Immunity

Immunity
• Ability of the body to protect itself from harmful effects of
diseases.

Types

• In general, there are two types of immunity.

1. Innate immunity

2. Adaptive immunity
Antigen
- A foreign substance that provokes immunity or when introduced
into the tissues stimulates antibody production is called an
antigen.
- More specifically called immunogen. So, immunogen and
antigen although slightly different but used interchangeably.
- Proteins are best antigen, though glycoproteins and lipoproteins
can also act as antigens.
- Carbohydrates and lipid alone are poor antigens.
Epitopes:
- Specific regions on an antigen. In other words, any antigen has
multiple regions and each one of those acts as a small antigen.
These are called epitopes.
- These epitopes are also called antigenic determinants.
- Most antigens have MW >10,000 D. Molecules that are less than
10,000 D are generally poor antigens.
Hapten
- It is a non-protein substance which has no antigenic properties,
but on combining with a protein can form a new antigen capable
of forming antibodies.
Structure of immune system
Organs of immune system Cells of immune system
a. Primary lymphoid organs: a. Lymphocytes
o Thymus b. Monocytes and macrophages
o Bone marrow c. Mast cells and basophils
b. Secondary lymphoid organs: d. Neutrophils
o Lymph nodes e. Eosinophils
o Spleen
o MALT (Mucosa-Associated
Lymphoid Tissue located in
the respiratory tract and
GIT).
Anatomical position of MALT
Types of immunity
Innate immunity
Innate immunity : (Non-specific Host
Defense)
• Present at birth.

• Always present and available to provide rapid responses.

• Does not involve specific recognition of microbes.

• Does not have a memory response i.e. a more rapid and stronger
immune reaction to the same microbe at a later date.
Components of Innate immunity:

• It has following major components:

a) Humoral: complement proteins, cytokines,

b) Cellular: Neutrophils, Macrophages, and Natural killer (NK)

cells, Dendritic cells.

c) Physical and Physiological defenses: Skin & mucous

membranes, cilia ,flora, acidic gastric contents, tear, saliva
- Toll like receptors (TLRs): Protein molecules on defensive cells
which act like a receptor binding to pathogen associated
molecular patterns (PAMPs) mentioned below.
- Pathogen associated molecular patterns (PAMPs): Formed by
LPS, flagellin, peptidoglycan, DNA, RNA, these are repetitive
patterns which the cells of the innate immune system recognize
and get activated to release cytokines and reactive radicals that
kill the organisms.
- Cytokines: They are released as a result of defense cell
stimulation by PAMPs and TLRs interactions. Cytokines recruits
more immune cells and also stimulate adaptive immune response.
Physical barrier
- Skin: The skin is physical barrier of body. Its outer tough layer,
the stratum corneum prevents the entry of bacteria and viruses.
- Mucous Membranes: Mucus secreted by mucous membrane traps
the microorganisms and immobilizes them. Microorganisms and
dust particles can enter the respiratory tract with air during
breathing which are trapped in the mucus. The cilia sweep the
mucus loaded with microorganisms and dust particles into the
throat. From the throat it is thrown out or swallowed for
elimination with the faeces.
Physiological Barriers

- Acid of the stomach: It kills most ingested microorganisms.

- Lysozyme: It is present in tissue fluids and in almost all secretions
except in cerebrospinal fluid, sweat and urine. Lysozyme is in
good quantity in tears from eyes. Lysozyme is also found in
saliva. Lysozyme attacks bacteria and dissolves their cell walls.
- Sebum/Sweat: It forms a protective acid film over the skin surface
that inhibits growth of many microbes.
- Urine. It washes microbes from urethra.
- Vaginal Secretion. It is slightly acidic which discourages
bacterial growth and flush microbes out of vagina.
- Bile does not allow growth of microorganisms.
- Nasal Hair. They filter out microbes and dust in nose.
- Cerumen (ear wax): It traps dust particles, kills bacteria and
repels insects.
- Peristalsis: Provides motility to the intestine propelling the
digesta caudally and out of the rectum removing the organisms
Macrophages and monocytes
• Salient features and important immune functions of macrophages
are as follows:
• Antigen recognition

• Phagocytosis:

