Biology: Immune System
the adaptive immune system is divided into:
antibody-mediated immunity (humoral) and cell-mediated immunity
B cells can differentiate into two types of cells
plasma cells and memory B cells
autoimmune diseases occur when
when the immune system mistakenly attack self cells, such as in type I diabetes when the pancreatic cells are destroyed by the immune system and lose their functions
IgD
• monomer • the function is not well understood, and only a small amount is produced • tip: IgD* stands for IgDon't, as we don't know much about it!
IgE
• monomer • these are antigen receptors found on basophils and mast cells → whenever there is an allergen, IgE will bind and trigger the release of histamine from these two cells → allergic reaction • tip: IgE* stands for IgEve, Eve is one girl (monomer) who is allergic to many things.
IgM
• pentamer (the only pentamer out of the 5 classes of antibodies) — contains 5 Y-shaped forks in one IgM → IgM is the largest antibody → IgMost because IgM has the most number of Y shaped monomer forks • first to be produced in response to an antigen • activates complement system (innate immunity)
adaptive (specific) immune response (3rd line of defense)
• relatively slow • very specific (bc it targets specific antigens) • effective immune response controlled by lymphocytes
(adaptive) B cells → memory B cells
• these cells live for a long time, sometimes even for decades in our body • they do not release antibodies • they save/retain the information about the antigen, and if the same antigen intrudes again within their lifespan, they will rapidly differentiate and proliferate into plasma cells to secrete corresponding antibodies.
chemokines
induce migration of leukocytes via chemical messengers (small proteins that cells release as a signaling mechanism)
Suppressor T cells
inhibit the activation and function of both T cells and B cells
(innate) inflammatory response → mast cells
injured tissue and mast cells work together to release a substance called histamine, which (1) dilate nearby capillaries (vasodilation) → increase blood flow and (2) make capillary walls more permeable → fluid and immune cells leak out to the site of injury
adaptive immunity → antibody-mediated (humoral) immunity
1. Humoral immunity involves leukocytes called B-lymphocytes. B-lymphocytes are produced and mature in the bone marrow and usually found in the lymph nodes. 2. During innate immune response → macrophages engulf and destroy pathogens → they keep pathogenic antigens and display them on their membrane → B-lymphocytes contain B-cell receptors on their membrane that binds to these macrophage-bound antigens 3. B-lymphocyte binds specific antigen → calls upon Helper T-cell which helps it differentiate further by releasing chemicals called interleukins and interferons → these chemicals B-lymphocytes mature into → plasma cells and memory B cells → via clonal selection 4. plasma cells are "factories" that produce antibodies that are specific to the antigen that the B-lymphocytes was bound to. Memory cells however keep a copy of that antibody in case of reinfection. 5. Antibodies, also called immunoglobulins, bind only to specific antigens → tag antigen for phagocytosis by other leukocytes, aggregate to form large insoluble complexes via a process called agglutination, or activate complement system Humoral immunity is effective against bacterial cells, parasites, fungi, viruses, and toxins
These interferons can also bind to, stimulate and recruit specialized leukocytes:
1. Natural Killer Cells: are mobilized after interacting with interferons. They can seek out destroy infected cells as well as cancer cells 2. Macrophages: interferons recruit these large phagocytes that can engulf and break down infected cells. Macrophages themselves can release their own interferons, amplifying the immune response. Interferons can also stimulate cell death of the infected host cell
1st line of defense (innate immunity)
1st line of defense (innate immunity) = barriers to infection (block pathogen entry) • skin layers forms a physical and chemical barrier against pathogens - our skin consists of several layers that create a first line of defense against invading pathogens. The skin also contains sebaceous glands that secrete fatty acids (antimicrobial properties) and this creates an environment in which most bacteria cannot grow. • mucous + cilia: goblet cells found along our air passageways produce a sticky and slimy layer of mucous membrane that traps pathogens. Cilia in the respiratory tract removes pathogens to the outside or to the stomach. • acidity of stomach: parietel cells release HCl, which creates a highly acidic environment that kills off most pathogens that enter the stomach via food or via mucous • tears and saliva: lysozyme found in tears and saliva helps breakdown bacterial cell wall • symbiotic bacteria: not all bacteria are bad! Symbiotic bacteria are our allies and out-compete their more hostile relatives.
