Immune System and Adaptive Immunity

• Innate and acquired immunity are the subjects of Lesson 2.
• A case study involves Norman, a 68-year-old who gets a flu vaccine and seeks advice on protection and visiting his grandchildren.
• The study questions addresses educating on the adaptive immune system and advising on the waiting period before seeing grandchildren.
• The body has 3 lines of defence

Innate vs Adaptive Immunity

• Innate immunity represents the first and second lines of defence
• Adaptive immunity represents the third line of defence

Innate Immunity

• Physical barriers include skin, gastrointestinal, respiratory tracts, the nasopharynx, cilia, eyelashes, and other body parts
• Defence mechanisms include secretions, mucus, bile, gastric acid, saliva, tears, and sweat
• General immune responses include inflammation, complement, and non-specific cellular responses
• Leukocytes involved are phagocytes, macrophages, mast cells, neutrophils, eosinophils, basophils, natural killer cells, and dendritic cells
• Complement system-related responses are opsonisation, chemotaxis, cell lysis, and agglutination
• Innate immunity is non-specific and provides a fast response (minutes or hours)

Adaptive Immunity ('Acquired’)

• B cells mature in bone marrow and contribute antibodies for specific antigens and humoral immunity
• T cells mature in the thymus; they express T cell receptors and CD4 or CD8 to contribute to cell-mediated immunity
• T cell receptors only recognize antigens bound to major histocompatibility complex (MHC) class I or II
• CD4 and CD8 contribute to T cell recognition and activation by binding to either MHCI or MHCII
• Adaptive immunity is highly specific and identifies pathogens and molecular structure differences, but is slow (days)

Innate Immune System

• Innate immunity is encoded in your genes and is inherited
• Cellular: refers to what immune cells do

Adaptive Immune System

• Adaptive immunity involves learned responses to antigens upon previous encounters
• Humoral: involves non-cellular components

Cellular

• Innate: neutrophils, monocytes, macrophages, mast cells, basophils, and eosinophils
• Adaptive: Natural Killer cells, Innate lymphoid cells, B cells, and T cells

Humoral

• Innate: complement, anti-microbial peptides, and Chelators of nutrients
• Adaptive: Cytokines, Chemokines and Antibodies

Characteristics of Innate Immune System

• Cellular and Humoral protection against infection relies on mechanisms that exist before infection
• Capable of a rapid response to microbes
• Reacts the same way to repeated infections
• Exists at birth and is the first and second line of defence against infection
• Indiscriminate and non-specific
• Has no immune memory.
• Cannot be enhanced by the second stimulation of the same antigen

Characteristics of Adaptive Immune System

• Cellular and Humoral protection relies on mechanisms developing as a result of infection and exposure to pathogenic antigens
• Takes time to develop
• Specific to a pathogen and an antigen
• Requires exposure to a pathogenic antigen to develop
• The third line of defence against infection
• Distinguishes between self and non-self
• Antigen and epitope-specific
• Has immune memory
• Can be enhanced by the second stimulation of the same antigen

Immune System

• Consists of organs, cells, and proteins
• Includes barriers

Immune Cell Origin

• Immune system starts with a stem cell
• Myeloid progenitor cells are the first line of defence
• Lymphoid progenitor cells can learn and adapt

Myeloid Progenitor Cell Functions

• Macrophages and neutrophils engulf and destroy pathogens in intracellular vesicles in both innate and adaptive immune responses
• Dendritic become antigen-presenting cells to T cells, and initiate adaptive immune responses.
• Macrophages can also present antigens to T cells and can activate them.
• Myeloid cells release contents of granules upon activation via antibody during an adaptive immune response.
• Eosinophils attack large antibody-coated parasites such as worms.
• The role of basophils is less clear
• Mast cells trigger a local inflammatory response by releasing substances that act on local blood vessels.

Macrophages

• Macrophages are large mononuclear phagocytic cells
• One of three types of phagocytes
• Distributed widely in the body tissues
• Also the mature form of monocytes that differentiates upon migration into tissues
• Important in innate immunity and early non-adaptive phases of host defence
• Act as antigen-presenting cells and effector cells in humoral (B cell) and cell-mediated (T cell) adaptive immunity.
• Migratory cells from bone marrow precursors are found in most tissues

Dendritic Cells

• They are specialized to take up antigen and display it for recognition by lymphocytes
• Immature dendritic cells migrate from the blood to tissues, are phagocytic, macropinocytic, and ingest extracellular fluid
• Upon encountering a pathogen, they rapidly mature and migrate to lymph nodes.
• Found in T-cell areas of lymphoid tissues.
• They have branched or dendritic morphology and stimulate T-cell responses.
• Nonlymphoid tissues also contain dendritic cells, but these are unable to stimulate T-cell responses until activated and migrate to lymphoid tissues.

Mast Cells

• Mast cells differentiate in the tissues and are large cells found in connective tissues throughout the body

• Most are abundant in the submucosal tissues and the dermis

• They reside near small vessels and release substances affecting vascular permeability when activated.

• Mast cells that store mediator molecules like vasoactive amine histamine contains large granules

• Have high-affinity Fce receptors (FcɛRI) that allow them to bind IgE monomers.

• Antigen-binding to IgE triggers mast-cell degranulation and mast-cell activation

• Can produce a local or systemic immediate hypersensitivity reaction

• Plays a crucial role in allergic reactions

Neutrophil

• Neutrophils are granulocyte or polymorphonuclear leukocytes
• Three types are short-lived and migrate to sites of infection/inflammation in blood
• Neutrophils, or polymorphonuclear leukocytes, are a white blood cell in human peripheral blood.
• They have a multilobed nucleus and neutrophilic granules
• Neutrophils are phagocytes that play an important role in engulfing and killing extracellular pathogens
• The most numerous and important cellular component of the innate immune response
• Hereditary deficiencies in their function lead to bacterial infection, which is fatal if untreated.

