introduction to immunology
TRANSCRIPT
I. EVOLUTION OF THE IMMUNE SYSTEM Phylogeny of vertebrate and
invertebrate immunity (see Fig. JL-1 and Fig. JL-2)
• Self vs not-self:• Graft rejection:• CMI - humoral immunity:• Bi-functional system• Epithelium from gills of fish-Lymphoid
Organ
II. HISTORICAL PERSPECTIVES
•immunis•variolation•vaccine•2. Vaccination•1718 - Lady Mary Wortley Montagu•1789 - Edward Jenner•>100 years later - Louis Pasteur
1. Concepts of immunity
Exp. I. Vaccine vs fowl cholera“Serendipity”Attentuation of virulent cultures
Exp. II. Vaccine vs Bacillus anthracis (1881)Attenuated bacillus culturesimmunized sheep
Exp. III. Immunizing human against rabiesJoseph MeisterEthics?
3. Discovery of humoral immunity and Cellular immunity
•cellular immunity•phagocytosis•concept of cell-mediated•immunity (CMI)•*Nobel Prize for Metchnifoff in 1908
1883 - Metchnikoff
1890 - • von Behring* &
Kitasato • in serum - humors• humors =
antibodies• humoral
immunity • *Nobel Prize for
von Behring in 1901
•1900 - Paul Ehrlich•Side chain receptors•Ag binding•Cells induced•more side chains produced
Selective Theory
•1930-1940 - Breinl & Haurowitz •popularized by Linus Pauling•Ag as template•Ab would fold, assumes•configurations complementary•to that Ag•more Ab made
Instructional theory
1950 - Clonal Selectional theory (Fig. 1-11) Burnet, Nils Jerne, Talmadge & Macfarlane
4. Early theories of Immunity How is specificity achieved?
AntigenAntibody
Definition:
The immunology may be define as the branch of Animal Science which deals with the defense mechanism adopted by the host body against any invading pathogens
Resistance against infectious disease agents was the principal concern of bacteriologists and pathologists, establishing the basis of classical immunology in the latter half of the 19th and early 20th centuries.
What immune System does?
Specifically
recognizes
selectively
eliminates
displays a long-term memory
Immune
System
Effectively Attack
Pathogens are always every where
Environme
nt
It is Environment which decides weather disease will occur or not…………………
Host Pathoge
ns
Environment
Interaction
Diseases
metabolism
Vertebrates are protected by a dual immune system known as cell-mediated immunity and humoral immunity
Immune System
Cellular
Specific
Nonspecific
Humoral
Specific
Nonspecific
Nonspecific Cellular Response
Specific Cellular
Nonspecific Humoral
Specific Humoral
Who do it?
Cells: Macrophages, Monocytes, Polymarphonucleocyts
T-Lymphocytes
Acute phage proteins, like CRP, Ceruloplasmin, Transferrine Lysozymes etc
Antibodies (Immunoglobuline) i.e. IgA, IgD, IgE, IgG, IgM
What they do?
Phagocytosis, Apoptosis, Kiiling by Cytotoxic Lymphocytes
The whole components cause hindrence in establishment of pathogenic gr
Form Ag-Ab complex to neutralized the harmful components
Components of immune system
Location of Lymphoid Organs in human Body
Lymphoid Organs: Classification
Lymphoid organs
central or primary
Lymphocytes, monocytes and granulocytes derive from precursor
stem cells in the bone marrow.
peripheral or secondary
Immune cells includes:
Lymphocytes,
Natural killer cells
Mononuclear
phagocytes,
Dendratic Cells,
Eosinophils,
Basophils, and Neutrophils.
Cells in Immune Response
Granulocytes Cells with various types of
granules
Agranulocytes Cells without granules
Eosinophils Stain with acidic dyes
Lymphocytes
BasophilsSatin with basic dyes
Monocytes
NeutrophilsStain with neutral dyes
Organization of the Immune System
Immune System
Nonspecific immunity includes mechanisms that resist a variety of threatening agents or
conditions.
Specific immunity involves mechanisms that recognize specific threatening agents and respond by
targeting their activity against these agents--and these agents
only.
Nonspecific Immunity :
It do not act on one or two
specific invaders, but rather provide
a more general defense by simply acting against any thing recognized
as not self
Specific resistanc
e Refers to a phenomenon in which genetic characteristics common to a particular kind of organism, or species, provide defense against
certain pathogens.
For example, humans do not have to worry about getting Dutch Elm Disease or canine
viral distemper.
Usually, species resistance in humans results from the fact
that our internal environment is not suitable for certain
pathogens.
Mechanical and Chemical BarriersOH- T-136 Nonspecific Defenses
•Often called the first line of defense
Internal environment of the human body is protected by a continuous mechanical barrier formed by the cutaneous membrane (skin) and mucous membranes.
