The Bodys Defense

Introduction
All animals must have a way of defending themselves
against pathogenic organisms such as bacteria and
viruses.
We must also protect our self from abnormal cells like
cancer
3 Lines of defense have evolved to protect us

The Front Line

Intact skin is a barrier that cannot normally be penetrated
by bacteria or viruses, but small abrasion may allow them
in.
mucous membranes that line the digestive, respiratory,
and genitourinary tracts bar the entry of potentially harmful
microbes
Not Just Physical Barriers: secretions from sebaceous
and sweat glands give the skin a pH ranging from 3 to 5,
which is acidic enough to prevent colonization by many
microbes
inhibited by the washing action of saliva, tears, and
mucous secretions that continually bathe the exposed
epithelium.
All these secretions contain antimicrobial proteins

Front Line Cont

Mucus traps many invaders but what about those present
in food or water, or those in swallowed mucus, they must
contend with the highly acidic environment of the stomach
virus hepatitis A, can survive gastric acidity
What if They get Through????
Second Line: which depends mainly on phagocytosis,
the ingestion of invading organisms by certain types of
white cells
phagocytic cells called neutrophils constitute about 60%70% of all white blood cells (leukocytes
Cells damaged by invading microbes release chemical
signals that attract neutrophils from the blood Chemotaxis

neutrophils enter the infected tissue, engulfing and

destroying microbes there: average life span is only a
few days

Second Line--Nonspecific
Monocytes, about 5% of leukocytes, provide an even
more effective phagocytic defense
they migrate into tissues and develop into macrophages:
large, long-lived phagocytes
Picture: 1st Slide
Once inside lysosomes break down the invaders by
generating toxic forms of oxygen or enzymes
microbes that have evolved mechanisms for evading
phagocytic destruction.
Some bacteria have outer capsules to which a
macrophage cannot attach
Mycobacterium tuberculosis, are readily engulfed but
are resistant to lysosomal destruction and can even
reproduce inside a macrophage

Cont.
macrophages migrate throughout the body, while others
reside permanently in certain tissues, including the lung,
liver, kidney, connective tissue, brain, and especially in
lymph nodes and the spleen.
Interstitial fluid, perhaps containing pathogens, is taken
up by lymphatic capillaries, and flows as lymph,
eventually returning to the blood circulatory system.
Along the way, lymph must pass through numerous
lymph nodes, where any pathogens present encounter
macrophages and lymphocytes
Eosinophils, about 1.5% of all leukocytes, contribute to
defense against large parasitic invaders, such as the blood
fluke
position themselves against the external wall of a parasite
and discharge destructive enzymes from cytoplasmic
granules

Cont
Natural killer (NK) cells do not attack microorganisms
directly, destroy virus-infected body cellsLike Nuclear
weapons
Also attack deformed body cells that could become
cancer---they destroy a cells membrane causing it to
lyse
Damage to tissue by a physical injury or by the entry of
microorganisms triggers a localized inflammatory
response.
chemical signals of the inflamatory response is histamine.
Histamine is released by circulating leucocytes called
basophils and by mast cells in connective tissue
triggers both dilation and increased permeability of
nearby capillaries.

Immune Response Example

Inflammation

Cont
Chemical Defense: interferons- are proteins that are
secreted by viral infected cells that bond to healthy cells
and prevent virus from bonding. Defensins or complement
are proteins produced by neutrophils that when activated
can punch holes in infected cells literally blowing them up.
Collectins- are proteins that recognize foreign structure or
sugar arrangement and stick
Fever: Hypothalmus heat regulation can be reset by
pyrogens (secreted by white blood cells)
High temperatures inhibit the release of iron and zinc from
liver and spleen needed by bacteria
Fever also increases the speed of tissue repair

Nonspecific Summary
To summarize the nonspecific defense systems, the
first line of defense, the skin and mucous
membranes, prevents most microbes from entering
the body.
The second line of defense uses phagocytes,
natural killer cells, inflammation, and antimicrobial
proteins to defend against microbes that have
managed to enter the body.
These two lines of defense are nonspecific in that
they do not distinguish among pathogens

Specific 3rd Line of Defense

Like snipers in the military they have a specific target
lymphocytes, the key cells of the immune system - the
bodys third line of defense
Lymphocytes generate efficient and selective immune
responses
Antigen specific recognizes and acts against particular
foreign substances
Systemic not restricted to the initial infection site
Has memory recognizes and mounts a stronger attack
on previously encountered pathogens
Distinguish self from non-selfCan be Problematic!!
2 main types of lymphocytes: B lymphocytes (B cells)
and T lymphocytes (T cells).