• Secretory function

• Antigen presentation
Antigen recognition
• They possess cell surface receptors to several extracellular
molecules— receptor for cytokines, component of complement
(C3b), selectins, integrins and Fc (constant fragment) of antibody.
These receptors recognize the organisms and initiate intracellular
mechanisms in macrophages. Antigen to become recognizable can
also get coated by antibodies or complement, the process being
termed as opsonization.
Phagocytosis
• Antigen that has been recognized by the macrophages due to
availability of surface receptors, or the opsonized antigen, is ready
to be engulfed by the process of cell-eating by macrophages.
Secretory function
• Macrophages secrete important substances as follows:
- Cytokines (IL-1, IL-2, IL-6, 8, IL-10, IL-12, tumor necrosis
factor-α) and prostaglandins (PGE, thromboxane-A, leukotrienes)
which are chemical mediators of inflammation and activate other
leucocytes.
- 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.
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 immunocompetent T cells
(subtype CD4+ or CD8+ cells), or to B cells. Accordingly, the
lymphoid cell would then deal with such antigen.
Neutrophils and Eosinophil
Neutrophils

• 40-75% in circulation

• Contain lysosomal granule

• Same function as macrophages

Eosinophils

• circulating granulocytes (1-6%)

• play a role in allergic reactions

• contain lysosomal enzymes, peroxidases, and chemical mediators of

inflammation
Basophils and Mast cells
• circulating granulocytes (0-1%)

• Basophils and mast cells have IgE surface receptor

• Mast cells and basophils are thus involved in mediating

inflammation in allergic reactions and have a role in wound
healing.
Complement System
• made up of about 30 proteins that work together to assist the
action of antibodies in destroying bacteria.

• It helps to get rid the body of antigen-antibody complexes

• Complement proteins  vasodilation and then leaky  contribute

to the redness, warmth, swelling, pain, and loss of function that
characterize an inflammatory response.
Complement activation
• CP circulate in blood in inactive form

• When the first protein in complement series is activated typically

by antibody that has locked onto an antigen, it sets in motion a
domino effect.

• Each component takes its turn in a precise chain of steps known as

the complement cascade.

• The end products are inserted into and puncture holes in the cell
walls that surround the invading bacteria.

• With fluids and molecules flowing in and out, the bacterial cells
swell, burst, and die
Adaptive Immunity
Adaptive immunity : (Acquired Immunity)
(Specific Host Defense)

• Based on a specific response to a specific microbe once a microbe has

breached the innate immunity defenses.

• Adapts or adjusts to handle a particular microbe.

• Slower to respond, but it does have a memory component.

Components of Adaptive (Acquired) immunity:

• Humoral: consisting of antibodies formed by B-cells

• Cellular: T-cell

• Other: natural killer cells

Components of Adaptive immunity
1. Dendritic cell

2. Lymphocytes

i. CD 4 and CD8 types of T cells

ii. CD4 or helper T lymphocytes

iii. CD8 or cytotoxic T lymphocytes

iv. Memory Lymphocytes

3. Antibodies
1. Dendritic cells
• These are antigen presenting cells (APC) i.e. they express MHC
protein and present antigen to T cells.

• They are located under the skin and the mucosa, e.g. Langerhans’
cells in the skin.
2. Lymphocytes

 Master of Human immune system.

 Morphologically, lymphocytes appear as a homogeneous group
but functionally two major lymphocyte populations:
- T lymphocytes
- B lymphocytes
- while a third type, NK (natural killer) cells
i. B- Lymphocytes

 involved in humoral immunity by inciting antibody response.

 10-15% of lymphocytes in circulation
 Activated to proliferate and transform into plasmacytoid
lymphocytes and then into plasma cells
 These cells also possess B cell receptors (BCR) for surface
immunoglobulins (IgM and IgG) and Fc receptor for attaching to
antibody molecule.
ii. T-Lymphocytes
 inciting cell-mediated immunity and delayed type of
hypersensitivity.
 75-80% of lymphocytes in circulation.
 T-cells also carry receptor (TCR) for recognition of MHC
molecules.
 There are 2 types
 Cytotoxic T-cells
 Helper T-cells
 Helper T-cells signal cytotoxic T-cells, B-cells and another type
of white blood cell called a macrophage.
Cytotoxic T-cells
 also called CD8+ cells because they have a CD8 receptor on their
membranes.
 These cells get their name from “cyto,” which means cell, and
“toxic,” which means poisonous or harmful.
 kill cells infected with viruses and bacteria, and they also destroy
tumor cells.
Helper T-cells
• also called CD4+ cells because they have a CD4 receptor on their
membranes.

