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Immunity

BY Dr. Tamseela Mumtaz

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Immunity – The Basic Concept

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Contents

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Introduction
Types of immunity
Innate Immunity
Acquired Immunity
Specific and non specific defenses
Conclusion
References

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Introduction

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The Latin term “IMMUNIS” means EXEMPT, referring to protection against foreign agents.
Immunity is referred to the resistance exhibited by the host towards injury caused by microorganisms and their products.
Its classified as
Innate immunity (Native)

Non specific: species, racial, individual
Specific: Species, racial, individual

Acquired Immunity (Adaptive)

Active: Natural or Artificial
Passive: Natural or Artificial

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Immune system

Immune system is a biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumour cells.
It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own healthy cells and tissues in order to function properly.

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Types of immunity

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Innate Immunity

Acquired

Immunity

Special Immunity

Individual Immunity

Racial Immunity

Natural

Active

Artificial

Passive

Active

Passive

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Types of immunity

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Innate Immunity

Acquired

Immunity

Natural

Active

Artificial

Passive

Active

Passive

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1) Innate immunity

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It is also called natural or native immunity.
It refers to nonspecific defense mechanisms that come into play immediately or within hours of an antigen's appearance in the body. These mechanisms include
physical barriers such as skin
chemicals in the blood and immune system cells that attack foreign cells in the body.

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Types of innate immunity-

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Species

immunity

It is the total

immunity shown by all members of a species against pathogen; e.g. birds immune to tetanus.

Racial immunity

It is that in which various

races show marked

difference in their resistance

to certain

infectious disease.

Individual immunity

It is very specific for

each and every individual

despite having same racial background

and opportunity for exposure.

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Mechanism of innate immunity

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Anatomical barriers

Skin

🡺It acts as a mechanical barrier t provide bactericidal secretions.

🡺Resident microflora of skin and m help to prevent colonisation by p

o microorganisms and

ucous membrane suface athogens.

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b)Respiratory tract:

Inhaled particals are arrested in the nasal passage on the moist mucous membrane surface.
Mucous membrane acts as a trapping mechanism. It has hair like cilia that propels the particals towards pharynx where its swallowed or coughed out.
Cough reflex acts as a defence mechanism.

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c) Intestinal tract:

Mouth possesses saliva which has a inhibitory effect on many micro-organisms some bacteria are destroyed by acidic pH of gastric juices.
Normal bacterial flora of intestine exerts a protective colonisation of pathogenic bacteria.

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Cellular factors:

Pathogens invading blood & tissue are destroyed by phagocytic cells
Types-

Phagocytes
Microphages are polymorphonuclear leucocytes
Macrophages are wandering amoeboid cells in tissues, reticuloendothelial cells & monocytes in blood.

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Phagocytes

The white blood cells that protect the body by ingesting (phagocytosing) harmful foreign particles, bacteria and dead or dying cells.
Phagocytic Cells: Macrophages (Monocytes), Neutrophils & Eosinophils (Macrophages)

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Phagocytic action of phagocytes is divided in 4 stages:
Chemotaxis:

Phagocytic cells attracted by chemotactic substances → reach site of inflammation

Attachment:

Infective agent gets attached to phagocytic membrane

Ingestion:

Bacteria are engulfed by phagocytes
Membrane of phagosome fuses with lysosome to form phagolysosome

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Intracellular killing:

Lytic enzymes in phagolysosome destroy bacteria
Some bacteria (mycobacteria) resist such killing & can multiply within phagolysosome
A class of lymphocyts called Natural killer (NK) cells play important role in non-specific defence against viral infections & tumor

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Natural Killer Cells

All nucleated cells in body have membrane major histocompatibility complex (MCH) i.e. tissue typing antigens.
In virus-infected cells, MHC is reduced in amount or contains virus peptides.
NK cells recognize this altered MHC and kill virus-infected cells (also tumor cells).

