Transcript Immunology powerpoint

The Lymphatic System
System which launches fight
against infections
Lymphatic System
The major components of the lymphatic system are
lymphatic vessels, lymph, lymph nodes, and some
other lymphatic organs
Lymphatic vessels carry lymph, a colorless liquid,
throughout the body. Along lymph vessels are small
bean-shaped glandular nodules called lymph nodes.
Other lymphatic organs are:
Tonsil: clusters of lymphatic tissues just under the mucous
membranes that line the nose, mouth, and pharynx.
Spleen: it is similar to a lymph node in shape and
structure but it is much larger.
Thymus: a soft organ with two lobes that is located
anterior to the ascending aorta and posterior to the sternum.
Peyer patch: lymphoid tissue on the visceral surface of the
small intestine.
Lymphatic System
Primary Lymphoid Organs
– Bone marrow and Thymus
Secondary Lymphoid Organs
– Spleen, tonsils, Peyer’s patches
Lymphatic system, upper respiratory
system and muscular system ALL contain
lymphatic vessels
Lymphatic Vessels
Lymphatic vessels carry excess fluid from
tissues and return it to the bloodstream.
Have flaplike valves that help prevent
backflow of lymph
Vessels lead to lymph nodes
After leaving the nodes, the vessels merge
to form lymphatic trunks
Lymphatic Capillaries
Thinned walled
capillaries which allow
fluid to enter.
Fluid inside is called
“lymph”
Lacteals: lymphatic
capillaries located in
lining of small
intestines which
absorb fat and
transport them to
venous circulation
Lymph nodes
and ducts
The right lymphatic duct drains
lymph from the upper R side,
whereas the thoracic duct drains
lymph from the rest of the body.
Lymphatic capillary
Lymphatic vessel
Lymph node
Lymphatic vessel
Lymphatic trunk
Collecting duct
Subclavian vein
Lymph nodes
Glands which are located along the lymphatic
pathways
Contain large #s of lymphocytes and
macrophages
Located in neck, thoracic cavity, armpit
(axillary), abdomen, pelvic area, inguinal area
and supratrochlear nodes (where is this???)
2 functions: filtration and providing
lymphocytes and macrophages for immunity
Do not trap wbcs but they do trap bacteria,
and toxins
Immunology
The body’s defense system
Terminology
Immunology: the study of how body
components respond and interact
Immunoglobulins: class of proteins that
make up antibodies
Phagocytosis: process where cells engulf and
destroy foreign particles such microorganisms or
damaged cells. Macrophages and segmented
neutrophils are the most important phagocytic
cells
Terminology
Immunogenicity: the degree to which an
antigen elicits an immune response
Immunogen: antigen that stimulates an
immune response
Soluble antigen: free floating antigen
recognized by B cell receptors
Terminology
Epitope: the small piece of an antigen that
is bound by an antibody or a T cell
receptor
Chemotaxis: release of substances which
attract phagocytic wbc to bacteria. Cells
move from an area of low to high
concentration of chemokines.
Immune System
Immune System: cells in our bone
marrow, thymus, and the lymphatic system
of ducts and nodes, spleen, and blood that
function to protect us.
Function is to recognize self from nonself
and to defend the body against nonself.
Lines of Defense
1st line of Defense
– Non specific
Innate or inborn
General response which protects us daily
Non Specific Responses
– Inflammation
– Phagocytosis
– Physical barriers
– Chemical barriers
Immune System
1st line of defense:
– Skin and mucosal membrane surfaces
– Secretions: mucous on membranes in nose
trap microorganisms and are secreted
through sneezing. What other secretions can
you think of?
Tears, saliva, ear wax, sweat, production and
elimination of urine
– Phagocytic wbc in the mucous membrane
Immune System
1st line of defense continued:
– Normal flora deter penetration of
microorganisms
– pH of body fluids such as gastric juices
– Cilia movement helps protect the respiratory
tract
– The enzyme lysozyme which is found in tears
and saliva attacks and destroys the cell wall of
susceptible bacteria especially some gram
positive bacteria
Immune System
Non specific cellular and chemical response
– Fever production resulting from pyrogenic secretions
from pathogens
– Interleukin 1 produced resulting from stimulated
macrophages.
Polypeptide secreted by macrophages, enhance T cell
activation and activity
– Phagocytosis: process of surrounding and engulfing
foreign matter.
Antibodies coating an invading microbe for phagocytosis is
called opsonization.