• don’t kill cells directly  they send signals that tell other cells in
your immune system how to coordinate an attack against invaders.
iii. Natural killer cells

• They specializes in killing virus infected cells and tumor cells by

secreting cytokines(perforins)

• They are called as natural killer cells because they are active
without prior exposure to antigen, their activity is not enhanced by
exposure, and are not specific for any antigen.
iv. Memory Lymphocytes
• A central feature of adaptive immunity is the phenomenon of
immunological memory.

• Once an initial infection has been overcome by a primary adaptive

immune response, there is development of populations of
memory lymphocytes, both T and B cells, resulting in immunity
against re-infection by the same organism.

• These secondary responses are much larger and more rapid, and
usually lead to highly efficient clearance of the infectious agent.
3. Antibodies
• Proteins that recognize and bind to a particular antigen with very
high specificity.

• Made in response to exposure to the antigen.

• Each antibody has at least two identical sites that bind antigen:
Antigen binding sites
 Antibody Structure

• Immunoglobulins are glycoproteins made up

of four polypeptide chains

a- Two light (L) polypeptide chains

b- Two heavy (H) polypeptide chains

• The four chains are linked by disulfide bonds

Classes of Antibodies

1. Immunoglobulin M (IgM)

• First immunoglobulin made following Ag exposure and is

relatively short-lived.

• Effective in activating complement.

• Participates in the lysis of cells

2. Immunoglobulin G (IgG)

• The most abundant class of antibody, constituting approximately 80%

of all antibodies in serum.

• Produced slowly upon primary exposure to an antigen.

• Produced rapidly during secondary or subsequent exposure,

becoming the major antibody present.

• The only antibody that crosses the placenta. It helps protect the
newborn from infection through passive immunity
3.Immunoglobulin A (IgA)

• Prevents or interferes with the attachment of viruses and bacteria to

mucus of respiratory and digestive systems.

• Protects against enterotoxins released by certain bacteria.

• The main secretory immunoglobulin; found in exocrine secretions (e.g.,

breast milk, saliva, tears, respiratory and digestive secretions, urine).
4.Immunoglobulin E (IgE)

• Minute concentration in serum. Involved in mediating allergic

reactions. Elevated in people with hypersensitivity to allergens, as well
as those with eczema, asthma, or other respiratory problems. Especially
useful against parasitic infections

• 5.Immunoglobulin D (IgD)

• Constitutes only a very small fraction (0.2%) of immunoglobulin in the

body. In serum function is unknown. On B cell surface, initiate
immune response
Major Histocompatibility Complex (MHC)
• play a crucial role in immunology by helping the immune system
recognize and respond to foreign antigens, such as those from
pathogens or abnormal host cells.

• These molecules are glycoproteins found on the surface of nearly all

nucleated cells in the body.

• They are divided into two main classes:

• MHC class I molecules

• MHC class II molecules

MHC Class I Molecules:
• Found on the surface of almost all nucleated
cells in the body.

Structure:

• They consist of a single polypeptide chain,

which has three domains: α1, α2, and α3.
These domains form a peptide-binding cleft.

• The peptide-binding cleft of MHC class I

molecules binds to short peptides, typically 8-
10 amino acids in length.
Function

• Primarily present endogenous antigens, which are peptides derived

from intracellular proteins. These proteins can originate from the
cytoplasm or the endoplasmic reticulum.

• The peptides presented by MHC class I molecules are recognized by

CD8+ cytotoxic T cells (CTLs), also known as killer T cells.

• The interaction between MHC class I and CD8+ T cells is crucial for
the immune system's ability to recognize and eliminate infected or
abnormal cells, such as virus-infected cells or cancer cells.

• MHC class I molecules play a role in immune surveillance and the

detection of cells that may be harboring intracellular pathogens.
MHC class II molecules
• primarily found on the surface of antigen-
presenting cells (APCs), such as dendritic
cells, macrophages, and B cells.

• Structure:

• They consist of two polypeptide chains, α and

β, each with two domains: α1, α2, β1, and β2.
These domains form a peptide-binding cleft.

• The peptide-binding cleft of MHC class II

molecules binds to longer peptides, typically
13-25 amino acids in length.
Function
• Primarily present exogenous antigens, which are peptides derived
from extracellular pathogens like bacteria, fungi, and parasites.

