Immunology in Fish

Immunity

  • Immunity is the ability of the body to resist becoming infected upon exposure to a microorganism or parasite. The body’s various modes of resistance to attack give rise to different terminology to describe the types of immunity.
  • All the mechanisms used by the body to resist environmental agents (microbes or their products, foods, chemicals, drugs, pollen, animal hair, dander etc.) that are foreign to it.

Immunology

That branch of medical science which deals with the study of development and function of both cellular and humoral components of the immune system by which the body reacts to expel, destroy or neutralize foreign substances including pathogenic microorganism.”



Innate immunity 

Acquired Immunity (adaptive Immunity/specific Immunity)

This prevents entry of micro-organisms into tissues or, once they have gained entry, eliminates them prior to the occurrence of disease.

 

Characteristics

  • Present from birth.
  • Non-specific – acts on many organisms and does not show specificity.
  • Does not become more efficient on subsequent exposure to same organisms.

     

Important factors

A.     mechanical / physical factors

  1. Keratin layer of intact skin
  2. Intact mucosal lining of different organs.
  3. Washing action of tears, saliva and urine.
  4. Respiratory cilia- expel foreign substances including microbes.
  5. Mucous layer present over the inner surfaces of the body acts as a protective barriers to block the adherence of bacteria to epithelial cells.
  6. Coughing and sneezing reflexes- expel trapped foreign substance on the mucous lining of the respiratory tract.

 

B. Chemical factors

  1. Fatty acids of skin – inhibits growth of microorganisms.
  2. Acid pH of sweat and sevaceous seretions- inhibitory to micro-organisms.
  3. Lysozyme in tears, nasal sections and saliva- degrades peptidoglycan, an essential element present in bacterial cell wall.
  4. Spermine and zinc in the semen – are bactericidal.
  5. Lactoperoxidase in milk- has bactericidal action.
  6. Low pH (acidic environment) of stomach and vagina- inhibits growth of many microbes.

C. Biological factors

  • Normal bacterial flora present in the throat, colon and vagina – inhibits colonization by other pathogens (bacterial interference)
  • Phagocytosis by neutrophils and macrophages.

Natural killer (NK)cells – are involved in extra cellular killing of target

This type of immunity occurs in response to infection called ADAPTIVE as the immune system must adapt itself to previously unseen molecules. Following recovery from certain infections with a particular micro-organism, individuals will never again develop infection with the same organism,

but can become infected with other micro-organisms, i.e. he/she is protected against one micro-organism. This form of protection is called IMMUNITY and an individual is said to be IMMUNISED against that organism.

 

Cardinal features of acquired immunity

 

Specificity: the ability to discriminate among different type of antigenic determinants.

Memory: the ability to recall previous contact with a particular tupe of antigen, such that subsequent exposure leads to a more rapid and larger production of antibody or T cell responses.

Adaptive-ness: the ability to respond to previously unseen antigens, which may never have existed before on the earth or not defined.

Self-limitations: all normal immune responses die out with time after antigen stimulation.

Discrimination of self from non-self: lymphocytes are able to recognize and respond to many foreign antigens but are normally unresponsive to the potentially antigenic substances present in that individual.

Non-specific elimination of micro-organisms

 

Phagocytosis 

Opsonisation 

ingestion and killing of micro-organisms by specialized cells (phagocytes). 

the process of coating micro-organisms with some of the proteins found in plasma, to make them more easily phagocytosable.

Phagocytes: polymorphonuclear leukocytes (neutrophils), mononuclear phagocytes (monocytes, macrophages). 

An OPSONIN is a plasma protein binding to bacteria. This promotes adhesion between the opsonised bacteria and macrophages because the opsonin binds to receptors on phagocyte membrane e.g. complement with complement receptors and phagocytes.

 

Complement and phagocytes exist mainly in blood so a mechanism is required to recruit these elements to the site of tissue invasion

Opsonisation and phagocytosis are more efficient in immune individuals.

Determinants of innate immunity

There are many factors which can modify the non-specific immune mechanisms of which following determinants are important.

Genetic factors: whole immune response is under the active control of the immune response gene. In determining the disease susceptibility, the role of genetic factors are gaining importance day by day.

There is difference in immune response among different species and races. For example, black Africans are less susceptible to develop falciparum malaria and there is also racial difference in susceptibility to other diseases like tuberculosis and coccidiiodomycosis.

Age: immune system is hypo functional in extremes of age. Therefore newborns and very old peoples are more susceptible to many infections.

Humoral and metabolic conditions of the individual: certain hormones affect immune response e.g. diabetic patients are more susceptible to bacterial infections.

Nutritional status: malnutrition is associated with lower immunity and makes the individual more susceptible to infections.

