Innate and Adaptive Immunity

Learning Objectives

• Distinguish primary and secondary lymphoid organs
• Define immunity
• Describe the components of the first and second lines of innate immunity
• Adaptive immunity, the function of T cells and B cells, and the relationship between an antigen and an antibody should be described
• Explain the functions of antibody-mediated (Humoral) immunity, and cell-mediated (Cellular) immunity and how both are important for adaptive immunity

Lymphatic System Functions

• This system has three key functions
• Draining excess interstitial fluid
• Transporting dietary fats
• Carrying out immune responses

Classifying Lymphoid Organs

• They fall into two groups depending on function
• Primary lymphoid organs include red bone marrow and the thymus
• Secondary lymphoid organs and tissues include lymph nodes, spleen, and lymphoid nodules found in the small intestines and appendix

Primary Lymphatic Organs and Tissues

• Stem cells divide and become immunocompetent
• Immunocompetent means they gain the ability to mount an immune response
• Primary lymphatic Organs include red bone marrow (B cells) and the thymus gland (site of T cell maturation)

Thymus

• All lymphoid organs directly fight antigens except the thymus
• Bilobed structure extends from the inferior neck into the superior thorax, posterior to the sternum
• Location of T-lymphocyte maturation occurs here
• Hormonal secretions such as thymosin and thymopoietin, enable T lymphocytes to develop immunocompetence
• The Thymus is prominent in newborns and early childhood, but starts to atrophy after puberty
• The thymus is different from other lymphoid organs because it has no follicles and lacks B cells. It doesn't directly fight antigens

Secondary Lymphatic Organs and Tissues

• Most immune responses occur here
• Lymph nodes present
• Spleen present
• Lymphoid nodules, mucosa-associated lymphatic tissue (MALT) are present, they form the tonsils, Peyer's patches, and the appendix
• These organs store immunocompetent lymphocytes and memory lymphocytes
• The secondary lymphatic organs gather and destroy infectious microorganisms within lymphoid tissue

Lymph Nodes

• Lymph nodes serve two protective functions
• Cleansing the lymph as macrophages filter and serve as an early alert system
• Immune system activation with B-cell division in the follicular cortex, T-cell surveillance, and phagocytic activity

Health Issues with Lymph Nodes

• Antigen accumulation and metastasizing cancers causes nodes to swell without pain
• Lymphedema results from a build-up of fluid and edema in soft body tissues
• This is a consequence of lymph system damage due to tumors or surgical removal of lymphatic nodes and vessels

Spleen

• The Spleen’s size is about the size of a fist and it is the largest lymphoid organ and is a blood-rich organ
• The spleen consists of two components:
  • White pulp: lymphocyte suspended on reticular fibers
  • Red pulp: aged RBCs and macrophages

Functions of the Spleen

• Lymphocyte activation and proliferation
• Blood cleansing by extracting defective RBCs and platelets with splenic macrophages, also removes debris, and foreign matter
• RBC production in the fetus, also known as hematopoiesis, ceases after birth
• It stores platelets, monocytes, and iron
• Splenectomy is the surgical procedure to remove it

Lymphatic Nodules

• These are egg-shaped masses of lymphatic tissue that are not surrounded by a capsule
• Scattered throughout the connective tissue of mucous membranes lining the gastrointestinal, urinary, reproductive tracts, and the respiratory airways
• Tonsils are located around the entrance to the pharynx "throat"
• Peyer's patch is located in the walls of the small intestine (distal part)
• The appendix is located in the walls of a small tube structure that branches off the first part of the large intestine

Immunity and Resistance

• Immunity, or resistance, is the ability to ward off damage or disease through defenses, which can keep the body healthy
• Vulnerability, or the lack of resistance, is termed susceptibility
• The immune system has two intrinsic systems, innate and adaptive

Two Defense Systems

• Innate is mostly nonspecific, and is the first and second line of defense
• Adaptive is specific, attacking particular foreign substances with the third line of defense

First Line of Defense

• The components are skin and mucous membrane
• Skin forms a physical barrier to entrance of microbes
• Mucous membranes inhibit entrance of many microbes, but not as effective as intact skin

Innate Immunity's Second Line of Defense

• This includes cells and chemicals, which are nonspecific cellular and chemical
• Necessary if microorganisms invade deeper tissues