• Exogenous antigens are typically internalized by APCs through

phagocytosis or endocytosis, processed in endosomes, and presented
as peptides on the cell surface.

• The peptides presented by MHC class II molecules are recognized by

CD4+ helper T cells.

• The interaction between MHC class II and CD4+ T cells is crucial

for initiating immune responses, including the production of
antibodies, activation of cytotoxic T cell responses, and modulation
of immune reactions.
Humoral immune response
1) First, a macrophage phagocytoses pathogen and partially
digested antigens are displayed in association with class II
MHC molecules, imbedded in plasm membrane of a macrophage

2) A T-helper cell recognizes this self/non-self complex on the

macrophage and binds to it.

3) This contact stimulates the T-helper cell to form clones of T cells

keyed to the specific antigen

4) At the same time, a limited number of B cells also become attached

to pathogen, and incorporate antigen into their cytoplasm.
4) The cloned T cells actively seek out B cells that display same
antigen

5) When the T cells form a complex with the B cells, they begin
producing cytokines

6) This stimulation of the B cells by cytokines causes them to rapidly

divide (clone) and develop into many plasma cells that manufacture
and secrete antibodies against the original pathogen

7) The plasma cells can secrete as many as 2000 antibody molecules per
second for their 4-5 days of existence, i.e., as many
as 864,000,000 in a life-time
Cell mediated immunity

• Cell-associated antigens are displayed by MHC molecules and are

recognized by CD4 helper T cells or by CD8 Cytotoxic T-cells.
• After antigen recognition, the antigen-specific T cells expand in
number, and begin to differentiate into effector cells, which
perform the task of attacking and eliminating microbes.
• Activated CD4 or helper T cells work largely by secreting soluble
proteins called cytokines.
• Different cytokines have different functions;
• Activate CD8 cytotoxic lymphocytes.
• Activate NK cells.
• Attract and activate macrophages
• Stimulate B cells to differentiate into plasma cells to secrete
antigen specific antibodies
Hypersensitivity reactions
• The immune system is an integral part of human protection
against disease, but the normally protective immune
mechanisms can sometimes cause detrimental reactions in the
host.

• Such reactions are known as hypersensitivity reactions/Allergy,

and the study of these is termed immunopathology.
Hypersensitivity
• Hypersensitivity refers to the undesirable or abnormal, sometimes
fatal immune reactions produced by the normal immune system.

• Results from:

• repeated exposure to an antigen/allergen

• response of adaptive immune system to antigens (Auto

immune diseases)
Causes of Hypersensitivity
Reactions against self antigen (Autoimmunity)
• Normally immune system do not activate against body’s own
antigens called self tolerance
• Occasionally self tolerance fails and damages body’s own cells and
tissues
• Also called autoimmunity diseases
Reactions against microbes
• Reactions against microbial antigens which can cause disease
• In case of excessive infection or if the microbial antigen can not be
eradicated
• Antibodies form complexes with these microbes and get deposited
in tissues causing abnormal immune reactions
Reactions against environmental antigens
• Some times body perceive normally harmless environmental
substances (pollens, animal danders, dust mites and pollutants) as
antigens
• And start immune response against them
Types of Hypersensitivity
• Hypersensitivity reactions can be divided into four types: based on
the mechanisms involved and time taken for the reaction.
• (type I) Immediate hypersensitivity
• (type II) Antibody-mediated hypersensitivity
• (type III) Immune complex-mediated hypersensitivity
• (type IV) Cell-mediated hypersensitivity
 Type I Hypersensitivity
• Type I, hypersensitivity is IgE-mediated
• also known as immediate or anaphylactic hypersensitivity e.g., food
and pollen allergies, asthma and anaphylaxis
• Commonly called Allergy
• Examples are: Rhinitis, hay fever, asthma, anaphylaxis
Mechanism
• Type I hypersensitivity results from cross-linking of membrane-
bound IgE on blood basophils or tissue mast cells by antigen.

• This cross-linking causes cells to degranulate, releasing substances

such as histamine, leukotrienes, and eosinophil chemotactic factor,
which induce anaphylaxis, asthma, hay fever, or urticaria (hives) in
affected individuals.

