1. Next we will consider inflammation and infection which is the 2nd stage of
the wound healing process. Hematopoietically derived cells are involved
in this process.
Last time
This time

2. Hematopoietically derived cells are involved
in this process. These blood cells do the following things:
Remove cellular and tissue debris
Destroy foreign material such as bacteria that cause infection
Secrete chemical signals that message other cells types to come
to the site of injury to repair, remodel, and make new tissue
Inflammation is a normal process or part of wound healing and will also
occur in the vicinity of an implant.
Inflammation does not imply infection, infection is contamination of the
wound by bacteria, fungi, viruses etc.
Infected wounds suppurate (form pus)
Inflammation has 4 cardinal signs as
summarized in the table on the next slide; redness, swelling, heat, pain

3. swelling
redness
heat
pain

4. Cellular attacks on foreign materials mediated by leukocytes which come in two flavors: lymphocytic and nonlymphocytic, which are derived either from the lymphoid stem cell line or the myeloid stem cell line as
shown below.
Myeloid derived nonlymphocytic
leukocytes or PMN’s
(polymorphonucleocytes) are:
Neutrophils
Eosinophils
Basophils
Monocytes  macrophages
 foreign body giant cells
granulocytes
There mission is to kill, consume,
destroy foreign objects
Eat particulate debris from biomaterials,
bacteria, damaged tissues & cells

6. neutrophils
eosinophil
neutrophil
monocyte

7. neutrophil
eosinophil
lymphocytes
basophil

8. Macrophages

9. These nonlymphatic leuokocytes are formed in the bone marrow and
circulate in the blood with the ability to enter and migrate through the
tissue. There goal is seek out, kill, consume, and destroy any and all
foreign objects and particulate debris from biomaterials, bacteria,
damaged cells and tissue. Note their granular nature hence granulocytes.
Basophils – release histamine, bradykinin, serotonin which are all chemicals
That act to mobilize other cells and increase vascular permeability
Eosinophils – more involved in parasitic defense and consumption of Ab-Ag
Complexes
Neutrophils – are mostly involved in phagocytosis, “eating”
Monocytes – when activated become macrophages which enter the tissue
and phagocytize foreign objects, can also fuse together to form the foreign
body giant cells that are huge microns in diameter
Chemotaxis is the process by which these cells move to a site of an injury

10. Phagocytosis – shown in figure below involves C3b a complement component
which connects the Ab binding to a particular Ag say on a bacterium to form
what is called an “opsonin” which is to opsonize which means to “prepare to eat”.
The phagocyte experiences a metabolic burst that increases glucose metabolism
about 10x’s and oxygen consumption by 2-3 x’s resulting in the formation of
highly reactive oxygen species and hydrogen peroxide

12. Diapedesis – shown below, endothelial cells due to presence of localized
injury chemicals express cell-cell adhesion receptors causing the neutrophils
to stick to the endothelium and they tend to roll along the endothelium as shown
Below, then they finally stick and migrate along the surface and then
diapedesis their way across the endothelial wall to the injured tissue, chemicals
from the site of the injury also find their way to the bone marrow stimulating
the production of more neutrophils

13. Tissue macrophage levels are generally low so the monocytes first have to
be activated and mature to macrophages which enter the injury site much like
the neutrophils but somewhat delayed in comparison to the neutrophils.
Infection means colonization of the wound with microbes. The hallmark sign is
pus formation or suppuration. Sustained infection leads to fibrotic capsule
formation around the liquified infected region.
3 general types of infection associated with implanted medical devices:
Superficial immediate infection, from skin and air bacteria, example from sutures
Deep immediate infection, occurs soon after invasive procedures, usually a’
result of the translocation of skin bacteria
3. Deep late infection, occurs months or years later in areas where everything
was assumed to be fine
a. delay of action of bacteria from implant
b. bacteria from another incident making there way to the implant and setting
up their shop
c. very difficult to treat but fortunately rare

14. Chapter 10 discusses the immune system and our interest is in how the
immune system is involved in the process of inflammation and its role
with respect to medical implants as well as bioartificial organs that use
immunoisolation
2 types of immunity
1. innate – processes and structures of the body that naturally
resist attack; the skin, stomach acid, digestion/liver,
neutrophils/macrophages, fever, plasma proteins,
cough; the hallmark is lack of specificity
2. acquired – mechanism that develops as a defense based on
specific attacks, usually provides some memory and in
many cases results in what we call “immunity”. Specificity
and memory are the hallmarks of this type. The challenge
though is for the immune system to distinguish between
“self” and “non-self”, otherwise you get so-called
autoimmune diseases; type I diabetes, lupus, multiple
sclerosis etc.

15. 2 types of acquired immunity
1. humoral immunity – based on chemicals or proteins called Ab’s,
depends on B lymphocytes
2. cell-mediated immunity – results from the cytotoxic effects of
lymphocytes called T lymphocytes
B lymphocytes or B cells mature in the bone marrow
T lymphocytes or T cells travel from the bone marrow to the thymus where
they mature, go to college, or maybe they go to college and then mature,
and the self-indulgent or self-reacting ones flunk out or are eliminated by
some magical and mysterious process
B and T cells typically like to hang out in lymphoid tissue such as the spleen,
tonsils, and the lymph nodes
There is also another lymphocyte called the NK lymphocyte (natural killer)
which goes after things like tumor cells (Ab dependent cell-mediated cyto-
toxicity or ADCC, wherein the Fab region of an Ab binds to an invader and
the Fc region of the Ab binds to the NK cell)

17. Pathogen – is any disease causing agent
Immunogen – is a molecule or a molecular feature, or a collection of molecules
that can induce an immune response by the body
- examples are things like bacteria, viruses, pollens (allergens),
food components, drugs

18. Antigen (Ag) – is any substance that is specifically recognized by an
immunoglobulin (antibody, Ab) or by a surface receptor of the
T cell membrane
- not all antigens cause an immune response, i.e. not all are
immunogenic
- binding site on the antigen is called an epitope or the antigenic
determinant
- a given antigen can have multiple epitopes

19. Immunoglobulins (Ig’s) are antibodies which are proteins secreted by
the B lymphocytes that bind with high specificity to a given epitope on an
antigen.
Fab sites
Fc site

20. Best at agglutination

21. Adjuvants – are substances either chemicals or particles that enhance the
immune response to a given immunogen
Haptens – are small molecules that by themselves are not antigens but
become antigens when bound to other larger molecules, typical
for small drugs, industrial chemicals, some toxins, subsequent
exposure may not require binding to the larger molecule since
the immune system is now primed