immunity pathology point of view

1. IMMUNITY

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Immunity and immunopathology are proverbial two edges of ‘double-
edged sword’ i.e. it is a defense mechanism but it can be injurious to the
human body in a variety of ways.
• Immunity or body defense mechanism is divided into 2 types: -
Natural (innate) –
Specific (adaptive) which are interlinked to each other in their functions

3. While normal function of immunity is for body defense, its failure or
derangement in any way results in diseases of the immune system
which are broadly classified into the following 4 groups:
• 1. Immunodeficiency disorders
• 2. Hypersensitivity reactions
• 3. Autoimmune diseases
• 4. Idiopathic immune disorder
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Natural or Innate immunity It has 2 major components:
a) Humoral: complement proteins, cytokines,
b) Cellular: Neutrophils, Macrophages, and Natural killer (NK) cells,
Dendritic cells

6. AREAS OF GROWTH
B2B SUPPLY CHAIN ROI E-COMMERCE
Q1 4.5 2.3 1.7 5.0
Q2 3.2 5.1 4.4 3.0
Q3 2.1 1.7 2.5 2.8
Q4 4.5 2.2 1.7 7.0
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7. Specific or Adaptive immunity
It is specific and is characterized by antigenic specificity.
It too has 2 main components:
a) Humoral: consisting of antibodies formed by B cells.
b) Cellular: mediated by T cells.
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10. The major functions of immune system are as under:
• i) Recognition of self from non-self
• ii) Mounting a specific response against non-self
• iii) Memory of what was earlier recognised as non-self
• iv) Antibody formation
• v) Cell-mediated reactions
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Antigen (Ag):
Usually a substance, usually protein in nature, which when introduced into the
tissues stimulates antibody production.
Antibody (Ab):
A protein substance produced as a result of antigenic stimulation.
Circulating antibodies are immunoglobulins (Igs) of which there are 5 classes:
IgG, IgA, IgM, IgE and IgD.

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The antigen may combine with antibody to form antigen-antibody complex.
The reaction of Ag with Ab in vitro may be primary or secondary
phenomena, the secondary reaction induces a number of processes such
as:
- Agglutination,
- Precipitation,
- Immobilisation,
- Neutralization,
- Lysis - Complement Fixation
In vivo, the Ag-Ab reaction may cause tissue damage

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ORGANS AND CELLS OF IMMUNE SYSTEM
The organs of immune system are distributed at different
places in the body. These are as under:
Primary lymphoid organs:
i) Thymus
ii) Bone marrow
Secondary lymphoid organs:
1. Lymph nodes
2. Spleen
3. MALT (Mucosa-Associated Lymphoid Tissue located in
the respiratory tract and GIT)

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The cells comprising immune system are as follows:
Lymphocytes
Monocytes and Macrophages
Mast cells and Basophils
Neutrophils
Eosinophil

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Monocytes and Macrophages
Circulating monocytes are immature macrophages and constitute about
5% of peripheral leucocytes.
• They remain in circulation for about 3 days before they enter tissues to
become macrophages

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• IMPORTANT IMMUNE FUNCTIONS OF MACROPHAGES:
• 1. Antigen recognition
• They possess cell surface receptors to several extracellular molecules:
like
• Cytokines,
• Component Of Complement (C3b),
• Selectin
• Integrins
• Fc (Constant Fragment) Of Antibody

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2. Phagocytosis:
Antigen that has been recognized by the macrophages due to availability of above
mentioned surface receptors is ready to be engulfed by the process of cell-eating
by macrophages.
3. Secretory function:
Macrophages secrete important substances as follows:
• Cytokines: IL-1, IL-2, IL-6, IL-8, IL-10, IL-12, Tumour Necrosis Factor-α
• Prostaglandins: PGE, Thromboxane-A, Leukotrienes, Cytokines and
prostaglandins which are chemical mediators of inflammation and activate
other leucocytes.