the body has 3 lines of defense against infection:
1st line of defense - barriers to infection 2nd line of defense - nonspecific response or inflammatory response 3rd line of defense - immune response or specific immunity
2nd line of defense (innate immunity)
2nd line of defense (innate immunity) = nonspecific response or inflammatory response Inflammation: Once the anatomical physical barriers are breached and the pathogen enters our tissue; The innate immunity then initiates the process of inflammation. In this process, blood flow is increased to the infected area. This blood brings several important white blood cells - neutrophils, eosinophils, basophils, and macrophages, NK cells
pathogen
A pathogen is any agent, living or non-living, that can cause harm to the cells of the body (bacteria, virus, harmful chemicals)
Active immunity:
Active immunity is developed by the organism when a pathogen invades the body and prompts an innate or adaptive immune response. When we administer pathogens in vaccination, it provokes active immunity. The vaccination introduces a small amount of weakened or dead pathogen to our body (in a form that is not pathogenic, or disease causing), which stimulates an immune response. This type of active immunity is artificially acquired. Vaccines will induce the formation of memory B cells and T cells that remain in our body to protect us against future exposures of the real pathogen.
adaptive immunity → B cells
B cells → antibody-mediated immunity, which means that they control the production and release of antibodies → also called humoral immunity because humor = body fluid, and antibodies are found in various types of body fluids such as blood and lymph.
why do transplant patients need to take immunosuppressants on a life-long basis?
In cases of organ transplantation, the donor organ will bear a different MHC I molecule which will be labelled as an antigen by our immune system. As a result, our immune system will attack the "enemy" organ. This will lead to organ failure and transplant rejection. This is why transplant patients need to take immunosuppressants on a life-long basis to lower/eliminate the immune system's response towards the foreign organ. However, lowering the immune system also makes these patients more susceptible to general infections.
diapedesis
Leukocytes are amoeba-like cells that are capable of moving independently. They can move against the flow of blood and can slip through the walls of capillaries and enter our tissue in a process called diapedesis
(innate) inflammatory response → lymphocytes → NK cells
Lymphocytes Lymphocytes are your artillery units, the ones who identify and acquire a target before killing it. The lymphocytes are B cells, T cells, natural killer cells (NK). • B cells and T cells → adaptive immune response • natural killer cells → attack and kill virus-infected cells or cancerous body cells → innate immune response bc do not require activation — they are always "on" NK cells fight enemies with two main weapons: Perforin perforates (poke holes in) pathogenic cell membranes, causing cell lysis (cell breakdown). Granzymes, a protease which stimulates a target cell to undergo apoptosis (programmed cell death)—useful for killing cancerous cells.
antigens can be presented on either
MHC I or MHC II
5 classes of antibodies
Mnemonic: Me And Eve Don't Go IgM, IgA, IgE, IgD, IgG
(innate) inflammatory response → neutrophils (phagocytes)
Neutrophils (phagocytes) most numerous and common type of leukocytes (make up ~40-70% of them). These cells are recruited to the infected area and engulf bacterial cells (phagocytosis) and other harmful agents and kill them intracellularly. They are part of the innate response because they are not picky eaters — they engulf all kinds of pathogens.
relative number of leukocytes circulating in the blood from highest number of cells to lowest number of cells in circulation:
Never Let Monkeys Eat Bananas Neutrophils > Lymphocytes > Monocytes/Macrophages > Eosinophils > Basophils
primary response vs. secondary response
Primary Response: elicited by first exposure to some particular pathogenic antigen 1. Relatively long latent period (adaptive immune system is being mobilized and the appropriate lymphocytes are being cloned) 2. amt of antibodies produced is low 3. During decline phase the number of antibodies drops to a very low value 4. IgM - major antibody synthesized Secondary Response: elicited when body is reinfected with same type of pathogen 1. Relatively short latent period (quick) bc of memory cells 2. Amt of antibodies produced is much greater 3. During decline phase, antibody level persists at higher value for longer 4. IgG - major antibody synthesized
fever
Sometimes, fever can result from an inflammatory response. Fever is turned on and off by the brain. It is not a local response anymore — it becomes systemic (body-wide). When our body's temperature increases, it helps to hinder the growth of pathogens, and may sometimes kill the temperature-sensitive ones as well.
epitope
The epitope is important because it is the section of the antigen that is recognized by immune cells like B cells and T cells
immune system
The immune system utilizes a series of internal defense mechanisms that help protect the cells of the body from pathogens.
non-specific (innate) immunity
The innate immune system consists of non-specific defense mechanisms that act immediately following infection. This is the primary line of defense against pathogens. Non-specific implies that it does not depend on the presence of specific antigens; that is, the innate immune system attacks all pathogens with equal likelihood
how do pathogens enter the body?
