Immune System: Innate and Adaptive

Immune System Function

• The immune system's primary function is to defend the body against harmful microorganisms, pathogens, and abnormal cells, like cancer cells.
• Homeostasis is maintained by distinguishing between self and non-self entities and eliminating threats to the body.
• Foreign invaders (antigens) are recognized and responded to through both innate and adaptive immunity
• The immune system has the ability to "remember" past infections, which helps to mount quicker and stronger responses if the body encounters the same pathogen again.

Innate vs Adaptive Immunity

• Innate immunity is the body's first line of defense and is non-specific, responding to all pathogens in the same manner.
• Physical barriers, phagocytic cells, natural killer cells and antimicrobial proteins are part of this rapid, broad defense mechanism.
• Innate immunity reacts in the same way every time a pathogen is encountered and does not have memory
• Adaptive immunity is highly specific and involves specialized lymphocytes (T cells and B cells)
• Memory cells give this type of immunity the ability to "remember" pathogens for a quicker and stronger response.
• Humoral immunity, mediated by B cells and antibodies, and Cellular immunity, mediated by T cells, are the two main branches of adaptive immunity.

Innate Body Defenses

• First line of defense (Surface membrane barriers) includes the skin, mucous membranes, and secretions.
• Skin acts as a physical barrier and prevents the entry of pathogens.
• Mucous membranes line body cavities exposed to the external environment and secrete mucus to trap pathogens.
• Tears, saliva, and mucus contain lysozyme and other enzymes that break down bacterial cell walls for antimicrobial action
• Second line of defense are the internal defenses
• Phagocytes such as neutrophils and macrophages engulf and digest pathogens and debris.
• Natural killer (NK) cells can induce apoptosis to kill infected or abnormal cells (programmed cell death).
• Proteins like complement proteins and interferons are antimicrobial; they directly kill pathogens, and enhance phagocytosis and help protect neighboring cells from viral infections.
• Tissue injury or infection triggers an inflammation response consisting of vasodilation and increased permeability which allows immune cells to reach the affected area.
• Fever, or an elevated body temperature, inhibits the growth of pathogens and enhances the immune response.

Non-Specific Immunity Examples

• The skin's acidic pH and physical barrier prevents pathogen entry and inhibits bacterial growth.
• Pathogens are trapped in the mucus that lines the respiratory, gastrointestinal, and urogenital systems
• Lysozyme, which breaks down bacterial cell walls, is present in saliva and tears.
• Neutrophils and macrophages are examples of phagocytes
• They engulf and digest pathogens, acting to defend the body within
• Pathogens are engulfed into a vesicle and fuses with a lysosome for digestion.

Nature of Inflammatory Response

• Redness is a result of increased blood flow.
• Heat results from the dilation of blood vessels and increased blood flow to the area.
• Swelling happens due to the accumulation of fluid and immune cells at the site
• Pain is the result of the release of chemical mediators, like bradykinin and prostaglandins, which increase the sensitivity of pain receptors.
• Blood vessels dilate during vasodilation, which increases blood flow to the affected area
• Blood vessel walls become more permeable during increased permeability which allows immune cells and proteins travel into the tissue, causing swelling and helping fight the infection.
• Neutrophils and macrophages engulf and digest pathogens and tissue debris during phagocytosis.
• The inflammation subsides once the pathogen is cleared and tissue repair begins.

Phagocytes & Immunity

• Neutrophils and macrophages (phagocytes), are important in the innate immune response.
• They identify, engulf, and digest foreign invaders (pathogens), dead cells, and debris to promote immunity.
• Pathogens are enclosed in a vesicle (phagosome) during phagocytosis, which then fuses with a lysosome to degrade the pathogen.
• Phagocytes function as antigen-presenting cells (APCs) by displaying pathogen pieces (antigens) on their surface to activate T cells and initiate adaptive immune responses.

