Transcript the immune system

Immune System
1
Dr. Salwa Hachim
2013
Introduction
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Immunity is defined as resistance to disease,
specifically infectious disease.
the immune system. The collection of cells, tissues,
and molecules that mediate resistance to
infections(Defense body mechanism)
the immune response: is the coordinated reaction of
these cells and molecules to infectious microbes.
Immunology is the study of immune system and its
responses to invading pathogens.
Introduction
• The immune system must be able to:
differentiate between material that is a
normal component of the body (“self”) and
material that is not native to the body
“nonself”
• A highly specialized receptors present for
discriminating between ”self” and “nonself”
body components
The Structure of the Immune System
The Immune System - includes all parts of the
body that help in the recognition and
destruction of foreign materials. White blood
cells, [phagocytes and lymphocytes], bone
marrow, lymph nodes, tonsils, thymus, and
your spleen are all part of the immune
system.
ANATOMY OF THE IMMUNE SYSTEM
Cells of the Immune System
• All immune cells begin as immature stem cells
in the bone marrow. They respond to different
cytokines and other chemical signals to grow
into specific immune cell types, such as T cells,
B cells, or phagocytes.
Cells of the Immune System
Source: http://www.biologymad.com/
Reviewing the Cells of the Immune System
Eosinophil
Erythrocyte
Lymphocyte
Basophil
Monocyte
Neutrophil
polymorph
Lymphocytes of the Immune System
• T Lymphocytes:
- Immunocompetency
occurs in
thymus
- Non antibody producing
cells
- Conduct Cellular
Immunity
• B Lymphocytes:
– Immunocompetency
occurs in bone marrow
– Produce Antibodies
– Conduct Humoral
Immunity
www.academic.brooklyn.cuny.edu/biology/bio4fv/page/aviruses/cellular-immune.html
T lymphocytes
• T cells contribute to immune defenses in two
major ways:
1. direct
2. regulate immune responses.
GENERAL SCHEME ofCELLULAR EVENTS
• APCs (Macrophages, Dendritic Cells)
• T-Cells (Control Everything)
–CD4 “Regulators” (Helper)
–CD8 “Effectors”
• B-Cells Plasma Cells AB’s
• NK CellsNatural Killer
T lymphocytes cells
• CD4+ T cells are called Helper T cells, or Th cells,
coordinate immune responses by communicating
with other cells.
• stimulate nearby B cells to produce antibodies.
• call in microbe-gobbling cells called phagocytes.
• activate other T cells.
• Some Th cells belong to a special subset that
functions to prevent or limit immune responses
( called regulatory T lymphocytes).
T lymphocytes
• CD8+T called Cytotoxic T lymphocytes
(CTLs)—also called killer T cells—perform a
different function. These cells directly attack
other cells carrying certain foreign or
abnormal molecules on their surfaces.
• CTLs are especially useful for attacking viruses.
• CTLs recognize small fragments of these
viruses peeking out from the cell membrane
and launch an attack to kill the infected cell.
lymphocytes
• Natural killer (NK) cells are another kind of lethal white
cell, or lymphocyte, can recognize surface markers on
other cells labeled for destruction
• Like CTLs, NK cells are armed with granules filled with
potent chemicals. But CTLs look for antigen fragments
bound to self-MHC molecules, whereas NK cells
recognize cells lacking self-MHC molecules. Thus, NK cells
have the potential to attack many types of foreign cells.
• Both kinds of killer cells kill on contact. These cells bind
to their targets, and then deliver a lethal chemicals.
NK CELLS
 Here, a smaller Killer T Cell (arrow) is attacking and killing a much
larger flu virus-infected target. The sequence represents 30 minutes
elapsed time. NK cells play a major role in the rejection of tumors
and cells infected by viruses. The cells kill by releasing
small cytoplasmic granules of proteins
called perforin and granzyme that cause the target cell to die
by apoptosis.
