) Sweat and sebaceous secretions especially due to fatty acid, lactic acid and acid pH. These have antimicrobial properties, (c) Sweat can flush microbes.
2. Mucous Membrane: Intact mucous membrane. Mucus secreted by the mucous membrane coats the epithelial cells of mucosa. Microorganisms are trapped in sticky mucus and are removed by mechanical process. Mucus acts as barrier and blocks the adherence of bacteria to epithelial cells. Treponema pallidum can enter through intact mucous membrane.
(a) Respiratory Tract: Mucociliary apparatus removes microbes in the respiratory tract.
Nose: Microorganisms inhaled from the atmosphere are trapped in the mucus and are carried by the rhythmic beating of the cilia towards the back in the pharynx, where they are swallowed. Sneezing dislodges and helps to remove microbes. Nasal secretions contain lysozyme. Lysozyme is a muramidase which splits the peptidoglycan wall of susceptible bacteria, and thus bactericidal.
Trachea: Beating of cilia creates an upward flow of mucus which removes microorganisms. Coughing dislodges and helps to expel the microbes trapped in mucus. Mucociliary defence system can be suppressed by cigarette smoke, alcohol and other harmful injuries.
Lungs: Pulmonary macrophages destroy microorganisms. Lung surfactant provides protection against inhaled microbes.
(b) Gastrointestinal Tract. Shedding of mucus cells of the gastrointestinal tract leads to mechanical removal of microorganisms.
Mouth: Saliva has a washing effect on microbes. Lysozyme is present in saliva and is bactericidal.
Stomach: Acid pH due to hydrochloric acid kills most pathogenic microorganisms (e.g. V. cholerae).
Small intestine: Proteolytic enzymes and macrophages are protective. Bile salts in intestine inhibit growth of Gram-positive bacteria.
Innate immunity is nonspecific, i.e. it acts against many infectious agents and not to a particular agent, as for example,
surface barrier like skin will protect against different infectious agents, and phagocytes which can engulf a variety of infectious agents.
Components of the innate arm are preformed and thus can function immediately. Innate immunity may limit entry of microorganisms into the body and growth of microorganisms within the body.
Components and Mechanisms of Nonspecific Immunity
A. Barriers at the Portal of Entry. Anatomic and physiologic barriers against infection.
Anatomic Barriers: Skin and mucous membrane are mechanical barriers. They provide an effective barrier to the entry of most organisms.
Physiological Barriers. These include pH, various, chemical mediators like complement, interferon, lysozyme and temperature.
1. Skin : (a) Intact skin, (b) Sweat and sebaceous secretions especially due to fatty acid, lactic acid and acid pH. These have antimicrobial properties, (c) Sweat can flush microbes.
2. Mucous Membrane: Intact mucous membrane. Mucus secreted by the mucous membrane coats the epithelial cells of mucosa. Microorganisms are trapped in sticky mucus and are removed by mechanical process. Mucus acts as barrier and blocks the adherence of bacteria to epithelial cells. Treponema pallidum can enter through intact mucous membrane.
(a) Respiratory Tract: Mucociliary apparatus removes microbes in the respiratory tract.
Nose: Microorganisms inhaled from the atmosphere are trapped in the mucus and are carried by the rhythmic beating of the cilia towards the back in the pharynx, where they are swallowed. Sneezing dislodges and helps to remove microbes. Nasal secretions contain lysozyme. Lysozyme is a muramidase which splits the peptidoglycan wall of susceptible bacteria, and thus bactericidal.
Trachea: Beating of cilia creates an upward flow of mucus which removes microorganisms. Coughing dislodges and helps to expel the microbes trapped in mucus. Mucociliary defence system can be suppressed by cigarette smoke, alcohol and other harmful injuries.
Lungs: Pulmonary macrophages destroy microorganisms. Lung surfactant provides protection against inhaled microbes.
(b) Gastrointestinal Tract. Shedding of mucus cells of the gastrointestinal tract leads to mechanical removal of microorganisms.
Mouth: Saliva has a washing effect on microbes. Lysozyme is present in saliva and is bactericidal.
Stomach: Acid pH due to hydrochloric acid kills most pathogenic microorganisms (e.g. V. cholerae).
Small intestine: Proteolytic enzymes and macrophages are protective. Bile salts in intestine inhibit growth of Gram-positive bacteria.
_ Large intestine: Mucus and microbial antagonism.
(c) Eye: Tear flushes microbes from eye. It also contains lysozyme.
(d) Vagina: In adult female, vaginal secretions maintain acidic microenvironment and prevent gonococcal vaginitis.
3. Microbial antagonism: Normal bacterial flora of the body serves a protective role: (a) Inhibits growth of many pathogenic microorganisms by competition for essential nutrients, or (b) Produces inhibitory substances, e.g. gut commensals produce colicins which are bactericidins.
