3. Introduction
â˘Immunology is the science that is concerned
with the immune response to foreign challenges.
â˘Immunity (derived from Latin term immunis,
meaning exempt), is the ability of an organism to
resist infections by pathogens or state of
protection against foreign organisms or
substances.
â˘The array of cells, tissues and organs which
carry out this activity constitute the immune
system.
4. â˘Refers to the resistance exhibited by the host
towards injury caused by microorganism and
their products;
â˘Protection against infectious diseases
â˘Distinguishes self from non-self
â˘Eliminate potentially destructive foreign substances
from body
â˘Immunity to microorganism is usually indicated by the
presence of antibody to that organism.
â˘Immunity is generally specific to a single organism or
group of closely related organism.
â˘There are two basic mechanism for acquiring immunity,
they are active and passive immunity.
5. â˘Active immunity is protection that is produced by
the persons own immune system. This type of
immunity is usually permanent.
â˘Passive immunity is protection by products
produced by an animal or human transferred to
human, usually by injection.
â˘Passive immunity often provides effective
protection, but this disappears with time, usually
within weeks or months.
6. â˘Immunity is classified into two types:
1. Innate immunity
i. Species
ii. Racial
iii. Individual
2. Acquired immunity
I. Active
i. Natural
ii. Artificial
II. Passive
i. Natural
ii. Artificial
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8.
9. â˘Innate immunity (natural/native) is present
since birth and consists of many factors that
are relatively nonspecific that is, it operates
against almost any foreign molecules and
pathogens.
â˘It provides first line defense against
pathogens.
â˘It is non specific to any one pathogen but
rather acts against all foreign molecules and
pathogens.
â˘It also does not rely on previous exposure to
a pathogen and response is functional since
birth and has no memory.
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20. â˘Physical barriers are the first line of defence against
microbes. It includes skin, mucous and mucous
membrane. Most organisms and foreign substance
cannot penetrate intact skin but can enter the body if the
skin is damaged. Secondly, the acidic pH of sweat and
sebaceous secretions and the presence of various fatty
acids and hydrolytic enzymes like lysozyme inhibit
growth of most microorganism. Similarly, respiratory
and gastrointestinal tracts are line by mucous
membranes. Mucus membranes entraps foreign
microbes. The respiratory tracts is also covered by cilia,
which are hair like projections of the epithelial-cell
membranes. The synchronous movement of cilia
propels mucus-entrapped microorganism out of these
tracts.
21. â˘Similarly, conjunctiva is a specialized mucus-
secreting epithelial membrane that lines the
interior surface of the each eyelid.
â˘It keep moist by the continuous flushing action
of tears (lacrimal fluid). Tears contain lysozyme,
lactoferrin, IgA and thus provide chemical as
well as physical protection.
â˘In case of innate immune response several
antimicrobial chemicals and phagocytic cells
provide protection against pathogens.
22.
23. â˘Chemical mediator, variety of chemical
mediate protection against microbes during the
period before adaptive immunity develops.
â˘The molecules of the innate system include
complement proteins, cytokines, pattern
recognition molecules, acute-phase proteins,
cationic peptides, enzyme like lysozymes and
many others.
24. â˘Complement proteins are soluble proteins/
glycoproteins that are synthesized by liver and circulate
in the blood and extracellular fluids.
â˘They were originally identified by their ability to
amplify and complement the action of antibodies; hence
the name complement.
â˘It also bridge innate and adaptive immunity and
removes immune complexes.
â˘The complement system is composed of over 30 serum
proteins.
â˘Activation of complement proteins in response to
certain microorganism results in a controlled enzymatic
cascade, which target membrane of pathogenic
organism and leads to their destruction.
25. â˘Cytokines term is a generic term for any low
molecular weight soluble protein or glycoprotein
released by one cell population which act as an
intercellular mediator.
â˘It includes monokines, lymphokines, interleukins,
inerferons and others.
â˘Cytokines are required for immunoregulation of both
innate as well as adaptive immune responses.
