T Lymphocytes

Introduction to Immunity

• Immunity is the body's ability to resist or eliminate harmful foreign materials or abnormal cells.
• The immune system defends against invading pathogens.
• Removes cells and tissue damaged by trauma.
• Immune surveillance identifies and destroys abnormal or mutant cells originating in the body.
• Inappropriate immune responses can lead to allergies or autoimmune diseases.

Types of Immunity

• There are two types of immunity: Innate and Adaptive.
• Adaptive immunity: Active and Passive.
• Active Immunity includes: Cellular and Humoral components.

Innate Immunity

• Also known as non-specific or natural immunity.
• It's a nonspecific defense against foreign invaders and the first line of defense.
• Responses work immediately when the body is exposed to a threatening agent.
• There are three components to innate immunity: Barriers, Defensive cells, and Chemical defenses.
• Barriers include physical and chemical barriers.
• Physical barriers include skin.
• Chemical barriers include lysozyme, acidity associated with stomach, urine, vagina.
• Defensive cells include WBCs, macrophages and natural killer cells (NK).
• Chemical defenses include the complement system.
• Interferons are named after their ability to "interfere" with viral replication.
• Types of Interferon: α, β, and y interferon.
• Interferons are released by virus infected cells.
• They function by blocking viral reproduction.
• Complement system helps antibodies and phagocytic cells clear pathogens from an organism.
• It comprises a series of approximately 20 proteins that are activated by microorganisms.
• Complement system coats the microorganisms aiding in adherence and activates mast cells.
• Complement system components also contribute to adherence reactions and forms biological active fragments.

Adaptive Immunity

• Also known as acquired immunity.
• It specifically targets foreign material to which the body has already been exposed.
• It takes the body time to prepare to attack.
• Adaptive immunity responses are mediated by B and T lymphocytes and the ultimate defense against most pathogens.
• The formation of memory cells allows the system to react swiftly against specific invaders in the future.
• Adaptive Immunity includes two types: Active and Passive immunity.
• Active immunity involves direct encounter with the antigen, as well as antibodies, and is transferred from mother to the fetus.
• Immunization is a form of passive immunuty administering antibodies.

B and T Lymphocytes

• Adaptive immunity is mainly produced from lymphoid colonies in lymphoid tissues.
• Lymphoid tissues produce, store, or process lymphocytes.
• Lymphocytes include structures like bone marrow, lymph nodes, spleen, thymus, tonsils, adenoids, appendix, and Peyer's patches in the GIT.

Antigens and Antibodies

• An antigen is any substance that stimulates antibody production when introduced.
• Examples are bacteria, fungus, viral particles, and parasites.
• Pathogens are antigens that cause disease.
• Hapten is not antigenic by itself, but becomes an antigen when combined with a protein.
• An antibody is a Y-shaped protein found on the surface of B-Cells or free in the blood, that neutralize antigens by binding specifically to the antigen.
• Antibodies are also known as immunoglobulins.

Immune Response

• Phases of the immune response: Initial phase, Central phase, Effector phase, Declining phase
• The initial phase involves antigen recognition.
• Entry of the antigen and its contact with the specific receptor on the lymphocytic membrane.
• The central phase involves activation, a cooperation among different subset of lymphocytes that proliferate and differentiate to form T & B lymphocytes + memory cells.
• The effector phase consists of Inactivation of antigen by sensitized T & B lymphocytes.
• The declining phase occurs after eradication of the microorganism.
• Activated cells die and a small proportion remain as memory cells.

Inflammation

• Roles of inflammation in innate immunity includes: Initiation of phagocytosis, limiting the spread of infection, stimulating adaptive immune response, and initiating tissue repair

B Lymphocytes

• Two classes of adaptive immunity: Antibody-mediated (humoral) immunity and Cell-mediated immunity.
• Antibody-mediated immunity involves the production of antibodies by B lymphocyte derivatives known as plasma cells.
• Cell-mediated immunity involves the production of activated T lymphocytes that directly attack unwanted cells.
• T-independent antigens activate B cells without assistance from T-helper cells, after binding with polysaccharide antigens.
• T-dependent antigens, polypeptide antigens, cannot stimulate B cells without the help of T-helper cells.
• Most antigens to which B cells respond are T-dependent.
• Upon binding with processed and presented antigen, most B cells differentiate into active plasma cells, while other B cells becomes dormant memory cells.
• Mature plasma cells produce antibodies rapidly at a rate of 2000 antibodies/sec.
• Antibodies eventually enter blood and are known as gamma globulins or immunoglobulins(Ig).

Immunoglobulin Subclasses

• IgM serves as the B cell surface receptor for antigen attachment and is secreted in early stages of plasma cell response.
• IgG is the most abundant immunoglobulin in the blood and is produced in large amounts when the body is exposed to the same antigen.
• IgE helps protects against parasitic worms and mediates common allergic responses.
• IgA is found in secretions of digestive, respiratory, and genitourinary systems, as well as milk and tears.
• IgD is present on the surface of many B cells and its function is uncertain.
• Antibodies are Y-shaped molecules composed of 4 interlinked polypeptide chains: two long, heavy chains and two short, light chains.
• The tail portion of the antibody determines its functional properties after binding with antigen.
• Antibodies can physically hinder antigens by neutralization which prevents harmful chemicals from interacting with susceptible cells and agglutination by binding to foreign cells.
• Pregnancy diagnosis tests use the principle of agglutination to detect hCG hormone present in urine after conception.
• Antibodies enhance activity of other defense systems like activating complement system, enhancing phagocytosis, and stimulating natural killer (K) cells.