4. Urine can flush microbes.
5. Semen: Spermine in semen inhibits growth of Gram positive bacteria.
B. Phagocytic Barriers. Phagocytes (mainly macrophages and neutrophils) play the role. Discussed under D.1.
C. Inflammatory Barriers : Invasion of a pathogen by evading the surface defences usually results in inflammation which is the main defensive mechanism. In inflammation, cellular and humoral factors take part in antimicrobial activity.
D. Cellular Factors in Innate (Nonspecific) Immunity
1. Phagocytes: The major phagocytic cells are neutrophils, cells of mononuclear phagocyte system (reticulo-endothelial system), e.g. macrophages (histiocytes) of connective tissues, alveolar macrophages, Kupffer cells of the liver. Phagocytosis by mononuclear phagocytic cells leads to filtering of microorganisms from the blood stream. Phagocytes are recruited to sites of infection, resulting in inflammation. Phagocytosis consists of three steps: (a) Recognition and adherence of the organisms to their surface. Phagocytes recognize microbes by several membrane receptors, e,g. TLRs (Toll-like receptors). (b) Engulfment and formation of phagolysosome, and (c) Killing (i) Oxygen-dependent killing. Reactive oxygen intermediates (02-, OH-, H202), and reactive nitrogen intermediates (e.g. NO, NO2, HNO2), and (ii) Oxygen-independent (e.g. lysozyme, lactoferrin, defensins) microbicidal mechanisms. Defensins create pores in the membrane of bacteria and thereby kill them.
2. NK cells: Extracellular killing of virus infected cells can be performed by NK cells. They are also cytotoxic for tumour cells. NK cells secrete IFN-,/ which activates, macrophages to destroy ingested ,microbes.
3. Eosinophils: Extracellular killing of helminths can be by C3b-bound eosinophils.
E. Humoral Factors in Innate (Nonspecific) Immunity
1. Complement: Complement system is activated by binding to microbes and endotoxin using the alternative and lectin pathways in innate immunity. Complement facilitates phagocytosis, may cause cell lysis and leads to acute inflammatory reaction. Active complement fragments may play the following roles:
(a) Biologic functions: C5a is a chemotactic agent for neutrophil and monocyte; C3b and iC3b are opsonins; C3a and C5a are anaphylatoxins that can trigger release of histamine from mast cells; and membrane attack complex (MAC) causes cell lysis, (b) Complement-mediated acute inflammatory reaction. It can be mediated by complement fragments. Mast cell activators may also be released by neutrophils and tissue macrophages. The mast cells play the central role in the inflammatory reaction.
(c) Eye: Tear flushes microbes from eye. It also contains lysozyme.
(d) Vagina: In adult female, vaginal secretions maintain acidic microenvironment and prevent gonococcal vaginitis.
3. Microbial antagonism: Normal bacterial flora of the body serves a protective role: (a) Inhibits growth of many pathogenic microorganisms by competition for essential nutrients, or (b) Produces inhibitory substances, e.g. gut commensals produce colicins which are bactericidins.
4. Urine can flush microbes.
5. Semen: Spermine in semen inhibits growth of Gram positive bacteria.
B. Phagocytic Barriers. Phagocytes (mainly macrophages and neutrophils) play the role. Discussed under D.1.
C. Inflammatory Barriers : Invasion of a pathogen by evading the surface defences usually results in inflammation which is the main defensive mechanism. In inflammation, cellular and humoral factors take part in antimicrobial activity.
D. Cellular Factors in Innate (Nonspecific) Immunity
1. Phagocytes: The major phagocytic cells are neutrophils, cells of mononuclear phagocyte system (reticulo-endothelial system), e.g. macrophages (histiocytes) of connective tissues, alveolar macrophages, Kupffer cells of the liver. Phagocytosis by mononuclear phagocytic cells leads to filtering of microorganisms from the blood stream. Phagocytes are recruited to sites of infection, resulting in inflammation. Phagocytosis consists of three steps: (a) Recognition and adherence of the organisms to their surface. Phagocytes recognize microbes by several membrane receptors, e,g. TLRs (Toll-like receptors). (b) Engulfment and formation of phagolysosome, and (c) Killing (i) Oxygen-dependent killing. Reactive oxygen intermediates (02-, OH-, H202), and reactive nitrogen intermediates (e.g. NO, NO2, HNO2), and (ii) Oxygen-independent (e.g. lysozyme, lactoferrin, defensins) microbicidal mechanisms. Defensins create pores in the membrane of bacteria and thereby kill them.
2. NK cells: Extracellular killing of virus infected cells can be performed by NK cells. They are also cytotoxic for tumour cells. NK cells secrete IFN-,/ which activates, macrophages to destroy ingested ,microbes.