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Role of Natural killer Cells

Natural killer cells (or NK cells) are a type of cytotoxic lymphocyte
NK cells play a major role in the rejection of tumours and cells infected by viruses.
The cells kill by releasing small cytoplasmic granules of proteins called perforin and granzyme that cause the target cell to die by apoptosis.

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Inflammation:

Entry of pathogens causes tissue injury & irritation which leads to inflammation
Inflammation leads to vasodilation, increased vascular permiability & cellular infiltration
Arterioles at the site of infection constrict initially & then dilate leading to increased blood flow → leucocytes escape into tissues by diapedesis → accumulate in large numbers

→ attracted by chemotactic substances at site of injury → phagocytose microbes.

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Inflammation is characterised by:

Pain
Redness
Heat
Swelling
Loss of function.

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5)Fever:

Rise in temperature after infection: helps to accelerate physiological processes
Fever stimulates production of interferons & helps in recovery from viral infections

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Factors affecting individual innate immunity

1) Age:

Very young & very old: more susceptible to infectious disease.
Fetus in uterus is protected from maternal infection by placental barrier. But some pathogens cross the barrier causing overwhelming infection resulting in fetal death.
Some infections are more severe in adults than in young children due to hypersensitivity.
Old persons are highly susceptible to infections due to declined immune responses.

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2)Hormonal influence:

Endocrine disorders (diabetes, hypothyroidism, adrenal dysfunction) are associated with enhanced sensitivity to infections.
High incidence of staphylococcal sepsis in diabetes is due to increased level of carbohydrates in tissues.
Corticosteroid hormones have anti-inflammatory & anti- phagocytic effect which depress host’s resistance.
Elevated steroid level during pregnancy results in increase susceptibility to many infections.

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3)Nutrition:

Malnutrition which causes reduced cell mediated & humoral immunity.
Cell mediated immune responses decrease in severe protein deficiency.

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Types of immunity

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Innate Immunity

Acquired

Immunity

Special Immunity

Individual Immunity

Racial Immunity

Natural

Active

Artificial

Passive

Active

Passive

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Acquired immunity

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It is the second line of defence which is based upon resistance acquired during life. It relies on genetic events and cellular growth.
Responds slowly, over few days
It is specific

each cell responds to a single epitope on an antigen

Has anamnestic memory

repeated exposure leads to faster, stronger response

Leads to clonal expansion

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Types of immunity

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Innate Immunity

Acquired

Immunity

Special Immunity

Individual Immunity

Racial Immunity

Active

Natural

Passive

Artificial

Natural

Artificial

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1) Active immunity:

Resistance developed by individual as a result of antigenic stimulus.
Involves active functioning of host’s immune apparatus to produce antibodies & immunologically active cells. Active immunity sets in after a latent period.
During its development, there is often a negative phase (immunity lower than it was before antigenic stimulus): because antigen combines with pre-existing Ab in circulation
Once developed, it is long-lasting. When actively immunised individual encounters subsequent attack of same antigen, immune response occurs more quickly (called as secondary

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a) Natural active immunity:

Results from either clinical or inapparent infection by a microbe.
Eg: person recovered from attack of measles develops natural active immunity.
Such immunity is usually long-lasting but duration varies with types of pathogen
Immunity is lifelong following many viral diseases
Immunity following bacterial infection is generally less permanent

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b)Artificial active immunity:

Resistance induced by vaccine
Examples of vaccines:

🡺 Bacterial vaccines:

🡺 Live (BCG for tuberculosis)

🡺 Killed (Cholera vaccine)

🡺 Subunit (Typhoid VI antigen)

🡺 Bacterial products (Tetanus toxoid)

🡺 Viral vaccines:

🡺 Live (Oral polio vaccine- Sabin)

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Live vaccines initiate an infection without causing any injury or disease
Immunity following live vaccine administration resembles that following natural infection
Immunity lasts for several years but booster doses may be required
Live vaccines can be administered orally or parenterally
Killed vaccines are less immunogenic than live vaccines, & protection lasts for short period.
Thus, administered repeatedly

