Elements of the Immune System and their Roles in Defense
Immunology- study of physiological mechanisms that humans and other
animals use to defend their bodies from invasion by other organisms.
Origins- practice of medicine.
Why did some die and others live and even continue to be
Immune to infection.
Bad guys out number the good guys.
Microorganisms can reproduce faster than humans can. Collectively the
immune system fights for us and for our body.
Takes time to put all the players into play.
Kids versus adults. EAT dirt.
Protective immunity….. in order to have you must first do battle once.
Highest risk is at the first infection.
Bird flue, Native Americans and chicken pox….. you and chicken
pox. Vaccinations. Acquired immunity, passive immunity.
Edward Jenner- cow pox, small pox. 1796.
Vaccinations are made from a small form of the infectious agent, live
Defenses. The Dark Side….. Those who shall not be named,.
All cells originate in the bone marrow. Leave the marrow and circulate
some into the lymphoid system.
Pathogens. Any organism with the potential to cause disease is known as
Wrong place at the wrong time. E. coli….. others, sterile versus normal
Pathogens = four kinds
We want to consider controlling the infection and the
Constantly changing. If you die too early not good. We make
adjustments. On each side.
Healthy population versus compromised.
How you get infected.
Who are you?
Barriers. Time, exposure, temperature, place.
Where you get the organism or the pathogen.
Skin is the body’s first line against infection.
Tough impenetrable barrier. Even a pH advantage that works
in our favor.
Skin, Respiratory, think of anatomy and histology of the cells.
Physical and chemical barrier.
Inflammation at the sites of infection.
Two parts. Recognition that there is a pathogen.
Recruitment to do something about it. Effector mechanisms
that kill and eliminate.
Cells and serum proteins… complement.
These together are innate immunity or innate immune
Innate…… what you got is what you get. Your inheritance.
MAKE A POINT OF LOOKING AT PAGE 5 = The
Diversity of human Pathogens… Figure 1.3
Two step process:
1. Recognition of something as a pathogen
2. Destruction of the pathogen
Effector cells and complement.
An infection begins and the surrounding cells secrete cytokines (soluble
proteins). This triggers the innate immune response = inflammation.
Calor, dolor, rubor and tumor.
Heat, pain, redness and swelling.
Not from the infection but from the response.
Figure 1.6 Innate mechanism a state of inflammation.
Healthy skin. Underlying blood supply and intact skin barrier.
Abrasion or invasion of the skin.
Release of cytokines also causes vasodilation = fluid comes out of the
blood stream, enters the surrounding area, causing edema, swelling,
affects nerve endings causing pain. Other effector cells and
inflammatory cells come to engulf and phagocytosis the bacteria and
you get redness.
Despite your constant barrage and exposure to pathogens, your innate
immunity manages to keep most of us healthy , most of the time.
Innate mechanism is the same for basically everything you encounter, it
is not specific.
Doesn’t make any difference the worm, the sliver.
Sometimes the innate immune response doesn’t work. The innate
response slows things down, but you must have a specific adaptive
The body’s immune response calls upon the WHITE CELLS….. the
lymphocytes to increase the power and focus of the immune response.
ADAPTIVE IMMUNITY. Provides a highly specialized defense against
one pathogen, but is of little effect against infection by a different
Different effector mechanisms, but similar.
The important difference is in the cell-surface receptors used by
lymphocytes to recognize pathogens.
Make sure you can write a response to this test question:
Compare and contrast the different recognition mechanisms of innate
immunity and adaptive immunity. See figure 1.7
Only specific cell types with the correct recognition for the pathogen are
selected to participate in the adaptive response. Then their numbers are
expanded (clonal expansion) to produce huge numbers of effector cells.
This process takes time, and therefore the benefits of adaptive immunity
only is effective about a week after the infection begins
Think of how long it takes to really recover…. 2 weeks.
You’re getting sicker during the first week; you’re recovering the
second week and getting better.
Protective or acquired immunity.
The lymphocyte populations that expand during as adaptive immune
response persist in the body and provide long-term immunological
memory of the pathogen. These memory cells allow subsequent
encounters with the same pathogen to elicit a stronger and faster
adaptive immune response which terminates infection with minimal
illness. The adaptive immunity provided by immunological memory is
also called acquired immunity or protective immunity.
You should be able to write a response to this test question: clearly
define these immunities:
Compare and contrast differences and responses.
Measles, mumps,….. one time deal provided life long immunity
Influenzae ….. pathogen shifts immune receptors and changes the
The system remembers, the pathogen changes.
Immune system cells with different functions all derive from
hematopoietic stem cells.