The pathogens can only cause harm if they enter our body. They can enter the body through the air we breathe, the food we eat, through the wounds and cuts in our skin and so forth. physical contact; soil, food, water, contaminated objects, bites and open wounds
chemotaxis
The process of moving to a location in response to a chemical signal is called chemotaxis. Chemo = chemicals, and taxis = movement. In the inflammatory response, many white blood cells are drawn to the site of injury via chemical signals to arrive.
MHC Class II
These protein complexes are found on only specific immune cells, such as B lymphocytes, macrophages, dendritic cells, and T lymphocytes → antigen presenting cells (APCs) MHC Class II functions in helping immune cells communicate with each other After APCs phagocytose the pathogen and break off the antigen, APCs will load the antigen on the MHC molecule and present it to immune cells. For example, an immature T cell (CD4+) can bind to the antigen on the MHC II of the APC via its T Cell Receptor (TCR), and become activated to Helper T cells → thus further activating immune response.
MHC Class I
These protein markers are found on the membrane of almost all nucleated cells. They are used to differentiate healthy host cells from infected cells (infected by viruses). A healthy cell will bind one of its normal peptides (self-antigens) onto the MHC Class I. When a leukocyte approaches, it can recognize the healthy cell by the self-antigen and will leave it alone In the case of an infected cell, it will produce a viral peptide (antigen) and place it onto the MHC class I. Leukocytes can recognize these foreign antigens, bind to them and initiate a defensive mechanism that can destroy the infected cell
adaptive immunity → cell-mediated immune response
This involves leukocytes called T-lymphocytes. They are formed in the bone marrow but mature in the thymus where they are tested to ensure that they do not attack the bodys own cells One type of T-lymphocyte, immature CD4+, binds to MHC Class II on an APC and turns into activated Helper T cell. The APC & Helper T cells release cytokines that stimulate T cells to clone itself. Helper T cells release chemicals called interleukins and interferons. These chemicals help B-lymphocytes mature into plasma cells and memory B cells. They also release cytokines that activate another type of T-lymphocyte (CD8+) to Cytotoxic T cells (binds to MHC Class I). These cytotoxic T cells travel to the infected area and bind to specific antigens. Once bound, they release powerful proteins (perforins & granzymes) to kill the pathogen. In addition, T-lymphocytes can also form its own memory T cells as well as Suppressor cells that can regulate and tone down the immune response. Cell-mediated immunity is effective against infected cells.
adaptive immunity → antibody-mediated → clonal selection model
This theory states that since each B cell has a unique BCR, the antigen selects which BCR it can bind to, and which B cell to activate. Therefore, out of thousands of pre-existing B cells, only one specific B cell is selected to proliferate and make clones of itself. We have amplification of the B cell that is specific to the antigen that is present in the pathogen of attack.
Passive immunity:
This type of immunity is temporarily provided to an organism by the transfer of active immunity components from one animal to another - that is, antibodies are given to the animal, rather than generated by that animal. Out of the 5 antibodies, only IgG can cross the placenta, and IgA is found in body secretions such as milk. A fetus/newborn baby is immuno-naive, which means that they have not been exposed to the world with pathogenic microbes. Therefore, the fetus has not generated its own active immunity. This is where the mother steps in and protects the baby by passing down her own antibodies to the fetus through placenta (IgG) or breastfeeding (IgA). These antibodies will safeguard the baby until the infant generates their own active immune response.
antigen
a marker from a toxin or other foreign substance that induces an immune response in the body, especially the production of antibodies. Antigens serve as a target, and our body will mark the cells bearing the antigen as non-self
adaptive immunity → antibody-mediated → after antibodies are released into the humor, they can:
antibodies - patrol humor (blood & lymph) where they combat viruses and bacteria, moving around the interstitial space between cells • tag the specific corresponding antigen for removal → signal it should be phagocytosed • coat the antigen in antibodies, which neutralizes it (physically block binding sites on pathogen) → agglutination • activate the complement system these functions all share a common goal — annihilate the pathogen containing the specific antigen.