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2) Passive immunity:

Resistance transmitted passively to recipient in a readymade form
Recipient’s immune system plays no active role
There is no antigenic stimulus; instead, preformed antibodies are administered
No latent period
No negative phase
Immunity is transient lasting for days or weeks

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No secondary type response occurs in this immunity.
When antibodies are administered 2^ndtime, they are eliminated more rapidly
Passive immunisation is less effective
Employed when instant immunity is desired

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a) Natural passive immunity:

Resistance passively transferred from mother to baby
In human infants, maternal antibodies are transmitted predominantly through placenta
In animals such as pigs, antibodies are transmitted through colostrum
Human fetus acquires ability to produce antibodies from 20^th week of life. Till then, maternal antibodies give passive protection against infectious diseases

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b)Artificial passive immunity:

Resistance passively transferred to recipient by administration of antibodies
Agents used for this purpose:

Hyperimmune sera of animal or human origin
Convalescent sera
Pooled human gammaglobulin

These are used for prophylaxis & therapy

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Mechanism of Acquired Immunity

Cell-mediated immune response (CMIR)

T-lymphocytes
eliminate intracellular microbes that survive within phagocytes or other infected cells

Humoral immune response (HIR)

B-lymphocytes
mediated by antibodies
eliminate extra-cellular microbes and their toxins

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Cell-mediated immune response

T-cell

recognizes peptide antigen on macrophage in association with major histo- compatibility complex (MHC) class
identifies molecules on cell surfaces
helps body to distinguish between self from non-self

T-cell goes into effectors cells stage that is able to kill infected cells

Cell-mediated immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to antigen. Historically, the immune system was separated into two branches: humoral immunity, for which the protective function of immunization could be found in the humor (cell-free bodily fluid or serum) and cellular immunity, for which the protective function of immunization was associated with cells. CD4 cells or helper T cells provide protection against different pathogens. Naive T cells, which are immature T cells that have yet to encounter an antigen, are converted into activated effector T cells after encountering antigen-presenting cells (APCs). These APCs, such as macrophages, dendritic cells, and B cells in some circumstances, load antigenic peptides onto the MHC of the cell, in turn presenting the peptide to receptors on T cells. The most important of these APCs are highly specialized dendritic cells; conceivably operating solely to ingest and present antigens. ^[1]

Activated Effector T cells can be placed into three functioning classes, detecting peptide antigens originating from various types of pathogen: The first class being 1) Cytotoxic T cells, which kill infected target cells by apoptosis without using cytokines, 2) TH1 cells, which primarily function to activate macrophages, and 3) TH2 cells, which primarily function to stimulate B cells into producing antibodies.^[1]

The innate immune system and the adaptive immune system each comprise both humoral and cell-mediated components.

Cellular immunity protects the body through:

T-cell mediated immunity or T-cell immunity: activating antigen-specific cytotoxic T cells that are able to induce apoptosis in body cells displaying epitopes of foreign antigen on their surface, such as virus-infected cells, cells with intracellular bacteria, and cancer cells displaying tumor antigens;

Macrophage and natural killer cell action: enabling the destruction of pathogens via recognition and secretion of cytotoxic granules (for natural killer cells)^[2] and phagocytosis (for macrophages)^[3]; and

Stimulating cells to secrete a variety of cytokines that influence the function of other cells involved in adaptive immune responses and innate immune responses.^[2]^[3]

Cell-mediated immunity is directed primarily at microbes that survive in phagocytes and microbes that infect non-phagocytic cells. It is most effective in removing virus-infected cells, but also participates in defending against fungi, protozoans, cancers, and intracellular bacteria. It also plays a major role in transplant rejection.