3. Eosinophils: Extracellular killing of helminths can be by C3b-bound eosinophils.
E. Humoral Factors in Innate (Nonspecific) Immunity
1. Complement: Complement system is activated by binding to microbes and endotoxin using the alternative and lectin pathways in innate immunity. Complement facilitates phagocytosis, may cause cell lysis and leads to acute inflammatory reaction. Active complement fragments may play the following roles:
(a) Biologic functions: C5a is a chemotactic agent for neutrophil and monocyte; C3b and iC3b are opsonins; C3a and C5a are anaphylatoxins that can trigger release of histamine from mast cells; and membrane attack complex (MAC) causes cell lysis, (b) Complement-mediated acute inflammatory reaction. It can be mediated by complement fragments. Mast cell activators may also be released by neutrophils and tissue macrophages. The mast cells play the central role in the inflammatory reaction.
__2. Cytokines
(a) IL-1 and TNF initiate nonspecific inflammatory response.
(b) Interferon: IFN-a and IFN-β help to control viral replication by inhibiting protein synthesis in cells. Cells synthesize interferon, when infected by a virus, which binds to specific receptors of uninfected neighbouring cells.
3. Acute Phase Proteins (Acute phase response)
About 12 plasma proteins are collectively termed acute phase proteins produced by the liver. The first four shows dramatic increase in concentration and others a moderate increase in response to interleukin-1. These are released as a result of infection or tissue injury. The function of some are given in brackets: (1) C-reactive protein (Fixes complement, opsonizes),
(2) Mannose binding protein(Fixes complement, opsonizes),
(3) a1-acid glycoprotein (transport protein), (4) Serum amyloid P component, (5) C3, C9, factor 6, (6) al-antitrypsin, (7) a1-proteinase inhibitors, (8) Fibrinogen, (9) Ceruloplasmin, (10) Haptoglobin, (11) Serum amyloid A, (12) Fibronectin.
F. Other Factors in Innate Immunity
1. Age: Children below 3 years and old people above 75 years are more susceptible to infection.
2. Individual variation of innate immunity exists.
3. Nutritional status. Malnutrition increases susceptibility to infection.
4. Hormones. An increase in corticosteroids decreases the inflammatory response and lowers resistance to infection.
5. Fever. It is said that fever may have some beneficial effects on the control of some infection.
6. Racial immunity. Existence of racial immunity is controversial. The example cited is that 'Africans are more susceptible to tuberculosis than the Europeans'.
7. Species immunity. An infection occurs in a species but not in another, e.g. syphilis caused by Treponema pallidum occurs only in man.
NOTE:
Innate immunity may be discussed under:
1. Factors that limit entry of microorganisms into the body: Anatomic and physiologic barriers, surface phagocytes (e.g. alveolar macrophage), normal flora of throat, colon, and vagina, defensins.
2. Factors that limit growth of microorganisms within the body: Phagocytes, natural killer cells, complement, interferons, inflammatory response, fever.
(a) IL-1 and TNF initiate nonspecific inflammatory response.
(b) Interferon: IFN-a and IFN-β help to control viral replication by inhibiting protein synthesis in cells. Cells synthesize interferon, when infected by a virus, which binds to specific receptors of uninfected neighbouring cells.
3. Acute Phase Proteins (Acute phase response)
About 12 plasma proteins are collectively termed acute phase proteins produced by the liver. The first four shows dramatic increase in concentration and others a moderate increase in response to interleukin-1. These are released as a result of infection or tissue injury. The function of some are given in brackets: (1) C-reactive protein (Fixes complement, opsonizes),
(2) Mannose binding protein(Fixes complement, opsonizes),
(3) a1-acid glycoprotein (transport protein), (4) Serum amyloid P component, (5) C3, C9, factor 6, (6) al-antitrypsin, (7) a1-proteinase inhibitors, (8) Fibrinogen, (9) Ceruloplasmin, (10) Haptoglobin, (11) Serum amyloid A, (12) Fibronectin.
F. Other Factors in Innate Immunity
1. Age: Children below 3 years and old people above 75 years are more susceptible to infection.
2. Individual variation of innate immunity exists.
3. Nutritional status. Malnutrition increases susceptibility to infection.
4. Hormones. An increase in corticosteroids decreases the inflammatory response and lowers resistance to infection.
5. Fever. It is said that fever may have some beneficial effects on the control of some infection.
6. Racial immunity. Existence of racial immunity is controversial. The example cited is that 'Africans are more susceptible to tuberculosis than the Europeans'.
7. Species immunity. An infection occurs in a species but not in another, e.g. syphilis caused by Treponema pallidum occurs only in man.
NOTE:
Innate immunity may be discussed under:
1. Factors that limit entry of microorganisms into the body: Anatomic and physiologic barriers, surface phagocytes (e.g. alveolar macrophage), normal flora of throat, colon, and vagina, defensins.
2. Factors that limit growth of microorganisms within the body: Phagocytes, natural killer cells, complement, interferons, inflammatory response, fever.