Phagocytes

• Phagocytes include neutrophils and macrophages
• Adherence of phagocytes to pathogen (phagocytosis) is necessary
• This is facilitated by opsonization with a coating of pathogen by complement proteins or antibodies so that the phagocyte can recognize it and undergo phagocytosis

Natural Killer Cells

• Natural killer (NK) cells are a type of lymphocyte for host rejection of tumors and virally infected cells

Inflammatory Response

• Macrophages and mast cells, which are cells filled with basophil granules, and WBCs, participate in the inflammatory response

Antimicrobial Proteins

• Interferons, which are signaling proteins, and complement proteins participate in the antimicrobial process

Fever

• Fever is a systemic response initiated by pathogens

Macrophages

• Macrophages come from monocytes to become the chief phagocytic cells
• Free macrophages roam through tissue spaces, such as alveolar macrophages
• Fixed macrophages are permanent residents of some organs, such as Kupffer cells in the liver and microglia in the brain

Neutrophils

• Neutrophils become phagocytic when encountering infectious material in tissues

Natural Killer Cells

• Natural killer cells are large granular lymphocytes, but NOT phagocytic cells
• Target cells lack "self" cell-surface receptors
• Natural killer cells directly contact the target cells to induce apoptosis, also known as programmed cell death, in cancer cells and virus-infected cells
• Mast cells release histamine during allergic reaction by secreting potent chemicals to enhance the inflammatory response

Inflammation

• "Tissue Response to Injury"
• Inflammation clears the injured place from pathogens, dead tissue cells, and other debris
• Inflammation happens when body tissues are injured by physical trauma, intense heat, irritating chemicals, or infection by bacteria, viruses and fungi

Benefits of Inflammation

• Prevents the spread of damaging agents
• Disposes of cell debris and pathogens
• Alerts the adaptive immune system
• Sets the stage for tissue repair

Steps for Phagocyte Mobilization

• Leukocytosis is the first step and involves neutrophils releasing from bone marrow
• All in response to leukocytosis-inducing factors from injured cells
• Margination with neutrophils then cling to the capillary walls in the inflamed area through cell adhesion molecules (CAMs)
• Diapedesis and Emigration with the neutrophils squeezing between capillary cells
• Chemotaxis where inflammatory chemicals promote positive chemotaxis of neutrophils

Interferons

• Signalling proteins
• Interferons (IFNs) and complement proteins enhance innate defenses
• They enhance defenses by attacking microorganisms directly
• They can also stop the microorganisms' ability to reproduce
• Interferons are not specific to a specific invader
• Viral-infected cells are activated to secrete IFNs
• IFNs enter neighboring cells so they produce antiviral proteins that block viral reproduction

Complement System

• This is known as complement cascade and is part of the humoral, innate immune system
• This has a group of 20 plasma proteins
• The major mechanism for destroying foreign substances is not specific
• Functions of activated complement include amplified inflammatory response, promoted phagocytosis, killing bacteria and certain other cell types by cell lysis, and enhanced innate and adaptive defenses

Fever

• Fever is a systemic response to invading microorganisms
• Leukocytes and macrophages when exposed to foreign substances, secrete pyrogens, resetting the body's thermostat upward
• Benefits include the liver and spleen being caused to sequester iron and zinc, which are needed by microorganisms
• Metabolic rate is increased

Adaptive Immune System

• This is the third line of defense, also known as the adaptive immune
• This is a specific defense system with a humoral, antibody-mediated immunity and a cellular, cell-mediated immunity

Adaptive Immune Actors

• Protects against infectious agents and abnormal body cells
• Amplifies the inflammatory response
• Activates complement
• When it fails, AIDS and cancer can result

Antigens

• Substances that trigger adaptive defenses and provoke an immune response
• Most antigens are large, complex molecules not normally found in the body, called non-self

Types of Antigens

• Complete antigens have immunogenicity along with reactivity
• Immunogenicity stimulates the proliferation of specific lymphocytes and release antibodies
• Reactivity reacts with activated lymphocytes and released antibodies, such as foreign proteins, polysaccharides, lipids, nucleic acids/pollens and grains/bacteria, and fungi
• Incomplete antigens/Haptens are small molecules like hormones, peptides and nucleotides
• They become immunogenic when attached to body proteins (antibodies), such as poison ivy, animal dander, detergents, and cosmetics