Red cells, white cells, and platelets = magakaryocytes. Pluripotent
hematopoietic stem cells. = hematopoiesis.
Age dependant as to where this occurs. Fetal versus adult.
Bone marrow, iliac crest, sternum.
Self renewal of stem cells. They can also become mature and go into
three different cell lines. Erythroid, myeloid and lymphoid.
Erythroid = RBC’s and platelets.
Myeloid = granulocytes = polymorphonuclear leukocytes.
Most abundant is the neutrophil.
Neutrophil is specialized to capture, engulf and kill microorganisms.
Can work under anaerobic conditions = no oxygen.
Short lived and die at the site = pus.
Eosinophils. = parasitic worms and intestinal parasites.
Basophils. So rare that not much is known.
Names these based on cell staining techniques.
Second group in the myeloid cell line are the monocytes macrophages
and dendritic cells.
Monocytes are leukocytes that circulate in the blood.
Bigger in size and mono nucleus. Once they migrate into a tissue they
become Macrophages. These too can capture, engulf and kill cells.
They are the general scavenger cells of the body. Phagocytosing
Long lived commanders and orchestrate the local response to infection.
They secrete cytokines to recruit the neutrophils.
Myeloid dendritic cells are found in the tissues, Unique star shape.
Act as messengers to help in the adaptive immune response.
Mast cells. This is found in all connective tissue. Not much known.
Lymphoid cell progenitor.
Large and small:
Large has very granular cytoplasm = natural killer cells. NK cells.
Small has almost no cytoplasm.
Small lymphs are responsible for adaptive immunity.
They are small because they circulate in an immature form that is
Recognition of a pathogen by small lymphocytes drives a process of
lymphocyte selection, growth and differentiation that after 1-2 weeks
produces a powerful response tailored to the invading organism.
Visually you can’t tell the difference…… they all look small…..
But there are very distinctive differences on the cell surfaces and their
specific cell surface receptors and the functions that they are
programmed to perform.
The most important difference is between B lymphocytes or B cells and
T lymphocytes or T cells.
B cells the cell-surface receptors for pathogens are immunoglobulins
T cells are known as t-cell receptors.
Immunoglobulins and T-cell receptors are structurally similar
molecules that are the products of genes that are cut, spliced and
modified during lymphocyte development……. What does that sound
like………….. RNA modification anyone???!!!...
As a result of these processes each B cell expresses a SINGLE TYPE OF
And each T cell expressed a SINGLE T-CELL RECEPTOR.
Within the small lymphocyte population BILLIONS of DIFFERENT
IMMUNOGLOULINS and T-CELL RECEPTORS are represented.
BILLIONS and BILLIONS and they are all DIFFERENT>>>>>>>
Specialized lymph tissue.
They circulate in the blood, but they are found and formed in
specialized tissue. Functionally divided into two groups.
Primary or central lymphoid tissues = bone marrow and thymus.
This is where the lymphocytes develop and mature to the stage where
they can fight and engage the pathogen.
Secondary or peripheral lymphoid tissues = tonsils, spleen,
adenoids, appendix, lymph nodes, and Peyer’s patches.
This is where nature lymphocytes become stimulated to respond to
Lymphatic tissue and system,
Nodes. Network. Make sure you understand the way lymph tissue
works. Plasma leaking from the blood system into the tissues and then
collects back via the thoracic ducts. Left sub clavian and right thoracic.
Spleen. While part of the lymphoid system there is no physical
connection. It becomes a filter
Lymph = fluid that recirculates. Both T and B cells originate from
precursors in the bone marrow. B cells complete their maturation I the
bone marrow before entering the circulation. T cells leave the bone
marrow at an immature stage and migrate in the blood to the thymus.
In the thymus they complete their maturation.
Lymphocyte maturation is a highly selective process in which the
majority of immature lymphocytes are destroyed because they fail to
develop immunoglobulins or T-cell receptors that are useful to the
A small fraction of immature B and T cells that successfully complete
development depart from the primary lymphoid organs and enter the
They develop in the primary tissue…….. they get activated in the
secondary lymphoid tissues.
Meeting places where lymphocytes circulating in the blood encounter
pathogens and their products brought from a site of infection.
They get carried to the nearest lymph node = draining lymph node.
Dendritic cells arrive with engulfed pathogens and processed
Test question. Make sure that you understand the lymph system. It does
not have a driving cardiac output. It does not have a pump. Make sure
you understand the flow. Lots of potential for infection, for spread, for
Edema…. Fluid accumulation.
Understand the anatomy and histology of the node.
