Immunity –

(Innate and Acquired)

 Learning objectives
By the end of this session student will be able to
 Define innate immunity, acquired immunity
 To understand cells involved in innate and acquired immunity
 IMMUNITY
 Theterm 'immunity' (Latin word ‘immunitas’, means
freedom from disease) is defined as resistance offered by
the host against microorganism(s) or any foreign
substance(s).

 Immunity can be broadly classified into two types-

o Innate immunity- present right from the birth
o Acquired / Adaptive- acquired during the course of the life
Immunity
Differences between innate and acquired immunity

Innate immunity Acquired / Adaptive immunity

Resistance to infection that an individual Resistance to infection that an

possesses since birth individual acquires during his
lifetime
Immune response occurs in minutes Immune response occurs in days

Prior exposure to the antigen is not Develops following the antigenic

required exposure
Diversity is limited, acts through a More varied and specialized
restricted set of reactions responses
Differences between innate and acquired immunity

Innate immunity Acquired / Adaptive immunity

Immunological memory responses are absent Immunological memory responses
are present
Respond to microbial antigens that are not Respond to specific microbial
specific to some microbe, rather shared by antigens
many microbes (called as microbes-
associated molecular patterns)
Host cell receptors (pattern recognition Host cell receptors are specific- e.g.
receptors) are non- specific – e.g. Toll-like T cell receptors and B cell
receptor immunoglobulin receptors
Innate immunity Acquired / Adaptive
immunity
Components of innate immunity Components of acquired
Anatomical barriers such as skin and mucosa immunity
Physiological barriers (e.g. body temperature) T cell
Phagocytes (neutrophils, macrophages & monocytes) B cell
Natural killer (NK) cells Classical complement
Other Classes of lymphocytes -γδ T cells , NK-T cells, B-1 cells pathway
and marginal-zone B cells Antigen presenting cells
Mast cells Cytokines (IL-2, IL-4, IL-5,
Dendritic cells IFN-γ)
Complement pathways- alternate & mannose binding
pathways
Fever and inflammatory responses
Normal resident flora
Cytokines- TNF-α, certain interleukin (IL-1, IL-6, IL-8, IL-12,
IL-16, IL-18), IFN-α, β and TGF- β
Acute phase reactant proteins (APRs)
 INNATE IMMUNITY

 Innate immunity is the inborn resistance against infections that an individual

possesses right from the birth, due to his genetic or constitutional makeup.

Features of innate immunity:

 Acts in minutes
 Prior microbial exposure is not required
 Diversity is limited
 Non-specific
 No memory
 Innate immunity
Type of innate Explanation Examples
immunity
Species Innate immunity towards a frogs are resistant to Bacillus
immunity microbe exhibited by all anthracis; while toads are
members of a given species susceptible.
Racial innate immunity confined to a Negroes of America are more
immunity particular race; may be absent in susceptible to tuberculosis
other communities than the whites.
Individual Antimicrobial defense One exception is identical
immunity mechanisms that are confined to twins
a particular individual; may not
be exhibited by others.
 Factors influencing innate immunity
Age
 Very old or very young more susceptible to infectious disease
Hormone
 Endocrine disorders such as Diabetes Mellitus, hypothyroidism and adrenal
dysfunctions – enhanced susceptibility to infection
Nutrition
 Immune response is reduced in malnutrition patient
 MECHANISMS OF INNATE IMMUNITY
 Receptor interaction
o Following the exposure of microorganisms, several mediators of innate immunity
are recruited to the site of infection.
o The first step that takes place is attachment, which involves binding of the
surface molecules of microorganisms to the receptors of cells of innate immunity.
 Microbial surface molecules-
o Repeating patterns of conserved molecules which are common to most microbial
surfaces; called as Microbes-associated molecular patterns (MAMPs).
o Examples - peptidoglycan, lipopolysaccharides (LPS), teichoic acid and
lipoproteins present on bacterial surface.
 MECHANISMS OF INNATE IMMUNITY

 Pattern recognition receptors (PRRs)-

o Molecules present on the surface of host cells (e.g. phagocytes) that recognize
MAMPs.
o Conserved regions, encoded by germ line genes.
o Toll like receptors(TLRs) - classical examples of pattern recognition receptors.
 There are 13 types of Toll like receptors (TLR 1 to 13). Important ones are-
o TLR-2 binds to bacterial peptidoglycan
o TLR-3 binds to dsRNA of viruses
o TLR-4 binds to LPS of Gram negative bacteria
o TLR-5 binds to flagella of bacteria
o TLR-7 & 8 bind to ssRNA of viruses
o TLR-9 binds to bacterial DNA
 Components of innate immunity
1. Anatomical and physiological barriers
2. Antibacterial substance in blood and tissues
3. Complement pathways
4. Inflammatory response
5. Microbial antagonism
6. Cytokines
7. Acute phase reactant proteins (APRs)
 Anatomical and physiological barriers

