Nonspecific Body Defenses

and Immunity

Defense Systems

1.Innate
(nonspecific)
defenses
External body
membranes
Inflammation

Antimicrobial
proteins,
phagocytes and
other cells

2.Adaptive
(specific)
defenses
T cells and B cells

Innate Defense System

Surface Barriers

First line of defense: mechanical and chemical

protection
1. Skin
2. Mucosal Membranes

Internal Nonspecific Defenses

1.
2.
3.
4.
5.

Second line of defenses

Phagocytes
Natural Killer cells (NK lymphocytes)
Inflammation
Antimicrobial proteins
Fever

Skin and Mucosal Membranes

Mechanical Protection
Epidermis
nose hairs, nails

Mucous membranes - line certain organ systems

mucus prevents drying, traps foreign things
respiratory tract cilia sweep mucus out

Lacrimal apparatus -- tear glands and ducts

wash the eye to dilute microbial growth

Saliva - dilute microbes on the oral cavity

Urine - flow dilutes, and acid pH helps kill,
microorganisms
Defecation and vomiting - expel toxins and
microbes

Skin and Mucosal Membranes

Chemical Protection: reduce bacterial growth
Skin
sebum (unsaturated FAs) forms oily layer
perspiration has fatty acids, salts (NaCl), and mildly acid pH

Lysozyme
in perspiration, tears, saliva, nasal secretions, other tissue
fluids
enzyme breaks down bacterial cell walls

Hyaluronic acid
gel-like matrix in most connective tissues
slows the spread of many infectious agents

Gastric juice - stomach nearly sterile due to acid pH,

~2
Vaginal secretions mildly acid pH

Innate Defense: Phagocytes

Macrophages (derived from monocytes)
are the chief tissue phagocytic cells
Free macrophages wander through tissues in
search of microbes and cellular debris
Fixed macrophages: Kupffer cells (liver),
microglia (brain), dust cells (lungs)

Neutrophils become phagocytic when

encountering infectious material
Eosinophils are weakly phagocytic, deploy
destructive granules against parasitic
worms

Mechanism of Phagocytosis

Chemotaxis
Adherence recognition
of external
carbohydrates and
proteins
Aided by opsonins

Ingestion
Killing and digestion

Innate Defense: Natural Killer

Cells
Distinct group of large granular lymphocytes
(NK lymphocytes = Null Killer lymphocytes)
Nonspecific killers respond to the lack of
self-antigens and to the presence of certain
surface oligosaccharides
Kill virus-infected body cells and some
tumor cells by releasing various defensive
molecules not by phagocytosis
Act before the antigen-specific immune
system is activated
Secrete potent chemical signals that
enhance the inflammatory response

Innate Defense: Inflammation

1. Inflammation
Signs:
1.
2.
3.
4.
5.

Redness
Heat
Swelling
Pain
Loss of Function

Function:
1. Prevent spread of
damage
2. Dispose of
pathogens and
debris
3. Set stage for tissue
repair

Inflammation: Stage 1
Edema increased plasma filtrate seeps
into tissue spaces bringing some immune
proteins
Helps to dilute harmful substances
Increases supply of oxygen and nutrients
needed for metabolism, inflammation and
repair
Allows entry of clotting proteins, which
reduces the spread of mibrobes

Inflammation
Stage 2. Phagocyte
moblization
1. Leukocytosis-inducing
factors: increase
neutrophil production
2. Margination
(pavementing)
3. Diapedesis (amoeboid
movement)
4. Chemotaxis of WBCs
neutrophils rapid arrival
monocytes slower
arrival

Inflammation
Stage 3. Tissue
repair
Tissue regrowth and
repair of damage or
scar formation
Pus
dead phagocytes and
other WBCs,
damaged tissue, and
perhaps microbes
if too numerous for
effective removal by
phagocytes, an
abscess may develop

Effects of Inflammation
Increased blood
flow results in
increased local
temperature and
local cellular
metabolism
Increased
capillary
permeability and
phagocytic
migration to the
injured tissue

Innate Defense: Antimicrobial

Proteins
1. Attack microorganisms directly
2. Interfere with microbial reproduction
The most important are:
1. Interferons
2. The Complement System
3. Transferrins which bind Fe2+ in plasma,
inhibiting bacterial growth

Interferons
(IFNs)

Produced by most tissue cells

when infected by a virus
Diffuses to uninfected cells
and binds to surface
receptors
stimulates macrophages and
natural killer lymphocytes
stimulates production of
antiviral proteins which block
viral replication
inhibits growth of virally
infected cells
suppresses growth of tumor
cells

Alpha IFN is used against:

hepatitis C virus
herpes virus (genital warts)

The Complement System

20 plasma and cell membrane proteins that
exist as inactive precursors
When activated, the complement system
functions to complement or enhance
certain immune, inflammatory, and allergic
responses
Kills bacteria and certain other microbial cell
types (our cells normally are protected from
complement attack)
Stimulates chemotaxis in leuckocytes
Enhances the effectiveness of both
nonspecific and specific defenses

Complement Pathways
Classical Pathway is triggered by the
specific immune system
Requires binding of antibodies to antigens of
invading organisms
Complement C1 then binds to the antigenantibody complexes (complement fixation)

