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(Mucus producers)
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Non-Specific Resistance
First Line of Defense
Second Line of Defense:
* Leukocytes & Lymphatic System
* Phagocytosis
* Fever &Inflammatory Responses
* Competent Cascade Response
* Interferon Responses
1st - Line (external physical
barriers and chemical defenses):
• Intact Skin – low moisture; low pH; oily (sebum) residues inhibit
microbes; desquamation (shed dead skin layers)
• Outer Ear – antibacterial activity of waxes
• Conjunctiva (Eyes) (lacrimal apparatus) tear dilution and lysozyme
• Mucous membranes (gastrointestinal, genitourinary, respiratory)
– Gastrointestinal: Saliva (swallowing, lysozyme, antibodies); stomach
acids; intestinal mucus with antibacterial substances and antibodies)
– Genitourinary: Low pH and high salt of urine flush urinary tract; acidic
vagina; lysozyme in seminal fluids)
– Respiratory: nasal hairs; nasal passages; ciliated epithelium
(escalator); clearing/coughing; alveoli macrophage.
• Normal flora (bacterial antagonism) - harmless bacteria compete
with pathogens and may produce bacteriocins or intolerable conditions.
Origin of Cell Types
in Blood and Lymph:
Can release
histimine.
2nd –Line (generalized internal
cellular and chemical defenses):
• White Blood Cells = Leukocytes (see Table 16.1)
– Granulocytes are polymorphonuclear (PMN) with
intracellular granules that can be stained and seen by
microscopy. All involved in non-specific resistance.
• Neutrophils: highly phagocytic and microbiocidal; 60-70% all
leukocytes; will travel from blood to infected tissues via chemotaxis;
live only days.
• Basophils: release histamine, prostaglandins, serotinin, and
leukotreins via degranularization; these stimulate vasodilation
(permeability and dilation of capillaries) initiating the inflammation
response; binding by IgE and/or complement protein C3b further
stimulates release of these inflammatory mediators.
• Eosinophils: mobile phagocyte; very antagonistic to multicellular
parasite (worms).
Computer Color Enhanced Image
Is it an TEM or and SEM?
- Agranulocytes (monomorphonuclear;
momonocytes and lymphocytes)
• Monocytes (mostly non-specific resistance)
– Macrophage: highly phagocytic; high surface area of
pseudopods; may be “wandering” in blood or “fixxed” in
association with mucosal membranes of healthy tissues.
– Dendritic cells: molecular pattern-associated receptors for
detecting microorganisms; present antigens to T-cells. Located
throughout lymph system, skin, and other tissues.
• Lymphocytes: (involved in specific resistance)
– Natural Killer Cells: granular!; kill viral infected and tumor
cells.
– B-cells: lymph system associated; specific clones recognize
antigen and stimulate multiplication; some mature to antibody
releasing plasma cells; others become a long living dormant
population of “memory cells”.
– T-cells: lymph system associated; involved in chemical
communication and stimulation of B cell antibody production,
and may become cytotoxic to kill infected cells.
Lymphatic
System
Functions to drain fluid between cells in tissues for water
and salt conservation; transports infectious microbes to
lymph nodes for destruction and specific immunity response.
Some lymphocytes mature to
B-cells in the bone marrow of
adult humans. Others enter
blood to thymus where they
mature to T-cells and may
become stored. Other T-cells
and the B-cells travel to lymph
nodes, spleen etc… and
become stored for months.
Mast cells also mature in bone
marrow and reside in
connective tissues; release
large stores of histamine upon
injury and binding of IgE or
C5a; stimulates inflammation.
Phagocytosis: It’s enhanced in neutrophils and
macrophage by opsonization (phagocyte adhesion to
antibodies and/or complement protein C3b bound to microbe).
Pyrogenic Response: Fever as a Defense
• Phagocytic cells release IL-1 when exposed to endotoxins.
• Hypothalmus resets temperature; resulting in blood vessel contraction,
increased metabolic rate and shivering (raising body temperature). Skin
stays cold; “the chills”.
• Higher temperatures increase rate of luekocyte production and maturation
to T-cells and nuetrophils. Similarly, the rate of tissue repair is increased.
Other fortuitous biochemical reactions are enhanced as well. Kills bacteria.
• When IL-1 levels drop off, hypothalmus resets to normal, heat-loss
mechanisms engage, i.e. vasodilation and excessive sweating (“crisis”).
Inflammation as a defense
(Pyogenic Response)
Any direct damage to host cells
results in release of inflammatory
mediators (IMs) and acidification
that activates kallikrein protease
to liberate bradykinin, which
further stimulates release of IMs.
Further damage by bacterial
toxins enhances this effect.
Histimine and bradykinin dilate &
increase permeability of vessels
increasing blood supply
(redness), plasma release
causing edema (swelling),
clotting factor release (abscess
isolates infection and toxin), and
prostoglandin fires nerves
creating a pain response.
Capillary endothelial cells
stimulated by IMs express
selectins. Phagocytes slow
and stick to endothelium,
migrate via chemotaxis to
sites adjacent to wound
(high levels of IMs), attach
by their integrins, and then
emigrate from capillary.
Scabbing/healing
Phagocytosis of bacteria and
damaged host cells results
in reducing IMs
commensurate with healing.
Complement System
A class of antimicrobial blood (serum) proteins that participate in foreign cell lysis,
enhance inflammation and increase the effectiveness of phagocytosis.
The system is activated by two mechanisms, each of which initiates a cascading
sequence of interactions among complement proteins. Central is the C3 protein.
Classic Pathway: Specific Resistance generates antibodies that bind to microbes;
C1 protein is activated when bound to multiple antibodies; activation cleaves C2 &
C4 whose “b” subunits bind to create a chimeric protein (C2b/C4b) that cleaves C3.
Alternate Pathway: Low blood levels of C3b and protein factors B, D & P respond
to foreign polysaccharides and endotoxins; results in cleaving more C3 protein.
Complement
System
Summary
Complement & Opsonization:
C3b protein readily binds to Gram- outer
membrane and “flags” these for
phagocytosis.
Complement and Inflammation
Stimulation of Vasodilation:
Chemotaxis:
Both C3a and C5a bind to mast cells,
basophils and platelets which
induces degranularization and
release of histamine and other IMs.
C5a also functions as a chemotaxis
attractant to bring more phagocytes
to the infection site.
Complement Cytolysis:
“MAC attack”
C3b protein cleaves C5, which initiates further cascading interaction among
C5 – C9 proteins. The result is directed assembly of C9 proteins into a
circular array that creates a transmembrane channel (pores) through which
cytoplasmic contents of the bacterium leaks out, causing bacterial cell death.
Interferons
A class of antiviral proteins produced by viral
infected cells. Their action is to prevent viral replication in adjacent
uninfected host cells. Interferon (IFN) binding to host membrane stimulates
intracellular antiviral proteins (AVPs) that defend against future infection.