â˘Interferons are cytokines made by cells in response to
virus infection, which essentially induce a generalized
antiviral state in surrounding cells.
â˘Chemokines are small, positively charged secreted
proteins that have a central role in guiding the
migrations of various type of WBC.
26. â˘Pattern recognition molecules, many molecules
involved in innate immunity have the ability to
recognize Pathogen-Associated Molecular Pattern
(PAMP) for the initial detection of microbes.
â˘PAMPs are micro-specific molecular signatures.
â˘PAMPs are recognized by Pattern-Recognition
Receptors (PRRs).
â˘Mammals have several classes of PRRs including Toll-
like receptors (TLRs), RIG-I-like receptors (RLRs),
Nod-like receptors (NLRs), AIM2-like receptors
(ALRs) and C-type lectin receptors (CLRs).
â˘TLRs were the first to be identified, and are the best
characterized.
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29. â˘Cellular defenses, many specialized cell type like
neutrophils, macrophages, monocytes, natural killer
cells (NK cells) participate in innate host defense
mechanisms.
â˘Once pathogen evades physical and chemical barriers,
these specialized cells play important role in protection.
â˘Phagocytosis is a fundamental protective mechanism
carried out by these cell types, neutrophils,
macrophages, monocytes and dendritic cells.
â˘In vertebrates, macrophages reside in tissues throughout
the body. Macrophages are long lived cells, which
patrol the tissues of the body.
30. â˘The second major type of phagocytic cells in
vertebrates, the neutrophils, are short lived cells which
are abundant in blood but are not present in normal
healthy tissues.
â˘Phagocytosis is the ingestion of invading foreign
particles, such as bacteria by individual cell.
â˘Phagocytosis may enhanced by a variety of factors
collectively referred to as Opsonins (Greek word
meaning âprepared food forâ) which consists of
antibodies and various serum components of
complement.
â˘The process by which particle more susceptible to
phagocytosis is called opsonization.
â˘After ingestion it forms phagosome, which fuses with
lysosomes forming the phagolysosome.
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33. â˘Inflammatory barriers is an important nonspecific
defense reaction to cell injury.
â˘The hallmark signs of inflammatory are pain, redness
(erythema), swelling (edema) and heat.
â˘Each of these result of specific changes in the local
blood vessels.
â˘Erythema is caused by increased vascular diameter,
which leads to increased blood flow, thereby causing
heat and redness in the area.
â˘The blood vessels become permeable to fluid and
proteins, leading to local swelling and an accumulation
of blood proteins that aid in defense.
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35. â˘Antigen specificity: It is the ability to
discriminate among different epitopes/antigens.
â˘Immunologic memory: It is the ability to recall
previous contract with a foreign molecule and
response to it in a learned manner-that is, with a
more rapid and larger response.
â˘Diversity: The ability to respond to different
epitopes even if the individual has not previously
encountered them.
â˘Self/non-self recognition: It is the ability to
recognize and respond to molecules that are
foreign and to avoid making a response to those
molecules that are self (self tolerance).
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43.
44. Immune response of adaptive immunity
â˘There are two arms (branches) of acquired
immunity, which have different sets of participants
and different purposes but one common aim: to
eliminate antigen.
â˘Of this two arms of the acquired immune response,
one is mediated mainly by B-cells and circulating
antibodies, a form of immunity which is referred to
as humoral immunity (the word humors was
formerly used to define body fluids).
45. â˘The other is mediated by T-cells, which, do
not synthesize antibody but instead synthesize
and release various cytokines that affect other
cells.
â˘Hence, this arm of the acquired immune
response is termed cellular or cell-mediated
immunity.
46. Innate and adaptive immunity are not independent
⢠The innate and adaptive immunity operate in cooperative
and interdependent ways. They cooperate in many ways;
47. â˘The cells responsible for both non-specific and
specific immunity are the leukocytes or white
blood cells.
â˘All leukocytes arise from a type of cell called
the hematopoietic stem cell.
â˘A hematopoietic stem cell is multipotent cell.