Anatomical Function
Barrier
Skin Barrier
   Mechanically prevents entry of microbes
 Produces sebum containing antimicrobial peptides and fatty acids
 Killing of microbes by intraepithelial lymphocytes
Mucosal Barrier
1. Mucous Prevents entry of microbes mechanically and by producing mucous which entraps
membrane microbes
2.Cilia Cilia present in the lower respiratory tract propel the microbes outside
3.Normal flora Intestinal & respiratory mucosa are lined by normal flora.
 Anatomical and physiological barriers
Physiological Function
Barrier
1.Temperature Normal body temperature inhibits the growth of some microbes
2.Low pH Gastric acidity inhibits most of the microbes
3.Secretory products of mucosa
  Saliva Enzymes in saliva damage the cell wall and cell membrane of bacteria
  Tears Contains lysozyme, that destroys the peptidoglycan layer in bacterial cell wall
  Gastric juice HCl kills microbes by its low pH
  Trypsin Hydrolyse bacterial protein
  Bile salts Interfere with bacterial cell membrane
  Fatty acids Denature the bacterial proteins
  Spermine Present in semen, inhibits growth of Gram positive bacteria
  Lactoferrin Binds to iron, thus interferes with acquisition of iron by bacteria
 Phagocytosis
 Phagocytes - neutrophils, macrophages including monocytes are the main
component of innate immunity.
 Rapidly recruited to the infection site. Phagocytosis involves three sequential
steps:
o Engulfment of microbes and subsequent hosting in phagosome.
o Fusion of lysosome with phagosome to form phagolysosome
o Microbial killing
 Cellular components of Innate immunity

NK cells:
Class of lymphocytes that kill virus infected cells and tumor cells.

Mast cells:
Present lining the respiratory and other mucosa.
Activated by microbial products binding to toll like receptors or by IgE antibody dependent mechanism.
They release abundant cytoplasmic granules rich in histamine, prostaglandins & cytokines that initiate
inflammation and proteolytic enzymes that can kill bacteria

Dendritic cells:

Respond to microbes by producing numerous cytokines that initiate inflammation.

Serve as vehicle in transporting the antigen(s) from the skin and mucosal site to lymph nodes where they present the
antigen(s) to T cells - bridge between innate and acquired immunity.
 Complement pathways

 Alternate complement pathway is activated in response to bacterial endotoxin.

 Mannose binding pathway is stimulated by mannose carbohydrate residues on
bacterial surface.
Biological function;
 Lysis of the target microbes (by forming pores on the microbial surfaces)
 Stimulate inflammation (by secreting inflammatory mediators)
 Stimulate acquired immunity- Complements are another bridge between innate
and acquired immunity.
 Inflammatory response

 Vasodilation
 Leakage of plasma proteins
through blood vessels
 Recruitment of phagocytes (e.g.
neutrophils) to the site of
inflammation
 Engulfment of microbes and dead
material by the phagocytes
 Destruction of the microbes
Normal resident flora:Microbial antagonism

 Compete with the pathogens for nutrition .Produce antibacterial

substances.
 Alteration in bacterial flora – leads to invasion by extraneous microbes
 Followed by oral antibiotics
 Cytokines
 In response to the microbial antigens, dendritic cells, macrophages, and other cells
secrete several cytokines that mediate many of the cellular reactions of innate
immunity such as:
o Tumor necrosis factor (TNF),
o Interleukin-1 (IL-1), IL-6, IL-8, IL-10 & IL-16
o Interferons (IFN-α, β) and
o Transforming growth factor (TGF-β)
 Acute phase reactant proteins (APRs)
 Proteins synthesized by liver at steady concentration, but their synthesis
either increases or decreases exponentially during acute inflammatory
conditions.
 APRs can also be synthesized by various other cells such as endothelial
cells, fibroblasts, monocytes and adipocytes.
 APRs have various antimicrobial and anti-inflammatory activities (e.g.
complement factors)
 Positive APRs
 Proteins whose levels increase during acute inflammation. Examples include-
o Serum Amyloid A
o C- Reactive protein
o Complement proteins – Complement factors (C1-C9), factor B,D, and properdin
o Coagulation protein- e.g. fibrinogen, von-willebrand factor
o Proteinase inhibitors- e.g. α1 antitrypsin
o α1 acid glycoprotein
o Mannose binding protein
o Haptoglobin
o Metal binding proteins- e.g. Ceruloplasmin
 Negative APRs
 Proteins whose levels are decreased during acute inflammation thus creating a
negative feedback that stimulates the liver to produce positive APRs.
 Examples of negative APRs include:
o Albumin
o Transferrin
o Anti-thrombin.
 C- Reacting protein (CRP)

 CRP belongs to beta globulin family.