Activation of the Complement
System
Complement System
Activation of complement proteins
Opsonization: enhancing phagocytosis of Ags
Chemotaxis: attracting macrophages and
neutrophils
Lysis: rupturing membranes of foreign cells
Clumping of Ag bearing agents
Altering the molecular structure of viruses
Inflammatory Response
Involves granulocytes such as basophils
and eosinophils.
Mast cells are activated during an allergic
reaction and release histamine
Delayed hypersensitivity is also called Cell
Mediated response
Immune Responses
2nd line of Defense
– Specific
– Production of Abs in response to Ag
Specific Responses
– Associated with Ag and Ab reaction
– Ab response occurs after exposure to Ag
– Ab may neutralize, kill, or cause clumping of foreign
microorganisms
– Complement system also works w/Abs to destroy the
invader
Complement system is a group of proteins produced in the
liver, circulating in the plasma and enhance the work of Abs
Types of Immunity
Types of Immunity
Example
Active natural immunity
Having a disease like
the mumps
Active artificial immunity Receiving a vaccination
like (MMR)
Passive natural
immunity
Passive artificial
immunity
Abs produced by the
body itself or received
from mom
Injection of antibodies
Natural Immunity
Also known as innate (inherited) immunity
Mechanism which kicks in after bacteria
gets past the first lines of defense
Natural immunity is a non specific
mechanism
Natural Immunity
Components of Natural Immune System
– Cellular components
Mast cells
Neutrophils: most abundant and 1st to arrive
Macrophages
– Humoral (fluid)
Complement
Lysozyme
Interferon
Leukocytes
Type
Polymorphonuclear
(granulocytes)
Function
Phagocytosis
Neutrophils
Phagocytosis, most active and voracious
Eosinophils
Allergic response
Basophils
Release histamine (so do mast cells)
Monocytes
Become macrophages and phagocytes
Macrophages
Phagocytosis
Lymphocytes
T Lymphocytes
Cell mediated immunity
B Lymphocytes
Humoral immunity
Plasma cells
Antibody production
Effector Cells
Plasma cells: derived from lymphocytes
(white blood cells) and are the cells which
secrete antibodies. They live a short time
and are constantly being replaced.
Macrophages: derived from monocytes
(wbc) w/primary function of phagocytosis
Adaptive Immunity
Also known as acquired immunity
Active immunity can leave the host
w/specific immunologic memory which
allows the host to respond more effectively
if re-infection with the same
microorganism occurs
Specific Immune Response
Primary Immune Response: 10 to 17 days after
initial exposure to Ag. Selected lymphocytes
generate a maximum effector cell response.
While effector cells are developing an infected
person may become ill but eventually the
symptoms of the illness disappear as Abs and
effector T cells clear antigens from the body.
Secondary Immune Response: later exposure to
the Ag that results in a much faster (2-7 days),
much faster, and more prolonged response by
Abs and effector T cells
Immunoglobulin Structure
Composed of glycoproteins
4 protein chains held together w/ disulfide bonds
Fc region: constant region dictates the type of
immunoglobulin A, E, D, M, or G
Fab portion: antigen binding region of the Ab.
This region is highly diverse so that the variety of
antigens recognized by these receptors is
extremely numerous
Heavy chains
Light chains
Immunoglobulin Structure
Composed of 2 identical
Heavy chains and 2
identical light chains
Constant regions are
located on both the light
and heavy chains
The very end of the
variable Regions is
called the hypervariable
as that is the region
where the amino acid
sequencing varies the
most
Antibodies
Variable region is what determines the
antigen specificity
The constant region (Fc) is what
determines the antibody immunological
class or isotype (A,E,M,G, D)
Antibodies do not destroy antigens directly
– Neutralize
– Target for elimination
Agglutination, precipitation, complement fixation
Antibodies
IgM: first type of antibody secreted during
a primary immune response (promotes
agglutination or clotting)
IgG: major type of antibody secreted
during a secondary immune response
IgE: type most associated with allergic
reactions (promotes release of histamine)
Antibodies
IgA: this is the antibody found in most
abundance in bodily secretions such as saliva
and mother’s milk
IgD: this antibody serves as a B cell surface
receptor.
