2. List of References
Essential Books
•Veterinary Immunology ,An Introduction ,Seven Edition ,Ian R.Tizard 2000
•Immunology: A Short Course. 5th Edn. Benjamani, E. Coico, R. & Sunshine G.
Wiley Liss,2003.
•Immunology. 3rd ed. Kuby, J. Freeman, 1997
3. History of Veterinary immunology
• 12 th Century the Chinese had observed that
those individuals who recovered from smallpox
• Outbreak of Rinderpest in ninth century .
• 1754 inoculation may help (Nasal discharge).
• 1798 Edward jenner demonstrate that material
frome cow pox lesion could be substituted for
smallpox in virolation
• 1879 Louis pasteur investigate fowl cholera
• 1882 Discover vacine agains Anthrax
4.
5.
6.
7. IMMUNOLOGY CONCEPT
Immunology is:
the study of host immune system from the moment o
birth and sometimes even before that, the body exists in
an environment filled with potentially harmful organisms
and agents. Over the course of thousand of years of
evolution, protective mechanism have developed in
human – animal immune system reflects many aspect of
this evolution ranging from the innate immunity afforded
by the skin and mucous membranes to the highly complex
specific response of T -cells and antibodies which
recognizes invading pathogens if they are encountered
again.
8. Immunology
Immunology is the study of immunity or protein
against infectious or other agents and conditions
arising from the mechanisms involved in
immunity. Immunity is the protection against
infectious agents and other substance.
9. There are two types of immunity,
1. Non adaptive immune response or Innate
immunity. This is the immunity that is not affected
by prior contact with the infectious agent or other
material involved and is not mediated by
lymphocytes.
2. Adaptive immune response/ specific immune
response/Acquired immunity. This is the immune
response that depends on the recognition and the
elimination of antigens specific lymphocytes.
12. Innate (Nonspecific) Immunity
• Innate immunity is the First-Line Defense
against infections, its properties
• 1- Does not improve after exposure
• 2- Has no memory
• 3- Non specific
• 4- Act within minute after exposure
13. Innate HostDefenses Against Infection
•Anatomical barriers
–Mechanical factors
–Chemical factors
–Biological factors
•Humoral components
–Complement
–Coagulation system
–Cytokines
•Cellular components
–Neutrophils
–Monocytes and macrophages
–NK cells
–Eosinophils
14. Mechanisms of Innate Immunity
A. Physical Barriers
Lines (Barriers):
1-mechanical barrier: intact skin *(keratin and epithelial
cells) provides mechanical barrier to the invading
pathogens, Movement due to cilia or peristalsis, Cough
reflex, the trapping effect of mucus and the flushing
action of tears, saliva and urine help to protect from
invaders
2. Chemical factors: Fatty acids in sebum inhibit the growth
of bacteria. Lysozyme and phospholipase found in tears,
saliva and nasal secretions can breakdown the cell wall of
bacteria and destabilize bacterial membranes.
15. 3. Biological factors: Members of the normal
floral competitively exclude pathogens
(colonization resistance) and stimulate the
host defenses.
16. B. Tissue factors:
once the infective agent cross the barrier of the
body surface, the tissue factors come into play
for body defence
• 1. The Complement System (alternative pathway
activation)
Complement proteins circulate in the blood and the
fluid that batches tissues. The major protective
outcomes of complement activation include
opsonization, lysis of foreign cells, and initiation
of inflammation.
17. 2. Lysozyme, peroxidase, enzymes, lactoferrin,
and defensins are antimicrobial substances
that inhibit or kill microorganisms
3. Secretory IgA that inhibit attachment of
gonococci and Escherichia coli to surface
epithelial cells.
18. 4. Type I Interferons: Viral infection induces the expression
of antiviral proteins known as interferons. These proteins,
called interferon- α (IFN-α) and interferon- β (IFN-β), they
induce cells in the vicinity of a virally infected cell to
prepare to cease protein synthesis in the event they
become infected with a virus (inhibit viral replication)
5. Cytokines:Low molecular weight soluble proteins and
peptides secreted by leukocytes and other cells involved
in innate immunity, adaptive immunity, and inflammation.
