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IMMUNITY

Dr Maimona
Assistant Professor
FCPS Physiology
IMMUNIT
Y

The ability of the body to resist against invading organisms or


damaging toxins is known as immunity.

Two types:

1. Innate--------- general and non specific


2. Acquired-------- powerful, specific

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Innate Immunity

1. Skin acts as barrier to microbes and viruses


2. Mucus traps foreign particles
3. Phagocytic cells (WBCs)
- Neutrophils, eosinophils
- Tissue Macrophages
4. Gastric stomach acid
5. Presence in the blood of certain chemicals
(a) lysozyme (b) basic polypeptides (c) complement complex (d)
natural killer lymphocytes that can recognize and destroy foreign
cells, tumor cells, and viral infected cells
Aquired immunity
 Depends on the presence of antibodies or the formation of activated
T lymphocytes, that attack and destroy the specific invading organism or
toxin
 acquired immunity does not develop until after invasion by a foreign
organism or toxin

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Types of acquired Immunity
1. Cell mediated immunity
• Depends upon activated T lymphocytes
• Defense against cancer cells, virus-infected cells, fungi,
parasites, & foreign cells from transplants.

• 2. Humoral immunity
• Depends on activated B lymphocytes which produces
antibodies that are dissolved in the blood plasma.
• Defense against bacteria, bacterial toxins, & viruses.

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Lymphocyte Formation

Thymosin enhances proliferation of new T cells


within the peripheral lymphoid tissues, augments
the immune capabilities of existing T cells

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Antigens
Any foreign substance that elicits an immune response
when introduced into the tissues
Generally high molecular weight>8000 Da
Less than 8000---- Haptens
Typically, proteins or polysaccharides.
Microbes are antigenic and they contain and produce
many antigens
• Antigens have specific sites that bind to antibodies
called epitopes

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B Cells

• Pre processing and maturation occurs in bone marrow


• Involved in humoral immunity
• Once activated by antigen, proliferate into two clones of
cells: plasma cells that secrete antibodies and memory
cells that play a role in secondary response

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B2 cells binds its specific antibody

Lymphoblast→ memory cells (B2
lymphocytes)

Plasmablast

Plasma cells

antibodies

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Clonal Selection of B
Cells is Due to
Antigenic
Stimulation

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Classification of Immunoglobins
IgM
• 1st response to antigen IgD
• Effective in agglutination • B cell activation
• Can’t cross placenta • Can’t cross placenta
• 10 binding sites
IgG
• Most common form
• Major ig in 2nd response IgE
• • Role in allergic reactions
Crosses placenta (passive
• Present on the surface of
immunity to fetus)
• 2 binding sites basophil and mast cells

IgA
• Secreted from mucus membranes e.g. GIT,
Resp. system, Urinary system
• Prevents attachment of bacteria to epithelial
surface
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• In mucous secretions eg saliva, tears
Antibody Molecule
antigen binding sites

antigen

light chains heavy chains

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Immunoglobulin structure

IgG antibody molecule


• Composed of
• Two heavy chain paralleled by Two light chain at one end called
• VARIABLE PORTION --- 10 BILLION Combinations ( different
in each antibody), antigen attachment occurs, also known as
Fab
• CONSTANT PORTION heavy chains not paralleled by light
chain, determine biological properties, also known as Fc.
• Chains are attached through Disulfide linkages
• Each IgG antibody molecule can bind 2 antigens at one time
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Primary response Secondary response
1. Occurs as a result of first contact of the 1. Occurs during second and subsequent
individual with an antigen contact with the same antigen
2. Its response is weak 2. Response is strong
3. It takes longer time to establish 3. Its rapid
immunity 4. Last longer, sometimes lifelong
4. It declines rapidly 5. Type of antibody formed is igG, high
5. Type of antibody formed mainly is titer
igM, low titer 6. Responding cells are memory cells
6. Responding cells are B cells

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Cell Mediated Immune System: T lymphocytes
• T-cells mature in the thymus (thus the name T-cell)

• Act on antigens appearing on the surface of individual cells.

• Over a million different kinds of T-cells


• Each produces a different receptor in the cell membrane
• Each receptor binds a specific antigen but has only one
binding site

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T lymphocytes, Types
(1)Helper T cells --------CD4
(2) Cytotoxic T cells --------CD8
(3) Suppressor T cells ------ regulatory T cells
Activation of T lymphocytes: Upon exposure to a specific antigen,
as presented by antigen presenting cells, the T lymphocytes of a
specific clone proliferate and release large numbers of activated T
cells, some of these become T-lymphocyte memory cells in the
same way that B memory cells are formed

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Antigen presenting cells


• 1. Macrophages
• 2. B lymphocytes
• 3. Dendritic cells (most potent)
•APCs have MHCII protein on their surface, antigen
binds with it to be presented to Helper T
lymphocytes
•There are two types of MHC proteins:
• MHC I proteins (present on surface of all
nucleated cells), which present antigens to
cytotoxic T cells (CD8 cells)
• MHC II proteins, which present antigens to T-
helper cells (CD4 cells)
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Helper T lymphocytes
T-Helper Cells are the Most Numerous of the T Cells
They serve as the major regulator of virtually all immune functions. In the
absence of the lymphokines from the T-helper cells, the remainder of the
immune system is almost paralyzed.
T-helper cells are destroyed by the human immunodeficiency virus (HIV)
The most important lymphokines secreted by the T-helper cells are the
following:
Interleukin-2
Interleukin-3
Interleukin-4
Interleukin-5
Interleukin-6
Granulocyte-monocyte colony-stimulating factor
Interferon-γ
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FUNCTIONS OF LYMPHOKINES
1. interleukin-2 --------- growth and proliferation of cytotoxic and
suppressor T cells.
2. interleukins 4, 5, and 6----- Stimulation of B-Cell Growth and
Differentiation to Form Plasma Cells and Antibodies
3. Activation of the Macrophage System. Lymphokines stop the
migration of the macrophages from the inflamed tissues, thus
causing great accumulation of macrophages. Also activate the
macrophages to cause more efficient phagocytosis
4. Feedback Stimulatory Effect on the T-Helper Cells.
interleukin-2, have a direct positive feedback effect in stimulating
activation of the T-helper cells.