Soluble antibodies are involved in the following
– Cause clotting
– Can bind active sites on toxins
– Tag foreign microbes for destructions
Antibodies
IgM and IgD are the first antibodies expressed
by a B cell
Each B cell has ~ 100,000 IgM or IgD receptors
on its surface
These antibodies can bind free Ags whereas T
cell receptors can only bind to Abs when they
are presented by Ag presenting cells (discussed
later)
Antibodies
Binding the IgM or IgD on the B cell surface
provokes a primary immune response resulting
in secretion of IgM, B cell division, and clonal
expansion
Secretion of the IgM Abs stimulates the
activation of the complement system
IgG Abs are then produced and promote
phagocytosis
Antibody Response Graph
B Cell Maturation
Stem cell
Pro- B cell
Pre B cell
Immature B cell
mature B cell
During this time of development the Ab/Ag
specificity is being determined through a
process of random genetic recombination. Also
undergoes a process of negative selection to
screen for self versus non self molecules.
During the immature B cell stage: if the antigen
receptor matches with a self antigen the cell dies
by apoptosis called Clonal Deletion
B Cell Maturation and Function
When antigen binds to the B cell receptor,
the B cell is activated and begins to
undergo clonal expansion, which results in
the proliferation of exact duplicates of the
original B cell.
When B cells are mature the must
undergo a process to determine self
tolerance. This process is Ag dependent.
Humoral Immunity Summary
Involves the production of Abs that circulate in
the blood and lymph to defend against free
bacteria, toxin, and viruses
Involves B cells that eventually differentiate into
plasma cells or memory cells
Also requires the use of Helper T cells and
certain cytokines such as IL-2
Plasma cells produce antibodies while memory
cells wait for re-exposure
Antibodies tag foreign microbes for destruction
through several processes
Cell Mediated Response Overview
Involves direct killing of infected cells via TC cells
Does not involve the production of Abs
Requires both the activation of TH cells and TC
cells
Some cells will become effector cells and some
cells will become memory cells to wait for reexposure
Most important cell is the TH cell
Overlaps with Humoral Response
T Lymphocytes
Originate in the bone marrow but mature in the
thymus
Stored in the secondary lymphatic tissue
Basis for Cell Mediated immunity
Lifespan: resting 1-3 weeks, activated 3-4 days,
memory years/lifetime
Respond to specific Ag and cancer cells
Do not produce Abs
2 Primary types: cytotoxic and helper T cells
T Cell Maturation
Stem Cell
Pro T cell
Pre T cell
Double positive T cell
Double positive alpha beta TCR T
cell
Single positive T alpha beta TCR cell
During this time of development T cell receptor (TCR)
specificity is being determined
Undergoes process of both positive and negative
screening for productive gene arrangement, self versus
non-self molecules, and appropriate CD surface protein
molecules
CD 8 = Cytotoxic T cell, CD 4 = Helper T cell
Stem Cell differentiation
Stem cells
originate in
the bone
marrow
Antigens
Elicit an immune response
2 general types exist
– Exogenous: foreign from outside the host
– Endogenous: foreign from within the host
Viruses, bacteria, fungi, protozoa, and
parasites are all antigens
Antigenic determinants = epitope
Antigens
Chemical composition are proteins and
large polysaccharides (carbs)
Proteins make the best immunogens due
to their high MW and structural complexity
Polysaccharides (carbs or sugars) are OK
immunogens but their small size make
them less effective than proteins
Antigens
Lipids are inferior antigens because of
their relative simplicity and lack of
structural stability
Nucleic acids are poor Ag due to lack of
molecular flexibility and rapid degradation
Antigen Receptors
The way that B cells and T cells recognize
specific molecules and trigger an immune
response
Plasma membrane bound
All antigen receptors on a B cell or T cell have
the same specificity
Determined by random genetic events
– Occurs before any contact w/foreign antigen is made
– Allows for an enormous variety of B and T
lymphocytes
Autoimmunity
Immune system fails to distinguish self
from non self producing autoantibodies
and cytotoxic T cells that attack and
damage the body’s tissues
May be caused by a virus replicating
within a host cell or faulty T cells or
antigen which closely resembles self Ag
(example strep infection in heart valves)
Autoimmunity diseases and conditions
Cancer of the lymph nodes: when lymphocytes
undergo a mutation and multiply out of control
Rheumatoid arthritis: involves the joints, RF
factor is test method
Grave’s disease: hyperthyroidism, affects young
women, goiter is common side effect as well as
exophthalmos (protrusion of the eyes)
Pernicious anemia: mucous lining of stomach
does not secrete protein called intrinsic factor
which is needed for B12 absorption resulting in
anemia
HIV infection: reverse transcription coverts viral
RNA into DNA