Immunity

IMMUNITY:

 

  •  Every day, we encounter numerous infectious agents, yet not all exposures lead to disease. This is attributed to the body's remarkable ability to defend itself, a phenomenon known as immunity. 
  •  Immunity aims to protect the body from harmful invaders, including bacteria, viruses, fungi, and parasites.
  •  Involves various immune cells (white blood cells) and molecules (antibodies, cytokines) working collaboratively.
  • Exhibits immunological memory, allowing a quicker and more targeted response upon subsequent exposures. 
  • Understanding immunity is vital in appreciating the body's ability to maintain health by recognizing and combating potential threats, ensuring a delicate balance between protection and self-preservation. 
  • Types of Immunity-

i) Innate Immunity and

ii) Acquired immunity.

 

Innate Immunity-

  • Innate immunity is like our body's own security system, always ready from the moment we are born. It's a set of defenses that doesn't target specific invaders but offers a quick and general response to a variety of potential threats. 
  •  Innate immunity doesn't aim at specific pathogens. Instead, it acts as a general safeguard against a wide range of invaders. 
  •  Acting as the initial line of defense, innate immunity is the immediate responder to potential threats encountered by the body. 
  • The non-specific nature of innate immunity ensures rapid and immediate protection against a broad range of pathogens. This is crucial for early defense before more specific responses can be mounted. 
  •  Unlike acquired immunity, innate immunity lacks specificity and memory. It does not tailor its response to specific pathogens and does not exhibit an enhanced reaction upon subsequent exposures. 
  • Utilizes barriers to hinder foreign agent entry. 
  •  Barriers include physical, physiological, cellular, and cytokine defenses. 

1. Physical Barriers:

- Skin acts as a primary defense, preventing microorganisms' entry. 

- Mucus coating in respiratory, gastrointestinal, and urogenital tracts traps microbes. 

2. Physiological Barriers:

- Stomach acid, saliva, and tears inhibit microbial growth. 

3. Cellular Barriers:

- Certain types of white blood cells (leukocytes) act as cellular barriers in innate immunity. 

- Among these are polymorpho-nuclear leukocytes (PMNL-neutrophils) and monocytes circulating in the blood, along with natural killer cells (a type of lymphocyte). 

- Additionally, macrophages in tissues play a crucial role. These cells exhibit phagocytosis, engulfing and destroying microbes as part of the body's immediate defense. 

4. Cytokine Barriers:

- Innate immunity employs cytokine barriers as a defense mechanism.

- When cells become infected by viruses, they release proteins known as interferons.

- These interferons serve to protect non-infected cells from further viral infection.

- By inducing an antiviral state in neighboring cells, interferons contribute to limiting the spread of the virus within the body. 

 

Acquired Immunity-

  • Acquired immunity displays memory, leading to a heightened response upon reencountering a previously encountered pathogen. 
  • Acquired immunity is distinctively pathogen-specific and characterized by memory. When the body encounters a pathogen for the first time, it triggers a primary response of low intensity. 
  • Upon subsequent encounters with the same pathogen, a highly intensified secondary or anamnestic response occurs, indicating the body's memory of the initial exposure. 
  •  Two types of lymphocytes play crucial roles:

- B-lymphocytes produce antibodies, proteins that fight pathogens. 

- T-lymphocytes, while not secreting antibodies themselves, assist B cells in antibody production. 

  • Antibodies consist of four peptide chains: two light chains and two heavy chains (represented as H2 L2). 
  • Various antibodies, including IgA, IgM, IgE, IgG, are produced in response to different pathogens. 
  • The humoral immune response, also known as antibody-mediated immunity, involves the production and circulation of antibodies in the bloodstream. This process is orchestrated by B-lymphocytes, a type of white blood cell. 
  •  In the humoral immune response, B-lymphocytes undergo a sophisticated process of recognizing specific antigens (foreign substances) present on pathogens. Once activated, these B-cells transform into plasma cells, which are specialized factories for producing antibodies. Antibodies, also known as immunoglobulins (Igs), are proteins designed to lock onto and neutralize specific antigens. They circulate in the bloodstream, ready to encounter and counteract pathogens. The diverse types of antibodies, such as IgA, IgM, IgE, and IgG, play distinct roles in immune defense. This humoral response provides a swift and tailored defense against pathogens circulating in the blood or those attempting to enter through the bloodstream. 
  • The second type of acquired immune response is the cell-mediated immune response (CMI). Unlike the humoral response, which relies on antibodies, CMI is mediated by T-lymphocytes. 
  • In contrast to the humoral response, the cell-mediated immune response (CMI) is orchestrated by T-lymphocytes. T-cells play a pivotal role in recognizing and directly interacting with infected or abnormal cells. This type of response is particularly essential in addressing intracellular pathogens (those that reside within host cells) and in the rejection of transplanted tissues. CMI is crucial for distinguishing "self" from "nonself" and is responsible for graft rejection in organ transplantation. The immune memory developed through CMI ensures a rapid and intensified secondary response upon reencountering previously recognized antigens, enhancing the body's ability to combat specific threats. 
  • Cell-mediated immune response plays a role in rejecting grafts/transplants. Tissue and blood group matching are crucial, and even with matching, patients often need lifelong immunosuppressants. 