• A severe type I hypersensitivity reaction such as systemic

anaphylaxis (e.g. from insect envenomation, ingestion of certain
foods, or drug hypersensitivity) requires immediate medical
intervention.
Sequence of events:
1. First exposure to Allergen:

• Allergens introduced to the body through inhalation, ingestion or

injection

• Type 2 helper T cells (TH2) are activated via antigen presenting cells

• TH2 cells release cytokines IL-4 (activate B cells to produce IgE), IL-5
activate eosinophils (recruited to reaction site) and IL-13 act on
epithelial cells (mucus production)

• IgE antibodies attach to the mast cell surface on Fc receptors activating

them against the antigen (mast cells are widely distributed in body
specially near blood vessels, nerves and under epithelial linings)
2. Subsequent Exposure to allergen:

• Allergen binds to the antibodies on surface of mast cells activating

them

• Activated mast cells release mediators

• Histamine from its granules (cause vasodilation, increased

permeability and increased secretion of mucus,)

• Prostaglandins PGD2 and leukotrienes LTB4 LTC4 LTD4

(bronchospasm, increased vascular permeability and
chemotaxis for neutrophils, eosinophils and monocytes),
• cytokines (TNF & chemokines recruit leukocytes, IL-4 & IL-
5 amplification of TH2 mediated response)
Clinical Manifestations of Type-I reactions

• Type –I reactions have 2 well defined phases

1.Immediate response:
• Caused by released contents of mast cells (vasodilation, vascular
leakage, and smooth muscle spasm) usually evident within 5 to 30
minutes after exposure
2. Late response:
• Stimulated by cytokines starts in 2-8 hours and may last for
several days
• characterized by inflammation as well as tissue destruction, such
as mucosal epithelial cell damage
• The dominant inflammatory cells in the late-phase reaction are
neutrophils, eosinophils, and lymphocytes, especially TH2 cells.
Anaphylaxis
• It is a life threatening form of Type-I reactions normally happen against
protein antigens (bee’s venom) and drugs (penicillins).
• Within minutes of the exposure in a sensitized host, itching, urticaria
(hives), and skin erythema appear
• Bronchospasm, over secretion of mucus cause respiratory difficulty

• In GIT vomiting, abdominal cramps, diarrhea

• Severe vasodilation and dangerous fall in blood pressure

undermining blood supply to brain leading to unconsciousness
(anaphylactic shock)
• If untreated this circulatory failure may lead to death in minutes
Laboratory Tests for Type I Hypersensitivity
Treatment of Type I HS
• Avoid Allergens

• Drugs:

• Anti-histamines: Compete histamine for its receptors

• Epinephrine : best for anaphylactic shock, (reverse effects of

granules) quick but short duration.
• Cortisone: Blocks histamine synthesis

• Hypo sensitization: repeated injections of allergens may shift from IgE

to IgG
Type II Hypersensitivity
• Cytotoxic T cells
• IgG or IgM antibody mediated
• Involves complement system, phagocytes and T cells. Which directly
damage cell surface
• The reaction time is minutes to hours.
• Examples are:
• Transfusion reactions: Incompatible donor cells are lysed
• Hemolytic disease of newborn: Fetal cells are destroyed by
maternal anti-Rh antibodies that cross the placenta
• Autoimmune haemolytic anemia resulted from drugs like
Penicillin
Hemolytic Disease of newborn:
• Involves Rh blood group system
• Rh- mom with Rh+ fetus, makes antibodies that enter mom’s
circulation at birth
• Next pregnancy: IgG antibodies cross placenta, destroy fetal RBC,
leading to jaundice and brain damage
• Diagnosis:
• include detection of circulating antibody against the tissues
involved the presence of antibody and complement in the lesion
(biopsy) by immunofluorescence.
• The immunofluorescent staining in type II HS is linear
• Prevention:
• Giving mother RhoGAM right after birth
Mechanisms involved in Type-II
Hypersensitivity
Antibodies can cause disease by targeting cells for phagocytosis,
activating complement system or interfering with normal cellular
function. Different mechanism involved are

1. Opsonization and phagocytosis:

2. Inflammation

3. Antibody-mediated cellular dysfunction

1. Opsonization and phagocytosis:

• When circulating cells such as RBCs or platelets are coated

(opsonization) with autoantibodies, with or without complement
proteins. they become target for phagocytosis by macrophages and
neutrophils

• Phagocytes have receptors for Fc tails of IgG antibodies and

complement proteins. Through these receptors phagocytes bind and
ingest the opsonized particles

