PRINCIPLES OF IMMUNE SYSTEMPRINCIPLES OF IMMUNE SYSTEM
الرحيم الرحمن اللة بسمالرحيم الرحمن اللة بسم
Immunity : Defence capacity of the body to combat
diseases counter infection.
The cells and molecules responsible for immunity
constitute the immune system.
Their collective and coordinative response to
introduction of foreign substance represent the immune
Components of immune system :
1. Innate / natural immunity
- defense mechanisms present prior to exposure to
infectious microbes or foreign molecules.
- exist since fetal development period and persist
permanently throughout life.
- create nonspecific response → nonspecific immunity
- represent the first line of defense mechanisms
against foreign invasion into the body.
2. Acquired / adaptive immunity
- defense mechanisms acquired in a certain period of
- create specific response → specific immunity.
- develop due to induction / stimulation of foreign
substance that successfully invade the body.
- foreign substances capable of inducing immune
response are called antigen.
Acquired as a result of induction & exposure to foreign
Fundamental characteristics of specific immunity :
- create immune memory → provide more effective
response in further secondary infection basic
principle of vaccination.
- create focus response to certain/fixed antigen that
invades body & eliminate/destroy it → increase
protective capacity of innate immunity.
1. Humoral immunity : is mediated by molecules (serum
proteins) which recognize and eliminate free antigens
(do not attach the cell or are not cell component)
called antibody → bind and react specifically to
2. Cellular immunity (cell mediated immunity) : is
mediated by cells T lymphocytes → recognize and
bind antigen on the cell surface or nonself antigen →
produce immune mediator or lyse/destroy such cell
Antibodies and specific T lymphocytes are potentially
transferred to naive individuals passive immunisation.
Humoral and cellular response to antigen stimulation
indicate fundamental characteristics :
The immune response is specific to a particular antigen.
The antibody or lymphocyte are able to recognize part of
protein complex or any other macromolecules. Part of
molecules recognized by specific antibody or
lymphocyte is called determinant or epitope.
The total number of antigenic specificities of the
lymphocytes in an individual lymphocyte repertoire →
estimated the capacity to discriminate 109
When a lymphocyte is stimulated by antigen → the
lymphocyte is going to proliferate yielding a specific
clone “clonal selection theory”.
The effectiveness of immune response to a particular
antigen is increasing in secondary exposure to this
antigen and so on called “immunological memory” &
mediated by “memory cells”.
4. Self limitation
Normal immune response is declining & disappearing
after a period of destimulation (stimulation is sunpended)
5. Discrimination of self from nonself
Able to discriminate foreign antigen from self
components. Lymphocytes react to foreign antigen
stimulation otherwise give no response to self molecules
or self components immune tolerance.
Failure of immune tolerance to self components →
autoimmune diseases create pathological
consequences for the sufferer.
Organs involved in immune system
Organs of immune system are classified into two groups
based on their function in immune system :
- primary (central) lymphoid organs.
- secondary (peripheral) lymphoid organs.
Immature lymphocytes are undergoing maturation to
become mature lymphocytes in primary lymphoid organs
→ becoming immunocompetent cells.
The primary lymphoid organs in mammals are :
- bone marrow B lymphocyte maturation
- thymus T lymphocyte maturation
Secondary lymphoid organs → collect antigens from
tissues or circulation & provide sites for immuno-
competent cells to interact effectively with antigens.
Lymph nodes collect antigens from intracellular fluid
of various tissues.
Lien (spleen) filtered antigen from blood/circulation →
create response to systemic infection.
Mucous associated lymphoid tissue (MALT) in gut,
respiratory tract, genitourinary tract (Peyer’s patch,
tonsils, adenoids) trapped antigens which enter via
Cells involved in specific immune system
The entire cells of specific immune system derive from
pluripotent “stem cells” in bone marrow & develop
through hematopoeisis process.
They differentiate into 2 lineages :
1. myeloid lineage produce phagocytes and other
2. lymphoid lineage produce lymphocytes.
Phagocytes are differentiated into two groups :
- monocytes able to pass away from vascular system
& transform to tissue phagocytes →
- Polymorphonuclear cells neutrophyls, basophyls,
Lymphocytes are produced in bone marrow, circulate in
blood and lymphoid system & occupy lymphoid organs.
Lymphocyte recognize & interact with antigen through its
receptor on the cell surface.
2 types of lymphocytes discriminated based on their
membrane protein marker :
B lymphocytes CD 11 marker on their surface.
T lymphocytes CD 3 marker on their surface.
Produced and develop in bone marrow. Equipped with
Ab molecules as antigen receptor; the ab receptor is
fixed in cell membrane through its Ch terminal. When
naive B cell get in contact with specific antigen it will
proliferate & differentiate to be B memory cells capable
of secreting specific antibody plasma cells.