â˘During hematopoiesis, hematopoietic stem cell
differentiates along one of the two pathways
â˘Lymphoid progenitor cell
â˘Myeloid progenitor cell
Cells of immune system
48.
49. â˘Responsible for adaptive immune response
â˘Lymphocytes are mononuclear leukocytes (20-40% of
total WBC)
â˘Occurs in large number in lymph and in lymphoid
organs such as the thymus, lymph nodes, spleen and
appendix.
â˘Up to 99% of lymphocytes cell in lymph.
â˘Three main types;
⢠B-lymphocytes (B-cells)
⢠T-lymphocytes (T-cells)
⢠Natural Killer (NK cells) cells
Lymphoid progenitor
50. â˘Matures in the bone marrow in mammalian species
â˘Expresses membrane bound antibody
â˘After interacting, it differentiates into antibody
secreting plasma cells and memory cells
â˘Only cell type capable of producing antibody
molecules
â˘Central cellular component of humoral immune
responses
â˘Serves as Antigen Presenting Cells (APCs)
B-lymphocytes (B-cells)
51. â˘Arise in bone marrow
â˘Maturation in thymus gland
â˘T-cells do not make antibodies
â˘Performs various effectors function when APC
bring antigen into secondary lymphoid organ
â˘Helps in eliminating APCs, cancer cells, virus-
infected cells or grafts which have altered self-
cells
â˘Helper T-cells are crucial for defense against
both extracellular and intracellular pathogens
T-lymphocytes
52.
53. Properties B-cells T-cells
Origin Bone marrow Bone marrow
Maturation Bone marrow Thymus
Expression of Ag
receptors
Bone marrow Thymus
Differentiation In lymphoid tissue Lymphoid tissue
Surface Ig Present Absent
Immunity Humoral Cell mediated
Secretory product Antibodies and Cytokines Cytokines
Receptos Present TCR on membrane
54. â˘NK cells are neither T-cells nor B-cells
â˘Plays role in destroying cells infected with
intracellular pathogens
â˘5-10% of total lymphocyte population
â˘NK cells destroys target cell not by phagocytosis
but by releasing biologically potent molecules
Natural killer cells (NK cells)
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56. â˘Bone marrow derived cells
â˘Rises from both the myeloid and lymphoid
â˘Dendritic cells are classified into;
â˘Langerhans cells
â˘Intestinal dendritic cells
â˘Myeloid dendritic cells
â˘Lymphoid dendritic cells
Dendritic cells
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58. â˘Cells arises from a common myeloid progenitor
includes RBC (erythroid cells) as well as various
types of WBC (myeloid cells such as
granulocytes, monocytes, macrophages and
some dendritic cells).
Myeloid progenitor
59. â˘Irregular shaped nuclei
â˘Also called polymorphonuclear neutrophils or
PMNs
â˘Multilobed nucleus
â˘Granular cytoplasm (stains with both acidic and
basic dyes)
â˘50-70% of the circulating white blood cells
â˘Produced in bone marrow
Neutrophils
60.
61. â˘Bilobed nucleus
â˘Stains with acidic dyes (eosin)
â˘2-5% of WBC
â˘Motile phagocytic cells
â˘Can migrate from blood into tissue space
â˘Role is important in the defense against
protozoan and helminth parasites
Eosinophils
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63. â˘Lobed nucleus
â˘Stains with basic dye (methylene blue)
â˘Less than 1% of WBC
â˘Non-phagocytic, release substances that cause
an allergic responses
â˘Includes histamine, prostaglandins, serotonin
and leukotrienes
â˘Posses high affinity receptors for one type of
antibody, known as IgE.