• Examples are blood transfusion reactions, erythroblastosis fetalis

(Anti RBC IgG antibodies from mother cause destruction of RBCs in
newborn), autoimmune hemolytic anemia, thrombocytopenia,
agranulocytosis (antibodies against own blood cells).
2. Inflammation
• Antibodies bound to cellular or tissue antigens activate
complement system by classical pathway.
• Products of complement recruit neutrophils and monocytes
causing inflammation in the tissues. Leukocytes may also be
recruited at site of inflammation.
• Examples of antibody mediated inflammation are
glomerulonephritis, vascular rejection in transplanted organ
grafts.
3. Antibody-mediated cellular dysfunction
• Some times antibodies directed against a specific host protein
cause dysfunction of the process mediated by that protein
without causing cellular injury
• For example in myasthenia gravis antibodies against
cholinergic receptors at neuromuscular junction causes
destruction of cholinergic receptors leading to muscle
weakness
Type III Hypersensitivity Reactions
• Antigen Antibody immune complex hypersensitivity
• Antigen may be endogenous or exogenous protein
• 3 - 10 hours after exposure to the antigen

• Mediated by soluble immune complexes, IgG/IgM antibodies and

complement (C3a, 4a and 5a)

• Large amounts of Antigen-Antibody complexes are accumulated in

blood

• When deposited in organs can cause inflammatory damages like:

• Rheumatoid arthritis
• Glomerulonephritis
• The damage is caused by platelets and neutrophils.

• Diagnosis involves examination of tissue biopsies for deposits of

immunoglobulin and complement by immunofluorescence
microscopy
• The immunofluorescent staining in type III hypersensitivity is granular
• Examples are:

• Serum Sickness from circulating complexes e.g;

Glomerulonephritis, RA, Chronic infections
• Arthus Reaction from localized complexes e.g insect bite,
hypersensitivity pneumonitis
Mechanism
1. Immune complex formation  Protein antigen  enter in blood 
produce production of antibodies  after 1 week  Ab reacts with
Ag  Ab-Ag complex formation

2. Deposition of Immune complexes  immune complex deposit into

tissue  increase complex conc.  inc. blood filtration rate (e.g.
urine in kidneys and synovial fluid in joints,)

3. Inflammation and tissue injury  deposited complexes activates

and recruitment  complement system and leukocytes  cell injury
cause  vasculitis if it occurs in blood vessel, glomerulonephritis if
it occurs in glomerulus and arthritis if it occurs in joint
1. Formation of immune complexes:
• Introduction of protein antigen into blood triggers production of
antibodies against the antigen
• After about 1 week of introduction antibodies enter blood
circulation and react with the antigen in the blood resulting in
formation of immune complexes
2. Deposition of Immune complexes:
• These circulating immune complexes may deposit in different
tissues
• Characteristics of disease will depend on where the complexes are
deposited
• These complexes concentrate in organs where blood is filtered at
high pressure to form other fluids e.g. urine in kidneys and synovial
fluid in joints, so these diseases often affect glomeruli and joints
3. Inflammation and tissue injury:
• Once deposited these complexes cause activation of complement
system and recruitment of leukocytes starting acute inflammatory
response.
• Antibodies involved are IgG and IgM
• Deposition of complement proteins at the site of injury can be
detected, serum levels of C3 protein drop in blood which can be
used as diagnostic tool
• During this phase Clinical features like fever, urticaria, joint pain,
lymph node enlargement and proteinuria appear
• The resultant injury is termed as vasculitis if it occurs in blood
vessel, glomerulonephritis if it occurs in glomerulus and arthritis
if it occurs in joint
Type IV Hypersensitivity
• Delayed Hypersensitivity

• T Cell mediated cytotoxicity

• Start after hours to days of exposure

• Release of cytokines, NK cells and macrophage activation

• No antibodies involved

• Localized reactions at site of antigen

• Examples are: TB. Leprosy. Poison IVY

Stages
• Sensitization stage: Memory T cells are generated by dendritic
cells

• Effector stage:

- On secondary contact, T memory cells are activated and produce

cytokines which cause tissue destruction and inflammation

- Continued exposure can cause chronic inflammation and result

in granuloma formation
Types of cell Mediated reaction
• There are two types of T cell mediated reactions

• CD4+ cell (Helper T cell) mediated inflammation

• CD8+ cell (Cytotoxic T cell) mediated cytotoxicity:

CD4+ cell (Helper T cell) mediated inflammation
• Also called cytokine mediated inflammation

