Immunity

Immunity
Dr. Sai Sailesh Kumar G
Associate Professor
Department of Physiology
RDGMC
DR Sai Sailesh Kumar G 1

Learning objectives
 Define terms active, passive, specific, and
nonspecific immunities
 Describe cellular and humoral immunity and give
examples
 Describe the complement system
 Describe immune tolerance and auto immunity
 Describe types of T lymphocytes and their
functions
 Describe allergy and hypersensitivity

Introduction
 Human body has ability to resist almost all types
of organisms or toxins that damages the tissues
 This capability is called immunity
 Much of immunity is acquired immunity
 Acquired immunity – develops only after
exposure to the bacteria/virus/toxin
 Weeks or months required to develop immunity

Innate immunity
 Phagocytosis of bacteria by WBC and tissue
macrophages
 Destruction of swallowed organisms by the acid
secretions of stomach and digestive enzymes
 Resistance of the skin to invasion by organisms
 Presence in the blood
1. lysozymes
2. Basic polypeptides
3. Compliment system
4. Natural killer lymphocytes

Acquired immunity
 Adaptive immunity
 Ability to develop extremely powerful, specific immunity
against invading agents such as lethal bacteria, virus,
toxins
 Caused by immune system that forms antibodies/
activated lymphocytes that attack and destroy invading
organism
 Offers extreme degree of protection
1. Paralytic botulinum toxin
2. Tetanizing toxin of tetanus
 For this reason, immunization is an effective treatment

Types of acquired immunity
 Two types
 Humoral or b cell immunity
 B lymphocytes produce antibodies
 Cell mediated immunity or T-cell immunity
 Activated T lymphocytes destroy the foreign
agent
 T and B lymphocytes are originated from
common lymphoid progenitor cells

Initiation of acquired immunity
 Develops only after invasion of the
bacteria/virus/toxin
 Body should have some mechanism to recognize
this invasion
 Each organism releases specific types of chemical
substances
 These substances are called antigens
 Antigens initiate acquired immunity
 For substance to be antigen, its molecular weight
should be 8000 or more

Acquired immunity
 Lymphocytes are responsible for acquired immunity
 Lack of lymphocytes or destroyed lymphocytes by
radiation or chemicals – no acquired immunity
 Lymphocytes are located most extensively in lymph
nodes
 Also found in special lymphoid tissues
1. Spleen
2. Sub mucosal areas of GIT
3. Thymus
4. Bone marrow

T and B lymphocytes
 All lymphocytes are produced by lymphocyte
committed stem cell
 Lymphocyte committed stem cell is incapable of
forming either activated T cells or antibodies
 Before they can do so, they must be further
differentiated in appropriate processing areas

T and B lymphocytes
 Activated T lymphocytes migrates to thymus and
pre processed
 So they are called T lymphocytes to designate role
of thymus
 B lymphocytes are processed in the liver in mid fetal
life and in bone marrow in late fetal life and after
birth
 B lymphocytes were first discovered in birds that
have specific processing organ – bursa of fabricus
 So they are called B lymphocytes to designate role
of bursa DR Sai Sailesh Kumar G 10

Preprocessing of T lymphocytes
 Lymphocytes originates in bone marrow
 Migrates to thymus
 Divides rapidly
 Develops extreme diversity for reacting against
specific antigens
 One thymic lymphocyte develops specific reactivity
against specific antigen
 Next lymphocyte develops specific reactivity
against other antigen
 This process continues

 Thousands of thymic lymphocytes develop
specificity against thousands of different
antigens
 After pre processing, T lymphocytes enters the
blood stream
 Lodges in lymphoid tissues
 The thymus also makes certain that no T
lymphocytes will react against body own
antigens DR Sai Sailesh Kumar G 12

 Before releasing the pre processed T
lymphocytes
 Thymus mixes all these lymphocytes with bodys
own antigens
 If any lymphocyte reacts, that will be
phagocytized
 Those which are non reactive with body self
antigens are released
 They reacts only to external antigens

 Most of the pre processing occurs in thymus
1. shortly before birth of baby and
2. for few months after birth

Preprocessing of B lymphocytes
 Most of the pre processing occurs in liver and bone
marrow
 Much less is known about this pre processing
 Liver – during mid fetal life
 Bone marrow – late fetal life and after birth
 B lymphocytes are different from T lymphocytes in
two ways
 Instead of whole cell develop reactivity against
antigen, B lymphocytes secrete antibodies that are
reactive agents DR Sai Sailesh Kumar G 15

Preprocessing of B lymphocytes
 B lymphocytes have greater diversity than T
lymphocytes
 Forms many millions of antibodies with different
specific reactivity
 After pre processing, B lymphocytes migrates to
lymphoid tissues through out the body

Clones of lymphocytes
 Antibodies and T lymphocytes are in millions
 Genes coding these antibodies and T
lymphocytes are in few hundreds to thousands
 How few genes can code millions of antibodies
and T lymphocytes