•Sebum--contains pathogen-inhibiting agents. •Mucus--pathogens may stick and be swept away. •Enzymes--may hydrolyze pathogens. •Hydrochloric acid--may destroy pathogens.
Besides forming a protective wall, the skin and mucous membranes operate various additional immune mechanisms.
InflammationAn inflammation is a more or less coordinated series of responses by the body to injuries and infections.
The characteristics of the inflammatory response are
swelling,
These cause …
When tissue is injured or invaded by microbes, a series of more or less
predictable events ensues.
A series of reactions in the tissue itself which induces the activation of a number
of proteolytic enzymes including plamin, fibrin,
kallikrein, and complement.
localized increases in vascular permeability, •smooth muscle contraction•and production of chemotactic molecules like some fragments of the complement proteins (C3a, C5a)
Pathogensdamages of tissue triggers the release of mediators from cells such as mast cells found in connective tissue.
These inflammation mediators include:
Histamine, Kinins, Prostaglandins,
Many of these mediators are substances that attract white blood cells to the area by a process called chemotaxis.
These chemotactic molecules lure …
…various cell types out of the blood stream, by binding to specific receptors on their cell surface and inducing a migratory behavior out of the blood stream into the tissues. • The first cells to extravasate are neutrophils • followed subsequently by monocytes (macrophages that
haven't yet made a commitment) • and lymphocytes.
Phagocytosis Phagocytosis is the ingestion and destruction of microorganisms or other small
particles by phagocytes. The most numerous types of phagocytes are the neutrophils and the macrophages.
Macrophages are phagocytocytic monocytes that have grown to several times their normal size after migrating out of the blood stream.
Natural Killer Cells Derivation and Distribution of Lymphocytes ▪ Are a group of lymphocytes that kill many types of tumor cells and cells
infected by different kinds of viruses. ▪ Generally kill cells by releasing enzymes that lyses the pathogen's cell
membrane or protein coat. Interferon
▪ Several types of cells, if invaded by viruses, respond rapidly by synthesizing the protein interferon and releasing some of it into circulation. ▪ Interferon proteins interfere with the ability of viruses to cause disease by
preventing the viruses from multiplying in the cell. ▪ Three (3) major types of interferon:
▪ Leukocytes interferon ▪ Fibroblast interferon ▪ Immune interferon
Complement ▪ Is the name given to each of a group of about twenty (20) inactive enzymes in
the plasma. ▪ Are activated in a cascade of chemical reactions triggered by either specific or
nonspecific mechanisms. ▪ The complement cascade causes lysis of the foreign cell that triggered it.
IV. ACQUIRED IMMUNITY
4 characteristics:
Antigenic specificity Diversity Memory
Self / non-self
recognition
Adaptive Heightened response
1. Cells of the immune system
- developed from hematopoietic stem cells Pluripotent
a) B lymphocytes - mature in bone marrow
unique Ag-binding surface receptors - Abs
encounter Ag
Memory cells
Plasma cells
Secret Ab
b) T lymphocytes - mature in thymus
have unique CD
surface Ags
once mature, express TCRs -
heterodimers of a & b polypeptid
es
bind processed Ag-MHC complex
Memory cells
Effector T cells
c) Antigen presenting cells (APC’s)
Macrophages
Dendritic cells B-Cells
Secrete cytokines
or exert killing function
2-Functions of humoral and cell-mediated immune response
antigen recognition
antigen processing and presentation (Fig. JL-3)
role of MHC
B cell specificity
T cell specificity
Generation of diversity
3. Clonal selection & expansion (Fig. 1-11)
stimulation due to interaction with antigens
proliferation of particular clones
provides diversity & specificity
4. Primary (1°) & secondary (2°) immune response (Fig. 1-12)
1° response - long lag phase,
modest level
2° response - shorter lag phase,
higher (heightened) level
B cells - produce AbsTc cells (CTLs)- lyse virus infected cells
TH cellsAPCs
Antigen processing and presentation by MHC molecules
Overview of Specific Immunity
Specific immunity involves mechanisms that recognize specific threatening agents and respond by targeting their activity against these agents; and these agents only.
These mechanisms often
take some
time to recognize
their targets
and react with
sufficient force to
overcome the
threat.
As in any body system, the work of the immune system is done by cells or substances made by cells.
Primary types of cells involved in nonspecific immunity.
The primary types of cells involved in specific immunity are: T-cells B-cells
•Specific immunity is orchestrated by two different classes of lymphocytes.
The various types of specific immune mechanisms attack specific agents that the body recognizes as "not self".
•Lymphocytes are formed in red bone marrow and are derived from primitive cells called stem cells. OH T-135 Derivation and Distribution of Lymphocytes
Production of Lymphocytes
Stem cells destined to become lymphocytes follow two developmental paths and differentiate into two major classes of lymphocytes. • B-lymphocytes or B-cells • T-lymphocytes or T-cells
B-cells do not attack pathogens themselves but, instead produce antibodies that attack the pathogens or direct other cells, such as phagocytes, to attack them. • B-cell mechanisms are often
classified as antibody-mediated-immunity.