 CRP is so named because it precipitates with C- carbohydrate (polysaccharide)
antigen of Pneumococcus.
 CRP not an antibody against the C- carbohydrate antigen of Pneumococcus; it is non-
specific, can be raised in any inflammatory conditions.
 Commonest markers of acute inflammation, used in most diagnostic laboratories.
 C- Reacting protein (CRP)
 Normal level - <0.2mg/dl.
 Increases by several folds in acute inflammatory conditions:
o Insignificant increase (<1 mg/dl) –heavy exercise, common cold, and pregnancy
o Moderate increase (1-10 mg/dl )- bronchitis, cystitis, malignancies, pancreatitis,
myocardial infarction
o Marked increase (>10 mg/dl)- acute bacterial infections, major trauma and
systemic vasculitis
 Detection of CRP
 Precipitation method using C carbohydrate antigen (obsolete, not in use now)
 Latex (passive) agglutination test using latex particles coated with anti-CRP
antibodies -most widely used.
 Detection limit of CRP by latex agglutination test – 0.6mg/dl
Highly sensitive CRP (hs-CRP)test
 Minute quantities of CRP can be detected by various methods (e.g. nephelometry,
enzyme immunoassays).
 Useful in assessing the risk to cardiovascular diseases
Acquired Immunity
 PROPERTIES OF ACQUIRED IMMUNITY
 Mediators- T cells & B cells are the chief mediators of acquired immunity.
Others include-
o Classical complement pathway
o Antigen presenting cells
o Cytokines (IL-2, IL-4, IL-5)
 Response occurs in days - It requires the activation of T and B cells against
the microbial antigens.
 Requires prior microbial exposure- Acquired immunity develops only after
the exposure to the microbes.
 PROPERTIES OF ACQUIRED IMMUNITY
 Specific-Acquired immunity is highly specific; directed against specific antigens that
are unique to the microbes.

 Memory present- A proportion of T and B cells become memory cells following

primary contact of the microbe, which play an important role when the microbe is
encountered subsequently.

 Diversity is wide- Acquired immunity though takes time to develop is active against a
wide range of repertoire of antigens.

 Host cell receptors of acquired immunity are specific for particular microbial
antigen-
o Examples include-T cell receptors and B cell immunoglobulin receptors
Types of Acquired immunity

 Active and passive immunity

 Artificial and natural immunity
Differences between active and passive immunity
Active immunity Passive immunity
Produced actively by host immune Immunoglobulins received passively
system
Induced by Acquired by-
 Infection (natural)  Mother to fetus IgG transfer (natural)
 Vaccination (artificial)  Readymade antibody transfer (artificial)
Long lasting Lasts for short time
Lag period present No Lag period
Memory present No Memory
Booster doses-useful Subsequent doses-Less effective
Negative phase may occur No Negative phase
In immunodeficiency individuals not Useful in immunodeficient individuals
useful
 ACTIVE IMMUNITY
 Active immunity is the resistance developed by an individual towards an antigenic ­
stimulus.
 Active immunity may be induced naturally or artificially:
o Natural active immunity (e.g. measles virus infection)
o Artificial active immunity (e.g. measles vaccine).
 ACTIVE IMMUNITY
 Long-lasting- Active immunity usually lasts for longer periods but the duration
varies depending on the type of pathogen.
o Last life long- e.g. following certain viral infections such as chicken pox,
measles, small pox, mumps and rubella.
o Last short- e.g. following influenza infection.
o Premunition or concomitant immunity – Immunity may last as long as the
microbe is present. Once the disease is cured, the patient becomes
susceptible to the microbe again (Spirochaetes and Plasmodium).
ACTIVE IMMUNITY

o Premunition or concomitant immunity – Immunity may last as long as the

microbe is present. Once the disease is cured, the patient becomes
susceptible to the microbe again (Spirochaetes and Plasmodium).

o Active immunity may not be protective at all- e.g. for Haemophilus

ducreyi, the patient may develop genital lesions following reinfection
even while the original infection is active.
 Primary immune response

 When the antigenic exposure occurs for the first time, the following events take
place-
o Latent or lag period - Active immunity develops which corresponds to the time
required for the host’s immune apparatus to become active.
o Effector cells-Majority of activated T and B cells against the antigenic stimulus
become effector T and B cells
 Effector T cells such as helper T cells and cytotoxic T cells
 Effector B cells include plasma cells
 Primary immune response

o Memory cells- A minor proportion of stimulated T and B cells become

memory cells, which are the key cells for secondary immune response.
o Antibody surge
 Activated B cells produce antibodies (mainly IgM type).
 Antibodies appear in the serum in slow & sluggish manner; reach peak,
maintain the level for a while and then fall down.
 Finally, a low titer of baseline antibodies may be maintained in the
serum.
 Secondary immune response