B- lymphocytes
• Produced in the bone marrow and matures in the
bone marrow, and reside in the lymphoid organs,
blood, and connective tissue.
• B lymphocytes are the only cells capable of
producing antibodies; therefore, they are the
cells that mediate humoral immunity.
• React and recognize small organisms- bacteria
and viruses.
• gives rise to many large cells known as plasma
cells, which produce antibodies.
B-lymphocytes
• Memory cells, generated from the progeny of
antigen-stimulated lymphocytes, survive for long
periods of time in the absence of antigen.
Therefore, the frequency of memory cells
increases with age. In fact, memory cells make up
less than 5% of peripheral blood T cells in a
newborn, but 50% or more in an adult.
• Memory cells are functionally inactive—they do
not perform effector functions unless stimulated
by antigen, and rapidly respond to give rise to
secondary immune responses.
Plasma Cells
1) ROUND NUCLEUS
2) OVOID CYTOPLASM
3) PERIPHERAL CHROMATIN
4) “CLEAR ZONE” BETWEEN NUCLEUS AND WIDER LIP OF CYTOPLASM
Phagocytes and Their Relatives(Granulocytes)
• Phagocytes are large white cells that can swallow and
digest microbes and other foreign particles.
• The macrophage is a large phagocyte. A phagocyte is an
eating cell (phago = "eating", cyte = "cell") which engulfs
invaders.
Phagocytes and Their Relatives
• Monocytes are phagocytes that circulate in the
blood. When monocytes migrate into tissues,
they develop into macrophages.
• Macrophages can be found in many organs,
including the lungs, kidneys, brain, and liver.
• Granulocytes: They contain granules filled with
strong chemicals, which allow the granulocytes to
destroy microorganisms, such as histamine.
• Neutrophils type of granulocyte, It is also a
phagocyte, use their prepackaged chemicals to
break down the microbes they ingest, also
contribute to inflammation and allergy.
Phagocytes and Their Relatives
• Eosinophils and basophils are granulocytes
that “degranulate” by spraying their chemicals
onto harmful cells or microbes nearby.
• Mast cells function much like basophils,
except they are not blood cells. Rather, they
are found in the lungs, skin, tongue, and
intestinal tract.
• they contribute to the symptoms of allergy.
The scanning electron micrograph above, shows a human macrophage
(gray) approaching a chain of Streptococcus pyogenes (yellow). Riding
atop the macrophage is a spherical lymphocyte. Both macrophages and
lymphocytes can be found near an infection, and the interaction
between these cells is important in eliminating infection.
Immune System
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Dr. Salwa Hachim
2013
Complement
• The complement system is made up of least 30
components enzymes, regulators and membrane
receptors -that work together to assist, or
“complement,” the action of antibodies in destroying
bacteria.
• Complement components are normally present in
body fluids as inactive form.
• Complement proteins, which cause blood vessels to
become dilated and then leaky, contribute to the
redness, warmth, swelling, pain, and loss of function
that characterize an inflammatory response.
Complement
• The alternative pathway of complement
activation can be stimulated directly by
microorganisms and is important in the early
stages of the infection before the production of
antibody. It is part of the innate immune system.
• Classical pathway of complement activation is
mainly initiated by complexes of antigen with
antibody.
• Both pathways can lead to the lytic or membrane
attack pathway. Complement factor C3 is the
central component of both the classical and
alternative pathway
Major Histocompatibility Complex
• major histocompatibility complex ( MHC molecules). MHC
molecules are proteins recognized by T cells when they
distinguish between self and non-self.
• In humans, products of the highly polymorphic MHC
genetic loci on chromosome 6. MHC antigens are called
human leukocyte antigens (HLA).
• MHC molecules are required for T cell responses against
foreign invaders.
• create problems during organ transplantations.
• Virtually every cell in the body is covered with MHC
proteins, but each person has a different set of these
proteins on his or her cells. If a T cell recognizes a non-selfMHC molecule on another cell, it will destroy the cell
Major Histocompatibility Complex
There are two classes of HLA molecules:
1. HLA-A, -B and -C (class I) are found on all nucleated
cells in the body.