B-CELLS AND ANTIBODY-MEDIATED IMMUNITY
First Stages in the Development and Activation of B-Cells: B-cells start their development in the embryonic yolk sac, then the red marrow or fetal liver.
By the time a human infant is a few months old, its pre-B-cells have completed the first stage of
development.
Are then known as inactive B-cells.
Inactive B-cells synthesize antibody molecules but secrete few if any of them.
Instead, they insert on the surface of their plasma
membranes perhaps 100,000 antibody molecules.
The combining sites of these surface antibody molecules are now ready to serve as
receptors for a specific antigen if it comes by.
After being released from the bone marrow, inactive B-cells circulate to the lymph nodes, spleen, and
other lymphoid structures.
Second Stage of B-Cell Development :Occurs when the inactive B-cells become activated.
Activation of a B-cell must be initiated by an encounter between an inactive B-cell and its specific antigen.
The antigen binds to these antibodies on the B-cell's surface.
Antigen-antibody binding activates the B-cell triggering a rapid series of mitotic divisions.
By dividing rapidly, a single B-cell produces a
clone.
Some of them become differentiated to form
plasma cells.
Others do not differentiate completely and remain in
lymphatic tissue as memory B-cells.
Plasma cells synthesize and secrete large amounts of
antibody.
Memory B-cells do not themselves secrete antibodies, but if they are later exposed to the antigen that
triggered their formation, memory B-cells become plasma cells and the plasma cells secrete antibodies
that can combine with the initiating antigen.
The ultimate function of B-cells is to serve as ancestors of antibody-secreting plasma
cells.
Structure of Antibody Molecules Chemical Structure of Immunoglobin G
Antibodies are proteins of the family called immunoglobulins. Each immunoglobulin molecule consists of four (4) polypeptide chains joined together by disulfide bonds (S-S)
Two (2)
heavy
chains.
Two (2)
light chains.
Each polypepti
de chain is
folded to form globular regio
ns that are
joined
together in
such a
way that the
whole
molecule is Y-shaped.
Each chai
n has a
V (variable) regio
n, whic
h has a markedly different amin
o acid sequence
in different antibodies, and a C
(constant) regio
n, which is essentiall
y identical in
different antibodies
of the
same class
.
The variable
regions are the
antigen-
binding
sites of
the antibody; henc
e each antibody monomer has two
binding
sites.
OH (b)
Enlargement
of an antigenic determina
nt bound to an
antigen-
binding
site.
OH (c)
Compute
r generate
d image of
antibody
structure.
Each tiny
colored
dot (sphere)
represents
an individual amino acid of
the polypeptide chain.
Each of us
is thought
normally to
have millions of
different kinds of
antibody
molecules
in our bodies.
Each of
these
has its own
uniquely shaped combining sites.
It is this
structura
l feature
that
enables
antibodies to recognize
and combine with
specific
antigens, both of
which are crucial first
steps in
the body's
defense
against
microbes and
other foreign
cells.
Classes of Antibodies There are five (5) classes of antibodies
identified by letter names as immunoglobulins M, G, A, E, and D.
Ig M (Immunoglobulin M) Is the antibody that immature B cells
synthesize and insert into their plasma membranes.
Is the predominate class of antibody produced after initial contact with an antigen in the blood.
Ig G (Immunoglobulin G) Most abundant circulating antibody. Normally makes up about 75% of the
antibodies in the blood. Ig A (Immunoglobulin A)
Major class of antibody present in the mucous membranes of the body, in saliva, and in tears.
Ig E (Immunoglobulin E) Minor in amount. Can produce harmful effects such as those
associated with allergies. Ig D (Immunoglobulin D)
Present in the blood in very small amounts and its precise function is unknown.
Functions of Antibodies The function of antibody molecules is to produce antibody-mediated immunity.
This type of immunity is also called humoral immunity because it occurs within the plasma. OH T-140 Humoral Immunity
Antigen-Antibody Reactions Antibodies fight disease by distinguishing non-self antigens from self antigens. Recognition occurs when an antigen's epitopes fit into and bind to an antibody molecule's antigen-
binding sites. The binding forms an antibody-antigen complex that may produce one or more effects.
▪ It transforms antigens that are toxins into harmless substances. ▪ It agglutinates antigens that are molecules on the surface of microorganisms which makes them stick together so
phagocytes can engulf them. Complement OH-T-137 Complement Activation
Is a component of blood plasma that consists of about twenty (20) protein compounds. Are inactive enzymes that become activated by the binding of an antibody to an antigen located on
the surface of a cell. By binding to these sites, complement protein becomes activated and touches off a cascade
reaction that causes cytolysis of the cell. Clonal Selection Theory
Proposed in 1959 by Sir Macfarlane Burnet Has two (2) basic tenets.