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Cytotoxic T lymphocytes
Cytotoxic T Cells Are “Killer” Cells

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Cytotoxic T cell (killer cells)

The receptor proteins of the cytotoxic cells----- bind tightly to the cells that contain
specific antigen.

41 Then cytotoxic T cell secretes hole-forming proteins, called perforins

punch round holes in the membrane of the attacked cell.

Fluid flows rapidly into the cell from the interstitial space, it becomes greatly swollen.
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Cytotoxic T cell also releases cytotoxic substances directly into the attacked cell and
cell dissolves shortly
Cytotoxic cells destroy mainly cancer cells, transplant cells and virus infected
cells
Suppressor T Cells

 Suppressor cells along with the T-helper cells, called as regulatory T cells.
 They suppress the functions of both cytotoxic and T-helper cells and
prevent the cytotoxic cells from causing excessive immune reactions that
might be damaging to the body’s own tissues.
 Suppressor T-cell plays an important role in limiting the ability of the
immune system to attack a person’s own body tissues, called immune
tolerance

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Immune
tolerance

During the pre processing of lymphocytes in the thymus and


bone marrow, all clones of lymphocytes that
are specific to damage the body’s own tissues are
self-destroyed because of their continual
exposure to the body’s antigens

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Autoimmunity:Failure of the Tolerance Mechanism Causes Auto- immune
Diseases

• Autoimmunity is immune response of our body against its own


healthy tissues
• examples:
• rheumatic fever
• rheumatoid arthritis
• myasthenia gravis
• Insulin dependent diabetes mellitus (IDDM)

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Undesirable side effect of immunity is the development, of allergy
or other types of immune hypersensitivity

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•There are four types of hypersensitivity reactions.
•Type I It is associated with allergens such as bee stings, hay fever,
asthma. This can lead to a life-threatening condition called
anaphylaxis.
•Type II examples are transfusion reactions, erythroblastosis
fetalis and hyperacute graft rejection.
•Type III SLE
•Type IV is known as delayed or cell-mediated hypersensitivity
reaction. Examples include chronic graft rejections, and contact
with poison ivy.

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“ATOPIC” ALLERGIES ASSOCIATED WITH
EXCESS IgE ANTIBODIES

 Some people have an “allergic” tendency. Their allergies are called atopic
allergies
 The allergic tendency is genetically passed from parent to child and is
characterized by the presence of large quantities of IgE antibodies in the
blood. These antibodies are called reagins or sensitizing antibodies.
 When an allergen enters the body, an allergen-reagin reaction takes place
and a subsequent allergic reaction occurs.

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Urticaria
 Urticaria results from antigen entering specific skin areas and causing
localized reactions.
 Histamine released locally causes
(1)vasodilation that induces an immediate red flare
(2) increased local permeability of the capillaries that leads to swelling of the
skin within another few minutes. The swellings are commonly called hives.

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Hay Fever
 In hay fever, the allergen-reagin reaction occurs in the nose.
 Histamine released causes intranasal vascular dilation and increased
capillary permeability. Both these effects cause rapid fluid leakage into the
nasal cavities and the nasal linings become swollen and secretory. Irritation
of the nose, eliciting the sneezing syndrome.

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Asthma

 The allergen-reagin reaction occurs in the bronchioles of the lungs.


 Mast cells releases slow-reacting substance of anaphylaxis (a mixture of
three leukotrienes), which causes spasm of the bronchiolar smooth muscle.
The person has difficulty breathing
 Administration of antihistamine medication has less effect on the course of
asthma because histamine does not appear to be the major factor eliciting
the asthmatic reaction.

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Anaphylaxis
 When a specific allergen is injected directly into the circulation, the
allergen can react with basophils of the blood and mast cells in the tissues
 A widespread allergic reaction occurs throughout the vascular system and
closely associated tissues. This reaction is called anaphylaxis.
 Histamine is released into the circulation and causes vasodilation and
increased permeability of the capillaries with resultant loss of plasma from
the circulation. Person can die of circulatory shock within a few minutes
 Basophils and mast cells also release slow-reacting substance of
anaphylaxis, can cause spasm of the smooth muscle of the bronchioles,
causing death by suffocation.

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Overview of Immune System Responses

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Types of
Acquired
Immunity

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Vaccination
• Vaccination is a method of giving antigen to stimulate the
immune response through active immunization.

• A vaccine is “antigenic” but not “pathogenic”.


• Active immunization:
• Vaccines include dead organisms----- typhoid fever,
whooping cough and other types of bacterial diseases
• inactivated toxins ------ tetanus
• Live organisms -----smallpox, poliomyelitis, measles, and
many other viral diseases.
• It takes several weeks to develop
• Active immunity is usually permanent
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Passive Immunity
• Passive Immunity- Protection
against disease through antibodies
produced by another human being or
animal.
• Effective, but temporary
• E.g. Maternal antibodies
• Tetnus immunoglobins

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