(innate) inflammatory response → basophils
basophils Finally, basophils are the least numerous kind of leukocytes (only make up less than 1% of all leukocytes) like eosinophils, basophils contain granules that's released to nearby tissues important granule contents are (1) histamine → vasodilation & make capillaries more permeable and (2) heparin → type of anticoagulant preventing blood from clotting too quickly. similar to mast cells in function, but they come from different cell lineages. The difference is that basophils leave bone marrow (site of blood cell production) as mature cells and remain circulating in the blood, whereas mast cells leave the bone marrow and circulate the blood as immature cells, only maturing when they enter the tissue.
innate immune response → dendritic cells
dendritic cells are the surveillance guards roaming in tissues detecting potential threats. dendritic cells scan its local environments by sipping from its surroundings through pinocytosis. Once it detects a pathogen, it will phagocytose it like macrophages and neutrophils. (pinocytosis = cell drinking & phagocytosis = cell eating) Similar to macrophages, dendritic cells also play the role of antigen-presenting cells. Dendritic cells then migrate to lymph nodes along with macrophages to activate the adaptive immune response.
(innate) inflammatory response → eosinophils
eosinophils → innate response their cytoplasms are filled with granules which contain proteins that can be released into the surrounding tissue to kill pathogens. They are especially effective against parasites.
adaptive immunity → b-cell receptor
every B cell has a unique and uniform BCR that binds to one kind of antigen, which means that a single B cell cannot have different BCRs that bind to different antigens.
innate immunity - complement system
focus on blood plasma proteins that participate in the innate immune response ~30 proteins included in the complement system - a system (group) of proteins that exist as a side-kick to the immune cell soldiers can generate a big effect by 'turning each other on' through a cascade series of activation. They activate each other through the release of cytokines. activated directly by pathogens or indirectly by pathogen-bound antibody When activated, the complement system: 1. improves 'eating' ability of phagocytosing cells (eg. macrophages) by binding complement protein C3b to antigens and tagging them for phagocytosis, a process called opsonization 2. amplify inflammatory responses - certain proteins bind mast cells to trigger stronger histamine release 3. lyse pathogen membranes - Some proteins form a membrane attack complex (MAC) which specifically functions to poke holes in pathogen membranes. Once holes are created, fluid and salts can go into the pathogen and make the cell burst and die.
adaptive immunity → cell-mediated → how Cytotoxic T cells kill pathogens:
how CD8 cells (cytotoxic killer T cells) kill pathogens: similar to NK cells: • release perforin: perforates (poke holes in) pathogenic cell membranes, causing cell lysis (cell breakdown) • release granzymes: a protease which stimulates a target cell to undergo apoptosis (programmed cell death)—useful for killing cancerous cells. different from NK cells: • NK cells react faster than CD8 cells because they do not require antigen-presentation and activation • CD8 cells are more specific than NK cells because they target a specific antigen on a pathogen
which molecule connects the innate and adaptive immune responses?
interferon Interferon is secreted by virus-infected cells to warn nearby non-infected cells. Interferon will act as a messenger and bind to non-infected cells to help them be prepared for a viral attack. Interferons also help activate dendritic cells, which helps kickstart the adaptive immune response. For instance, the cells begin producing anti-viral proteins that function to block viral replication, This way, when the infected cell lyses and releases more viruses, the nearby cells have already mounted a defense.
cytokines
intracellular signaling molecule
both B cells and T cells are...
lymphocytes which means that they are produced from the bone marrow B cells → born in bone marrow → mature in bone marrow → found in lymph nodes T cells → born in bone marrow → mature in thymus Natural killer cells → born in bone marrow → mature in many immune sites → found in bloodstream
how does our immune system distinguish between self and non-self cells?