Afferent lymphatic vessels, several come into the node and only one
EEEEEEEEEfferent lymphatic vessel comes out.
The filters are macrophages. SO now the pathogen is stuck inside a
lymph node ready to be utilized for activation. T-cell areas…
Review Figure 1.18.
Test Question: Explain the step, by step process of lymph and pathogen
as they enter a node. What happens, what gets activated and why?
SO the node:
T-cells enter the node via afferent vessels, congregate in the T-cell area.
Dendritic cells are also coming along. If the receptors on the T-cell
surface bind to the pathogen components displayed by a dendritic cell,
then the T cell is signaled to divide and differentiate into functional
1. Some T cells differentiate into helper T cells that stay in the lymph
node and provide soluble proteins and intercellular contacts that drive
the differentiation of B cells possessing immunoglobulin receptors that
bind the pathogen.
2. Effector B cells called plasma cells can either stay in the lymph node
or migrate to the bone marrow via lymph and blood.
Plasma cells make and secrete large amounts of antibody, a
soluble form of their cell-surface immunoglobulin.
3. A second type of T cells differentiates into helper T cells that leave the
lymph node and travel via the efferent lymph and the blood to the
These helper T cells interact with macrophages and secrete
soluble cytokines to amplify the inflammation.
4. A third type of effector T cell is called the cytotoxic T cell because
these cells kill cells infected with viruses or other intracellular
Make sure you understand this point. Bacteria, fungi, most pathogens
are freely associated. Viruses and some intracellular parasites are
HIDDEN from cellular presentation.
IN reality only a small minority of the circulating small lymphocytes
will be activated, the rest pass through the node and continue to
Now should they “Miss” the node presentation they can infact find a
similar function in the spleen. Remember the spleen acts as a filter for
the blood. It also functions as a secondary lymphoid tissue. Infectious
agents are removed and used to activate lymphocytes. Only real
difference is that both the pathogen and the lymphocytes enter and
leave the spleen in the blood ----NO lymph.
Know the terms:
GALT- gut-associated lymphoid tissues ( tonsils, adenoids, appendix
and Peyer’s patches) line the small intestine.
BALT- bronchial-associated lymphoid tissue (respiratory tract).
MALT. Mucosa-associated lymphoid tissue.
Systems act the same way, the differences are chiefly the routes of
Make sure you understand the Summary on page 20.
Know the four key elements of innate immunity:
Molecules that noncovalently bond to surface macromolecules of
Molecules that covalently bond to pathogen surfaces forming
ligands for phagocyte receptors.
Phagocytic cells that engulf and kill pathogens
Cytotoxic cells that kill virus-infected cells.
Principles of Adaptive immunity
Know the differences between innate and adaptive immunity. Page 20.
Innate – you recognize anything foreign and set patterns that are
shared. In adaptive those T and B cells have specific immunoglobulins
and T cell receptors. Unique to only one and then it makes a response of
stimulation, divide, proliferate and become effector lymphocytes.
Found only in vertebrate animals. Evolution with high degree of cellular
complexity. Immunoglobulins are expressed on the surface of B cells,
Effector B cells are plasma cells and these secrete the soluble form of the
immunoglobulin or ANTIBODIES.
T-cell receptors are only expressed as cell0surface recognition molecules
never soluble proteins.
Ay molecule, macromolecule, virus particle of cell that contains a
structure recognized and bound by an immunoglobulin or T-cell
receptor is known as an antigen.
The particular part of the antigen bound by the immunoglobulin or T-
cell receptor is known as the antigenic determinant or epitope.
Immunoglobulins can bind to a vast variety of different chemical
structures, T-cell receptors recognize a more limited range of epitopes.
They are specific. Or have specificity for the antigens that they bind.
Immunoglobulins and T-cell receptors are structurally related
molecules whose diversity is generated by similar genetic mechanisms.
Immunoglobulins are formed from two different polypeptides called
heavy and light chairs. Each “Y” shaped immunoglobulin molecule
consists of two identical heavy chains and two identical light chains.
Both have a variable region that differs from one immunoglobulin from
another and a constant region that is identical to the other
The variable region contains the sites that bind antigens.
You anchor these into the cell membrane by Transmembrane regions
located at the carboxyl ends of the heavy chains. Antibodies are
identical, but they circulate so they do not have the trans membrane
The T-cell receptor consists of am alpha chain and a beta chain. Both
areas anchored in the T-cell membrane. Like the heavy and light chains
of the immunoglobulins, the alpha and beta chains of T-cell receptors
each consist of a variable region and a constant region. The variable
regions form an antigen binding site.