Eosinophil

• Are granulocyte or Polymorphonuclear leukocytes with short life span that migrate to infection/inflammation sites
• Eosinophils defend against parasitic infections
• Are activated by lymphocytes of the adaptive immune response
• Their levels in the blood are normally low, but increase markedly in atopy, causing eosinophilia, an abnormally large number of eosinophils in the blood.

Basophil

• Basophil are granulocyte or Polymorphonuclear leukocytes with short life span that migrate to infection/inflammation sites
• Basophils are highly granular mononuclear cells, and are circulating leukocytes
• The function of basophils is probably similar and complementary to that of eosinophils and mast cells
• Are thought to be important in immune responses to parasites like ticks
• Basophils become activated by antigen crosslinking of Fc-receptor-bound IgE to undergo rapid degranulation and release their cellular contents
• They can be directly activated by a variety of pathogen-associated molecular patterns (PAMPs).

Lymphoid Progenitor Cell Function

• Arise from common lymphoid progenitor
• B lymphocytes or B cells differentiate into antibody secreting plasma cells
• T lymphocytes or T cells; one class differentiates on activation into cytotoxic T cells that kills virally infected cells, second class differentiates into T helper cells who activate for example macrophages and B-cells

Lymphoid Progenitor Cells

• They are small, featureless cells with few cytoplasmic organelles and inactive chromatin, typical of inactive cells
• Have no activity until they encounter antigen, which triggers their proliferation and differentiation

Lymphocytes

• Small B and T lymphocytes that have matured in the bone marrow and thymus but have not yet encountered antigen are naive lymphocytes.
• They circulate continually from the blood and enter peripheral lymphoid tissues
• Return to blood via the lymphatic vessels or spleen
• If lymphocytes recognize the infectious agent, they are arrested in the lymphoid tissue, where they proliferate and differentiate into effector cells to combat the infection
• When an infection occurs in the periphery, antigen is taken up by dendritic cells which travel through lymphatic vessels into the draining lymph nodes.
• Lymphocytes display the antigen to recirculating T lymphocytes, also helping to activate.
• B cells that encounter antigen as they migrate through the lymph node are also arrested and activated, with the help of some of the activated T cells.
• Once antigen-specific lymphocytes have undergone proliferation and differentiation, they leave the lymph nodes as effector cells through the efferent lymphatic vessel
• Lymph nodes expand as B lymphocytes proliferate, which causes enlarged lymph nodes

Lymphocytes Remarkable Ability

• Lymphocytes can mount a specific immune response against virtually any foreign antigen
• Each lymphocyte matures bearing a unique receptor, with highly diverse antigen-binding sites
• B-cell antigen receptor (BCR) is a membrane-bound antibody that the B cell will secrete after activation and differentiation to plasma cells
• Antibody molecules are immunoglobulins (lg), and the antigen receptor of B lymphocytes is membrane immunoglobulin (mlg)
• T-cell antigen receptor (TCR) is related to immunoglobulin but is specially adapted to detect antigens from foreign proteins or pathogens that have entered into host cells.

Natural Killer Cells

• A third lineage of lymphoid cells, called natural killer cells, lack antigen-specific receptors
• Are part of the innate immune system.
• Circulate as large lymphocytes with distinctive cytotoxic granules
• Able to recognize and kill some abnormal cells, including tumour and virus-infected cells
• Important in the innate immune defence against intracellular pathogens

Innate Immunity vs Adaptive Immunity - Memory

• Primary immunization, or priming, generates both the primary immune response and immunological memory
• Immunological memory is specific for a particular long-lived antigen
• Subsequent encounters with the same antigen are speedier and more effective
• It gives the immune system the ability to respond rapidly and effectively to pathogens encountered previously and reflects the pre-existence of clonally expanded antigen-specific lymphocytes
• Memory responses, depends on the number of exposures to the antigen
• Immunological memory need not be maintained by repeated exposure to infectious virus
• Sustained by long-lived antigen-specific lymphocytes induced by the original exposure that persist until a second encounter with the pathogen
• On priming with an antigen, a naive T cell divides and differentiates and some become long-lived memory T cells, which may be sustained by cytokines

Primary and Secondary Antibody Response

• Memory B cells can be distinguished by immunoglobulin genes because of isotype switching
• Primary response: -- B cells proliferate into plasma cells, secrete antibodies, create IgM memory B cells
• Secondary response: -- Antigen-specific memory, B cells secrete antibodies, isotype switching to IgG.
• Higher affinity and titre (serum concentration)
• Immunological memory is long-lived after infection
• Illustration shows an animation of developing immunological memory

Innate and Adaptive Immunity Response Time

• A graph shows a comparison of the two immune systems
• The innate immune systems reacts rapidly
• The adaptive immune system takes longer to react

Problem-Based Learning - Case Study

• Adaptive immunity takes time to develop (days to week(s))
• Adaptive immunity is specific and develops memory
• Flu vaccine does not need a booster; the patient should wait one week to see his school-aged children so the immunity builds up
• School-aged children are one of the main groups that spread the flu

Test your knowledge of the immune system, focusing on adaptive immunity, macrophages, eosinophils, mast cells, and dendritic cells. This quiz covers key concepts in immunology. Includes cell types and immune responses.