2. HLA-DQ, -DR and -DP (class II) molecules are usually
only found on monocytes/macrophages, B cells,
dendritic cells (i.e. APCs), some epithelial cells and
activated T cells. each individual expresses up to six class.
Class I molecules present peptides to CD8+ T
lymphocytes, while CD4+ T cells are restricted to MHC
class II.
Cytokines
• Cells of the immune system communicate with
one another by releasing and responding to
chemical messengers called cytokines.
• These proteins are secreted by immune cells, but
usually LYMPHOCYTES and MACROPHAGES,
numerous roles in acute and chronic
inflammation, and immunity
• act on other cells to coordinate appropriate
immune responses.
• Cytokines include a varied collection of
interleukins, interferons, and growth factors.
Cytokines
• Mediate Innate (Natural) Immunity, IL-1, TNF,
Interferons
• Regulate Lymphocyte Growth (many interleukins,
ILs)
• Activate Inflammatory Cells
• Stimulate Hematopoiesis, (CSFs, or Colony
Stimulating Factors)
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Antigens are macromolecules that stimulate an immune
response in the body. The most common antigens are
proteins and polysaccharides.
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An antibody is a protein produced in response to an
antigen.
Antigens.
• Antigens: are macromolecules that stimulate an
immune response in the body. Either proteins or large
polysaccharides.
• Microbes: Capsules, cell walls, toxins, viral capsids,
flagella, etc.
• Nonmicrobes: Pollen, egg white , red blood cell surface
molecules, serum proteins, and surface molecules from
transplanted tissue.
• Lipids and nucleic acids are only antigenic when
combined with proteins or polysaccharides
• Stimulate the production and maturation of 2 types of
lymphocytes(T and B).
Antigens can be classified in order of their origins
• Exogenous antigens - are antigens that have
entered the body from the outside, ex. by
inhalation, ingestion, or injection. By endocytosis
or phagocytosis, these antigens are taken into the
antigen-presenting cells (APCs) and processed
into fragments.
• Endogenous antigens - antigens that have been
generated within the cell, as a result of: normal
cell metabolism, or viral or intracellular bacterial
infection.
Haptens
• A hapten is a low-molecular-weight substance that
cannot cause the formation of antibodies unless
combined with a carrier molecule;
• But when combined with a larger carrier molecule (serum)
function as antigen and stimulate response (their
antibodies independent of the carrier molecule)
Figure 17.4
Antigenic Determinants (epitopes)
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is the part of an antigen that is recognized by the immune system,
specifically by antibodies.
• Nature of interaction depends on size, shape, and chemical nature
of the epitope.
• Any given antigen may have several epitopes.
• Each epitope is recognized by a different antibody and may interact
with them by paratopes of Antibody
Immunoglobulins (antibodies)
Antibodies, or immunoglobulins (Igs), are the secreted
products of B lymphocytes,
Antibodies work by four basic functions,
neutralization, opsonization, activation of
inflammation, and activation of complement
• neutralization of the antigen (e.g. soluble toxins,
viruses)
• removal of the complex by phagocytic cells.
• killing of antigen-bearing cells by the membrane
attack complex of complement or by natural killer (NK)
cells, monocyte/macrophages or granulocytes.
Antibody Structure
Figure 17.5a-c
IgG
1. is a kind of antibody that works efficiently to coat microbes,
speeding their uptake by other cells in the immune system.
2. Major antibody of secondary (memory) response
3. Neutralization of toxins
4. Complement activation (except IgG4)
5. Opsonization
6. Antibody-dependent cell mediated cytotoxicity
7. Placental transfer–protection of infant during first 6–9
months
Protection of mucosal surfaces
Secretory component protects against proteolysis
Secretory IgA present in:
Saliva , bronchial secretions, colostrum, breast milk,
genitourinary secretions, gastrointestinal tract
Major antibody of primary immune response
Agglutination
Complement activation
very effective at killing bacteria
plays a key role in initiating
early B cell response, and
remains attached to B cells
Immunity to helminthes Binds to
basophils and mast cells, activating
mediators of allergy
The Immune Response
3
Dr. Salwa Hachim
2013
How The body's Defense against
Foreign Ag Entrance?
