Lecture 1 - Innate ( Nonspecific ) Immunity

The characteristics of the innate immune response include to following:
    Responses are Broad-Spectrum (non-specific)
    There is no memory or lasting protective immunity
    There is a limited repertoire of recognition molecules
    The responses are phylogenetically ancient

Potential pathogens are encountered routinely, but only rarely cause disease.  The vast majority of microorganisms are destroyed within minutes or hours by innate defenses.  The acquired specific immune response comes into play only if these innate defenses are breached.

In this lecture we will review the elements of the innate immune response.

                 Anatomic Barriers 

Skin (physical barrier, low pH due to lactic and fatty acids)
    epidermis- thin outer layer containing tightly packed epidermal cells and keratin (water-proofing)
    completely renewed every 15-30 days.

    dermis- thicker inner layer
    contains sebaceous glands associated with hair follicles - produce sebum which consists of lactic and fatty acids maintaining a pH 3-5.

Mucous membranes  (ciliated epithelial cells; saliva, tears and mucous secretions)  -  GI, urogenital, respiratory tracts - collectively represents a huge surface area..

                 Physiologic Barriers

Temperature - normal body temperature inhibits growth of most microorganisms.
Elevated body temperature (fever) can have a direct effect on pathogenic microorganisms.

pH - low pH of stomach, skin, & vagina (inhibits microbial growth)

oxygen tension

Huge number of chemical factors (a few examples given below):

     Fatty acids, lactic acid

     Pepsin (digestive enzyme which hyrdrolyzes proteins)

     Lysozyme -hydrolytic enzyme found in mucous secretions -   able to cleave the petidoglycan layer of the bacterial cell wall

     Anti-microbial substances which directly destroy microorganims:
            cryptidins and a-defensins (produced in base of crypts of small intestine - damage cell membranes)
            b-defensins (produced within skin, respiratory tract - also damages cell membranes)
            surfactant proteins A & D (present in lungs - function as opsonins which enhance the efficiency of phagocytosis)

     Interferons - group of proteins produced by cells following viral infection.  Secreted by the cells, and then binds to nearby cells and
        induces mechanisms which inhibit viral replication.
 

    Complement - a group of serum proteins that circulate in an inactive proenzyme state.  These proteins can be activated by a variety of
        specific and nonspecific immunologic mechanisms that convert the inactive proenzymes into active enzymes.ssss  The activated
        complement components participate in a controlled enzymatic cascade that results in membrane-damaging reactions which
        destroy pathogenic organisms by formation of a membrane attack comples (MAC).

                      Endocytic and Phagocytic Barriers

Endocytosis - Process by which macromolecules contained within the extracellular tissue fluid are internalized by cells.
Internalization occurs as small regions of the plasma membrane invaginate, or fold inward, forming small endocytic
vesicles known as endosomes.  Occurs through pinocytosis or receptor-mediated endocytosis.

     Pinocytosis - nonspecific membrane invagination
     Receptor-mediated endocytosis - specific, macromolecules are selectively internalized after binding to specific membrane receptors.

Following internalization, the endosomes fuse with primary lysosmes.  Lysosomes contain large numbers of degradative enzymes (> 20 different hydrolytic enzymes including proteases, nucleases, lipases, etc).  The ingested macromolecules are subsequently digested into small breakdown products.  Products not utilized by the cell are released through the process known as exocytosis.

Phagocytosis
Involves the ingestion of particulate material including whole pathogenic microorganisms.  The plasma membrane expands around the particulate material to form large vesicles called phagosomes (10-20times larger than endosome).  Only specialized cells are capable of phagocytosis, whereas endocytosis is carried out by virtually all cells.  Once particulate matter is ingested into phagosomes, the phagosomes fuse with lysosomes and the ingested material is then digested by a process similar to that seen in endocytosis.
    The so-called "professional phagocytes" include:  monocytes & macrophages, neutrophils, and dendritic cells

    There are a few other cells which can be induced to become phagocytic under certain circumstances (i.e. during intense inflammation)
     Both fibroblasts and epithelial cells are known as "non-professional" phagocytes.