The Innate and Adaptive Immune Systems

• The immune system lectures discuss the innate and adaptive immune systems and related complications
• It reviews how the cellular and humoral divisions of the adaptive immune system target pathogens
• It looks into how B and T cells are activated
• The function of antibodies, and possible complications of the immune system are outlined

Pathogens and Immunity

• The body constantly defends against pathogens like bacteria, viruses, and fungi
• Complex defense systems evolved to prevent infection
• The immune system has innate and adaptive branches
• Immunity is defined as the ability to fight off disease

Innate Defenses

• Innate defenses are non-specific and always ready to fight off foreign agents
• Barriers, like skin and mucosae, are the first line of defense
• Internal defenses consist of antimicrobial cells and proteins

Adaptive Defenses

• The adaptive immune response is the third line of defense which targets identified foreign substances
• This response is specific to the substance that has been recognized

Surface Barriers

• Skin and mucous membranes are highly effective at preventing microorganisms from invading
• The skin is a thick epithelial membrane and a physical barrier
• Mucous membranes lining body cavities open to the external environment
• Mucous membranes are a mechanical barriers that secrete protective chemicals
• Acidic secretions like sweat and stomach acid contribute to defense
• Enzymes such as lysozyme and proteases are involved
• Mucin traps and directs microorganisms to the stomach
• Defensins are antimicrobial peptides with a positive charge
• Lipids can be toxic to bacteria

Innate Internal Defenses

• The body uses many cells and chemicals targeting pathogens in a non-specific manner
• Pathogens possess shapes or unusual surface characteristics that are not part of human cells
• Pattern recognition is carried out by Toll-like receptors (TLRs of which there are 11)

Phagocytes

• Phagocytes engulf and digest unwanted matter
• Neutrophils (most abundant white blood cell) and macrophages are key phagocytotic cells recognizing microbes using TLRs

Natural Killer Cells

• Natural killer (NK) cells target and eradicate virus-infected body cells and cancer cells
• Instead of phagocytosis, NK cells directly contact targets and secrete cytotoxic molecules
• Cytotoxic molecules induce apoptosis in target cells
• NK cells detect abnormalities on the surface proteins of target cells

MHC and Immune Cell Discrimination

• All nucleated cells present molecules on the cell surface, identifying themselves as 'self' cells using Major Histocompatibility Complex molecules (MHC class I)
• MHC class II molecules are found on specialized antigen-presenting cells in the adaptive immune system
• Both MHC class I and MHC class II present antigens
• Antigens presented by MHC class I in non-infected cells are endogenous (made by the body)
• MHC class II present pathogen (exogenous) peptides
• Cells from an organ transplanted into a new host will have MHC class I molecules presenting peptides from the donor

Inflammation

• Inflammation is a nonspecific response to tissue injury with the advantages of:
  • Preventing spread of damaging agents
  • Disposing of cell debris and pathogens
  • Alerting the adaptive immune system
  • Preparing the body for repair
• Signs of inflammation include redness, heat, swelling, and pain
• Inflammation may result in rejection or dysfunction of a biomaterial

Events During Inflammation

• Inflammatory chemicals like histidine are released into extracellular fluid
• Local arterioles dilate and capillaries become more permeable
• Increased tissue fluid causes swelling and pain, but helps move pathogens into the lymphatic system
• Phagocytes are attracted to the injured area
• Clotting factors form a 'mesh' to prevent spread to undamaged tissue

Fever

• Fever is a systemic increase in body temperature
• Pyrogens released from white blood cells cause fever
• A higher temperature improves overall immune response and makes the body more hostile to pathogens

Antimicrobial Proteins

• Antimicrobial proteins released from immune cells attack pathogens
• Interferons and complement proteins are the main antimicrobial proteins
• Interferons can prevent viral replication by blocking protein synthesis and activate NK cells
• Inactive complement proteins circulating in the blood stimulate inflammatory response and directly lyse microbes when activated