Specific Defenses of the Host: The Immune Response
•Acquired immunity
Developed during an
individual's lifetime
• First-Line Defenses /Innate Immune System•
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The body's first line of defense against pathogens
uses mostly physical and chemical barriers such as
Skin – acts as a barrier to invasion.
Sweat – has chemicals which can kill different
pathogens.
Tears - have lysozyme which has powerful digestive
abilities that render antigens harmless.
Saliva – also has lysozyme.
Mucus - can trap pathogens, which are then sneezed,
coughed, washed away, or destroyed by chemicals.
Stomach Acid – destroys pathogens
• Second-Line Defenses - If a pathogen is able
to get past the body's first line of defense, and
an infection starts, the body can rely on it's
second line of defense. This will result in what
is called an……….
Inflammatory response causes
• Redness - due to capillary dilation resulting in
increased blood flow
• Heat - due to capillary dilation resulting in
increased blood flow
• Swelling – due to passage of plasma from the
blood stream into the damaged tissue
• Pain – due mainly to tissue destruction and, to
a lesser extent, swelling.
• Third-Line Defenses - Sometimes the second
line of defense is still not enough and the
pathogen is then heading for the body's last
line of defense, the immune system.
• The immune system recognizes, attacks,
destroys, and remembers each pathogen that
enters the body. This done by making
specialized cells and antibodies that reduce
the pathogens harmless.
• Unlike the first line and second line defense
the immune system differentiates among
pathogens.
• For each type of pathogen, the immune
system produces cells that are specific for
that particular pathogen.
The innate immune system
The first line of defense in innate immunity is provided by
1. epithelial barriers .
2. specialized cells phagocytes, specialized lymphocytes
called natural killer cells all of which function to block the
entry of microbes and to rapidly eliminate microbes that
do succeed in entering host tissues or circulation.
3. cytokines/chemokines
4. several plasma proteins, including the proteins of the
complement system and Coagulation Factors.
• Innate immunity can be seen to comprise four types of
defensive barriers: anatomic, physiologic, phagocytic, and
inflammatory.
The principal
mechanisms
of innate
immunity.
(non-specific)
The adaptive immune system
• Adaptive immune responses are activated
only if microbes or their antigens pass
through epithelial barriers and are delivered
to lymphoid organs where they can be
recognized by lymphocytes. Adaptive immune
responses are specialized to combat different
types of infections.
The Adaptive Response is a “TwoEdged Sword”
 Protection
 Damage to the host (hypersensitivities)
 Allergies
 Cell and tissue damage due to
autoimmunity
Types of Adaptive Immunity
 The two types of adaptive immunity are,
1. humoral immunity
B lymphocytes secrete antibodies that eliminate
extracellular microbes.
1. cell-mediated immunity,
T lymphocytes either activate macrophages to destroy
phagocytized microbes or kill infected cells
(intracellular microbes)
Phases of an adaptive immune response
• Recognition: Naive lymphocytes recognize foreign
antigens to initiate adaptive immune responses.
• Effector phase: Some of the progeny of these
lymphocytes differentiated into effector cells, whose
function is to eliminate antigens.
• The effector cells of the B lymphocyte lineage are
antibody-secreting plasma cells.
• The effector cells of the CD4+ T lymphocyte lineage
produce cytokines.
• Other progeny of the antigen-stimulated lymphocytes
differentiate into long-lived memory cells
Stages of Humoral Immune
• Recognition phase: resting mature B cells and
Igs converted to activated cells after Ag
invasion
• Activation phase: B cell proliferation(clonal
expansion) and differentiation
Stages of Humoral Immune Response