▪ The body contains an enormous number of diverse clones of cells, each committed by certain of its genes to synthesize a different antibody.
▪ When an antigen enters the body, it selects the clone whose cells are committed to synthesizing its specific antibody and stimulated these cells to proliferate and to produce more antibody.
We now know that the clones selected by the antigens consist of lymphocytes. We also know how antigens select lymphocytes--by the shape of the antigen receptors on the
lymphocyte's plasma membrane. By selecting the precise clone committed to making its specific antibody, each antigen
provides its own destruction.
T-CELLS AND CELL- MEDIATED IMMUNITY Development of T-Cells: Stimulation and Effects of T Cells By definition, T-cells are lymphocytes that have made a detour through the thymus
gland before migrating to the lymph nodes and spleen. During their residence in the thymus, pre-T-cells develop into thymocytes.
Thymocytes divide up to three (3) times/day and their numbers increase enormously in a relatively short period of time.
They leave the thymus and move into the blood and take up residence in areas of the lymph nodes and spleen called t-dependent zones. ▪ From this time on they are known as T-cells.
Activation and Function of T-Cells Each T-cell, like each B-cell, displays antigen receptors in its surface membrane. When an antigen (preprocessed and presented by macrophages) encounters a T-cell
whose surface receptors fit the antigen's epitopes, the antigen binds to the T-cell's receptors. This activated or sensitizes the T-cell, causing it to divide repeatedly to form a clone of sensitized
T-cells. The sensitized T-cells then travel to the site where the antigen originally entered the
body. There in inflamed tissue, the sensitized T-cells bind to antigens of the same kind that led to their
formation. ▪ T-cells will bind to their specific antigen only if the antigen is presented by a macrophage.
The antigen-bound sensitized T-cells then release chemical messengers into the inflamed tissues called cytokines. Names of some cytokines and their function.
▪ Chemotactic factors--attracts macrophages causing hundreds of then to migrate into the vicinity of the antigen bound, sensitized T-cells.
▪ Macrophage activating factor--causes the macrophages to destroy antigens by phagocytosing them at a rapid rate.
▪ Lymphotoxin--powerful poison that acts more directly, quickly killing any cell it attacks. Sensitized T-cells that release lymphotoxin are called killer T-cells or cytotoxic T-
cells. Types of Specific Immunity Inherited immunity--immunity to certain diseases develops before birth--also called
inborn immunity. Example--inborn resistance to diseases that affect animals--viral canine distemper.
Type of Immunity Acquired immunity
Natural immunity--Exposure to the causative agent is not deliberate. ▪ Active (exposure)--A child develops measles and
acquires an immunity to subsequent infection. ▪ Passive (exposure)--A fetus receives protection from
the mother through the placenta, or an infant receives protection by way of the mother's milk.
Artificial immunity--exposure is deliberate. ▪ Active--injection of the causative agent, such as
vaccination against polio, confers immunity. ▪ Passive--injection of protective material (antibodies)
that was developed by another individual's immune system.
How Immune Response Acts Non specific Specific Humoral Cellular Humoral Cellular
Bacterium Acute phage proteins cause hindrance/ or even kill the pathogens
By the phagocytes the host cell engulf & Destroy the pathogens
Antibodies so produced by the B- cells, form a Ag-Ab complex & deteriorate the efficiency of pathogens
Finally T-Cells proliferate into Th & CTL, and cause the elimination of pathogens
Virus
Fungus
A VERY simplified overview of an immune response
You receive a cut Bacteria enter the wound. Many are destroyed rapidly by complement and the phagocytes
recruited through acute inflammation (innate immunity). Some of the dead bacteria or their breakdown products are taken up
by the tissue resident dendritic cells. The combined action of bacterial products and cytokines (from acute
inflammation etc.) activate the tissue dendritic cells. This causes them to migrate to the local lymph node via afferent
lymphatic. Dendritic cells enter the node in the T cell areas. They become
resident there displaying their 'wares' T cells enter the node from the blood, trafficking through the T cell
area to the efferent lymph. Those which recognize the bacterial antigenic peptides displayed on the dendritic cells stop, activate, divide and differentiate; some later become memory T cells.
B cells entering nodes from the blood must cross the T rich area in transit to the B cell rich areas. The antigen-specific ones must acquire antigen too, presumably via the lymph. Then they can have their MHC-peptide complexes recognized by activated T cells and receive help.
Some become IgM secreting plasma cells. Some migrate to the B cell rich areas and form germinal centers. Here B cells proliferate and give rise to progeny with high affinity for antigen through a process called affinity maturation. The products of germinal centers become IgG,A etc plasma cells and memory B cells.