Clones of lymphocytes
 The whole gene for forming each type of T cell or B cells never present
in the original stem cell
 Instead there are only gene segments
 Hundreds of such segments
 Gene segments are mixed with one another in random combinations
 Forms whole genes

Activation of clone of
lymphocytes
 Specific antigens activates the clone of lymphocytes
 In the cell membrane of the B lymphocytes, antibody
molecules are present
 These antibodies are activated by specific antigens
 In the cell membrane of the T lymphocytes, surface
receptor proteins (T-cell markers) are present
 These antibodies are specific for specific antigens

Activation of T & B lymphocytes
 Most of the antigens activates both T & B
lymphocytes simultaneously
 T-helper cells secrete lymphokines
 Lymphokines activates specific B lymphocytes
 With out lymphokines, the amount of antibodies
formed is very slight

Humoral immunity
 Before the exposure to antigen, the clones of B lymphocytes
remain dormant
 When a foreign antigen enters the body, macrophages will
phagocytize and present it to B lymphocytes
 In addition, the antigen is presented to T lymphocytes at the
same time
 This leads to formation of activated T helper cells
 Further activates B lymphocytes
 Activation of specific B lymphocytes
 Enlarges and form lymphoblast
 Lymphoblast further form plasmablast

Humoral immunity
 Plasmablasts are precursor for plasma cells
 One plasma blast forms 500 plasma cells
 Mature plasma cells produce gamma globulin antibodies
 Extremely rapid rate
 2000 antibodies per second from each plasma cell
 Antibodies are secreted into lymph and carried to the
blood
 This process continues several weeks until the plasma
cell dies

Memory cells
 Few lymphoblasts formed by activation of a clone of B
lymphocyte do not form plasma cells
 Instead forms moderate number of new B lymphocytes similar
to that of original clone
 These new B lymphocytes are added to the original
lymphocytes of the same clone
 Circulate in the blood
 Remain dormant until activated once again by same antigen
 These antibodies are called memory cells
 Subsequent exposure to the same antigen cause more potent
response

Primary and secondary response

Primary and secondary response
Primary response
1. One week delay in appearance
2. Weak potency
3. Short duration
Secondary response
1. Occurs with in hours of exposure
2. More potent
3. More antibodies formed
4. Duration many months
 Increase in potency and duration of secondary response is
basis for immunization

Immunization
 Injecting antigens
 Injecting dead organisms that are not capable of developing disease
but have some of their chemical antigens
 Produce acquired immunity against specific disease
 Immunization is used to protect against typhoid fever, whooping
cough and many other types of bacterial diseases
 Immunity can also be achieved against toxins – tetanus, botulinum
 Injecting live organisms that is attenuated helps to develop
immunity against small pox, yellow fever, polio myelitis and other
viral diseases
 Active immunity – person’s own antibodies develops in response to
foreign antigen DR Sai Sailesh Kumar G 26

Passive immunity
 Temporary immunity
 With out injecting antigen
 Infusing antibodies or activated T cells or both
 Antibodies are collected from immunized
individual or animal

Nature of antibodies
 Antibodies are gamma globulins called immuno
globulins (Ig)
 Molecular weight between 160,000 and 970,000
 Constitute 20% of all the plasma proteins
 Composed of light and heavy poly peptide chains
 Heavy and light chains are in paralled ( pair)
 2 to 10 pairs exist in each Ig
 A combination of covalent and non covalent bonds holds
the light and heavy chains together

 Variable portion is different for each specific
antibody
 Variable portion attaches to specific antigen
 Constant portion determine antibody properties
1. Antibody diffusivity
2. Adherence of antibody
3. Attachment to complement complex
4. Ease with which antibody pass through
membrane

Specificity of antibodies
 Each antibody is specific for particular antigen
 Unique structural organization of amino acids in
the variable portion is responsible for specificity
 The bonds between antibody-antigen
1. Hydrophobic bonds
2. Hydrogen bonds
3. Ionic attractions
4. Van der walls forces

Classes of antibodies
 Five classes of antibodies
 IgG, IgA, IgM, IgD, IgE
 Ig- immuno globulin
1. 75% of antibodies in a normal person - IgG
2. Antibody involved in allergy - IgE
3. Large number of antibodies formed in primary
response – IgM
4. IgM has 10 binding sites

Action of antibodies
 Two ways of action
1. Direct attack on the invader – Not strong
enough to play a major role in protecting the
body against the invader
2. Activation of complement system – plays major
role and offers most of the protection

Direct action of antibodies
 Several ways
1. Agglutination: Multiple large particles with antigens on
their surface such as bacteria or RBC bound together
into a clump
2. Precipitation: Molecular complex of soluble antigen
such as tetanus toxin and antibody becomes so large
and become insoluble and precipitates
3. Neutralization: Antibodies covers the toxic sites of
antigen
4. Lysis: cell membrane of antigen destroyed by

Compliment system
 Compliment – system of 20 proteins
 The principle actor in this system are 11 proteins
designated as C1-C9, B and D
 These proteins are present normally among the plasma
proteins in the blood
 The enzyme precursors are normally inactive
 They are activated mainly by classical pathway

Classical pathway
 Initiated by antigen-antibody reaction
 Binding of antibody with antigen
 Activation of specific reactive site
 It binds with c1 molecule of complement system
 Cascade of sequential reactions
 Multiple end products are formed
 Helps to prevent damage to the body tissues caused by
invading organism
 Most important effects?

