immunity

Leukocytes ~ macrophages, neutrophils, mast cells, natural killer cells, dendritic cells
- macrophages = phagocytose pathogen and then act as antigen presenting cell.
- neutrophils = Polymorphonuclear leukocytes = PMNs = phagocytose pathogen and destroys it.
- mast cells: release histamine during an allergic response, bring about inflammation.
- natural killer cells: kills infected/abnormal cells.
- dendritic cells: the best antigen presenting cells.

T-lymphocytes

- Matures in the Thymus.
- Cytotoxic T cells recognize antigen on infected cells, and signal for apoptosis.
- Helper T cells recognize antigen on antigen-presenting cells, and signal for activation of B cells, T cells, and macrophages.

B-lymphocytes, plasma cells

- Matures in Bone marrow.
- B cells form plasma cells and memory cells when exposed to antigen.
- Plasma cells = secrete Antibody.
- Memory cells = stick around in case the same Antigen attacks in the future.

 

Tissues

Spleen
- Provides a site for WBCs to reside and proliferate.
- Removes pathogens from blood.
- Removes old RBCs and platelets.

Thymus: T lymphocytes differentiate in the thymus.

Lymph nodes
- Provide a site for WBCs to reside and proliferate.
- Removes pathogens from lymph.
- Residing lymphocytes monitor lymph for foreign antigens, and initiate an immune response when exposed to foreign antigens.

 

Basic aspects of innate immunity and inflammatory response: INNATE immunity= first line of defense = kills anything that doesn’t look right = not specific to a particular pathogen / antigen

  • - Skin: natural flora, layer of keratin.
  • - Mucus membranes: traps pathogen in mucus, and cilia moves it out.
  • - Phagocytes: engulf pathogen.
  • - Natural killer cells: destroy infected cells.
  • - Antimicrobial proteins: tears (lyse bacteria), interferons (interfere with virus replication), complement (punches holes in cell/pathogen membrane).
  • ~Fever/inflammation: WBCs are more active at higher temperature, and inflammation recruits WBCs to site of infection by sending out chemical signals and making capillaries more permeable.

ADAPTIVE immunity = highly specific for a particular pathogen / antigen.
- Antigen presenting cells present foreign antigen on their surface.
- Antigen is recognized by T and B cells.
- Cytotoxic T cells kill infected cells.
- Helper T cells Activate Macrophages, T and B cells.
- B cells produce AntiBodies.
- AntiBodies bind to antigens and bring about: 
        ~~ Neutralization: pathogen can’t adhere to host cell
        ~~ Opsonization: makes it easier for phagocytosis
        ~~ Complement activation: kills infected cell by punching holes in cell membrane.
- Memory cells are made that are much more efficient (does NOT need T cell activation) in proliferating and making antibodies in case the same infection strikes in the future.
- Memory cells allow the body to mount a greater, and more sustained response against the same pathogen during secondary response.

Concept of Antigen and Antibody
- AntiBody = lock, Antigen = key. Each antibody is specific to the binding of an antigen.
- AntiBody is like a Y, the tips of the fork bind antigen.
- The tips of the fork are called hypervariable regions because they are unique to each antigen-specific antibody.
- The AntiBody consists of 2 light chains and 2 heavy chains linked together by disulfide bonds.

Mechanism of stimulation by antigen; antigen presentation
- pathogen enters antigen-presenting-cell (APC)
- pieces of the pathogen gets displayed at the surface of APCs.
- T cell receptors recognize the presented antigen, and activates various immune responses.

scenario 1: EXTRAcellular pathogen
1. Macrophage engulfs pathogen.
2. pieces of the pathogen becomes the antigen and gets presented at the macrophage’s cell surface.
3. Helper T cells recognize the presented antigen, and Activates Macrophages to destroy pathogen. Helper T cells also Activate B cells to produce antibodies against the pathogen.

scenario 2: INTRAcellular pathogen
1. pathogen invades host cell.
2. pieces of the pathogen gets presented on the host cell surface.
3. Cytotoxic T cells recognize the presented antigen, and signals the infected cell to self-destruct.

Immunity is the ability of the body to tolerate material that is indigenous to it and eliminate material that is foreign.

The success of the immune system depends on its ability to distinguish between host (self) and foreign (non-self) cells.

The body’s first line of defense against infectious agents, or pathogens, is our skin and mucous membranes.

If a pathogen breaks through these barriers, it encounters a series of nonspecific immune defenses, including specialized cells and chemicals that seek out, identify, and destroy the pathogen, regardless of its identity.

This general response is nearly identical for each pathogen, and even if the body is exposed to the same pathogen many times the response each time is the same (there is no immunologic memory).

If a pathogen evades non-specific defenses, the body mounts a specific acquired immune response tailored to each pathogen.

Acquired immunity is divided into two types based on how it is acquired by the host:

  • Active immunity is provided by a person’s own immune system. This type of immunity can come from exposure to a disease or from vaccination. Active immunity usually lasts for many years and often is permanent.
  • Passive immunity results when antibodies are transferred from one person or animal to another. The most common form of passive immunity occurs when a fetus receives antibodies from his or her parent across the placenta during pregnancy. Passive immunity disappears over time, usually within weeks or months.