 

Active and Passive Immunity-

Active Immunity:

  • Initiation: Activated when the host encounters antigens, including living or dead microbes or other proteins. 
  • Response: The body produces antibodies in response to antigen exposure. 
  • Timing: Gradual process, taking time to establish a full and effective immune response.
  •  Induction: Can be induced through deliberate injection of microbes during immunization or by natural infection.

 

Passive Immunity:

  • Transfer of Antibodies: Involves providing pre-formed antibodies directly to the body for defense against foreign agents.
  • Speed of Action: Acts swiftly, as it doesn't rely on the host's immune system to produce antibodies. 
  • Example - Mother's Milk: Colostrum, the initial milk produced during lactation, contains abundant antibodies (IgA) and provides passive immunity to newborn infants.
  • Transfer During Pregnancy: Antibodies are transferred from mother to fetus through the placenta during pregnancy.
  •  Significance of Passive Immunity:

- Mother's milk, particularly colostrum, is crucial for newborns, offering immediate protection with pre-formed antibodies.

- The transfer of antibodies during pregnancy ensures early defense for the infant before their immune system fully develops.

 

Antibodies

 

 

  • Antibodies, also known as immunoglobulins (Igs), are Y-shaped proteins produced by the immune system. 
  • Crucial components of the immune response, responsible for recognizing and neutralizing pathogens.

 

Structure-

  • Distinctive Y-shaped structure with two identical heavy chains and two identical light chains. 
  •  Variable and Constant Regions: Variable regions for antigen recognition, constant regions for immune system signaling. 
  • Antigen-Binding Sites: Located in the variable regions, allow specific binding to antigens. 
  •  Heavy Chains: Form the longer arms of the Y structure. 
  • Light Chains: Form the shorter arms and are structurally different from heavy chains. 
  • Linkage: Held together by disulfide bonds, contributing to antibody stability.

 

Types of Antibodies-

  • IgG (Immunoglobulin G):

- Most prevalent antibody in blood and tissue fluids.

- Functions: Enhances phagocytosis, neutralizes toxins, provides passive immunity to the fetus. 

  • IgM (Immunoglobulin M):

- Large pentameric structure.

- Function: Involved in initial immune response, activates complement system. 

  • IgA (Immunoglobulin A):

- Found in mucosal areas (saliva, tears, breast milk).

- Function: Provides localized immunity, prevents pathogen attachment. 

  •  IgD (Immunoglobulin D):

- Present on the surface of B cells.

- Function: Involved in B cell activation. 

  •  IgE (Immunoglobulin E):

Involved in allergic reactions and defense against parasitic infections.

 

Production of Antibodies:

  • B Cells: Main producers of antibodies. 
  • Antigen Stimulation: Recognition of antigens by B cells triggers antibody production. 
  • Plasma Cells: Differentiated B cells specialized in antibody production. 

Functions of Antibodies:

  • Neutralization: Binding and neutralization of pathogens, preventing their harmful effects. 
  • Opsonization: Coating pathogens to enhance phagocytosis by immune cells. 
  • Activation of Complement System: IgM and IgG activate the complement cascade. 
  • Antibody-Dependent Cellular Cytotoxicity (ADCC): Antibodies signal immune cells to destroy pathogens. 
  • Providing Immunity: Transfer of maternal antibodies to newborns provides passive immunity. 

Role in Immune Memory:

  • Memory Cells: Antibodies play a crucial role in the formation of memory B cells. 
  • Rapid Response: Memory cells enable a quick and robust immune response upon re-exposure to a pathogen.

 

Vaccination and Immunisation

  • Immunization or vaccination hinges on the remarkable 'memory' feature of the immune system. 
  • The process involves introducing a preparation of antigenic proteins from a pathogen or an inactivated/weakened pathogen (vaccine) into the body. 
  •  Vaccines aim to stimulate the production of antibodies against specific antigens, equipping the body to neutralize pathogenic agents during an actual infection. 
  • The introduced vaccines not only trigger the immediate production of antibodies but also establish a 'memory' in B and T-cells. This memory ensures a rapid and robust immune response upon subsequent exposure to the pathogen. 
  •  In instances where a quick immune response is crucial, such as tetanus or snakebites, direct injection of preformed antibodies, or antitoxins containing antibodies to toxins, is necessary. This form of immunization is termed passive immunization. 
  • Advancements in recombinant DNA technology have revolutionized vaccine production. Antigenic polypeptides of pathogens can now be produced in bacteria or yeast, enabling large-scale vaccine production. An example is the hepatitis B vaccine produced using yeast. 
  • Significance of Recombinant DNA Technology:

Recombinant DNA technology enhances the efficiency and availability of vaccines. The ability to produce antigenic polypeptides on a large scale ensures broader accessibility for immunization efforts.

