Immune System

Contents

Function
  • The function of the immune system is to protect the body against disease and infection by a pathogen.
    • A pathogen is an agent that causes disease. Pathogens include:
      • Bacteria
        • E.g. Pneumococcus, the most common cause of bacterial pneumonia
        • More on Bacteria
      • Fungi
        • E.g. Histoplasma capsulatum, which causes histoplasmosis
      • Protozoa
        • E.g. members of the genus Plasmodium, that cause malaria
      • Worms
        • E.g. Trichinella spiralis, which causes trichinosis
    • Infection is the invasion of an organism’s tissues by a pathogen and its proliferation within the organism.
      • Not to be confused with inflammation, a response by the immune system.
    • A disease is a condition of an organism that
      • impairs normal functioning,
      • is manifested by symptoms,
      • is not an injury
    • Pathogenic viruses cause disease by:
      • Invading cells and using their machinery to multiply
    • Pathogenic bacteria cause disease by multiplying and:
      • Interfering with the functioning of the body’s cells
      • Producing toxins, e.g. cholera and tetanus
      • Evading or crippling the immune system, e.g. tuberculosis and Legionnaires Disease
It’s Complicated
  • Half the immune system is messy and makeshift, the other half organized and directed. Both are complicated.
  • Immunology is where Intuition Goes to Die, Ed Yong, Atlantic
    • “Arguably the most complex part of the human body outside the brain, [the immune system is] an absurdly intricate network of cells and molecules that protect us from dangerous viruses and other microbes.”
  • There are two immune systems: the Innate and the Adaptive. The former is a patchwork of cells, proteins, and biochemicals whose functions overlap. The latter is organized and directed.
Components of the Immune System
Immune Response
  • When a pathogen is detected, signals are sent out and a hodgepodge of first-responders go into action:
    • Small proteins called cytokines are released, instructing cells to take various actions.
    • White blood cells are summoned.  Some eat pathogens. Others poison them.
    • Special proteins attack pathogens and infected cells, making them burst.
    • Body cells infected with a virus secrete interferons, a kind of cytokine that tells neighboring cells to produce proteins that prevent the virus from replicating within them.
    • The liver secretes acute-phase proteins that bind to bacteria, marking them for destruction.
    • Cytokines are released that raise body temperature.
    • Biochemicals are released that produce inflammation: redness, soreness, heat, swelling.
  • The first-responders form the Innate Immune System, providing a quick, generic response to an invasion of pathogens.
  • Meanwhile a second, precision system gears up for action: the Adaptive Immune System:
    • Certain kinds of cell, called antigen-presenting cells, eat pathogens, digest them, and display fragments of the pathogens on their surface.  The fragments are antigens
    • The cells travel to nearby lymph nodes, where they present the antigens for inspection.
    • Inside the lymph node are T-Cells, which have antigen receptors on their surface.  Each of the trillions of T-Cells has unique receptors, different from those of all other T-Cells, and matching only a single antigen.
    • A T-Cell, specifically a Helper T-Cell, is found whose receptors precisely match the antigens on the antigen-presenting cell. Thus, like a key fitting a lock, the Adaptive Immune System identifies the specific pathogen.
  • The Adaptive Immune System launches a two-pronged attack against the pathogen it’s identified.
    • Killer T-Cells kill body cells infected with the pathogen.
    • B-Cells make antibodies that glom onto pathogens, cramping their style and marking them for destruction.
  • Finally, Memory T Cells and B Cells memorize the pathogen’s antigens for future encounters
Innate Immune System (IIS)
Fast, Generic, and Makeshift
  • Fast
    • Acts within minutes
  • Generic
    • Doesn’t target a specific pathogen
    • Like dropping bombs from an aircraft.
  • Makeshift
    • The IIS is a patchwork of interconnected cells, proteins, and biochemicals whose functions overlap.
IIS Components
  • Eaters: Phagocytes (“Eating Cells”) eat pathogens
    • White Blood Cells
      • Macrophages
        • “Big Eaters” reside in tissues, especially the spleen and lymph nodes. Their digestive process is slow, allowing them to capture a pathogen for examination.
        • Macrophages are antigen-presenting cells.
      • Neutrophils
        • Neutrophils are the most abundant phagocyte, normally found in the bloodstream.
      • Dendritic Cells
        • Dendritic cells reside in tissues exposed to the environment, such as the skin and the inner lining of the nose, lungs, stomach, and intestines. Like macrophages, they capture pathogens for examination.
        • Dendritic cells are antigen-presenting cells.
  • Killers: Cells and proteins kill pathogens and infected human cells
    • White Blood Cells
      • 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
      • Eosinophils
        • Eosinophils inject poison into parasites.
  • Messengers: Cytokines pass signals from, to, and within the Immune System
    • Interferons
      • Interferons hinder the spread of viruses
      • Interferons, a type of cytokine, are released by infected cells to instruct nearby cells to terminate processes used by viruses.
      • More on Interferons
    •  Interleukins
      • Released by macrophages
      • Raise body temperature
      • Stimulate inflammation
      • Stimulate liver cells to secrete acute-phase proteins into the bloodstream, which bind to bacteria, activating complement proteins that destroy the pathogen. 
Adaptive Immune System (AIS)
Slow, Precise, Remembers
  • Slow
    • Takes four days to a week to several weeks.
  • Precise
    • Targets a specific pathogen, identified by molecules on its surface (antigens).
    • Like using guided missiles
  • Remembers
    • Memory cells of the AIS remember the pathogens they’ve identified.
AIS Immune Cells
  • T-Cells
    • Cytotoxic T-Cells (Killer T-Cells)
      • Cytotoxic T-Cells kill human cells infected by a specific pathogen
    • Memory T-Cells
      • Memory T-Cells remember pathogens.
    • Helper T-Cells
      • Helper T-Cells activate cytotoxic T cells and macrophages, enabling them to attack specific infected cells
      • Helper T-Cells activate B cells, enabling them to differentiate into plasma cells that secrete antibodies.
    • Regulatory T-Cells (Suppressor T-Cells)
      • Regulatory T-Cells control immune reactions
  • B-Cells
    • B-Cells
      • B-Cells differentiate into plasma cells, each secreting thousands of antibodies that bind to an antigen of a specific pathogen.
      • More on Antibodies
      • B-Cells are antigen-presenting cells.
    • Memory B-Cells
      • Memory B-Cells remember pathogens.
Antigens and Receptors
  • The Adaptive Immune System attacks a specific pathogen, identified by antigens on its surface.
  • An antigen receptor is a protein on a T-Cell or B-Cell that fits an antigen of a pathogen, like a key fits a lock.
  • Each of the trillions of T-Cells and B-Cells has a unique set of (identical) antigen receptors, enabling it to recognize and respond to a particular antigen of a specific pathogen.
  • Cytotoxic T-Cells kill human cells infected by pathogens matching their antigen receptors.
  • B-Cells make plasma cells that secrete thousands of antibodies, proteins having the same antigen receptors.  The antibodies latch onto matching antigens, causing the pathogen to be neutralized, eaten, or blown up:

