Medical

Immunology

Anas Abu-Humaidan
M.D. Ph.D.
Lecture 2
Immunology introduction

• The immune system includes the role of physical, cellular, and chemical systems that are
in place and that respond to all aspects of foreignness.

• The immune system targets any “foreign” object, so the first step is to recognize what is
self and non- self.

• The second step is to restore homeostasis by eliminating the foreign object.

• The third step is to remember the invading pathogen to respond better the next time it is
encountered .

• The immune system is not only active when danger arises, but is constantly sensing danger
and is important for normal physiology and homeostasis similar to the cardiovascular
and renal systems.
Immunology introduction/ co-evolution

Mechanisms for discriminating "self" from "non-self"

evolved to accomplish the task of fighting pathogens,
launching a long history of host-pathogen co-evolution.

Virtually all organisms have at least one form of defence Transplantation of parts of sponge to other
that helps repel disease-causing organisms.
Loading… sponges is met by an immune response

Pathogens evolve new strategies to over come immune

mechanisms, and so the host defence becomes more
complex to defend against invading pathogens.

Jawed vertebrates have developed higher complexity of

defence reflected in the adaptive immune response.
Immunology introduction / What is forgein?

Antigens are any substance that

stimulates the immune system to
produce antibodies. Antigens can be
bacteria, viruses, or fungi that cause
infection and disease.

Antigens may also originate from

within the body ("self-antigen"), but
should not be attacked by the immune
system in normal situations.
Immunology introduction / INNATE AND ADAPTIVE
IMMUNITY

Loading…

• Host defenses are grouped under innate immunity, which provides immediate protection
against microbial invasion, and adaptive immunity, which develops more slowly and
provides more specialized defense against infections
Immunology introduction / INNATE AND ADAPTIVE
IMMUNITY
Immunology introduction / Location of the immune system

The immune system duty is to survey the

whole body so it should be present
everywhere. But there are sites where
immune cells collect to fulfil their function
(e.g. lymph nodes).

For example, in the small intestine there is

lymphatic tissue that surveys intestinal
pathogens called Peyer's patches.

The bone marrow is an important place for

generation of immune and non-immune
blood cells.
Immunology introduction / Conclusions

• Immunology is a relatively recent science with applications that extend to other medical
sciences, thus it is important for medical students.

• The immune system in an ancient defence mechanism composed of tissues, cells and
molecules that interact with each other with great complexity.

• Parts of the immune system are continuously active and help in maintaining homeostasis.

• Specialized immune cells are mainly in the bone marrow and then circulate the blood or
aggregate in lymph nodes.

• The immune system arms can be divided in general into innate and adaptive.
Cells of the immune system

• The cells of the innate and adaptive immune system are normally present as circulating
cells in the blood and lymph, as anatomically defined collections in lymphoid organs,
and as scattered cells in virtually all tissues.
Cells of the immune system

• Phagocytes
• Mast Cells, Basophils, Eosinophils
• Antigen-Presenting Cells
• Lymphocytes
Cells of the immune system

Loading…

Although most of these cells are found in

the blood, their responses to microbes are
usually localized to tissues.
Cells of the immune system / Phagocytes

• Phagocytes, including
neutrophils and
macrophages, are cells
whose primary function is
to identify, ingest, and
destroy microbes.

• Phagocytes also
communicate with other
cells in ways that promote
or regulate immune
responses.
Cells of the immune system / Phagocytes/ Neutrophils

Neutrophils, also called

polymorphonuclear leukocytes, are the
most abundant population of circulating
white blood cells and mediate the earliest
phases of inflammatory reactions.

The nucleus of a neutrophil is segmented

into 3-5 connected lobules

Short lifespan, they circulate for about 6

hours, Production of neutrophils is
stimulated by granulocyte colony-
stimulating factor (G-CSF). An adult
human produces more than 1 × 1011
neutrophils per day
Cells of the immune system / Phagocytes/ Neutrophils

The cytoplasm contains granules of two

types. The majority, called specific granules,
are filled with enzymes such as lysozyme,
collagenase, and elastase. The remainder are
azurophilic granules, which are lysosomes
containing enzymes and other microbicidal
substances.

Neutrophils may migrate to sites of infection

within a few hours after the entry of
microbes.