The differences in the amino acid sequences of the variable regions of
immunoglobulins and T-cell receptors create a vast variety of binding
sites that are specific for different antigens and thus for different
pathogens. This is the hallmark of an adaptive immune response.
The diversity of immunoglobulins and T-cell receptors is generated by
You can have gene rearrangement in the heavy and light chain loci only
in B cells. There is diversity in the variable regions. When B cells go
through the secondary lymphoid tissue they can initiate a process of
somatic hyper mutation which introduces nucleotide substitutions into
the heavy and light chains of immunoglobulins.
B cells recognize intact pathogens, whereas T-cells recognize pathogen-
derived peptides bound to proteins of the major histocompatibility
Figure 1.24 REVIEW
Antibodies made by B cells are the soluble pathogen-binding molecules
of adaptive immunity. By circulating in the body fluids, antibodies can
bind to bacterial cells and intact viral particles in extracellular spaces,
targeting them for phagocytosis. To fulfill this function, the binding
sites of antibodies interact with intact components of the pathogen
surface such as glycoproteins and proteoglycans. The epitopes bound by
antibodies most commonly include carbohydrate groups, or clusters of
amino acids on the protein surface or combinations of the two.
Whereas antibodies bind directly to the native structures of biological
macromolecules, T-cell receptors can bind only to short peptides that
have been assembled into a complex with a membrane glycoprotein
called a major histocompatibility complex (MHC) molecule. T-cell
antigens are therefore peptides. They are produced within human cells
by the breakdown of pathogens or their protein products, a process
called antigen processing.
This processing occurs inside the cell where the antigen was processed.
It presents antigens in a complex with MHC. The cell becomes an
antigen presenting cell. The MHC antigens are presented to the cell
surface for the T-cell receptors.
There are two classes of MHC molecules:
Class I molecules present peptide antigens derived from pathogens that
replicate intracellularly, such as viruses and some bacteria. CD8
glycoprotein on their cell surfaces is the distinguishing factor for the T
cells that can function by killing infected cells. Since all nucleated cells
can be infected by viruses, MHC class I molecules are present on almost
all cell types. Cytotoxic T cells.
MHC class II present peptides obtained from pathogens and their
products that are present in the extra cellular fluid and have been taken
up in the endocytic vesicles of phogocytic cells. These are presented to
helper T cells, which then go on to activate B cells or macrophages.
Helper T cells have CD4 glycoproteins on their surface.
These MHC class II molecules are present on only a few cell types.
These antigen-presenting cells are dendritic cells, macrophages and B
The variability and immense variety of MCH molecules is the chief
cause of rejection of tissue transplants. Donor and recipient are of
different MHC types.
Figures 1.26 = MHC Class I Figure 1.27 = MHC class II.
While we have a HUGE variety of antigens and antibodies, once we
have an infection we get clonal selection. All of these cells are identical
…. All expressing the identical immunoglobulin or T-cell receptor. =
For this chapter you will not be held responsible for self-tolerant
selection. We will cover this more later. But you should know that there
is a process for self selection. Only a few T cells make it out to circulate.
Extracellular pathogens and their toxins are eliminated by antibodies.
Immunoglobulins are divided into five classes.
IgA. IgD, IgE, IgG, and IgM
IgM is the first antibody to be secreted in the immune response.
Immunity due to antibodies is often known as humoral immunity.
IgM, IgA, and IgG are the main antibodies present in blood, lymph and
the fluid in connective tissues.
Antibodies can also have the effect of neutralization. If they bind tightly
to a site on a pathogen, it can prevent growth, replication, inhibit
The most important function of IgG antibodies is to facilitate the
engulfment and destruction of extracellular microorganisms and toxins
by phagocytes. Neutrophils and macrophages have cell- surface
receptors that bind to the constant regions of the IgG heavy chains.
A bacteria coated with IgG is more efficiently phagocytosed than an
uncoated bacterium = opsonization.
Adaptive immune responses generally give rise to long-lived
immunological memory and protective immunity.
The immune system can be compromised by inherited
immunodeficiencies or by the actions of certain pathogens.
You can have one defective gene copy and the other takes care of the
immune response. Immunodeficiency diseases.
HIV – AIDS – CD4 T lymphocytes.
Death comes from an opportunistic infection.
Unwanted effects of adaptive immunity cause allergy, autoimmune
disease and rejection of transplanted tissues.
Allergy = IgE antibodies against substances in the environment, foods,
grass pollen, house dust….etc.
Autoimmune diseases, = rheumatoid arthritis, Grave’s disease, MS,
Known and review the summary.
Practice and complete the review questions. Very beneficial.