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3. Secretion of proteins involved in wound healing
e.g. Collagenase, Elastase, Fibroblast Growth Factor, Angiogenesis factor
Acute phase reactants
e.g. Fibronectin, Microglobulin, Complement Components.
4. Antigen presentation
When macrophages are unable to lyse an antigen or an organism, the next best
course adopted by them is to act as antigen presenting cells for presenting to T
cells (subtype CD4+ or CD8+ cells), or to B cells.
Accordingly, the lymphoid cell would then acts accordingly with such antigen.

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NEUTROPHILS
Polymorphonuclear neutrophils (PMNs) are normally the most numerous of the
circulating leucocytes (40-75%).
The cytoplasm of PMNs contains lysosomal granules of three types:
• Primary (Azurophilic): contain myeloperoxidase which creates antibacterial
compounds, acid hydrolases and defensins.
• Secondary granules (specific): are the most numerous type: contain
complement activators and enzymes e.g. collagenases.
• Tertiary granules: Either phosphatases or metalloproteinases

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• PMNs have similar function to those of macrophages and are therefore
appropriately referred to as ‘microphages’ owing to their role as first line of
defense against an invading foreign organism in the body.
• However, these cells have limitation of size and type of organisms to be
engulfed E.g. while they are capable of acting against bacteria and small foreign
particulate material but not against viruses and large particles

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Basophils and Mast Cells
Basophils are a type of circulating granulocytes (0-1%) while mast cells are
their counterparts seen in tissues, especially in connective tissue around blood
vessels and in sub mucosal location.
Basophils and mast cells have IgE surface receptor; thus on coming in
contact with antigen binding to IgE (e.g. allergic reaction to parasites), these
cells get activated and release granules i.e. they degranulate.

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Eosinophils
Eosinophils are also circulating granulocytes (1- 6%).
These cells play a role in allergic reactions and in intestinal helminthiasis.
The granules of eosinophils contain lysosomal enzymes, peroxidases, and
chemical mediators of inflammation (e.g. prostaglandins, leukotrienes).
On coming in contact with IgE opsonised antigen (eg. helminths), eosinophils
degranulate and release the chemicals stored in granules and incite inflammation

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• Lymphocytes
Lymphocyte is the master of human immune system.
The major lymphocyte populations: -
T and B lymphocytes
Third type: - NK (natural killer) cells (small percentage of circulating lymphocytes having the
distinct appearance of large granular lymphocytes)

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B- Lymphocytes
- undergo maturation and differentiation in the bone marrow.
T cells
- undergo maturation and differentiation in the Thymus.
During this process: They acquire certain genetic and immune surface characters which
determine their type and function. i.e., Cluster B cells differentiate into plasma cells which form
specific antibodies.
T cells get functionally activated on coming in contact with appropriate antigen. The Major
Histocompatibility complex on antigen presenting cell (eg: Macrophage) determine whether the
invading antigen is to be presented to B-Cell or T-Celler of differentiation (CD) molecules on their
surface

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Features and functions of subtypes of lymphocytes B cells:
They function in the humoral immunity component of the adaptive immune
system by secreting antibodies.
The undifferentiated B cells present surface antibodies like IgM and IgD also
known as B cell receptors (BCR) or surface antibodies.
And the differentiated B cell i.e., plasma cells secrete free antibodies into
blood plasma

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Depending upon the maturation stage of B cells, specific CD molecules appear
on the cell surface which can be identified by CD markers. Common B cell
markers are: - CD 45, 19, 20, 21, 22, 23
• T CELLS
Implicated in inciting cell-mediated immunity.
They are higher in number compared to Bcells.
Common T cell markers are CD45, CD3 Depending upon functional activity
T cells have two major subtypes:
1. T-helper (or CD4+) cells.
2. T suppressor (or CD8+) cells

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T helper cells
Abbreviated as TH cells, these cells promote and enhance the immune
reaction and are also termed as T-regulatory cells.
They carry special CD4 molecule along with CD45, CD3 on their surface
and hence are also called CD4+ cells.
CD4+ cells in circulation are about twice the number of CD8+ cells
(CD4+/CD8 ratio 2:1).