Classical pathway

Most important effects
 Opsonization and phagocytosis
 Lysis
 Agglutination
 Neutralization of viruses
 Chemotaxis
 Activation of mast cells and basophils
 Inflammatory effects

Opsonization and phagocytosis
 C3b, activates phagocytosis by neutrophils and
macrophages
 These cells engulf bacteria to which the antigen antibody
complexes are attached
 This process is called opsonization

Lysis
 One of the most important end products of cascade
pathway
 Lytic complex
 C5b6789
 Ruptures cell membrane of the bacteria

Agglutination
 Complement products changes the surface of the
invading organisms
 They adhere to each other
 Agglutination

Neutralization of viruses
 Complement products attack the structures of viruses
 Makes then avirulent

Chemotaxis
 C5a initiates chemotaxis of neutrophils and
macrophages
 Large number of WBC migrates to the area adjacent to
the antigenic agent

Activation of mast cells and
basophils
 C3a, C4a, C5a
 Activates mast cells and basophils
 Release of histamine and heparin
 Increase in local blood flow
 Increased leakage of fluid and plasma proteins into
tissues
 Inactive the antigen

Several types of T cells
 Multiple type of T cells
 Classified into three types
1. T helper cells
2. Cytotoxic T cells
3. Suppressor T cells
 T helper cells are numerous
 They serve as major regulator of all immune functions
 They forms lymphokines
 Interleukins 2,3,4,5,6
 In absence of lymphokines, immune system is almost
paralyzed

Cytotoxic T cells or killer cells
 Direct attack cell
 Kill microorganisms
 They have antigen specific receptors on its surface
 They bind with specific antigens
 Release hole forming proteins - perforins
 Punch holes in the membrane of attacked cells
 Attacked cell swollen
 Dissolves shortly

Suppressor T cells
 Much less is known
 Capable of suppressing the action of cytotoxic and
helper cells
 Prevent cytotoxic cells from causing excessive immune
reactions
 Limits the ability of immune system to attack person own
body tissues

Allergy and hyper sensitivity
 Undesirable effect of immunity
 Several types of allergies and hyper sensitivity
 Some of which occurs only in persons who have specific
allergic tendencies

Delayed reaction allergy
 Caused by T cells
 Poison ivy exposure – activated T cells
 The toxin of poison ivy do not cause much damage to
tissues
 Subsequent exposure to poison ivy
 T cells elicit a cell mediated immune reaction
 Damages tissues where antigen located
 Skin – serious tissue damage

Atopic allergies
 Some people have allergic tendency
 Allergic tendency genetically passed from parent to child
 Large number of IgE in the blood
 These antibodies are called reagins or sensitizing
antibodies
 When allergen/ antigen enters body
 Allergen-reagin reaction
 Allergic reactions

Anaphylaxis
 When a specific allergen is injected into the circulation
 Allergen reacts with basophils and mast cells
 Wide spread allergic reactions occurs through out the
vascular system
 Histamine released into circulation
 Vasodilation through out body
 Increased capillary permeability
 Loss of plasma
 Dies with circulatory shock

 An unusual cause of allergy: Case report of normal saline solution allergy
 Didem Ay 1 , Can Aktas 2 , Sezgin Sarikaya 2 , Asli Cetin 2
 Affiliations
 PMID: 19041557 DOI: 10.1016/j.ajem.2008.04.022
 Abstract
 Anaphylaxis and acute allergic reactions may sometimes be fatal. They occur within minutes in a
sensitized individual. So quick diagnosis and management are necessary issues. In the literature,
cases are widely reported against allergens found in drugs, foods and their additives,
radiocontrast material, bee stings, and many other materials. Here, we present a 37-year-old
woman who developed an anaphylactic reaction to normal saline infusion during evaluation for her
acute abdominal pain. We found only one report about normal saline allergy in the literature (Litvin
ME, Shemchuck AS, Lisetskii VA. Anaphylactic shock caused by intravenous injection of isotonic
solution of sodium chloride. Klin Khir 1976;(7):59-61).

Asthma
 Occurs in the allergic type of person
 Allergen – reagin reaction occurs in the bronchioles of
lungs
 Activation of mast cells
 Release of slow reacting substances
 Spasm of broncholar smooth muscle
 Difficulty in breathing until the reacting substance is
removed
 Administering antihistamines does not have much effect
in asthma patients
 Histamine is not main factor in causing allergies in
asthma

THANK YOU

Immunity

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