Memory Cells

• Small percentage of B lymphocytes become memory cells and remain dormant.
• Upon re-exposure to the same antigen, they are more ready for immediate action than the original lymphocytes of the clone.
• The secondary response is quicker, more potent, and longer-lasting
• Secondary response can be induced by disease or vaccination.
• Active immunity is "self-generated". It results from exposure to an antigen
• Passive immunity is "borrowed immunity" that results from transfer of preformed antibodies.
• Passive immunity can provide immediate protection.
• Transfer of IgG antibodies from mother to fetus is an example of passive immunity, protection against tetanus toxins, anti snake venom, and rabies virus.

T Lymphocytes

• T lymphocytes are involved in cell-mediated immunity.
• Lymphocyte precursors migrate from bone marrow to the thymus for processing to form “T” lymphocytes.
• T lymphocytes develop and mature in the thymus and cells divide rapidly.
• During this processing each cell develops specific reactivity for one antigen.
• The end result are thousands of T lymphocytes each with different specific reactivities for different antigens.
• Processing insures that each T lymphocyte does not react with the body's own antigens (self antigen).
• Processed cells will leave the thymus to lymphoid tissues.
• Most processing of T lymphocytes will occurs prior to birth and is completed after birth.
• Mature T-cells have T cell receptors that are specific to one antigen.
• Types of T Lymphocytes: Cytotoxic T cells, Helper T cells, Suppressor T Cells, Memory T cells
• Cytotoxic or killer T cells destroy host cells harboring antigen.
• Helper T cells mostly modulate activities of other immune cells.
• Helper T cells secrete chemicals that amplify the activity of other immune cells.
• Helper T cells secrete B-cell growth factor, T-cell growth factor (interleukin 2) and Macrophagemigration inhibition factor.
• Suppressor T Cells are known as regulatory T cells and capable of suppressing actions of cytotoxic and helper T cells.
• They prevent excessive damage to the body tissue.
• Cytotoxic T Cells are exposed to infected/dysfunctional somatic cells.
• Cytotoxic T Cells release the cytotoxins perforin, granzymes, and granulysin.
• Through the action of perforin, granzymes enter the cytoplasm of the target cell and eventually lead to apoptosis (programmed cell death)
• Helper T cells are the most numerous and secrete lymphokines (IL-2, 3, 4, 5, 6)
• They have regulatory functions of lymphokines like stimulation of B cell growth and differentiation, activation of the macrophage system, and positive feedback effect on the helper cells.
• They function in the functioning of Cytotoxic T – cells.
• HIV virus destroys helper T cells resulting in hence loss both types of adaptive immunity..

Antigen Presentation

• T-Lymphocytes respond only to antigens presented for them by antigen-presenting cells.
• Antigen presenting cells include Macrophage, dendritic cells and B lymphocytes.
• Antigen presenting cell engulfs and ingests microbe, and digests the microbe into antigenic peptides.
• Antigenic peptides will bind to a MHC molecule which transports the bound antigen to the cell surface where it is presented to lymphocytes.
• Antigen-presenting cell secrete interleukins which enhance differentiation and proliferation of now-activated T-cell clone.

Self-Antigens

• Self-antigens, major histocompatibility complex/MHC, - plasma membrane-bounds glycoproteins.
• Synthesis is directed by group of genes called major histocompatibility complex (MHC) genes.
• MHC molecules are varied from one individual to another (BIOCHEMIAL FINGER PRINTS/ " MOLECULAR IDENTIFICATION CART are directing response or T-lymphocytes and are subject to rejection of transplanted tissue.
• Tolerance refers to preventing the immune system from attacking the person's own tissues, by means of clonal deletion, clonal anergy, Inhibition (by regulatory T cells ) and/or immunological ignorance
• Clonal anergy is the the instance in which specific lymphocytes are present but functionally inactive.
• Immunological ignorance refers to instances that Lymphocytes could remain in resting status after exposure to the antigen.
• Immune privilege anatomical regions that are naturally less subject to immune responses than most other areas of the body.
• Immune-privileged sites include the central nervous system, the eyes and the testes.
• Even foreign antigens accessing these tissues do not generally trigger immune responses.

Immune Diseases

• Immune diseases includes Immunodeficiency diseases and Inappropriate immune attacks.
• Immunodeficency refers to "too little immune response", ex: severe combined immunodeficiency, and acquired immune deficiency syndrome, AIDS.
• Inappropriate immune attacks is referred to as "Too much or mistargeted immune response", ex: Autoimmune responses, Immune complex diseases,and allergies.
• Autoimmune diseases is the loss of tolerance to self-antigens such as with multiple sclerosis, rheumatoid arthritis, or myasthenia gravis.
• In autoimmune disease, normal self-antigens may be modified by drugs, environmental chemicals, viruses, or genetic mutations so that they are no longer recognized and tolerated by the immune system

Hypersensitivity

• Hypersensitivity is if an immune reaction results in considerable damage to the body
• Four types of hypersensitivity(damage): type I hypersensitivity (anaphylaxis), type II hypersensitivity (antibody mediated cytotoxicity), type III hypersensitivity(immune complex disorder) and type IV hypersensitivity(delayed type of hypersensitivity)
• Mast cell degranulation results in Ig E repsonses such as eg, Allergic rhinitis, Eczema or acute urticaria
• Response Occurs after activation of Mediators like Histamine and Slow reacting substance of anaphylaxis (SRS-A)
• Its called Atopy

Vaccine

• Vaccine (vaccinus – pertaining to cows).
• Edward Jenner discovered vaccines for small pox.
• Act on the principle of mock infection
• Types of Vaccines: Live, attenuated, Inactivated , subunit, and Toxoid vaccines
• Live, attenuated vaccines protect against Measles, mumps, rubella, and polio
• Inactivated or killed vaccines protect against Cholera, flu,and hepatitis A
• Toxoid vaccine protect against Diphtheria, and tetanus