Develop from stem cells in bone marrow. They migrate
to the thymus & differentiate to become mature
Mature T cells express “antigen binding protein” on their
surface, represent as T cell receptor (TCR) compose
of 2 protein subunits αβ or γδ, connected to each other
by disulphide bonds.
TCR recognize antigen on the cell surface in association
with (presented by) MHC (HLA) molecules.
When naive T cell contact to antigen → T cell proliferate
& differentiate to become memory and effector T cells.
Subpopulation of T cells :
Helper T cells (TH) & Cytotoxic T cells (TC)
discriminated based on their protein marker on the cell
surface → CD4 marker for TH
CD8 marker for TC
After contact with antigen TH cells develop into effector
capable of cytokine (lymphokine) secretion → activate
B cells, TC cells, phagocytic cells etc.
→ TC develop into effector which mediate cytotoxic
reactions → killing/ lysis cells expressing antigen :
- virus infected cells
- cells infected by intracellular microbes
- tumor cells
Major Histocompatibility Complex (MHC)
Membrane proteins, expressed by gene cluster &
inherited in tight linkage modes.
MHC products play important roles in antigen (Ag)
recognition by immunocompetent cells & discrimination
between self and nonself → define tissue compatibility
among individuals of the same species → called
MHC is also critical for the creation of humoral and cell
mediated immunity → TH & TC recognize Ag in
association with MHC molecules → establish antigen
repertoire which give response to TH & TC → implicate
in the susceptibility to disease & autoimmunity.
HLA code for 3 kind of molecules : HLA class I, class II
& class III.
HLA class I is coded by regio A, B and C
HLA class II is coded by regio DP, DQ and DR
each regio constitute alleles which are multiple → create
huge variation of individuals, despite of brothers or
HLA class I molecules present Ag recognized by TC →
carried by almost all nuclear cells.
HLA class II molecules present Ag recognized by TH →
carried by antigen presenting cells (APC)
macrophages, dendritic cells, B lymphocytes, etc.
Mediated by antibodies, proteins that are presence in
serum & body liquid of mammals belong to protein
serum fraction, γ globulin → immunoglobulin (Ig).
Produced and secreted by B lymphocytes that has been
stimulated by specific antigen → becoming committed
cells (sensitized B lymphocytes) and develop to plasma
Function as effector that mediate binding to free antigen
(no attachment or not part of cell components),
neutralize and eliminate such antigen away from the
Immunoglobulin molecule variations
1. Isotype variation defined by determinant present in
Ch and Cl which discriminate Ig of the same species.
2. Allotype variation defined by the variation of amino
acids in either H or L chain, coded by different alleles
→ expressed by individuals of the same species.
3. Idiotype variation defined by variation of Vh and Vl
constructing Ag binding site define the specificity of
Ig to Ag.
5 Ig classes available in all species, defined by Ig H
IgG – the predominant Ig in normal serum, constitute
70 – 75% of total Ig. Distribute intra and extra
vascular; represent dominant antibodies
accumulate during secondary immune response,
especially function as anti-toxin.
IgM – include 10% of total Ig. Present as pentamer
molecules, distribute intravascular. Represent
the predominant Ab in early response to
IgA – include 15 – 20% of total Ig. Present in dimeric
conformation, equipped with “secretory
component”, recognized as sIgA. Predominant in
mucous secret i.e. saliva, tracheobronchial secret
genitourinary mucous, etc.
IgD – less than 1% of total Ig, fixed in cell membrane of
B lymphocytes. Function as antigen receptor &
necessary for B cell stimulation to become
IgE – available in small proportion, attach to basophyl
and mast cell membrane. Involved in developing
immunity to parasites (helminthes) and
hypersensitivity disease i.e. asthma.
Phases of immune response :
1. Cognitive phase – antigen recognition through antigen
binding to specific receptor on lymphocyte surface.
B lymphocyte – bind Ag to surface Ig.
T lymphocyte – bind Ag fragment – MHC (HLA) to
2. Activation phase
- lymphocyte proliferation – clonal expansion of
specific lymphocyte to certain antigen.
- lymphocyte differentiation
B lymphocyte → secreting cells (plasma cells) →
Ab bind to free Ag (soluble Ag).
T lymphocyte → mediated killing
→ activate macrophages to kill
→ lysis of cells expressing foreign Ag or
3. Effector phase – elimination and neutralisation of Ag.
Require participation of nonlymphoid cells →
collectively recognized as effector cells.
Ag-Ab complex are phagocyted by polymorpho
nuclear & mononuclear cells (in circulation).
Ag-Ab complex activate complement system to
mediate lysis & phagocytosis of microorganisms.
Sensitized T lymphocytes secrete cytokine →
activate cytolysis & phagocytosis.