Cellular Response, Biology tutorial

Introduction:

Body responds to introduction of foreign compounds by eliciting the cellular response given by immune system. There are two kinds of immune response that is; adaptive immune response that gives life-long protection against the particular pathogen and has memory and specificity, and innate immune response, inherent immunity, gives first line of defense against pathogens and is non-specific.

Link exists between innate and adaptive immune response in two ways. First is that innate immune response to pathogens is liable for nature of adaptive immune responses. Second is that several effector mechanisms of innate immunity are significant to eliminate microbes in adaptive immunity.

Properties of Innate Immune Response:

Innate immune response which is the first line of defense against the intruding pathogen is very rapid and not capable to memorize intruder must it occur a second time. This kind of immunity is inherent and exists before infection by pathogen and will react in the similar manner if that same infection reoccurs. Innate immunity includes principal components like physical and chemical barriers, that is; epithelia and antimicrobial substances produced by epithelia surfaces, phagocytic cells mostly neutrophils, macrophages and natural killer cells, blood proteins comprising members of complement system and mediators of inflammation and cytokines that are responsible for regulation and coordination of cells of innate immunity.

Properties of Adaptive Immune Response:

This kind of immune response also known as specific or acquired immune response is specific as pathogen has been encountered before and cells still have immunologic memory which makes them react vigorously on second encounter with same microbe. It is able to detect subtle differences even among strongly associated microbes and macromolecules. Major components of adaptive immune response are lymphocytes and their products. This kind of immune response has six characteristics which are:

1) Specificity: It is specific for distinct antigen or different structural component of single complex proteins. Individual lymphocytes express membrane receptors which recognize little differences in structure between antigens.

2) Diversity: Total number of lymphocytes repertoire in individual is very large and this makes it possible for antigen binding sites of lymphocytes to be also diverse.

3) Memory: Once exposed to the particular antigen, immune system reacts rapidly to reoccurrence of same infection. Immunologic memory results from expansion of lymphocyte clones after exposure to antigen, and memory cells are more effective in destroying antigen than naive cells.

4) Specialization: Immune system responds in distinct manner and in special ways to different microbe.

5) Self limitation: Immune system after responding to antigenic stimulation return to basal state, a procedure known as homeostasis that is they wane with time.

Kinds of Adaptive Immune Response:

There are two classes of adaptive immune response performed by lymphocytes. They are cell mediated and humoral (antibody) immune response. Cell mediated immune response is performed by T lymphocytes and B lymphocytes are involved in humoral immune response. Cell mediated or cellular immunity defends against intracellular microbes like virus and bacteria that can survive and proliferate inside phagocytes and other host cells. When microbes are intracellular, they become inaccessible to circulating antibodies and it is only cell mediated immunity which can eliminate microbes inside phagocytes as well as able to lyse infected cell. Humoral immunity is mediated by molecules in blood called as antibodies produced by B lymphocytes. It is principal line of defense against extracellular microbes and their toxins.

Active and Passive Immunity:

There is also what is known as active immunity where the individual is keenly involved in responding to antigen. Here, immunity is induced either from the host's reaction to microbe, antibodies transferred to host or lymphocytes specific to the host. It is also likely to have immunity conferred to the individual without coming across pathogen. This is possible in cases where serum or lymphocytes from particularly immunized individual is transferred to the unimmunized individual, without having to be challenged by the pathogen. This is known as passive immunity and it is the form of immunity conferred to an unborn baby by the mother. This assists unborn baby to resist infections before baby is able to create antibodies.

Genetics of response to antigenic stimulation:

In response to antigenic invasion (antigenic stimulation), both Innate and Adaptive Immune response are elicited. Adaptive immune response (including B & T lymphocytes) is the most diverse and specific, while innate immune response, serving as first line of defense is unspecific generally reacting to all antigens same way.

Clonal Selection Theory:

Karl Landsteiner was the first to illustrate that there was collection of antibodies which could bind almost the infinite amount of pathogens in every individual. He proved this by showing that virtually a limitless range of molecules can elicit antibody production even synthetic materials.

F McFarlane Burnet proposed the clonal selection theory to describe diverse specificity of adaptive immune response. Hypothesis defines that antigen specific clones of lymphocytes develop before exposure to antigen. When antigen enters body, it selectively binds to the specific lymphocyte, therefore activating it. On activation, a clonal proliferation of bound lymphocyte takes place leading to production of lymphocytes of identical specificity to bound parent lymphocytes. Some of these newly generated clones distinguish in effector cells which assist to eliminate antigen, while some distinguish in memory cells which help to keep and save that specific antigenic determinant.

Postulates of clonal selection hypothesis:

  • Each lymphocytes bear single kind of receptor with the unique specificity
  • Interaction between the foreign peptide and lymphocyte receptor cable of binding that molecule with high affinity generally leads to lymphocyte action
  • Differentiated effector cells derived from the activated lymphocyte bear receptors of identical specificity to those of parental cells which lymphocyte was derived from
  • Lymphocytes bearing receptor specificity for ubiquitous self molecules are deleted early in state of development. They are generally absent in repertoire of mature lymphocytes.

Generation of Diversity in Adaptive Immune Response: Genetics of Response

Generation of Diversity in Antibodies:

Total collection of antibody specificity available in the individual is called as antibody repertoire. During maturation of B lymphocytes in bone marrow, the genes liable for creation of Immunoglobulin molecules (antibody) are expressed. Therefore specificity of each antibody in repertoire of every individual is determined even before B lymphocyte maturation. Amino acid sequence of variable region (V regions) of Immunoglobulin molecules is liable for specificity of each antibody.

Though genes coding for each variable region takes place in multiples, most of them are deleted during B lymphocyte maturation. Therefore, diverse specificity of antibody repertoire is attained through Somatic Recombination (random rearrangement of different genes) of remaining variable genes. After this, point mutations (single nucleotide changes in genes) are induced inside the rearranged genes, further increasing level of variability.

Diversity in T lymphocyte: MHC Molecules

T lymphocytes respond to peptide fragments of protein antigens which are shown by Antigen presenting cells (APCs). Task of showing antigens of cell-associated microbes for identification by T lymphocytes is performed by specialized proteins which are encoded by genes in Major Histocompatibiliy Complex (MHC). There are two different kinds of MHC gene products, known as class I MHC molecules and class II MHC molecules, that sample different pools of protein antigens (extracellular antigens which have undergone endocytosis and cytosolic intracellular antigens). Human MHC, also referred to as Human Leucocyte Antigen (HLA) locus is situated on the short arm of chromosome 6 spanning approx 4×106 base pairs.

Response to Antigenic Stimulation: A Practical Scenario

The B lymphocyte that recognises the bacterial epitope from the repertoire will selectively bind it (i.e. the antigenic determinant). Simultaneously, antigen presenting cells presents the extracellular antigens of the helper T lymphocytes or in some cases the B lymphocyte itself presents the antigen protein to the helper T cell. The helper T lymphocytes in turn recognises it has a foreign antigen, releases cytokines that activates the rapid proliferation of that particular Blymphocytes bound to the bacterial epitope to produce antibodies that collectively eliminate the bacterial and its toxins.

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