Antimicrobial Proteins

• Complement proteins circulate in the bloodstream and, upon activation, create holes in the membranes of pathogens, leading to their destruction via membrane attack complex (MAC) formation.
• Phagocytes' effectiveness is enhanced by complement/opsonization, and inflammation is triggered by attracting immune cells to the site of infection.
• Infected cells produce interferons, or cytokines, which protect surrounding cells from viral infections.
• Interferons signal neighboring cells to increase their antiviral defenses, by stimulating the production of proteins that inhibit viral replication, and enhance macrophages and NK cells activity.

Adaptive Body Defenses

• Adaptive immunity is a highly specific response to pathogens, where the body mounts a tailored attack against specific antigens.
• Compared to innate immunity, it is slower to respond, however it provides long-term protection through the formation of memory cells.
• Humoral immunity involves B cells which produce antibodies that bind to and neutralize pathogens in body fluids.
• Cellular immunity involves T cells, which directly attack infected or abnormal cells, and is responsible for dealing with intracellular pathogens and tumor cells.

Humoral vs Cellular Immunity

• B cells secrete antibodies into the bloodstream to mediate humoral immunity; they bind to specific antigens on the surface of pathogens or infected cells, marking them for destruction or neutralizing their harmful effects.
• Extracellular pathogens, like bacteria, fungi, and viruses in their free form, are primarily targeted by humoral immunity.
• T cells mediate cellular immunity to help activate other immune cells, while others directly attack and destroy infected or cancerous cells.
• Intracellular pathogens, like viruses or other pathogens that have infected host cells, as well as tumor cells, are targeted by cellular immunity.

Antigen vs Self-Antigen

• Antigens are foreign molecules or substances that trigger an immune response.
• They are often found on the surface of pathogens or in toxins and are recognized by the immune system as non-self, which provokes the production of antibodies or T cell activation.
• Self-antigens, molecules or proteins found on the body's own cells, are generally tolerated by the immune system.
• The immune system mistakenly identifies self-antigens as foreign and attacks the body's own tissues in autoimmune diseases under abnormal conditions.

Lymphocytes Within the Blood

• Adaptive immunity relies on lymphocytes, a type of white blood cell.
• B cells are responsible for humoral immunity.
• They differentiate into plasma cells, which produce antibodies, when activated and they also form memory cells to provide lasting immunity against a previously encountered pathogen.
• T cells are responsible for cellular immunity and consist of different types
• Helper T cells (CD4+) stimulate cytotoxic T cells, B cells, and other immune cells by secreting cytokines.
• Infected or cancerous cells are directly killed through apoptosis by Cytotoxic T cells (CD8+).
• Regulatory T cells suppress the immune response to avert hyperactive immune reactions or autoimmunity.
• Memory T cells are long-lived cells that provide immunity by responding to previously encountered antigens.

Cells Promoting Immunity

• The ability of B cells to make antibodies is central in order to achieve humoral immunity.
• By producing antibodies, plasma cells help to destroy pathogens.
• By ensuring a rapid response if the same pathogen is encountered again, memory B cells help you out in the future.
• By killing infected cells, cytotoxic T cells help manage and eliminate intracellular pathogens.
• The development and operation of other immune cells, such as B cells, is aided by helper T cells. They are crucial for assembling coordinated responses
• Autoimmune reactions and sustaining self-tolerance are supported by regulatory T cells.
• Natural killer (NK) cells, a part of the innate immune system, detect and kill infected or abnormal cells (without prior sensitization) to provide early defense against viral infections and tumor cells.
• Plasma cells secrete antibodies that bind to specific antigens, marking them for destruction or neutralization.
• Antigen-presenting cells (APCs), like dendritic cells, macrophages, and B cells, capture antigens and present them to T cells, initiating an adaptive immune response.
• APCs active helper T cells by presenting complexes on their surface.