Antigenic Determinants

• Epitopes
• Parts of an entire non-self antigen that are immunogenic and can be recognized by the immune system
• Antibodies and lymphocyte receptors bind to them
• Those that most naturally occur have numerous antigenic determinants that do the following:
  • Mobilizing several different lymphocyte populations
  • Forming different kinds of antibodies against it

Antibodies

• Immunoglobulins are the gamma globulin portion of blood plasma
• They are proteins secreted by plasma cells
• Capable of binding specifically with antigens detected by B cells
• They inactivate antigens by forming antigen-antibody and immune complexes

Adaptive Immunity Components

• B lymphocytes or B cells for humoral immunity
• T lymphocytes or T cells for cell-mediated immunity
• Antigen-presenting cells (APCs) do not respond to specific antigens
• Antigen-presenting cells play essential auxiliary roles in immunity
• Important types of APCs B cells, Langerhans cells, macrophages, and dendritic cells

T and B Cells

• Originate from red bone marrow, with B cells maturing there
• T cells mature in the thymus
• When both cell types mature, they become immunocompetent and self-tolerant
• Naïve B and T cells are exported to lymph nodes, spleen, and other lymphoid organs
• Naive B and T cells have not been exposed to antigens yet
• Once exposed, naïve B cells change to memory B cells or plasma cells that secrete antibodies

Antigen-Presenting Cells

• They engulf antigens and present fragments to be recognized by T cells to activate them
• Dendritic cells in connective tissues and the epidermis
• Macrophages in connective tissues and lymphoid organs
• B cells do not activate but present antigen to T helper cells

Immunological Memory

• Primary Immune Response
• Occurs on the first exposure to a specific antigen
• Lag period lasts three to six days
• Peak levels of plasma antibody are reached in 10 days

Secondary Immune Response

• Occurs on re-exposure to the same antigen
• Sensitized memory cells respond within hours
• Faster, more prolonged, and more effective response,
• Peak levels of plasma antibody are reached in 2 to 3 days

Active Humoral Immunity

• This happens when B cells encounter antigens and produce specific antibodies against them and is in two ways:
  • Through natural acquisition with a response to a bacterial or viral infection
• Through artificial acquisition with a response to a vaccine of dead or attenuated pathogens
• Passive Immunity happens two ways:
• Natural acquisition with antibodies delivered to a fetus via the placenta or to an infant through milk
• Artificial acquisition with an injection of serum that contains gamma globulin, which has immediate protection with only natural degradation of antibodies

Types of Antibodies are Called Immunoglobins

• These are secreted in response to an antigen by effector B cells and are a protein type secreted by plasma cells
• IgG, most abundant with 80%, is secreted by plasma cells in blood. It is able to cross the placenta into the fetus
• IgM may be attached to the surface of a B cell or secreted in blood during early immunity stages
• IgE protects against parasitic worms and is released during allergic reactions
• IgA is found in mucous, tears, saliva, and breast milk and it protects against pathogens
• IgD is part of B cell receptor and it activates mast cells and basophils

Defensive Mechanisms

• Disabling Antigens
• Neutralization blocks or neutralizes some bacterial toxins and prevents the attachment of some viruses to body cells
• Agglutination and Precipitation means the antigen-antibody reaction cross-links pathogens to one another to cause agglutination, and phagocytic cells ingest agglutinated microbes more readily
• The complement activation triggers cell lysis and molecules released from activation amplify the inflammatory response, promoting phagocytosis by opsonizing pathogen
• Phagocytes are enhanced by antibodies causing agglutination and precipitation, by activating complement, and by coating microbes to be more susceptible

Immune Cellular Response

• This consists of T lymphocytes that direct adaptive immunity or attack target cells directly, and two major types of T-cells are CD4 or CD8 glycoprotein
• CD4 cells become helper T cells when activated
• CD8 cells become cytotoxic T cells that destroy cells harboring foreign antigens
• Regulatory T cells present CD4 and Memory T cells present CD4 or CD8

Helper T Cells Role

• A role consists of immune system coordinators by activating other immune cells Stimulating B cells to produce antibodies, and activate macrophages to engulf pathogens
• Cytokines are released to enhance the immune response

Cytotoxic T Cells Role

• Killing virus-infected and cancerous cells directly with the MHC
• Recognizing the cells that are infected to MHC class I molecules
• Releasing perforins and granzymes to induce cell death or apoptosis
• Helper and Cytotoxic cells work together to protect the body from infections and abnormal cell growth