Immune System Addendum

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Contents
Acute-phase Proteins
  • Acute-phase proteins are a class of proteins whose concentrations in the blood increase or decrease in response to inflammation. They inhibit or stimulate various functions, e.g. coagulation and recruiting of immune cells to inflammatory sites.
Adaptive Immune System Diagrams

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Anaphylaxis
  • Anaphylaxis is a systemic allergic reaction to an antigen for which the adaptive immune system has previously developed T-Cells, B-Cells, and antibodies.
  • The antibodies (IgE antibodies) bind not only to the antigen but also to receptor molecules on mast cells and basophils, causing them to release inflammatory chemicals such as histamine, serotonin, and leukotrienes, resulting in:
    • the constriction of the smooth muscles, leading to breathing difficulty;
    • the dilation of blood vessels, causing skin flush and hives
    • an increase in vascular permeability, resulting in swelling and a decrease in blood pressure.
  • britannica.com/science/anaphylaxis
    • Symptoms of anaphylaxis include an itching of the scalp and tongue, difficulty in breathing because of swelling or spasm of the bronchi, skin flush of the whole body, an abrupt fall in blood pressure, vomiting or abdominal cramping, and unconsciousness. In milder cases hives may spread over the whole body, and often there is a severe headache. Treatment, which must begin within a few minutes of attack, involves the injection of epinephrine (adrenaline), followed by the administration of antihistamines, corticosteroids, bronchodilators, and fluids.
    • Almost any substance can induce anaphylaxis, but the most common agents are drugs such as penicillin, foods such as nuts and shellfish, and insect venom. Anaphylaxis may occur after contact with extremely small amounts of antigen and is more common in persons with a history of atopic dermatitis. In some cases anaphylaxis may be precipitated by exercise, and in other cases no cause is known.
Antibodies

Antibodies bind to matching antigens, causing the pathogen to be neutralized, eaten, or blown up:

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Image Credit: opentextbc.ca/biology/chapter/12-3-adaptive-immunity/#fig-ch17_03_03

Example: Antibodies (in green) attach to the spike proteins of the coronavirus, preventing them from binding to the receptors of a human cell.

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Antigen
  • An antigen is a molecule on a pathogen’s surface that binds to matching antibodies and antigen receptors on B-Cells and T-Cells. Specifically, the antibodies and receptors bind to parts of the antigen called epitopes, enabling different antibodies to attach to the same antigen.

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  • Antigens include proteins, peptides (amino acid chains) and polysaccharides (chains of monosaccharides/simple sugars).
  • Foreign antigens originate outside the body, e.g. parts of viruses and bacteria, snake venom, certain proteins in foods, and components in blood from other individuals.
  • Auto-antigens originate within the body.
Antigen-presenting Cell
  • An antigen-presenting cell (APC) is an immune cell that consumes a pathogen and displays fragments (i.e. antigens) of the pathogen on its surface for recognition by B-Cells and T-Cells.
  • Professional APCs are macrophages, B cells and dendritic cells.

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Bacteria
  • A bacterium is a single-celled organism that lacks a nucleus. 
  • Pathogenic bacteria cause disease by
    • Multiplying by producing toxins, e.g. cholera, botulism, and tetanus
    • Multiplying by crippling the immune system, e.g. tuberculosis, plague, and Legionnaires Disease

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Blood
  • Blood is a liquid (Plasma) which transports:
    • Red Blood Cells (Erythrocytes)
      • Transport oxygen from the lungs to tissues
    • Platelets (Thrombocytes)
      • Help form blood clots
    • White Blood Cells (Leucocytes)
      • T-Cells and B-Cells (Lymphocytes)
        • Attack specific pathogens
      •  Phagocytes
        • Eat pathogens

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Complement System
  • Complement is a system of over 30 proteins that “complements” the response of immune cells to a pathogen.
  • Complement
    • causes foreign and infected cells to burst
      • (Cell lysis in the diagram)
    • deposits molecules on the surface of a pathogen that attract phagocytes that eat it
      • (Opsonization in the diagram)
    • releases small protein fragments that promote an inflammatory response by causing the release of histamine
      • (Promotion of inflammatory response in the diagram).
  • Complement is activated in two ways:
    • The classical pathway is triggered by the presence of antibodies bound to antigens on surface of pathogens.
      • (Classical pathway in the diagram)
    • The alternative pathway is triggered by molecules on the surface of pathogens (without the need for antibodies).
      • (Alternative pathway in the diagram).