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

The Adaptive System Process
  • Identify the pathogen
  • Launch two-pronged attack
    • Killer T-Cells kill body cells infected with the pathogen.
    • B-Cells make antibodies that glom onto pathogens, cramping their style and marking them for destruction.
  • Remember the pathogen

Image Credit: biology-forums.com/index.php?action=gallery;sa=view;id=19712

  • Helper T Cells (Middle Section) 
    • Purple Cell
      • A phagocyte, e.g. a macrophage or dendritic cell, eats a pathogen, travels to the spleen or a lymph node, and displays an antigen of the pathogen on its surface.
        • (The antigen might be a spike protein of SARS-CoV-2.)
    • Blue Helper T Cell beneath the Purple Cell
      • A Helper T-Cell, with a matching antigen receptor, binds to the antigen of the Purple Cell and releases cytokines
      • The cell creates Memory Helper T-Cells
  • Humoral Immunity (Left Section)
    • Blue B-Cell to the left of the Helper T Cell
      • A naive B-Cell, with a matching antigen receptor, binds to an antigen of the pathogen. (naive = unactivated)
      • The B-Cell is activated by the cytokines released by the Helper T-Cell, which results in the creation of:
        • Plasma Cells, which secrete antibodies
        • Memory B-Cells
  • Cell-mediated (Right Immunity)
    • Blue Cytotoxic T-Cell to the right of the Helper T Cell
      • A naive Cytotoxic T-Cell, with a matching antigen receptor, binds to an antigen of a cell infected by the pathogen. (naive = unactivated)
      • The Cytotoxic T-Cell is activated by the cytokines released by the Helper T-Cell, which results in the creation of:
        • Cytotoxic T-Cell
        • Memory Cytotoxic T-Cells

View other Adaptive Immune System Diagrams

Pathogen Counterattack
  • Pathogens try to evade, defend against, or counterattack the Immune System.
    • Evasion
      • Hiding inside host cells, e.g. macrophages.
      • Hiding under a “cloak” of carbohydrates.
      • Releasing compounds that misdirect the immune response.
      • Rapidly changing surface proteins
      • Mimicking host molecules
    • Defense and Counterattack
      • Making proteins that bind to antibodies and B-Cells, making them ineffective
      • Interfering with Interferon’s attack against cells infected by a virus
      • Disrupting the inflammatory response
      • Forming biofilms which protect against the proteins and cells of the immune system.
      • Killing macrophages
        • Eaten by a macrophage, the bacterium that causes Legionnaires’ disease multiplies, kills the macrophage, and releases its copies to infect more macrophages
Vaccines
  • vaccine is a substance that stimulates the adaptive immune system to develop B-Cells and T-Cells that identify and remember a pathogen, without making the person sick. It does this in either of two ways:
    1. by injecting antigens of the pathogen into the body (without the pathogen itself).
      • Whole Virus Vaccines
        • How the Sinopharm Vaccine Works NYT
      • Protein-Based Vaccines
        • How the Novavax Vaccine Works NYT
    2. by getting the body’s cells to make the antigens
      • Genetic Vaccines
        • How Moderna’s Vaccine Works NYT
        • How the Pfizer-BioNTech Vaccine Works NYT
      • Viral Vector Vaccines
        • How the Johnson & Johnson Vaccine Works NYT
  • How Nine Covid-19 Vaccines WorkNYT
  • Preventing infection and disease:
    • Some vaccines prevent infection by the pathogen, providing sterilizing immunity.
    • Other vaccines prevent disease but not infection, e.g. flu shots and the Salk polio vaccine.
  • View Kinds of Vaccines
How the Pfizer Vaccine Works
  • SARS-CoV-2 is made up of:
    • an oily membrane
    • a strand of RNA, consisting of 29 genes
    • four structural proteins:
      • S protein, which forms spikes that attach to the target cell
      • N protein, which forms an envelope around the RNA
      • E and M proteins, which force the target cell to make copies of the virus

Image Credit Scientific American

  • The gene for the spike protein is a section of the virus’s RNA having 3861 nucleotides (named a, c, g ,u)
  • Each dose of the Pfizer vaccine contains 30 mcg of mRNA that codes for the spike protein.
  • Human cells contain ribosomes (10 million per cell), that make proteins from mRNA.
  • How the Pfizer-BioNTech Vaccine Works NYT