Basophils
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65. â˘Mast cell precursors are formed in bone marrow
and released into the blood in an undifferentiated
state, until they reach the tissues
â˘Large number of cytoplasmic granules
containing histamine
â˘Mast cell and Basophils play role in allergic
responses
Mast cells
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67. ⢠Phagocytes derived from blood monocytes
⢠Monocytes migrates into tissue to response to infection
can differentiate into specific tissue macrophages
⢠Monocytes is small, spherical cell with few projections,
abundant cytoplasm and many granules
⢠Migration of monocytes from blood to various tissues,
which undergo differentiation and all will play role of
phagocytosis, including;
⢠Kupffer cells, in liver
⢠Alveolar macrophages, in the lungs
⢠Splenic macrophages, in the white pulp
⢠Peritoneal macrophages, free-floating in peritoneal fluid
⢠Osteoclast, in bone
⢠Mesangial cells, in kidney, and
⢠Microglial cells, in the CNT
Macrophages
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70.
71. â˘Primary lymphoid organs
â˘Bone marrow
â˘Thymus
â˘Secondary lymphoid organs/tissues
â˘Spleen
â˘Lymph nodes
â˘Mucosa associated lymph tissue (MALT)
Organs involved in the adaptive
immune system
72. ⢠Adaptive immune response arise as a result of exposure
of foreign compounds. The compounds that evokes the
response is referred to as antigen.
⢠An antigen is any agent capable of binding specifically to
T-cell receptors (TCR) or an antibody molecules
(membrane bound or soluble).
⢠An ability of a compound to bind with an antibody or a
TCR is referred to as antigenicity.
⢠Functional distinction between the term antigen and
immunogen
⢠An immunogen is any agent capable of inducing an
immune response and is therefore immunogenic.
⢠All immunogens are antigens, but not all antigens are
immunogens.
Antigen
73. 1. Foreignness
2. Size
3. Chemical complexity (Eg. Homopolymer of
poly-gamma-D-glutamic acid)
4. Dosage and route of administration
Requirement for immunogenicity
97. â˘Ag-Ab interaction is highly specific and occurs in a
similar way as biomolecular association of an
enzyme-substrate.
â˘The binding between antigens and immune
components involves weak non-covalent
interactions.
â˘The binding forces are weak and reversible and
consists mainly of;
⢠Van der waals forces
⢠Hydrogen bond
⢠Electrostatic forces (Ionic bond)
⢠Hydrophobic forces
98.
99. â˘The smallest unit of antigen that is capable of
binding with antibodies is called an antigenic
determinant (or epitope)
â˘The corresponding area on the Ab molecule
combining with the epitope is called paratope
â˘The number of epitopes on the surface of an
antigen is its valence
â˘The valence determines the number of antibody
molecules that can bind with the antigen at one
time.
â˘Monovalent and Polyvalent
100.
101. â˘The intrinsic association constant that characterizes
the noncovalent interaction between single antigen
binding site of an antibody (paratope) with an epitope
is termed as affinity.
â˘Avidity is used to denote the overall binding between
antibodies and the multivalent antigen.
â˘So, when complex Ag having multiple repeating
epitopes, are mixed with Ab having multiple binding
sites the interaction of such type between multivalent
Ab and Ag is called, the Avidity.
Affinity and Avidity
102.
103.
104. â˘Although Ag-Ab reaction is very specific, sometimes
antibodies elicited by one antigen can cross-react with
an unrelated antigen.
â˘An immunologic reaction in which a particular
antibody or T-cell receptors react with two or more
antigens that posses a common epitope is called a
cross-reaction.
â˘Another form of cross-reaction is seen when
antibodies or cells with specificity to one epitope
bind, usually more quickly, to another epitope that is
not quite identical but has a structural resemblance to
the first epitope.
Cross-reactivity
105.
106.
107. 1. Affinity: Higher the affinity of the Ab for the Ag,
the more stable will be the interaction
2. Avidity: Reaction between multivalent antigens
and multivalent antibodies are more stable
3. Antigen to antibody ratio: The ratio between Ag
and Ab influences the detection of Ag-Ab
complexes because the size of complexes formed is
related to the concentration of the antigen and
antibody.
4. Physical form of the antigen: When the Ag is
particulate, the reaction of an antibody with the Ag
can be detected by agglutination of antigen.
Factors affecting Ag-Ab interaction