 

Allergies

  • Allergy, characterized by an exaggerated immune response to specific antigens in the environment, is a common occurrence. These antigens, known as allergens, trigger an immune response involving IgE antibodies. 
  • Allergens include substances like dust mites, pollens, and animal dander. Sensitivity to these allergens can vary based on geographical locations. 
  • Allergic reactions manifest through symptoms such as sneezing, watery eyes, a runny nose, and difficulty in breathing. 
  • The release of chemicals like histamine and serotonin from mast cells contributes to allergic symptoms. 
  • Determining the cause of allergy involves exposing or injecting the patient with small doses of potential allergens to study reactions. Drugs like anti-histamines, adrenaline, and steroids are utilized to rapidly alleviate allergy symptoms. 
  • The contemporary lifestyle has been associated with reduced immunity and heightened sensitivity to allergens. In metro cities, an increasing number of children experience allergies and asthma, potentially linked to environmental sensitivity and early-life protected environments.

 

Auto Immunity

  • Higher vertebrates have developed a sophisticated immune system characterized by memory-based acquired immunity. 
  • This immunity involves the ability to recognize and remember foreign organisms, differentiating them from the body's own cells. 
  • The immune system's ability to distinguish between foreign molecules and organisms is a crucial aspect of its function. 
  • Experimental immunology extensively explores how the immune system identifies and responds to external threats, such as pathogens. 
  • Corollaries of Immune System Function:

1. Recognition of Foreign Molecules: The immune system can identify and respond to foreign molecules, initiating immune responses to neutralize or eliminate potential threats.

2. Recognition of Foreign Organisms: In addition to molecules, the immune system is adept at recognizing and targeting entire foreign organisms, such as bacteria or viruses. 

  • Autoimmunity refers to a situation where the immune system mistakenly targets and attacks the body's own cells and tissues. 
  • Autoimmune Diseases: In certain instances, for reasons not entirely understood, the immune system may erroneously attack self-cells, leading to autoimmune diseases. 
  • Rheumatoid arthritis is cited as an example of an autoimmune disease affecting a significant portion of the population. 
  •  In Rheumatoid arthritis the immune system targets the synovium (lining of joint membranes), causing inflammation, joint damage, and deformities. 
  • Autoimmune diseases often have a genetic component, with certain individuals being more susceptible. 
  •  While genetic factors play a role, autoimmune diseases can also be triggered by environmental factors or events not yet fully understood. 
  • Autoimmune diseases result in the immune system mistakenly damaging the body's tissues, leading to various symptoms and, in some cases, chronic conditions.

 

Immune System in the Body (Lymphoid organs)

  • The human immune system comprises lymphoid organs, tissues, cells, and soluble molecules, including antibodies. 
  •  It possesses the unique ability to recognize foreign antigens, mount responses against them, and retain a memory of encountered threats. 
  • The immune system identifies foreign antigens, distinguishing them from the body's own components. 
  • It reacts to foreign antigens, initiating immune responses to neutralize or eliminate potential threats. 
  • The immune system memorizes encountered antigens, enabling a more rapid and effective response upon subsequent exposures.
  •  The immune system plays a role in allergic reactions, responding exaggeratedly to certain antigens, resulting in symptoms like sneezing and difficulty breathing. 
  •  It is involved in auto-immune diseases where the immune system mistakenly attacks the body's own cells, as seen in conditions like rheumatoid arthritis. 
  • The immune system plays a crucial role in organ transplantation, where it must be carefully managed to prevent rejection. 
  • Primary Lymphoid Organs:

Bone marrow and thymus are primary sites for the origin, maturation, and proliferation of lymphocytes. 

  • Maturation Process:

Immature lymphocytes differentiate into antigen-sensitive lymphocytes in these primary organs. 

  • Migration:

After maturation, lymphocytes migrate to secondary lymphoid organs. 

  • Secondary Lymphoid Organs:

- Spleen:

A large organ acting as a blood filter, containing lymphocytes and phagocytes. It traps blood-borne microorganisms and has a reservoir of erythrocytes. 

- Lymph Nodes:

Small structures along the lymphatic system that trap microorganisms or antigens, activating lymphocytes and initiating immune responses. 

- Other Organs:

Tonsils, Peyer’s patches (small intestine), and appendix also serve as secondary lymphoid organs. 

  • Micro-Environments for T-Lymphocytes:

- Bone Marrow and Thymus:

Provide specialized micro-environments supporting the development and maturation of T-lymphocytes. 

- Thymus Changes:

The thymus is larger at birth but diminishes in size with age, becoming considerably smaller by puberty. 

  • Mucosa-Associated Lymphoid Tissue (MALT):

- Location:

Found within the lining of major tracts (respiratory, digestive, urogenital). 

- Contribution:

Comprises approximately 50% of the lymphoid tissue in the human body.