Image Credit britannica.com/science/complement-immune-system-component

Cytokines
  • Cytokines are a class of small, short-lived proteins secreted by one cell to affect the behavior of other cells.
  • britannica.com/science/cytokine
    • Once secreted, the cytokine binds to a specific protein molecule, called a receptor, on the surface of the target cell, an event that triggers a signaling cascade inside that cell. The signal ultimately reaches the nucleus, where the effects of the cytokine are manifested in changes in gene transcription and protein expression—i.e., genes, which code for proteins, may be turned on or off, and protein production may be stimulated or inhibited.
    • Many different cytokines have been identified, and their activities, at least in part, are known. In some cases, one cytokine can interact with a variety of different cell types and elicit different responses from each cell. In other cases, different cytokines can elicit the same response from a cell.
  • Cytokines cause other cells to proliferate, make antibodies, promote inflammation, suppress inflammation, secrete more cytokines, activate B-Cells and T-Cells, suppress synthesis of proteins, and so on.
  • A cytokine storm is the quick release of large numbers of cytokines resulting in tissue and organ damage.

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Inflammation
  • Inflammation is a response by the Innate Immune System that involves the dilation and increased permeability of blood vessels, resulting in an increase of blood flow and white blood cells, mostly phagocytes.
  • Signs of inflammation:
    • redness, heat, swelling, pain, loss of function
  • Common causes:
    • Pathogens, e.g. bacteria, viruses, fungi
    • Damaged cells
    • Irritants, e.g chemicals, radiation, foreign objects
  • Inflammation is either acute or chronic.
  • Mast Cells mediate the inflammatory response, releasing chemical mediators such as histamine, interleukins, heparin, and various enzymes. The mediators produce increased permeability of blood vessels, contraction of smooth muscles, and increased mucus production.

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Interferons
  • Interferons, a cytokine, trigger an early response to a viral infection.
  • A cell infected by a virus releases interferons, which instruct neighboring cells to self-destruct if they’re infected or reduce protein synthesis (which slows viral replication) if they’re not.

Image Credit opentextbc.ca/biology/chapter/23-1-innate-immune-response/

Lymphatic System
  • The Lymphatic System is the body’s drainage system and home to T-Cells and B-Cells.
    • Drainage System
      • As blood circulates, blood plasma leaks through capillaries into tissues, supplying them with nutrients. Most of the interstitial fluid, as it’s then called, seeps directly back into the bloodstream. The rest enters the lymphatic system and, as lymph, flows through lymphatic vessels back to the blood.
    • Home of T-Cells and B-Cells.
      • As the lymph flows through lymph nodes, macrophages grab pathogens passing by and feed them to T-Cells, activating the Adaptive Immune Response. 
        • (Pathogens grabbed by Dendritic Cells, outside the lymphatic system, are also brought to the lymph nodes.)
      • Activated T-Cells and B-Cells make their way through lymphatic vessels to the bloodstream.
  • Lymphatic Organs
    • Primary lymphoid organs
      • Bone Marrow, where lymphocytes originate from stem cells, some maturing into B-Cells, others migrating to the Thymus. 
      • Thymus, where arriving lymphocytes mature into T-Cells.
    • Secondary lymphoid organs 
      • Lymph nodes, spleen, and small masses of lymph tissue such as the appendix and tonsils.

Image Credit wikipedia.org/wiki/Lymphatic_system

Microbe
  • A microbe or microorganism is a microscopic organism or smaller, e.g. bacteria, archaea, algae, fungi, protozoa, and viruses.
Natural Killer Cells
  • Natural Killer (NK) Cells bind to abnormally dividing human cells, either cancerous or infected with a virus, and inject poison into them.  Phagocytes then eat debris left behind.
  • NK cells are like Cytotoxic T Cells except for targeting a specific antigen.