Alternative Pathway is triggered by nonspecific interaction among factors B, D,

and P, and microbial cell wall
polysaccharides (complement fixation)
Both pathways involve an enzyme cascade

Complement
Pathways
Both pathways
converge on C3, which
cleaves into C3a and
C3b
C3b initiates formation
of a membrane attack
complex (MAC)
MAC causes cell lysis by
creating many hundreds
of microscopic holes in
the cells plasmalemma
C3b is also an opsonin

Innate Defense: Fever

Pyrogens reset the temperature set-point in
the hypothalamus
Inhibits some microbes from growing
Increases bodys metabolic rate, which speeds
up immune defenses and tissue repair
Increases effects of antimicrobial substances
produced by the immune system
Stimulates liver and spleen to sequester iron
and zinc (needed by microorganisms)

High fevers are dangerous

Innate Defense System: Review

Surface Barriers
1. Skin
2. Mucosal membranes

Internal Nonspecific Defenses

1.
2.
3.
4.
5.

Phagocytes
Natural Killer cells (NK lymphocytes)
Inflammation
Antimicrobial proteins
Fever

Adaptive Defense
The adaptive immune system:
Acts to immobilize, neutralize, or destroy
foreign substances and cells
Amplifies the inflammatory response and
activates complement
Is antigen-specific*, systemic, and has memory
*Recognizes specific foreign molecules

Has two interdependent arms

Humoral, or antibody-mediated immunity (AMI)
Cellular, or cell-mediated immunity (CMI)

Adaptive Defense
Definitions:
Immunity: the ability of the body to defend
itself against specific foreign invaders
(molecules or cells)
Immunogenicity: the ability to stimulate
proliferation of specific lymphocytes and
specific antibody production
Reactivity: the ability of activated
lymphocytes and their products, antibodies,
etc., to interact with specific antigens

Adaptive Defense
Definitions:
Specificity: the antigen triggers focused
immune defenses (from particular
lymphocytes lineages) that respond only to
the antigens of this foreign substance/cell
Memory: the immune system produces clones
of specific memory lymphocytes (T & B) which
react rapidly when the particular foreign
substance/cell is encountered again
Specificity and memory differentiate this
system from the nonspecific (innate) defenses

Adaptive Defense
Antigen any substance
which provokes specific
immune responses
Antigenic
determinants
Parts of antigens that
trigger the specific immune
response
An antigen may be an
entire microorganism or
only small structures or
subregions of large
molecules

Most antigens are

complex and express
multiple types of
antigenic
determinants.

Immunological Memory
Immunization is
possible because
memory B cells
and memory T
cells persist after
the initial Ag
exposure

with any subsequent exposure, the immune

system responds more quickly, forcefully
secondary response - antibodies produced
during subsequent exposures are produced in
greater quantities and have a greater attraction
for antigen

Antibodies
Are unique soluble proteins secreted by
activated B cells and plasma cells in
response to an antigen
Are capable of binding specifically with
that antigen
Constitute much of the gamma globulin
fraction of plasma proteins
Also called immunoglobulins

Basic Antibody Structure

Four polypeptide chains
linked together with
disulfide bonds
The four chains bound
together form an
antibody monomer
Each chain has a variable
(V) region at one end and
a constant (C) region at
the other
Variable regions of the
heavy and light chains
combine to form the
antigen-binding site

Ag

Antibody Structure
Antibodies responding to different antigens
have different V regions but the C region is
the same for all antibodies in a given
antibody class
C regions form the stem of the Y-shaped
antibody monomer and determine:
the class of the antibody
the cells and chemicals to which the antibody
can bind
how an antibody class functions in eliminating
antigens

Classes of Antibodies
IgD: monomer attached to the surface of B cells,
important in B cell activation
IgM: pentamer released by plasma cells during
the primary immune response
IgG: monomer that is the most abundant and
diverse antibody in primary and secondary
responses; crosses the placenta and confers
passive immunity
IgA: dimer that helps prevent attachment of
pathogens to mucosal surfaces
IgE: monomer that binds to mast cells and
basophils, causing histamine release when
activated

Antibody Functions
All antibodies form an antigen-antibody (immune)
complex
Antibodies do not directly destroy antigen, though
they may immobilize or inactivate Ag
Antibodies act as opsonins and tag Ag for immune
attack and destruction
Defensive mechanisms triggered by antibodies
include neutralization, agglutination, precipitation,
opsonization, and complement fixation

1.

Antibody Mechanisms of
Action bind to and block
Neutralization: Antibodies
specific sites on viruses or exotoxins, thus
preventing these antigens from binding to
receptors on tissue cells

Antibodies bind to the same determinant on more

than one antigen forming antigen-antibody
complexes that are cross-linked into large
lattices
2. Agglutination: Cellular antigens are crosslinked, causing cell clumping
3. Precipitation: Soluble molecules are crosslinked into large insoluble complexes

Antibody Mechanisms of Action

4. Opsonization: Bound Abs facilitate
phagocyte adherence
5. Complement Fixation: IgM and IgG
antibodies bound to cellular Ags bind
complement via the Classical Pathway
The complement cascade causes
chemotaxis, opsonization, phagocytosis and
cell lysis
Complement activation enhances the
inflammatory response

Summary of Antibody Actions

Figure 21.13

Summary
of the
Immune
Response

Clinical Classification of
Immunity

The End