Types:

 

ACTIVE IMMUNITY

PASSIVE IMMUNITY

The induction of immunity by infection or with a vaccine is called 

Historically it has been shown that a nonimmune individual can be made immune by transferring serum or lymphocytes from an immune individual. serum constituents (ANTIBODIES) and LYMPHOCYTES are involved in immunity.

Two types: natural active and artificial active. 

Two types: natural passive and artificial passive.

Natural A. 

Artificial A. 

natural 

artificial 

Occurs during infection.

Injecting or taking antigens by mouth.

Mother to child through placenta or milk.  

Used during potentially fatal diseases 

It is active because lymphocytes are activated by antigens on pathogen’s surface.

Takes time for T and B cells to be activated but gives long lasting immunity.

 

Provides an instant response but only temporary as antibodies are not the body’s own so memory cells are not created.

E.g. tetanus – injection of antitoxins given.

 

Memory cells

  • are only produced in active immunity.
  • Protection for active immunity is permanent whereas in passive immunity it is only temporary.
  • Antigens are only encountered in active immunity.

Active immunity takes several weeks to become active but passive is immediate.

Cells of innate immunity

Natural killer (NK)cells

Macrophages

Polymorphonuclear leukocytes(neutrophils)

Eosinophils

These are group of lymphoid cells that are functionally,morphologically, and developmentally distinct from T and B cells and are capable of producing non-specific cellular cyto-toxicity. There are large granular lymphocytes, which produce cytotoxic effect to virally infected cells and tumor cells.

The term macrophage is derived from macro large and phage to eat, i.e. ‘large eater’. Macrophages impart very important role in both innate and acquired immunity.

These are maturephagocytic cells derived from circulating monocytes,which act primarily by engulfing and digesting bacteria, cellular debris and other particulate matter.

They function as the principal scavenger cells of the body.

Neutrophils also called microphage are short lived, phagocytic cells that contain granules filled with hydrolytic enzymes involved in innate immunity.

The y arise in the bone marrow and makes up form 60%to 70% of the total leukocytes count in the peripheral blood.

Eosinophils are distinguish by coarse cytoplasmic granules contain Eosionophils peroxidase among other enzymes that can generate toxic oxygen metabolites.

They constitute about 1-3 percent of circulating leukocytes and are not professional phagocytic cells.

They can recognize there cells when come in contact with them and forms a transmembrane pore with an annular structure and induces cellular death.

If stimulated they can release cytokines.

However, the precise physiological role played by NK cells is still not very clear. Chondroitin sufate A protects the NK cell from autolysis by its own agents.

The cells secrete enzymes, reactive oxygen radicals, nitric oxide and prostaglandin, all of which serve to kill microbes and control the spread of infection. Macrophages produce cytokines that recruit other inflammatory cells specially neutrophis and are responsible for many systemic effects of inflammation.

The primary function of this cell is ingestion and digestion of particular material especially highly virulent bacteria through the process of phagycitosis.

They take part in inflammation through the edition of certain components of complement.

This process has been termed as ‘first line of defense’.

Eosinophils are consistently found in tissues where allergic conditions are operative, such as allergic rhinitis or certain parasitic infestations.

They play a unique role in killing large parasites such as helminthes by special mechanism that cannot be physically phagocytosed.

Basophil: A white blood cell that contributes to inflammatory reactions. Along with mast cells, basophils are responsible for the symptoms of allergy.

Complement: A complex series of blood proteins whose action “complements” the work of antibodies. Complement destroys bacteria, produces inflammation, and regulates immune reactions.

Eosinophil: A white blood cell that contains granules filled with chemicals damaging to parasites, and enzymes that damp down inflammatory reactions.

Kupffer cells: Specialized macrophages in the liver.

Acquired immunity cells

B cells: Small white blood cells crucial to the immune defenses. Also known as B lymphocytes, they are derived from bone marrow and develop into plasma cells that are the source of antibodies. Bone.

T cells: thymus cells. Direct capture.

Innate immunity cells.

Secreted molecules:Complements, cytokines and antibodies. All secreted in A. immun.. First two secreted in I. immune.

Antigens and Immunogens

Immunogen:

Any substance that induces a specific immune response mediated by either T-cell or B-cell or both but not react with antibody.

Antigen:

Is a substance usually protein or polysaccharide in nature which when introduced in a suitable animal through a suitable route produces antibody with which it reacts specifically.

Sometimes used to define as a substance that reacts with pre-formed products of immune response (antibody, T-cell) but is not necessarily immunogenic, i.e. it does not induces or initiate an immune response on its own. So, all Immunogens are Antigens but not vice-versa.

Hapten:

Greek word ‘Hapten’ means, ‘to fasten’. These are low molecular weight compounds that are not immunogenic by themselves but become immunogenic when they are conjugated to high molecular weight proteins known as carriers. e.g; drugs,antibiotics(penicillin),cosmetics and many small synthetic peptides.