Cytokines include interleukins (LLs), colony-stimulating
factors (CSFs), tumor necrosis factors (TNFs),chemokines,
and interferons.
19. 6. Chemokines: Low-molecular-weight proteins
that stimulate leukocyte movement
7. Fever: occurs as a result of certain pro-
inflammatory cytokines released by
macrophages when their toll-like receptors bind
microbial products.
Fever inhibits the growth of many pathogens and
increases the rate of various body defenses.
20. Cellular mechanisms of innate
immune system
• Phagocytosis
• Is the engulfment and degradation of
microbes by phagocytic cells that secrete
cytokines and chemokines to attract and
activate other cells of the innate immune
system. The oxidative burst, producing several
highly reactive oxygen metabolites, and a
series of degradation enzymes.
21. The step of phagocytosis includes
1. chemotaxis attraction of phagocyte to the site of
infection by chemotactic agent like C5a and IL-8
2. recognition and attachment which mediated via
pattern recognition receptors (PRR) or complement
receptors
3. engulfment of particulate material into a vacuole
(phagosome) and formation phagolysosome
4. destruction and digestion: intracellular killing of
microorganism, and exocytosis.
22. • Factors Affecting Phagocytosis
1. Opsonization: coating antigen or foreign
particle with antibody or complement or both,
in order to enhance its engulfment by
phagocytic cells.
2. Solid or rigid medium
23. Inflammation
A Coordinated Response to Invasion
or Damage
• Swelling, redness, heat, pain and loss of function
are the signs of inflammation, the attempt by the
body to contain a site of damage, localized the
response, and restore tissue function.
• Apoptosis –Controlled Cell Death that circumvent
the inflammatory process.
• Apoptosis is a mechanism of eliminating self-cells
without evoking an inflammatory response.
24. The Cell of the innate Immune System
:Myeloid lineage
• There are three types of granulocytes- neutrophils,
basophila and esinophilis.
• 1. Neutrophils
Also called polymorphonuclear leukocytes account for
60% of blood leukocytes. Short lived cells produced by
bone marrow and circulate in blood stream for 6-7
hours. Neutrophils play a critical role during the early
stages of inflammation, being the first cell type
recruited from the blood stream to the site of damage
under the effect of chemoattractant substances.After
taking up microorganisms the neutrophil will die.
25. 2. Basophils and mast cells: their granules
contain vasoactive amines (like histamine)
that cause contraction of smooth muscle,
they are important in allergic reactions
3. Eosinophils: important in immunity to
parasites
26. Mononuclear Phagocytes:
• 1. Monocytes account for approximately 5-7% of
blood leukocytes,produced by bone marrow, have a
longer life span than circulating granulocytic
phagocytes. Migrate into the tissues and differentiate
into Macrophages.
Macrophages in blood can be activated by various
stimulants, including microbes and their products
(LPS), antigen-antibody complexes, inflammation,
sensitized T lymphocytes, cytokines , and injury.
Activated macrophages have an increased number of
lysosomes (increased intracellular killing activity)
27. • Functions:
1. Phagocytose microorganisms
2. Present antigens to T cells
3. cytokine production ( IL-1, which has a wide
range of activity in inflammation. Interleukin-1
participates in fever production and in
activation of lymphoid cells), TNF(
inflammatory mediator), and IL-8 chemotactic
factor
28. The name of monocyte-derived cells depends
upon the tissue they reside in:
• Liver - Kupffer cells
• Lung - Alveolar macrophages
• CNS - Microglial cells
• Bone – Osteoclasts
29. • 2
Dendritic cells: another group of
phagocytic cells with both myeloid
and lymphoid origins they are so
called for their branchlike
cytoplasmic projections. Found
mainly in the portal of entry of
microbes (e.g. skin, lung and GIT),
they are professional phagocytes.