 When the same antigenic exposure occurs subsequently, the events which
take place are as follows:
o Latent period
o Negative phase
o Antibody surge
 PASSIVE IMMUNITY

 Passive immunity is defined as the resistance that is transferred passively to

a host in a 'readymade' form without active participation of the host’s
immune system.
 Passive immunity can also be induced naturally or artificially.
o Natural passive immunity involves the IgG antibody transfer from mother
to fetus across the placenta.
o Artificial passive immunity develops following readymade transfer of
commercially prepared immunoglobulin (e.g. Rabies immunoglobulin)
 Role of passive immunity
 Immunodeficient individuals (as host’s immune apparatus is not effective)
 Post exposure prophylaxis; when an immediate effect is warranted.
 Passive immunity develops faster; there is no lag phase or negative phase.
 There is no immunological memory as the memory cells are not involved.
 Booster doses are not effective
Differences between Primary and Secondary immune response

Primary immune response Secondary immune response

Immune response against primary antigenic Immune response against subsequent
challenge antigenic challenge
Slow, sluggish (appear late) and short Prompt, powerful & prolonged (long lasting)
lived
Lag period is longer (4-7 days) Lag period is absent or short (1-3 days)

No negative phase Negative phase may occur

Antibody produced in low titer & is of IgM Antibody produced in high titer & is of IgG
type. type
Antibodies are more specific but less avid Antibodies are less specific but more avid
Antibody producing cells- Naive B cells Antibody producing cells- Memory B cells

Both T dependent and T independent Only T dependent antigens are processed.

antigens are processed.
BRIDGES BETWEEN INNATE AND ACQUIRED IMMUNITY
 Macrophages and dendritic cells:
o Belong to innate immune system but as antigen presenting cells, they present the
antigenic peptides to T cells.
o Cytokines secreted from macrophages (interleukin-1) are also involved in T cell
activation.
 ADCC (antibody dependent cell mediated cytotoxicity):
o Type of cell mediated immune response (CMI), which involves both innate and
adaptive components.
o Cells of innate immunity such as NK cell, eosinophils, and neutrophils destroy (by
cytotoxic effect) the target cells coated with specific antibodies.
BRIDGES BETWEEN INNATE AND ACQUIRED IMMUNITY
 Complements (classical pathway)
o Part of both innate and adaptive immunity.
o Destroy the target cells which are coated with specific antibodies.
o Alternate and mannose binding pathways do not take help of antibodies.
 Cytokines
o Secreted from cells of innate immunity can activate cells of adaptive immunity
and vice versa.
o E.g. IL-1 secreted from macrophage activates helper T cells and interferon-γ
secreted by helper T cell can activate macrophage.
BRIDGES BETWEEN INNATE AND ACQUIRED IMMUNITY
 Rare classes of lymphocytes such as γδ T cells , NK-T cells, B-1 cells and
Marginal-zone B cells.
o These cells have many characteristics that place them in the border of innate &
acquired immunity.
o Function in the early defense against microbes as part of innate immunity.
o Although their receptors are encoded by somatic recombination of genes
(similar to that of classical T and B cells), but these receptors have limited
diversity.
o Develop a memory phenotype in contrast to the property of innate immunity.
 Local (or mucosal) immunity
 Immune response that is active at the mucosal surfaces such as intestinal or
respiratory or genitourinary mucosa.
 Mediated by a type of IgA antibody called secretory IgA.
 Local immunity can only be induced by natural infection or by live vaccination (but
not by killed vaccines).
 Herd immunity
 Herd immunity is defined as the overall immunity of a community (or herd) towards
a pathogen.
 Elements that contribute to create a strong herd immunity are-
o Occurrence of clinical and subclinical cases in the herd
o On-going immunization programme
o Herd structure i.e. type of population involved
o Type of pathogen-Herd immunity may not be strong in a community against all
the pathogens.
 Herd immunity
 Herdimmunity develops following effective vaccination against some
diseases like:
o Diphtheria and Pertussis vaccine
o Measles, Mumps and Rubella (MMR) vaccine
o Polio (Oral polio vaccine)
o Smallpox vaccine
 Adoptive immunity

 Special type of cell mediated immune response (CMI) which develops following
injection of immunologically competent T-lymphocytes known as Transfer factor.
 Useful for treatment when the CMI is low- e.g. in lepromatous leprosy.
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