    +                 

Hapten    Carrier     Antigen    Antibody

Hapten-carrier conjugates

  • Definition
  • Structure
    • native determinants
    • haptenic determinants

Epitope or Antigenic Determinant:

Naturally occurring small chemical groups present on the surface of an antigen against which all immune activity is directed.

It determines the specificity of antigen-antibody reaction. Size: quite small, 5-10 amino acids in case of protein antigens and 3-6 sugar molecules in case of polysaccharides.

Antibody:

Plasma Proteins which are produced in response to antigens with which they react specifically.

Factors Influencing Immunogenicity/ Antigenecity: Contribution of the Immunogen:

Foreignness

  • Must not be recognized as ‘self’ by the immune system (injecting serum of rabbit in its own body is not Immunogen)

Size

  • High molecular weight (MW): >1000dalton, optimum:100000
  • Exceptional: silk fibre (600-1000 D.) and glucogen (800 D.) are immu. But dextrin with 100000 is not.

Chemical Composition

Sequence determinants     increase of chemical complexity

  • Primary Structure

Conformational determinants     increase of immunogenicity

  • Secondary Structure
  • Tertiary Structure
  • Quaternary Structure

Amino acid homopolymers < Amino acid heteropolymers

Physical Form

  • Particulate > Soluble
  • Denatured > Native

Degradability

  • Ag processing by Ag Presenting Cells (APC)

Genetics

  • Species
  • Individual

Responders vs Non-responders

Age

Factors Influencing Immunogenicity: Method of Administration

  • Dose
  • Route
    • Subcutaneous > Intravenous > Intragastric
  • Adjuvant
    • Substances that enhance an immune response to an Ag

Classification of Immunogens

According to Chemical Nature of Immunogens

  • Proteins: All. lipoprotein, glycoprotein etc.
  • Polysaccharides: not always. ABO blood group antigens.
  • Nucleic Acids: less, when denatured or single. DNA not, but when denatured in case of Systemic Lupus Matosus (SLE) it acts as immu.
  • Lipids
    • Some glycolipids and phosopholipids can be immunogenic for T cells and illicit a cell mediated immune response.
    • Act as haptens

On the basis of mode of action

  1. T-dependent: require helps from T-lymphocytes.

Proteins

Structure

Examples

  • Microbial proteins
  • Non-self or Altered-self proteins
  1. T-independent: does not.

Polysaccharides

Properties

  • Polymeric structure
  • Polyclonal B cell activation

    • Yes -Type 1 (TI-1)
    • No – Type 2 (TI-2)
  • Resistance to degradation

Examples

  • Pneumococcal polysaccharide, lipopolysaccharide
  • Flagella

On the basis of Epitope or Antigenic Determinant

  1. Unideterminant univalent: single epitope of given specificity, e.g; hapten
  2. Unideterminant multivalent: Two or more dete. of the same kind, e.g; many polysaccharides
  3. Multideterminant multivalent: multiple dete. and different kinds, e.g; proteins

Antigenic Determinants

Recognized by B cells and Ab

Recognized by T cells

Composition

  • Proteins, polysaccharides, nucleic acids
  • Sequence (linear) determinants
  • Conformational determinants

Composition

  • Proteins (some lipids)
  • Sequence determinants
    • Processed
    • MHC presentation (lipid presentation by MHC-like CD1)

Size: 4-8 residues 

Size: 8 -15 residues 

Number

  • Limited (immunodominant epitopes)
  • Located on the external surfaces of the Ag

Number

Limited to those that can bind to MHC

Super-antigens

  • Definition : Superantigens are molecules that stimulate, independent of antigen, those T- cells displaying a particular beta chain variable region (Vbeta) of the T-cell receptor. These molecules are the most powerful T-cell mitogens known inducing biological effects at femtomolar concentrations. Recently it has been demonstrated that superantigens possess biological properties, e.g., lethality and emesis, which are separable from their T-cell mitogenicity. The best characterized superantigens are the microbial toxins from Staphylococcus aureus and Streptococcus pyogenes.



Monoclonal/Oligoclonal T cell response

1:104 – 1:105

  • Examples
    • Staphylococcal enterotoxins
    • Staphylococcal toxic shock toxin
    • Staphylococcal exfoliating toxin
    • Streptococcal pyrogenic exotoxins

Determinants Recognized by the Innate Immune System

  • Adaptive Immune System

    – Discrete Determinants

    • Reacts with a specific pathogen
  • Innate Immune System

    – Broad Molecular Patterns

    • Reacts with a variety of pathogens
  • PAMPs – Pathogen Associated Molecular Patterns
  • PRRs – Pattern Recognition Receptors

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