Clonal Selection of B Lymphocytes

• B lymphocytes undergo clonal selection in humoral immunity when they encounter their specific antigen.
• A B cell activates once an antigen binds to its receptor (BCR), needing assistance from helper T cells releasing cytokines.
• Clonal Expansion is when the B cell divides rapidly, creating a population (clone) of identical B cells, each able to produce antibodies against the same antigen.
• Differentiation is when some B cells differentiate into plasma cells, which secrete large amounts of antibodies into the bloodstream, and other B cells that become memory B cells, which persist in the body to respond quickly if the same pathogen is encountered again.

Antibody Classes

• The five main antibody classes (immunoglobulins) include IgG, IgA, IgM, IgE, and IgD.
• IgG is the most common antibody in the blood and extracellular fluid.
• Toxins, viruses, and bacteria are neutralized; and it activates the complement system and enhances phagocytosis.
• During pregnancy IgA is crucial in protecting mucosal surfaces from being pathogen adherent. It is primarily found in mucosal areas, and is secreted into bodily fluids like saliva, tears, and breast milk.
• IgM is the first antibody produced during a primary immune response and is effective at agglutinating antigens and activating the complement system. It is found in blood and lymph.
• Allergic reactions and defense against parasitic infections use IgE
• IgD is primarily located on the surface of B cells and is understood to be involved in the activation of B cells, playing a role in the initiation of immune responses.

Antibody Inactivation of Antigens

• Antibodies utilize neutralization to bind to the active sites of toxins or viruses, preventing them from interacting with host cells and neutralizing their harmful effects.
• Antibodies can combine with antigens on various pathogens to cause clumping, or agglutination, which facilitates the phagocytes' ability to engulf and eliminate the pathogens.
• Antibodies can bind to soluble antigens, forming large antigen-antibody complexes for phagocytes or the complement system, during precipitation
• Antibodies bind to antigens to activate complement proteins, the membrane attack complex (MAC) is formed, which destroys the pathogen.

Acquired Immunity Types

• Natural immunity occurs through antigen exposure, such as becoming infected; the immune system produces a response, including memory cells, protecting against future infections by the same pathogen.
• Vaccination is a means by which to pursue Artificial immunity, administering an inactivated or attenuated pathogen/component to stimulate an immune response without causing disease.
• Active immunity is developed when the body produces its own antibodies or T cells in response to an infection or via vaccination. It is considered longer-lasting as the immune system "remembers" the pathogen.
• Passive immunity is transferred either from another individual/organism or is produced via antibodies from the body's own immune system.

T Lymphocytes and APCs in Cellular Immune Response

• Helper T cells secrete cytokines to assist the activation of cytotoxic T cells and B cells as T-lymphocytes are responsible for cellular immune response.
• Infected cells or cancerous cells are directly attacked by Cytotoxic T cells by inducing apoptosis.
• Excessive immune responses are prevented by regulatory T-cells
• Long-term immunity is provided through Memory T cells, which promptly respond to subsequent exposures of the same pathogen
• In order to activate T-cells, dendritic cells, macrophages, and B cells also capture and process antigens and present those antigens on MHC molecules and are essential
• These presented antigens are identified by T cells, triggering the adaptive immune response.

Terms Relating to Immunity

• Immunization induces immunity by stimulating the body with a vaccine or exposure to antigen and produces antibodies and memory cells.
• A Vaccine is a biological preparation containing dead, weakened, or inactivated pathogens that stimulates the immune system to recognize the pathogen and trigger a response.

Immune System to Clinical Practice

• Allergy and anaphylaxis occur when the immune system overreacts to harmless substances like pollen, dust, or food proteins. This involves IgE antibodies and the release of histamine and other chemicals from mast cells.
• Severe allergic reaction that causes airway constriction, low blood pressure, and shock indicate Anaphylaxis.
• Organ transplants and grafts may occur when the recipient's immune system recognizes the transplanted organ as foreign and mounts a rejection response, but it is often prevented with immunosuppressive drugs.