major histocompatibility complex (MHC) molecule found on the surface of cells The ability of our immune system to recognize its own cells and distinguish those cells from foreign pathogens depends on a group of protein markers found on cell membranes called the major histocompatibility complex. These markers are present on the surface of every cell and in humans are called the human leukocytes-antigens
(innate) inflammatory response → monocytes → macrophages
monocytes → macrophages monocytes → innate response monocytes when they are in their immature state in the blood vessels → mature into macrophages after they cross into infected tissue through diapedesis similar to neutrophils in that they are also phagocytes - also 'eat things' that should not be in the body in a nonspecific way Later on, macrophages function as antigen-presenting cells to activate adaptive immunity. You can think of an antigen as the unique ID of the enemy. Macrophages act as messengers that carry vital information about the enemies from the frontline soldiers (innate immunity) to the backup troops (adaptive immunity).
the human immune system and its defense mechanisms can be divided into two types
non-specific (innate) immunity and specific (adaptive) immunity
leukocytes
white blood cells are specialized cells that can defend our body from pathogens. All leukocytes originate from cells in the bone marrow called hematopoietic stem cells. Leukocytes can in turn differentiate into a variety of different cell types that each have their own unique function.
explain the five signs associated with inflammation (innate/2nd line):
• Heat = result of dilation of capillaries. When there is increased blood flow, the tissue gets warmer. • Redness = result of dilation of capillaries. More blood = redder color. • Swelling = result of permeable capillaries. When blood vessels become leaky, fluid starts accumulating in nearby tissues, causing swelling (edema) • Pain = 2 types of pain when you get hurt: a sharp pain that happens right at the time of injury caused by nerve endings and a slower, throbbing pain that you feel afterwards, which is caused by inflammation. For the pain from inflammation, it is because the swollen areas exert pressure on free nerve endings, which causes a continuous pain. (That's why it hurts even more when you press a swollen ankle!) • Loss of function This is more of an indirect outcome of inflammation. When there is swelling and pain, that part of the body becomes less useable. For example, when people suffer from arthritis (inflammation of joints), they can't really walk normally. This has a beneficial effect of causing disuse of the injured area, aiding in healing inflammatory response → SLIPR: Swelling Loss of function Increased heat Pain Redness
adaptive immunity → T cells
• T cells → cell-mediated immunity • unlike B cells which send out antibodies to do the job of killing enemies (humoral response), T cells do the work themselves (cell mediated response) • similar to B cells, T cells have T cell receptors (TCR) on their surfaces • every T cell has a unique and uniform TCR that binds to only one kind of antigen → T cells also go through clonal selection • unlike B cells, T cells are more needy → cannot recognize free floating antigens → only bind to antigens presented by antigen presenting cells (APCs)
structure of an antibody (immunoglobulin):
• Y-shaped = light chain + heavy chain linked through disulphide bonds • the constant regions have very similar amino acid coding sequence (antibody is a protein after all!) within a particular class of antibodies • the variable regions are the ones that bind to different antigens, that's why they have different amino acid sequences
memory T cells
• a third type of T cells that form after clonal selection is memory T cells • these long-lived cells are crucial to protecting our body from future invasion of the same antigen. If there is another encounter with the same antigen, the memory T cells will help the adaptive immune response to 'turn on' more quickly.
b-cell receptors vs antibodies
• both are structurally identical • BCR = bounded version • BCR can bind to free or presented antigens • unique and uniform • antibodies/immunoglobulins are freely secreted • antibodies circulate in the blood and lymph
IgA
• dimer → tip: when you think of IgA*, think of IgAnd, when there is this and that → dimer • most abundant in body secretions e.g. breastmilk, tears, saliva → can give the newborn passive immunity through breastfeeding • functions to bind and stop pathogens externally before they enter circulation
adaptive immunity → vaccinations
• memory B cells are key to vaccinations • goal of vaccination is to introduce a small amt of weakened/dead pathogen to our body → right after injection, our B cells would produce memory B cells in response to that specific antigen → later on in our life, if we come across that same pathogen again, our immune system rapidly produces antibodies to counterattack before the pathogen proliferates
IgG
• monomer • most abundant antibody found in circulation e.g. blood, lymph • only antibody that can cross the placenta to give fetus passive immunity→ tip: IgG* stands for IgGo, so it can go through the placenta! • triggers opsonization → binds to antigen and triggers phagocytosis • activates complement system