30. Lymphocytes
Lymphocytes, which include
1. B cells, T cells are involved in adaptive immunity.
2. Natural Killer (NK) cells Non-T, non-B cells, large granular
lymphocyte (LGL) account for 5-10% of blood lymphocyte.
No classical antigen receptors. Part of the innate immune
system. Recognise and kill abnormal cells such as tumour
cells.
Directly induce apoptosis in virus infected cells by pumping
proteases through pores that they make in target cells.
Similar cytolytic mechanisms to cytotoxic T lymphocytes
(CTL)
Involved in antibody-dependent cellular cytotoxicity (ADCC)
31. Cells of Immune System
Stem cells of bon marrow
differentiate into
cytokines (IL-&, IL-3)
colony stimulating factor
Lymphoid series Myeloid series
B-lymphocytes T-lymphocytes NK
monocytee-macrophages dendritic cells eosinophils mast cells
32. Hematopoiesis
All blood cells arise from a type of cell called the
hematopoietic
stem cell (HSC). Stem cells are cells that can
differentiate into other cell types; they are self-
renewing—they maintain their population level
by cell division. In humans, hematopoiesis, the
formation and development of red and white
blood cells, begins in the embryonic yolk sac
during the first weeks of development.
33. Hematopoiesis
• Begins with hematopoietic stem cells (HSC)
– Few in # in bone marrow; difficult to culture
– Pluripotent; able to produce RBC’s, WBC’s, megakaryocytes
• HSC differentiates to become:
either a) Myeloid progenitor cell
or b) Lymphoid progenitor cell
Myeloid RBC’s and WBC’s and dendritic cells
Lymphoid B and T cells and dendritic cells
35. Cell Communication
Surface Receptors bind ligands that are on the outside of the
cell, enabling the cell to detect that the ligand is present.
Adhesion Molecules
1. Adhesion molecules allow cells to adhere to other cells.
Sensor Systems: Pattern recognition receptors: receptor of
innate immune system that recognize structures called
pathogen-associated molecular pattern produced by
microbes but not mammalian cellsand essential for
survival of microbes eg. CD14 on macrophage that bind to
bacterial endotoxin and activated it.
Toll-Like Receptor:Toll-like receptor a receptor located on the
immune cell enables cells to detect molecules that signify
the presence of microbe.
36. Factors affecting innate immunity
1. Age: two extremes of life, neonate and elderly
animals are more susceptible to infectous
diseases
2. Hormonal influence, e.g. diabetes mellitus there
is high incidence of staphylococcal sepsis due to
altered metabolism and elevated level of CHO in
tissues
3. Nutrition: malnutrition predispose to bacterial
infection like T.B., septicemia
37. 2. Acquired immunity. Adaptive
immunity,
which occurs after exposure to an antigen (eg,
an infectious agent) is specific and is
mediated by either antibody or lymphoid
cells. Cells of adaptive have long-term
memory. Improve after exposure and act
effectively after several days of exposure.
Adaptive/acquired Immunity can be active or
passive natural or artificial,
38. Adaptive Immunity
Adaptive immunity is capable of recognizing and selectively
eliminating specific foreign microorganisms and molecules
(i.e., foreign antigens). Unlike innate immune responses,
adaptive immune responses are not the same in all members
of a species but are reactions to specific antigenic challenges.
Adaptive immunity displays four characteristic attributes:
• Antigenic specificity
• Diversity
• Immunologic memory
• Self/nonself recognition
41. Antigens
• Antigenicity is the ability to bind to Ig or
immune cells; an
immune response need not result
• Immunogenicity is the capacity to induce an
immune
response by foreign, complex, high molecular
weight
compounds
• Therefore an antigen may not be an immunogen
but an
immunogen is an antigen!
• Epitope Discrete site on immunogen recognised
by
immune cells
42. Components of adaptive Immune
response
1. B cells
2. T cells
3. Antigen Presenting Cells (APC)
43. Strategy of the Adaptive Immune
Response
1. Humoral immunity is mediated by B.cells; in
response to extracellular antigens, these may be
triggered to proliferate and then differentiate
into plasma cells that function as antibody
producing factories.