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These cells act by production of variety of cytokines (EX: INTERLEUKINS)
Depending upon the type of cytokines produced, these TH cells are further of
two subclasses:
TH 1
&2-
• TH 1 cells produce- IL-2 and interferon (IFN)-γ.
• TH 2 cells produce- IL-4, IL-5, IL-6, and IL-10.
CD4+ cells are predominantly involved in cellmediated reactions to: -
• Viral infections (e.g. In HIV),
• Tissue transplant reactions
• Tumour lysis

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• T suppressor cells
Abbreviated as TS cells, they suppress immune reactions but are cytotoxic
and actually destroy the invading antigen; hence are also termed as cytotoxic
T lymphocytes (CTL) /Killer T cell.
These cells carry special CD8 molecule along with CD45, CD3 molecules on
their surface and hence are also called CD8+ cells.
CD8+ cells in circulation are about half the number of CD4+ cells.
CD8+ cells are particularly involved in - Destroying cells infected with viruses,
Foreign cells and Tumour cells

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NATURAL KILLER (NK) CELLS
• They are the circulating large granular lymphocytes.
• These lymphocytes do not have B or T cell markers (CD45), nor are these
cells dependent upon thymus for development unlike CD4+ and CD8+ T
cells.
• NK cells carry surface molecules of CD2, CD16 and CD56, but negative for
T cell marker CD3
NK cells are part of the natural or innate immunity.
• These cells recognize antibody-coated target cells and bring about killing of
the target directly.
• This process is termed as Antibody-dependent Cell-mediated Cytotoxicity
(ADCC

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• ANTIGEN PRESENTING CELL
An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen
complexed with major histocompatibility complexes (MHCs) on their surfaces; this
process is known as antigen presentation.
Examples:
1- Dendritic cells
2- Macrophages
3- B cells
Almost all cell types can serve as some form of APC.
They are found in a variety of tissue types. Professional antigen-presenting cells,
including macrophages, B cells and dendritic cells, present foreign antigens to
helper T cells, while other cell types can present antigens originating inside the cell
to cytotoxic T cells

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The T cell recognizes and interacts with the antigen-class II MHC molecule
complex on the membrane of the antigen-presenting cell.
An additional co-stimulatory signal is then produced by the antigen-
presenting cell, leading to activation of the T cell.

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Antibodies production by B-cells
Antibodies production by B-cells takes by following ways:
1 T-Helper cell independent B-Cell Activation
2 T- Helper cell dependent B-Cell Activation by interleukins (IL-4, IL-5, IL-10, IL-13)
T-Helper cell independent B-Cell Activation
Bacterial polysaccharides and lipopolysaccharides, and some polymeric proteins, can
stimulate B lymphocytes without involvement of T-Helper cells.
T-Helper cell dependent B-Cell Activation by interleukins (IL-4, IL-5, IL-10, IL-13).
For most protein antigens, the production of antibodies by B lymphocytes is dependent on
stimulation of T-Helper cells

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Now activated, B cells participate in a twostep differentiation process that yields
both
• Short-lived plasmablasts for immediate protection (plasmablasts produce early,
weak antibodies mostly of class IgM)
• Long-lived plasma cells and memory B cells for persistent protection (Strong
antibodies
Autoimmune disease can result from abnormal B cell recognition of self-antigens
followed by the production of autoantibodies.
Autoimmune diseases where disease activity is correlated with B cell activity
include Scleroderma, Multiple Sclerosis, Systemic Lupus Erythematosus, Type 1
Diabetes, and Rheumatoid Arthriti

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• CYTOKINES
Cytokine: Any low-molecular-weight regulatory protein or glycoprotein
secreted by immune cells or other cells of the body in response to an stimuli.
Cytokines through interaction with specific cell surface receptors, regulate the
development or function of another cell.
Cytokines are proteins with specific roles in communication between cells of
the immune system

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• Presently, about 200 cytokines have been identified.
Many cytokines are referred to as “interleukins” because they are secreted by
some leukocytes and act on other leukocytes
• MODE OF ACTION OF CYTOKINES
Cytokines may act in one of the following 3 ways:
1) Autocrine when a cytokine acts on the cell which produced it.
2) Paracrine when it acts on another target cell in the vicinity.
3) Endocrine when the cytokine secreted in circulation acts on a distant target