Cont.
antigen elicits an immune response is by activating B cells
to secrete proteins called antibodies-- Humoral
Immunity
Each antigen has a particular molecular shape and
stimulates certain B cells to secrete antibodies that interact
specifically with it
B and T cells recognize specific antigens through their
plasma membrane-bound antigen receptors
single T or B lymphocyte bears about 100,000 receptors
for antigen, all with exactly the same specificity
Although it encounters a large repertoire of B cells and T
cells, a microorganism interacts only with lymphocytes
bearing receptors specific for its various antigenic
molecules

Cont
selection of a lymphocyte by one of the microbes
antigens activates the lymphocyte, stimulating it to divide
and differentiate, and eventually, producing two clones of
cells
Plasma cells which produce antibodies specific to the
antigen that activated it and memory cells that are long
lived and have receptors specific to that antigen--Called Clonal selection

secrete about 2,000 antibody molecules per second

over the cells 4- to 5-day life span
This 1st encounter is called the Primary Immune
Response
You are sick while the response develops, but once
antibodies have been produced it is all over---unless the
invading organism change its surface receptors???

Cont.
second exposure to the same antigen at some later time
elicits the secondary immune responsestronger
then the 1st
response is faster (only 2 to 7 days), of greater
magnitude, and more prolonged
immune systems capacity to generate secondary immune
responses is called immunological memorythe basis of
the flu shot

Immune Response--Overview

Cell Mediated Immunity

B cells and T cells mature in the bone marrow and thymus,
their antigen receptors are tested for potential selfreactivity
lymphocytes bearing receptors specific for molecules
already present in the body are rendered nonfunctional or
destroyed by apoptosis, leaving only lymphocytes that
react to foreign molecules--- failures of self-tolerance can
lead to autoimmune diseases
T cells do have a crucial interaction with one important
group of native molecules whereas B-Cells do not
collections of cell surface glycoproteins encoded by a
family of genes called the major histocompatibility
complex (MHC) mark body cells as self

Cont
Class I MHC molecules are found on almost all nucleated
cells - that is, on almost every cell.
Class II MHC molecules are restricted to a few
specialized cell types, including macrophages, B cells,
activated T cells, and those inside the thymus
numerous possible alleles for each class I and class II
MHC gene it is unlikely that any two people, except
identical twins, will have exactly the same set of MHC
molecules---Think transplant
MHC Molecules are antigen presenters
2 main types of T cells, and each responds to one class
of MCH molecule.
Cytotoxic T cells (TC) have antigen receptors that bind
to protein fragments displayed by the bodys class I
MHC molecules.
Helper T cells (TH) have receptors that bind to peptides
displayed by the bodys class II MCH molecules

Antigen Presentation

 immune
responses of
B and T
lymphocytes
exhibit 4
things that
characterize
the immune
system as a
whole:
specificity,
diversity,
memory, and
the ability to
distinguish
self from
nonself

Review

What Are Antibodies and What can They

DO
Y shaped proteins that are completely specific
and have many uses for immunity and
science. Also known as immunoglobulin (Igs)
5 main types made of 4 amino acids chains
linked by di-sulfide bonds.

Here They Are

Getting
Immunity

Sounds Perfect---What About

Malfunctions
Malfunctions effects range from the minor inconvenience
of some allergies to the serious and often fatal
consequences of certain autoimmune and
immunodeficiency diseases
Allergies: Many small molecules (called haptens or
incomplete antigens) are not antigenic, but link up with our
own proteins
The immune system may recognize and respond to a
protein-hapten combination
The immune response is harmful rather than protective
because it attacks our own cells

Cont
anaphylactic shock, a life threatening reaction to injected
or ingested allergens.
Anaphylactic shock results when widespread mast cell
rupturing triggers abrupt dilation of peripheral blood
vessels, causing a precipitous drop in blood pressure.
Death may occur within minutesCaused when the
body produces IgE antibodies.

What if You Do Not Know Who You Are

Autoimmunity

Autoimmune Diseases
systemic lupus erythematosus (lupus), the immune system
generates antibodies against all sorts of self molecules,
including histamines.
Lupus is characterized by skin rashes, fever, arthritis,
and kidney dysfunction.
Rheumatoid arthritis leads to damage and painful
inflammation of the cartilage and bone of joints.
In insulin-dependent diabetes mellitus, the insulinproducing beta cells of the pancreas are the targets of
autoimmune cell-mediated responses.
Multiple sclerosis (MS) is the most common chronic
neurological disease in developed countries-- T cells
reactive against myelin infiltrate the central nervous
system and destroy the myelin of neurons.

SCID
severe combined immunodeficiency (SCID),
both branches of the immune system fail to
function.
For individuals with this disease, long-term
survival requires a bone marrow transplant
that will continue to supply functional
lymphocytes
Have cured In Lab Trials using Stem Cells
WOW!!!!!!!!!!!!!!!!!!!!!!!!!!!!

References
Jack Brown M.S. Biology
Shier,David, Jackie Butler, Ricki Lewis: Holes Human
Anatomy and Physiology 10th edition: 2004: McGraw-Hill
Marieb, Elaine: Essentials of Human Anatomy and
Physiology 7th edition. 2003: Pearson Education Inc:
Benjamin Cummings pub.
Microsoft Encarta Encyclopedia 2004
Starr and Taggart: The Unity and Diversity of Life 10th
edition: 2004: Thomson Brookes/Cole
Campbell and Reece: Biology 6th edition: 2002:
Benjamin Cummings.
Raven and Johnson: Holt Biology: 2004: Holt, Rinehart
and Winston.