• In this cytokines produced by CD4+ cells induce inflammation

that may be acute or chronic

• It is also called delayed type hypersensitivity because when

antigen is introduced in the skin of previously immunized
individual symptoms start to appear in 24-48 hours after exposure
cytotoxic T cells (CD8+ cells) reaction
• In these reactions cytotoxic T cells (CD8+ cells) kill the antigen
containing target cells
• They also act against virus infected cells and destroy them
• These reactions play an important role in reactions against
transplanted organs
• CD8+ cells may also damage normal tissue producing autoimmune
diseases
• CD8+ cells also produce cytokines responsible inflammation
 Type V Hypersensitivity
• This is an additional type that is sometimes used as a distinction from
Type 2.
• Instead of binding to cell surface components, the antibodies
recognize and bind to the cell surface receptors
• This either prevents the intended ligand binding with the receptor or
mimics the effects of the ligand, thus impairing cell signaling.
• Some clinical examples:
• Graves' disease
• Myasthenia gravis

• The use of Type 5 is rare. These conditions are more frequently

classified as Type 2,
 Table- Comparison of Different Types of hypersensitivity
Type-III
Type-I Type-II Type-IV
Characteristics (immune
(anaphylactic) (cytotoxic) (delayed type)
complex)
Antibody IgE IgG, IgM IgG, IgM None
Tissues and
Antigen Exogenous Cell surface Soluble
organs

Response time 15-30 minutes Minutes-hours 3-8 hours 48-72 hours

Erythema and Erythema and

Appearance Weal and flare Lysis and necrosis
edema, necrosis induration

Basophils and Antibody and Complement Monocytes and

Histology
eosinophil complement and neutrophils lymphocytes

Transferred with Antibody Antibody Antibody T-cells

Erythroblastosis
SLE, farmer's Tuberculin test,
Allergic asthma, fetalis
Examples lung disease poison ivy,
hay fever Goodpasture's granuloma
nephritis
Allergy
• Any change or altered reaction in the body is called allergy.
• It is an unusual response of an individual to a substance or condition
that is harmless to others.
Conditions of allergy
1. Primary exposure
• When the body is first subjected to the allergen (antigen), the
condition is referred to as the primary exposure. No symptoms of
allergy are produced during the primary exposure.
2. Subsequent exposure
• During secondary exposure, antigen combined with antibody, results
in antigen-antibody reaction producing symptoms.
Types of allergy
1. Physical allergy: It is due to heat and cold when a person comes
in a physical contact.

2. Environmental allergy: It occurs due to change in climate and

change in feeding habits may be due to pollen grains, dust etc.
such as Hay fever.

3. Psychometric allergy: It is due to anger and frustration.

4. Atopic allergy: In this type of allergy, the allergic tendency is

genetically passed on from parents to children and it is
characterized by the presence of large quantities of IgE
antibodies.
5. Anaphylactic allergy: It involves the humoral immunity
(antigen-antibody reaction) in which IgE is produced in
response to allergen. Mast cells and basophils are involved.

6. Cytotoxic allergy: It involves the humoral immunity in which

IgG and IgM are produced in response to allergen.
Macrophages and monocytes are involved.

7. Immune complex or Arthus reaction: In this type, allergen-IgG

complex principle is involved resulting inflammation in tissues.
Neutrophils are usually involved.

8. Delayed hypersensitivity: It is due to humoral immunity and the

cells are involved are lymphocytes and T-lymphocytes
Clinical features of allergy
• Allergy Symptoms and Signs
• Hives: A rash of round, red welts on the skin that itch intensely,
sometimes with dangerous swelling, caused by an allergic
reaction, typically to specific foods.
• Itching.
• Nasal Congestion.
• Rash.
• Reddened Skin.
• Runny Nose.
• Scratchy Throat.
• Shortness of Breath
Urticaria
• Urticaria, also known as hives,

• It is an outbreak of swollen, pale red bumps or plaques (wheals)

on the skin that appear suddenly either as a result of the body's
reaction to certain allergens, or for unknown reasons.
Angioedema
• Angioedema is a swelling of the area beneath the skin, similar to
urticaria, or hives.

• Urticaria affects only the upper dermis, or top layer of skin.

