Innate and Acquired Immunity
Aims and Objectives
- To understand how the body prevents entry of micro-organisms.
- To understand the difference between innate and acquired immunity.
Micro-organisms are ubiquitous. They are in the air we breathe and in/on the food we eat. Thus our epithelial surfaces (skin, respiratory tract, gastro-intestinal tract, genitourinary tract) are continuously exposed to micro-organisms. Disease occurs when micro-organisms invade epithelial surfaces. In view of our constant exposure to micro-organisms it is surprising that we enjoy long infection-free periods and that infections are the exception rather than the rule. This resistance (immunity) of epithelial surfaces to invasion, is a characteristic which is present from birth, and is therefore called innate (natural) immunity.
This prevents entry of micro-organisms into tissues or, once they have gained entry, eliminates them prior to the occurrence of disease.
- Present from birth.
- Non-specific - acts on many organisms and does not show specificity.
- Does not become more efficient on subsequent exposure to same organisms.
Prevention of entry of organisms
- Mechanical barriers at body surfaces, skin, mucous membranes - disruption leads to infection.
- Antibacterial substances in secretions, lysozyme, lactoferrin, low pH of stomach contents.
- Prevention of stasis.
- Peristalsis/flow of urine/upward movement of secretions in bronchial tree.
- Clinical relevance; urinary infection with urinary obstruction; decreased bronchial
- Ciliary activity - bronchiectasis (Kartagener's syndrome).
Non-specific elimination of micro-organisms
1. Phagocytosis - ingestion and killing of micro-organisms by specialised cells (phagocytes).
Phagocytes - polymorphonuclear leukocytes (neutrophils)
- mononuclear phagocytes (monocytes, macrophages).
2. Opsonisation - the process of coating micro-organisms with some of the proteins found in plasma, to make them more easily phagocytosable. An OPSONIN is a plasma protein binding to bacteria. This promotes adhesion between the opsonised bacteria and macrophages because the opsonin binds to receptors on phagocyte membrane e.g. complement with complement receptors and phagocytes. Opsonisation and phagocytosis are more efficient in immune individuals. Inflammation
Complement and phagocytes exist mainly in blood so a mechanism is required to recruit these elements to the site of tissue invasion - INFLAMMATORY RESPONSE (INFLAMMATION):
a) opening up of junctions between endothelial cells in post-capillary venule to allow plasma proteins to escape
b) adhesion of leukocytes to endothelial cells of post-capillary venule, followed by emigration of phagocytes into tissues.
Inflammation is localised to area of infection/tissue injury by release of substances from micro-organisms or chemicals (chemical mediators) released from cells in tissues, e.g. histamine from MAST CELLS. Once organisms destroyed inflammation settles down (RESOLVES).
Acquired Immunity (adaptive Immunity/specific Immunity)
This type of immunity occurs in response to infection called ADAPTIVE as the immune system must adapt itself to previously unseen molecules. Following recovery from certain infections with a particular micro-organism, individuals will never again develop infection with the same organism, but can become infected with other micro-organisms, i.e. he/she is protected against one micro-organism. This form of protection is called IMMUNITY and an individual is said to be IMMUNISED against that organism. The induction of immunity by infection or with a vaccine is called ACTIVE IMMUNITY.
Historically it has been shown that a non-immune individual can be made immune by transferring serum or lymphocytes from an immune individual - PASSIVE IMMUNITY - serum constituents (ANTIBODIES) and LYMPHOCYTES are involved in immunity.
It has been observed that the immune system responds to micro-organisms but not to its own cells and that the system knows that the body has been infected previously with a particular organism. This implies:
- IMMUNOLOGICAL RECOGNITION.
- SELF/NON-SELF DISCRIMINATION.
- IMMUNOLOGICAL SPECIFICITY.
- IMMUNOLOGICAL MEMORY.
Immunity is mediated by the IMMUNE SYSTEM, which responds to infection by mounting an IMMUNE RESPONSE. An immune response must:
- RECOGNISE a micro-organism as foreign (non-self) as distinct from self (AFFERENT
- RESPOND to a micro-organism by production of specific antibodies and specific
- MEDIATE the elimination of micro-organisms (EFFERENT LIMB).
An agent which evokes an immune response is called an IMMUNOGEN. The term ANTIGEN is applied to a substance which reacts with antibody.
Cellular Basis Of Immune Response
Key cells are lymphocytes - have capacity to recognise micro-organisms. There are two types which develop in bone marrow from a common precursor.
- T-cells - mature in thymus
- B-cells - mature in bone marrow
These two types of lymphocyte are used in 3 ways to fight infection.
Strategy One: elimination of extracellular micro-organisms
In response to infection B-cells mature into PLASMA cells which secrete soluble recognition molecules (ANTIBODIES). B cells recognise microbes because they express membrane bound antibody which acts as an antigen receptor.
At time of first infection there is no antibody in blood and level does not begin to increase until between 7-10 days afterwards. The level of antibody rises slowly to a low peak and then gradually declines towards baseline - PRIMARY RESPONSE.
On subsequent exposure to same micro-organisms the level of antibody begins to increase within 24 hours and reaches a high level which is sustained - SECONDARY RESPONSE.
Antibody recognises structures on surface of bacteria (proteins/
carbohydrates/lipids). When we have an infection we produce antibodies which recognise many different types of structure on bacterial surface. Thus serum from an immune individual contains many different types of antibodies each of which recognise different structures on surface of membrane. Each of these structures is called an EPITOPE (or ANTIGENIC DETERMINANT).
Antibody is soluble and diffuses through tissues to target extracellular micro-organisms. Binding of antibody to micro-organisms activate two EFFECTOR mechanisms to eliminate micro-organisms.
Strategy Two: Elimination of micro-organisms which normally survive for long periods in macrophages.
Even when antibody and complement opsonise certain bacteria and phagocytosis occurs, they are not killed but survive and multiply in macrophages, e.g. Mycobacterium tuberculosis. Elimination occurs by use of a subpopulation of cells called HELPER T cells. These cells recognise macrophages containing intracellular bacteria by means of T cells antigen receptor, which is not an antibody. They help macrophages to kill bacteria by synthesising soluble molecules (CYTOKINES) which stimulate bacterial killing mechanisms of macrophages.
Strategy Three - Elimination of micro-organisms which infect cells without an endogenous antimicrobial defence system.
Viruses are obligate intracellular pathogens, can infect any type of cells, and
most cells do not possess antimicrobial mechanisms. During intracellular replication
virus proteins appear on the surface of the infected cell. A second subset of
T cells - cytotoxic T cells - recognises these viruses (foreign) antigens and
secretes cytotoxic molecules which kill the infected cells.
© AJC 2007.