Image Credit opentextbc.ca/biology/chapter/23-2-adaptive-immune-response/

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Phagocytosis
  • Phagocytosis is the process by which certain cells, phagocytes, ingest cells and particles such as bacteria, dead tissue cells, protozoa, dust particles, pigments, and other small foreign bodies. 
  • The primary phagocytes of the immune system are neutrophils and macrophages.
  • Neutrophils make up about 60 to 70 percent of white blood cells. Macrophages, fewer in number, are “big eaters” that move and digest their food more slowly.

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Proteins
  • Proteins are one of the macromolecules of life, along with carbohydrates, lipids, and nucleic acids.
  • They consist of chains of 50 to 2000 individual amino acids (of about 20 different kinds)
  • And they’re really big. Compare the enzyme hexokinase to the average size molecules ATP and glucose in the upper right.
The enzyme hexokinase is shown as a ball-and-stick molecular model. For comparison, the average size molecules ATP and glucose are displayed in the upper right.

Image Credit wikipedia.org/wiki/Protein

  • Proteins are categorized by function:
    • Transporting substances
      • Hemoglobin in red blood cells transports oxygen
    • Fighting pathogens
      • Antibodies latch onto parts of a pathogen, e.g. the spikes of SARS-CoV-2.
    • Increasing the rate of chemical reactions (Enzymes)
      • Lactase catalyzes the breakdown of lactose into the simple sugars glucose and galactose. 
    • Providing Structure
      • Collagen is the structural protein of bones, tendons, ligaments, and skin.
      • Keratin is the structural protein of epithelial cells, in the outermost layers of skin.
    • Regulating the functioning of cells
      • Protein Receptors on a cell’s surface, or in its cytoplasm, respond to extracellular molecules, e.g. hormones, neurotransmitters, cytokines, growth factors, nutrients.
      • Insulin regulates the level of glucose in the blood.
      • Interferons warn neighboring cells of a viral infection.
    • Movement
      • Actin and myosin contract muscles
  • Proteins of the Immune System include cytokines, antibodies, and proteins of the Complement System.
White Blood Cells
  • White Blood Cells (Leucocytes) are found in tissues, in blood, and in the lymphatic system.
  • Lymphocytes (30% of WBC)
    • B-Cells
      • B-Cells multiply when activated, some differentiating into plasma cells that produce antibodies against a specific pathogen, others becoming Memory B-Cells.
    • T-Cells
      • Cytotoxic T-Cells (Killer T-Cells)
        • Kill human cells infected by a specific pathogen
      • Helper T-Cells
        • Activate cytotoxic T cells and macrophages, enabling them to attack infected cells
        • Activate B cells, enabling them to differentiate into plasma cells that secrete antibodies.
      • Memory T-Cells
        • Remember pathogens
      • Regulatory T-Cells (Suppressor T-Cells)
        • Control immune reactions
    • Natural Killer Cells
  • Granulocytes (contain chemical granules)
    • Neutrophils (50-80% of WBC)
      • Neutrophils and macrophages are the main phagocytes of the immune system
      • Neutrophils are among the first cells to arrive at the site of infection or injury.
      • Neutrophils focus on bacteria.
    • Eosinophils (<1% of WBC)
    • Basophils (<<1% of WBC)
      • Release histamine, heparin, serotonin, and leukotrienes that cause
        • constriction of the smooth muscles, leading to breathing difficulty
        • dilation of blood vessels, causing skin flush and hives
        • increase in vascular permeability, resulting in swelling and a decrease in blood pressure.
      • merriam-webster.com/dictionary/basophil
  • Monocytes (4-8% of WBC)
    • Macrophages (“Big Eater”)
      • Macrophages and neutrophils are the main phagocytes of the immune system
      • Macrophages are larger and longer-lived than neutrophils.
      • Their digestive process is slow, allowing them to capture a pathogen and present its antigens to Helper T-Cells, activating the Adaptive Immune Response 
    • Dendritic Cells
      • Reside in tissues exposed to the environment, such as the skin and the inner lining of the nose, lungs, stomach, and intestines.
      • Dendritic Cells and Macrophages present antigens to Helper T-Cells, activating the Adaptive Immune Response
CBC (Complete Blood Count)

1 microliter (uL) = 1/5000 of a teaspoon