• Angioedema affects the deeper layers, including the dermis,

subcutaneous tissue, the mucosa, and submucosal tissues.
Trigger by

• Angioedema can be triggered by an allergic reaction to:

• Certain types of food – particularly nuts, shellfish, milk and

eggs.
• Some types of medication – including some antibiotics,
aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs),
such as ibuprofen.
• Insect bites and stings – particularly wasp and bee stings
Treatment of allergy
• Avoid the cause.

• Cool, wet compresses.

• Loose, smooth-textured clothing can also help.

• Some people try phototherapy.

• Antihistamines prevent symptoms such as hives by blocking

histamine receptors so your body doesn't react to the allergens.

• Decongestants help clear your nose and are especially effective for
seasonal allergies.
Immune tolerance
• Immunological tolerance is a complex series of mechanisms that
help the immune system to support responses against self
antigens.

• Failure or breakdown of immunological tolerance results in

autoimmunity and autoimmune diseases.

• There are two major types of Immune Tolerance:

• Central tolerance

• Peripheral tolerance
Self-Tolerance
• The immune system can identify and not react against self-
produced antigens, which is known as self-tolerance.

• Autoimmune disease may occur if this ability is lost and the body
begins to attack its cells.

• The mechanisms of self-tolerance can be broadly classified into

two groups:
• central tolerance and
• peripheral tolerance
 DIVISION OF TOLERANCE

Central Peripheral
• The site for T cells is the • The site – everywhere in the
thymus body
• The site for B cells is the • Cells – both T and B
bone marrow • Mechanisms – anergy, cell
• The mechanism – clonal death, immune deviation
deletion
1. Central tolerance
• Central tolerance mechanisms operate during the development of
immune cells in central lymphoid organs like the thymus (for T
cells) and the bone marrow (for B cells).

• During this process:

• Immature immune cells are exposed to self-antigens

(molecules found on the body's own cells).
• Immune cells that recognize self-antigens too strongly are
eliminated or rendered non-reactive through processes like
negative selection and clonal deletion.
2. Peripheral tolerance
• Peripheral tolerance mechanisms regulate immune responses in
the periphery of the body and include:
• The activity of regulatory T cells (Tregs), which suppress
potentially harmful immune responses against self-antigens.
• Mechanisms such as anergy, where immune cells become
unresponsive to antigens due to a lack of appropriate co-
stimulatory signals.
Mechanism of Peripheral tolerance

• Several mechanisms silence potentially autoreactive T and B cells

in peripheral tissues
• Anergy

• Suppression by regulatory T cells

• Deletion by activation-induced cell death

Anergy
• Anergy is the a process by which the specialized T cell/B cell no
longer responds to its specific antigen (non- reactive) so, there is
the loss of immunity or suppressed immunity against a specific
antigen.

• Lymphocytes are said to be anergic when they fail to respond to

their specific antigen.

• Anergy is one of three processes that induce tolerance, modifying

the immune system to prevent self-destruction (the others being
clonal deletion and immunoregulation).
Negative selection
• It is a fundamental process in immunology that occurs during the
development of immune cells, particularly T cells, to ensure that
the immune system can distinguish between self-antigens
(molecules found on the body's own cells) and foreign antigens
(molecules from pathogens or other non-self sources).

• Negative selection plays a crucial role in establishing self-

tolerance and preventing autoimmune reactions.
Positive selection
• It is a crucial process that occurs during the development of T
cells in the thymus, a primary lymphoid organ.

• It plays a vital role in ensuring that T cells become functional and

capable of recognizing foreign antigens, while simultaneously
avoiding self-reactivity.
Clonal deletion
• It is the elimination or inactivation of immature immune cells (T
cells and B cells) that recognize and react strongly to self-antigens
(molecules found on the body's own cells).

• This process occurs in the thymus (for T cells) and the bone
marrow (for B cells) and ensures that only immune cells with
receptors that do not strongly react with self-antigens mature and
enter circulation.

• Clonal deletion is crucial for preventing autoimmune responses

and maintaining self-tolerance in the immune system.
Clonal Deletion Theory:

• The clonal deletion theory is a concept in immunology that

describes the selective elimination or inactivation of immature
immune cells (T cells and B cells) during their development in the
thymus (for T cells) and bone marrow (for B cells) if they
demonstrate strong reactivity to self-antigens (molecules found on
the body's own cells).

• This process helps establish self-tolerance by preventing the

production of immune cells that could potentially target and attack
the body's own tissues, thus minimizing the risk of autoimmune
diseases.