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Primary response

production of specific clones of effector T cells and memory clones
develops in several days
does not limit the infection

Secondary response

more pronounced, faster
more effective at limiting the infection

Example - cytotoxic reactions against intracellular parasites, delayed hypersensitivity (e.g., Tuberculin test) and allograft rejection

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Humoral immune response

1. B lymphocytes recognize specific antigens

- proliferate and differentiate into antibody-secreting plasma cells

Antibodies bind to specific antigens on microbes; destroy microbes via specific mechanisms
Some B lymphocytes evolve into the resting state

- memory cells

Humoral immunity or humoural immunity is the aspect of immunity that is mediated by macromolecules found in extracellular fluids such as secreted antibodies, complement proteins, and certain antimicrobial peptides. Humoral immunity is so named because it involves substances found in the humors, or body fluids. It contrasts with cell-mediated immunity. Its aspects involving antibodies are often called antibody-mediated immunity.

The study of the molecular and cellular components that form the immune system, including their function and interaction, is the central science of immunology. The immune system is divided into a more primitive innate immune system, and acquired or adaptive immune system of vertebrates, each of which contains humoral and cellular components.

Humoral immunity refers to antibody production and the accessory processes that accompany it, including: Th2 activation and cytokine production, germinal center formation and isotype switching, affinity maturation and memory cell generation. It also refers to the effector functions of antibodies, which include pathogen and toxin neutralization, classical complement activation, and opsonin promotion of phagocytosis and pathogen elimination

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ANTIGEN

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An antigen is a molecule that induces an immune response in the body .

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Antibody : immunoglobulin

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Immunoglobulin is a glycoprotein that is made in response to an antigen and can recognize and bind to the antigen that caused its production.
They are gamma globulins
Synthesized by plasma cells
Constitute 25-30 % of total serum proteins
Antibodies are present in serum, tissue fluids and mucosal surfaces.
All antibodies are immunoglobulins, but all immunoglobulins may not be antibodies.

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ANTIBODY STRUCTURE

It’s a large Y-shape protein produced by B cells that is used by the immune system to identify and neutralize foreign objects such as bacteria and viruses.
The antibody recognizes a unique part of the foreign target, called an antigen.

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Basic structure

Composed of 4 polypeptide chains.
2 identical light and 2 identical heavy chains
Linked by disulphide bonds
Light chains similar in all immunoglobulins
Light chains occur in 2 varieties kappa and lambda
Light and Heavy chains are subdivided into variable and constant region.
Each heavy and light chain contains amino terminal in variable region, carboxyl terminal in constant region

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Antibodies can occur in two physical forms
Soluble form that is secreted from the cell,
Membrane-bound form
That is attached to the surface of a B cell and is referred to as the B cell receptor (BCR).
Facilitates the activation of these cells and their subsequent differentiation into either antibody factories called plasma cells or memory B cells
That will survive in the body and remember that same antigen so the B cells can respond faster upon future exposure.

The BCR is only found on the surface of B cells

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Based on structure and antigenic nature of H chain the immunoglobulins are classified into 5 classes.
Ig G- (gamma)
Ig A- (alpha)
Ig M- (mu)
Ig D- (delta)
Ig E - (epsilon)

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Functions of Different Antibodies

IgA plays a role in localized defense mechanism in external secretions like tear
IgD is involved in recognition of the antigen by B lymphocytes
IgE is involved in allergic reactions
IgG is responsible for complement fixation
IgM is also responsible for complement fixation.

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References

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Ananthanarayan R. Ananthanarayan and Paniker's textbook of microbiology. Orient Blackswan; 2006.

Baveja CP. Textbook of microbiology. Arya Publications; 2005.

Shafer WG, Hine MK, Levy BM, Rajendran R, Sivapathasundharam B. A textbook of oral pathology. Philadelphia: Saunders; 1983 Sep 20.

Sembulingam K, Sembulingam P. Essentials of medical physiology. JP Medical Ltd; 2012 Sep 30.