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• TYPES OF CYTOKINES
INTERLEUKINS: (IL-1 to IL-38)
INTERFERONS: (INF- α, INF-β, INF- γ)
TUMOUR NECROSIS FACTORS: (TNF- α, TNF- β)
TUMOUR GROWTH FACTORS: (TGF- β1)
COLONY STIMULATING FACTORS: - MONOCYTE-COLONY
STIMULATING FACTOR (M-CSF) - GRANULOCYTE- COLONY
STIMULATING FACTOR (G-CSF) - GRANULOCYTE-MACROPHAGE
STIMULATING FACTOR (GM-CSF

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• INTERLEUKIN-1
IL-1 is intensely produced by tissue macrophages, monocytes, fibroblasts,
and dendritic cells, but is also expressed by B lymphocytes, NK cells,
microglia, and epithelial cells.
They form an important part of the inflammatory response of the body against
infection.
These cytokines increase the expression of adhesion factors on endothelial
cells to enable transmigration (also called diapedesis) of immunocompetent
cells, such as phagocytes, lymphocytes and others, to sites of infection

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• They also affect the activity of the hypothalamus, the thermoregulatory
center, which leads to a rise in body temperature (fever) .
• That is why IL-1 is called an endogenous pyrogen.
• Besides fever, IL-1 also causes hyperalgesia (increased pain sensitivity),
vasodilation and hypotension

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CLASSIFICATION:
Cytokine Families
1. Hematopoietin family.
2. Interferon (IFN) family.
3. Chemokine family.
4. Tumor Necrosis Factor (TNF) family
Cytokines of the hematopoietic system include
Interleukins (ILs) (IL-2, IL-3, IL-4, IL-5, IL-6, IL-6, IL-7, IL-9.)
Colony-Stimulating Factors (CSFs),
Erythropoietin (EPO) and
Thrombopoietin (TPO

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2. INTERFERONS FAMILY.
IFNs are class of proteins known as cytokines, molecules used for
communication between cells to trigger the protective defenses of the immune
system that help eradicate pathogens especially viruses.
Certain symptoms of infections, such as fever, muscle pain and "flu-like
symptoms", are also caused by the production of IFNs and other cytokines
They are typically divided among three classes:
Type I IFN, Type II IFN, and Type III IFN.
IFNs belonging to all three classes are important for fighting viral infections and
for the regulation of the immune system

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3.CHEMOKINES (Chemotactic cytokines)
Chemokines are small protein molecules that are produced by the cells of the
immune system.
These act as chemo-attractants, leading to the migration of immune cells to an
infection site so they can target and destroy invading bodies such as microbes.
Eg: The chemokines that attract Macrophages to the site of inflammation are
CCL2, CCL
Chemokines have been classified into four main subfamilies: - CXC, CC,
CX3C,CX3X

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4. TUMOR NECROSIS FACTOR FAMILY :
Also called cachexin, or cachectin
Produced chiefly by activated macrophages, although it can be produced by many other cell
types such as CD4+ Lymphocytes, NK Cells, Neutrophils, Mast Cells, Eosinophils.
TNF is able to induce fever, apoptotic cell death, cachexia, inflammation and to inhibit
tumorigenesis and viral replication
TNF is an important endogenous pyrogen, together with IL-1, it is responsible for many of the
hematological changes in septic shock.
A local increase in concentration of TNF will cause the cardinal signs of Inflammation to occur:
- Heat, - Swelling, - Redness, - Pain, - Loss of function

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A local increase in concentration of TNF will cause the cardinal signs of
Inflammation to occur:
• Heat
• Swelling
• Redness
• Pain
• Loss of function
Whereas high concentrations of TNF induce shock-like symptoms.
• The prolonged exposure to low concentrations of TNF can result in cachexia,
a wasting syndrome. This can be found, for example, in cancer patients

63. THANK YOU