Adaptive Immune System Features

• Adaptive immune system functions after exposure to a pathogen.
• There are two arms to the adaptive response: humoral and cellular
• Humoral immunity is provided by antibodies in blood or lymph fluid, made by lymphocytes that freely circulate and bind to extracellular antigens
• Cellular immunity lymphocytes defend the body by targeting and killing cells infected with pathogens, cancer cells, or foreign cells

Hallmarks of Adaptive Immune Reponses

• Involves B and T lymphocytes
• It is specific to the recognized target
• It is a systemic response
• It has memory

Cells of the Adaptive Immune Response

• The adaptive immune response requires B lymphocytes, T lymphocytes, and antigen-presenting cells (APCs)
• B cells control humoral immunity, T cells control cellular immunity
• APCs help T cells recognize pathogens by engulfing and presenting them with MHC class II complexes
• APCs include macrophages and dendritic cells

Dendritic Cells

• Dendritic cells are white blood cells that are antigen presenting cells
• They process antigen material and present it on the cell surface to T cells
• Dendritic cells are found in tissues that contact the external environment
• Their projections are similar to dendrites of neurons

Activation of B cells

• B cells have B cell receptors on their cell membranes
• These receptors recognize free antigens
• Once bound, the antigen is internalized
• The B cell then presents the antigen on MHC class II molecules to a T helper cell
• Cytokines released by the T helper cell activate the B cell and it multiplies
• Some B cells differentiate into plasma cells that secrete antibodies
• Other B cells become memory B cells that can recognize a pathogen if it returns

Activation of T cells

• Phagocytotic cells engulf pathogens.
• The pathogen is broken up and presented using MHC class I molecules
• The antigen is presented to a naive T cell that recognizes it with a T cell receptor (TCR).
• The T cell becomes activated and multiplies.
• Activated T cells can locate and kill pathogenic microbes presented by host cells via MHC class I molecules.
• Some T cells become ‘T helper cells' that regulate other immune cells, they are activated by extracellular antigens on MHC class II molecules on APCs

T an B cell development

• Both T and B cells develop in the bone marrow
• T cells mature in the thymus, B cells mature in bone marrow

Antibodies (Abs)

• Antibodies (Abs) are large Y-shaped proteins that detect antigens on pathogens
• Antibody binding to the antigen blocks function of the pathogen upon binding by
  • Neutralization
  • Agglutination or precipitation
  • Phagocytosis
  • Activation of complement proteins

Lymphatic System

• The lymphatic system includes lymph fluid, vessels, nodes, and ducts
• Lymphatic System functions for immune system including drainage an storage functions
• Lymph nodes are distributed around the body where pathogens are broken down

Organ Rejection

• Organ transplantation is possible after organ failure
• Immune rejection is a significant problem in transplantation
• NK cells, macrophages, antibodies, and T cells destroy foreign cells presenting cell surface proteins different from host cells
• Immunosuppressive therapy, along with drugs supressing rapidly dividing cells, is often given alongside transplantation

Immune Disorders

• Immune disorders include immunodeficiency and autoimmunity
• Immunodeficiency
  • Can be congenital, such as severe combined immunodeficiency (SCID) syndromes.
  • Characterized by a marked deficit in B and T cells
  • Can be acquired, such as acquired immune deficiency syndrome (AIDS), due to helper T cells being inactivated
  • Immunodeficiency means the body is unable to fight infectious organisms and without intervention will be fatal, since the body's defences become overwhelmed
• Autoimmunity
  • Occurs due to the immune system unable to distinguish between normal cells of the body from foreign antigens
  • Autoantibodies and cytotoxic T cells target host cells for destruction, resulting in several different auto immune disorders
  • Type 1 diabetes is an autoimmune disorder resulting from destruction of β cells in the pancreas with associated loss of insulin production
  • Lupus is a systemic autoimmune disease that affects many parts of the body causing pain and fatigue
  • Multiple sclerosis occurs when the immune system attacks the brain or spinal cord