2. Cellular Immunity: Effector T- cytotoxic cells are
able to induce apoptosis in ‘self” cells that
present abnormal protein that signify danger.
Effector T-helper orchestrates the various
response of cellular and humoral immunity.
44. Strategy of the Adaptive Immune
Response
• The Humoral Immunity
• Humoral immunity is mediateds by B.cells; in
response to extracellular antigens, these
maybe triggered to proliferate and then
differentiate into plasma cells that function as
antibody producing factories.
45. • Cellular Immunity
• Effector T- cytotoxic cells are able to induce
apoptosis in ‘self” cells that present abnormal
protein that signify danger. Effctor T-helper
orchestrates the various response of cellular
and humoral immunity.
46.
47.
48.
49. Immunoglobulin contd……
• Terminal regions of H & L chains are the variable regions
• The variable region is the site where Ig combines with
antigen
• This region’s variability is responsible for wide range of
antigen specificity
• The 5 classes of Ig are:
– IgM
– IgA
– IgD
– IgG
– IgE
50.
51.
52.
53.
54.
55.
56.
57.
58.
59. Anatomy of the lymphoid system
Lymphatic Vessels.
Lymph, which may contain antigens that have entered
tissues, flows in the lymphatic vessels to the lymph
nodes.
• Secondary lymphoid organs
Secondary lymphoid organs are the sites at which
lymphocytes gather to contact antigens; they facilitate
the interactions and transfer of cytokines between the
various cells of the immune system.
• Primary Lymphoid Organs
1. Primary lymphoid organs are the sites where B.cells
and T.cells mature.
60. Lymphocytes
the primary cells of the lymphoid system
• Respond to:
– Invading organisms
– Abnormal body cells, such as virus-infected cells
or cancer cells
– Foreign proteins such as the toxins released by
some bacteria
• Types of lymphocytes
– T cells (thymus-dependent)
– B cells (bone marrow-derived)
– NK cells (natural killer)
60
61.
62.
63. The primary lymphoid organs
The primary lymphoid organs provide sites
where lymphocytes mature and become
antigenically committed. T lymphocytes
mature within the thymus, and B lymphocytes
arise and mature within the bone marrow of
humans, mice, and several other animals, but
not all vertebrates.
64.
65. • Bilobed Organ on Top of Heart
• Reaches Max. Size During Puberty
– 70g infants, 3 g in adults
• 95-99% Of T Cells Die in Thymus
– self reactivity or no reactivity to Ag
• Consists of Cortex and Medulla
• Rat Thymocytes Sensitive to Glucorticoids
Thymus
67. • Mucous Membranes S.A=400m2
• Mucous Membr. Most Common Pathogen Entry Site
• M.M Protected by MALT
• Organization Varies (most organized P.P, Tonsils,
appendix
• GI Tract, IEL Unique TCRs
• Lamina Propia (below epithelium) M, B cells, TH
• M Cell Allows Ag Entry, Unique Architecture
Mucosal Associated Lymphoid
Tissue (MALT)
68. secondary lymphoid
There are several types of secondary lymphoid tissue:
lymph nodes, spleen, the loose clusters of follicles, and
Peyer’s patches of the intestine, and cutaneous-
associated lymphoid tissue. Lymph nodes trap antigen
from lymph, spleen traps blood-borne antigens,
intestinal-associated lymphoid tissues (as well as other
secondary lymphoid tissues) interact with antigens that
enter the body from the gastrointestinal tract, and
cutaneous-associated lymphoid tissue protects
epithelial tissues.
69. • Multiple Afferent Lymphatics
• Cortex
– B-cells, Follicular DCs, M, GCs, Primary Follicles
• Paracortex
– TH, M, DCs
• Medulla
– Plasma Cells
• Post Capillary Venule
– Allow Lymphocyte Migration From Circuilation Into Lymph Node
• One Efferent Lymphatic
– Rich In Abs and Lymphocytes
Lymph Node