After entering tissues, neutrophils function

for a few hours and then die.
Cells of the immune system / Phagocytes/ Neutrophils

• Neutrophil extracellular traps (NETs) are networks of extracellular fibers, primarily

composed of DNA from neutrophils, which bind pathogens.
 Blood film with a striking absence of neutrophils, leaving
only red blood cells and platelets

Neutropenia is an abnormally low concentration of neutrophils in the blood. Neutropenia has many causes
and can be congenital and acquired (e.g. cancer treatment, autoimmune diseases).
Febrile Neutropenia
JP is a 34-year-old Caucasian male who is admitted to inpatient oncology service
for induction chemotherapy for a recent diagnosis of acute myeloid leukemia
(AML). His induction chemotherapy regimen consists of 7 + 3 induction
chemotherapy with cytarabine and daunorubicin. He was placed on neutropenic
precautions, started on appropriate antimicrobial prophylaxis, and a port was
placed for chemotherapy administration. Ten days after the completion of his
induction chemotherapy (day 17), he spiked a fever of 38.8°C (101.8°F) and
complained of chills and nausea.
 Cells of the immune system / Phagocytes/ Mononuclear Phagocytes

• The cells of the mononuclear

phagocyte system originate from
a common precursor in the bone
marrow, circulate in the blood as
monocytes, and mature and
become activated in various
tissues.

• Once monocytes enter tissues,

mature and become
macrophages. Macrophages in
different tissues have been
given special names to designate
specific locations.
 Cells of the immune system / Phagocytes/ Macrophages

• In addition to ingesting microbes, macrophages also ingest dead host cells as part of the
cleaning up process after infection or sterile tissue injury.

• Activated macrophages secrete proteins, called cytokines, that bind to signalling receptors on
other cells and thereby instruct those cells to respond in ways that contribute to host defence.

• Macrophages serve as APCs that display antigens to and activate T lymphocytes.

• Another important function of macrophages is to promote repair of damaged tissues by

stimulating new blood vessel growth (angiogenesis) and synthesis of collagen-rich
extracellular matrix (fibrosis).
Cells of the immune system / Phagocytes/ Macrophages

Macrophage-like cells are phylogenetically the

oldest mediators of innate immunity. Drosophila
responds to infection by surrounding microbes with
“hemocytes,”
which are similar to macrophages, and these cells
phagocytose the microbes and wall off the
infection. Macrophages can acquire distinct functional
capabilities, depending on the types of
activating stimuli
 Cells of the immune system / Mast Cells, Basophils, Eosinophils

• All three cell types share the common feature of

having cytoplasmic granules filled with various
inflammatory and antimicrobial mediators.

• Another common feature of these cells is their

involvement in immune responses that protect
against helminths and immune responses that
cause allergic diseases
 Cells of the immune system / Mast Cells

• Mast cells are bone marrow–derived cells

that are present in the skin and mucosal
epithelium and contain abundant
cytoplasmic granules filled with cytokines
histamine, and other mediators.

• Mature mast cells are not found in the

circulation but are constitutively present in
healthy tissues, usually adjacent to small
blood vessels and nerves.

• Mast cells express plasma membrane

receptors for IgE and IgG antibodies and are
usually coated with these antibodies
 Cells of the immune system / Basophils

• Basophils are blood granulocytes with many structural and functional similarities to mast
cells.

• Like mast cells, basophils express IgG and IgE receptors, bind IgE, and can be triggered
by antigen binding to the IgE.

• Basophils constitute less than 1% of blood leukocytes, normally not present in tissues
and their importance is uncertain.

• When they participate in allergic reactions or responses to parasites, basophils release

histamine and many other biologically active molecules that can contribute to
inflammation.
 Cells of the immune system / Eosinophils

• Eosinophils were first described in 1879 by Paul

Ehrlich, who noted their unusual capacity to be
stained by acidophilic dyes.

• They are released into the peripheral blood in a

phenotypically mature state, and they are capable
of being activated and recruited into tissues in
response to appropriate stimuli, most notably the
cytokine interleukin-5 (IL-5) and the eotaxin
chemokines.

• Eosinophils spend only a brief time in the

peripheral blood (they have a half-life of ∼18
hrs) before they migrate to the thymus or
gastrointestinal tract, where they reside under
homeostatic conditions
Cells of the immune system / Eosinophils

Eosinophils are blood granulocytes that express

cytoplasmic granules containing enzymes that
are harmful to the cell walls of parasites but
can also damage host tissues.

Eosinophils are a common feature of the

inflammatory response that occurs in asthma,
as they are recruited to the lungs and airways
by cytokines that are released from activated
TH2 cells and by a range of chemokines, most Eosinophils: changing perspectives in health and disease
notably those of the eotaxin family. https://www.nature.com/articles/nri3341

Several lines of evidence suggest that

deficiency of eosinophils is not associated
with any characteristic abnormality.
Further reading:

Cellular and Molecular Immunology. 7th Edition..

Chapter 2. Cells and tissues of the immune system