Adaptive Immunity: Types and Responses

• Adaptive Immunity involves a specific defensive response to invasion by a foreign object
• Adaptive Immunity can be acquired naturally or artificially

Adaptive Immunity Types

• Natural Adaptive Immunity occurs when an organism or toxin enters the body and promotes an immune response
• Artificial Adaptive Immunity results from immunization with a vaccine
• Both types are specific and have a memory component
• Specificity means the immune response protects against one disease but not against other diseases
• An exception to specificity is when two diseases are closely related, like smallpox and cowpox
• The memory component results in a stronger response upon re-exposure, possibly leading to long-term immunity

Adaptive Immunity General Responses

• Adaptive Immunity involves Antibody Mediated Response and Cell Mediated Response
• Antibody Mediated Response, also known as the humoral response, is mediated by small molecules called antibodies or immunoglobulins (Ig)
• Antibodies specifically bind to and inactivate foreign particles such as cells, toxins, or pollen
• Cell Mediated Response is not mediated by small molecules
• The Cell Mediated Response triggers the activation of specific cells called lymphocytes
• These lymphocytes recognize and destroy abnormal or infected host cells and attack bigger targets like tumors

Antigens and Antibodies

• Antigens are foreign particles that enter the body
• Antigens can be broken into smaller parts called epitopes
• The epitope is the specific part of the antigen recognized by the antibody
• Antibodies are proteins produced in response to the antigen
• Antibodies bind to the antigen in a very specific manner, similar to a lock and key

Antibodies (Ab) = Immunoglobulins (Ig)

• Antibodies consist of 4 parts; 2 identical heavy chains and 2 identical light chains held together by covalent bonds
• Each antibody has 2 identical antigen-binding sites (Fab), with Fab being specific for one epitope
• Each antibody also has a constant fragment (Fc) that binds complement proteins and phagocytes

Five Classes of Antibodies

• Immunoglobulin G (IgG) is the most common antibody, found in the blood and able to enter tissues in regions of inflammation
• IgG can cross the placenta to confer passive immunity to a fetus and binds to antigens very tightly
• Immunoglobulin M (IgM) is a pentamer consisting of 5 antibody units that remains in blood and is often found attached to the surface of B cells
• IgM is the first type of antibody produced upon infection and is effective at aggregating antigens
• Immunoglobulin A (IgA) is a dimer (two antibodies stuck together) found in bodily secretions like saliva, mucous, tears, and milk
• IgA functions to protect mucosal surfaces and protects the gastrointestinal tract of newborns
• Immunoglobulin D (IgD) has an unknown function and is located on the surface of B cells
• Immunoglobulin E (IgE) is found on the surface of certain immune cells, particularly mast cells and basophils, and releases histamine when it binds to antigens
• IgE binding releases histamine and attracts complement and phagocytes to the area, and histamine is responsible for allergy symptoms

Antibody Functions

• Agglutination occurs when antigens become stuck together, reducing the number of infectious units to be dealt with
• Neutralization involves the antibody binding to and inactivating toxins, bacteria, and viruses
• Complement Activation occurs when the antibody binds to bacteria, acting as a starting point for the complement pathway (MAC attack)
• Opsonization flags down phagocytic cells to destroy the antigen

Cells of the Adaptive Immune System

• Lymphocytes consists of B Lymphocytes and T Lymphocytes
• B Lymphocytes (B cells) are antibody-producing cells involved in the humoral or antibody-mediated response, produced in the bone marrow by stem cells
• T Lymphocytes (T cells) are produced in the bone marrow but mature in the thymus gland
• Helper T Cells (TH Cells) help B and Tc cells prepare for an immune response and are part of humoral and cell-mediated immunity
• Cytotoxic T cells (Tc Cells) lyse foreign and abnormal host cells (infected or cancerous) and are part of the cell-mediated immune response

Antigen Presenting Cells (APC)

• Macrophages, B cells, and dendritic cells
• The foreign material, such as a bacterial cell, is engulfed by the APC
• The antigen is processed and presented to the T helper cells of the immune system along with self-antigens
• Self-antigens are part of the major histocompatibility complex (MHC) and prevent the destruction of our own cells by mistake
• T helper cells become activated against the foreign material

Antibody Production Stages

• The antigen enters the body, where it is phagocytized and digested by a B cell
• Small fragments of the antigen are presented on the surface of the B cell along with MHC
• A T helper cell binds to the antigen-presenting B cell after recognizing the antigen bound to the MHC protein
• The T helper cell delivers cytokines that stimulate the B cell to undergo clonal expansion
• The B cell multiplies to produce more identical B cells that then fight off the specific antigen

Clonal Expansion

• B cells divide and differentiate into Plasma cells and Memory cells
• Plasma cells produce antibodies and have a short lifespan
• Memory cells live for a very long time (20-30 years), circulate in the blood at a very low level, and quickly multiply and become antibody-producing plasma cells when they encounter an antigen

Primary Response vs Secondary Response

• The Primary Response is the response the first time the body encounters the antigen
• The antigen stimulates the production of low levels of antibody, in a slow process taking 5-7 days
• IgM is made first, followed by IgG (blood) and IgA (mucous membranes)
• The major outcome of the Primary Response is memory being built for the antigen
• The Secondary Response occurs during every subsequent encounter with the antigen
• High levels of antibody are produced, in a quick response taking only 1-2 days, so the infection is quickly overcome and memory cells are replenished

Cell Mediated Immune Response

• Is activated by invading cells or abnormal host cells
• Involves antigen-presenting cells (APCs), T helper cells, and cytotoxic T cells
• Cytotoxic T cells destroy abnormal cells in the body
• Recognition of Abnormal Host Cells involves cells infected with virus or bacteria, cancer cells, and foreign cells
• An example of cells infected could be cells infected with Mycobacterium tuberculosis
• An example of foreign cells could be blood transfusion or bone marrow transplant
• Endogenous Antigen is Processed and Displayed on Cell Surface

Cell Mediated Immune Response - Endogenous Antigen Processing

• The antigen is presented on the surface of the antigen-presenting cell together with the MHC I self-antigen
• This involves a different type of MHC than that used during the Ab mediated response
• Perforins are released from the cytotoxic T cell
• Perforins poke holes in the membrane of the abnormal cell

Active Immunization

• Active Immunization involves the body processes to generate a specific antibody or cytotoxic T cells
• Can be natural or artificial
• Natural Active Immunization occurs when the antigen is encountered from the environment (primary response)
• Artificial Active Immunization occurs when the antigen is injected as a vaccine

Passive Immunization

• Passive Immunization involves being given a ready-made antibody: does not result in lasting immunity
• Passive Immunization can be either natural or artificial
• An example of Natural Passive Immunization is IgG transferred from mother to fetus via the placenta or IgA transferred from mother to child via milk
• An example of Artificial Passive Immunization is pre-made antibody being injected which is very fast acting for life-threatening situations
• An anti-toxin antibody can be given (no memory) for snake venom