Some childhood vaccinations (e.g., measles) are scheduled so that the vaccine is given at the time when passive immunity from maternal antibodies is waning.

vaccine is a preparation of a weakened or killed microbe, or portion of it, that when administered, stimulates an immune response against the pathogen but which itself is incapable of causing severe infection.

If the body encounters the real disease-causing pathogen in the future, the immune system will “remember” the pathogen and can respond quickly to launch an immune response to prevent severe illness.

Each vaccine provides immunity against a particular disease; therefore, a series of vaccinations is administered to children and adults to protect them from many vaccine-preventable diseases.

Some vaccines are combined into a single injection. For example, DTP vaccine combines vaccines against three diseases — diphtheria, tetanus, and pertussis.

There are three main types of vaccines:

Live attenuated vaccines usually only require one dose to provide life-long immunity, with the exception of oral polio vaccine, which requires multiple doses. Examples include:

  • Virus (e.g., oral polio vaccine [OPV], measles, yellow fever)
     
  • Bacteria  (e.g., Bacillus Calmette-Guérin (BCG) vaccine, which prevents TB)

Inactivated vaccine may be whole-cell (made of an entire bacterial or viral cell) or fractional (composed of only part of a cell). Fractional vaccines are either protein- or polysaccharide-based. Examples include:

Whole

Virus (e.g., inactivated polio vaccine [IPV])

Bacteria (e.g., whole-cell pertussis)

Fractional

Protein-based

  • Subunit (e.g., acellular pertussis)
  • Toxoid (e.g., diphtheria and tetanus)

Polysaccharide-based

  • Pure (e.g., meningococcal)
  • Conjugate (e.g., Haemophilus influenzae type b [Hib])

Pure polysaccharide vaccines are generally NOT effective in children under the age of two UNLESS they are coupled with a protein.

This coupling process is known as conjugation.

Inactivated vaccines are not as effective as live vaccines.

Multiple doses are required for full protection.

And because protection by these vaccines diminishes over time, booster doses are needed to maintain immunity.

Recombinant vaccines are produced by inserting genetic material from a disease-causing organism into a harmless cell, which replicates the proteins of the disease-causing organism. The proteins are then purified and used as vaccine. An example of this is:

  • Hepatitis B

Individuals who have been immunized serve as a protective barrier for other individuals who have not been immunized, provided that the number immunized has reached a certain level, usually 80% or higher. Reaching and maintaining that level, which varies by communicable disease, provides "herd immunity" to unimmunized individuals. Herd immunity is especially important with extremely contagious diseases such as measles. -This is all from my my GlobalHealthLearning Immunization Essentials Class
Immunity - {RP: Bookmans-Lavi}

Allen walked with eyes open and alert, watching the other figures that mulled through the street with acute attention. The knowledge that very few could be trusted was an ever-present prick at the back of his mind, but he plastered an acknowledging smile on his face whenever anyone passed.

He self-consciously tugged his left sleep down a little more, despite that his deformed arm was fully covered alreay, as a passing man glared, a more common response to his smiles than actually having them returned. It didn’t bother him so much though, more than used to it. If people didn’t give him dirty looks for having glimpsed his abomination of an arm, they glared just because they could, because people were paranoid. It was reasonable enough though, he supposed.

He tried not to look skittish as a group of soldiers marched by, some giving him a visual once-over as if accusing him of some sort of hidden crime they needed only drag out into the open and expose, before doing what they did best… further sew animosity and fear into the uninfected with their own overly harsh tactics of “containment”.

The albino male jogged up a few steps to the entryway of an apartment building. He counted the doors lining the halls as he walked before settling on the one he had been searching for, giving an announcing knock first before cracking the door open, glad to find only one person currently inhabited the room.

"Hey, Lavi," Allen greeted casually. "Busy?"

Fruit fly fat body

WHAT’S THAT?
Our livers perform upwards of 500 different functions like storing energy molecules and playing roles in immunity. It turns out even small fruit flies have liver-like organs called fat bodies. In this image, a fat body (green) wraps around and cradles the gonad (blue sphere). This image was edited to look kaleidoscopic.

WHAT’S THE LATEST?
Organs need to communicate with each other about what’s happening in the body. When an animal becomes infected, cells must signal to one another to turn on pathogen defenses. The transmission of this signal is complex, but Dr. Beth Stronach’s lab at the University of Pittsburgh uses fruit fly fat bodies to study how different molecules move, transmit signals, and alert cells to invaders. Learning how cells talk to each other in many contexts - and what happens when this goes wrong - will help us understand how our bodies respond to diseases like cancer.

Image captured and submitted by Dr. Beth Stronach/University of Pittsburgh.

07 October 2014

Cancer-fighting Communication

Your immune system has two ways to protect you. Cells in the innate system take on all invaders in a generic fashion, whereas specialised cells in the adaptive system learn to recognise and eliminate otherwise evasive pathogens. Both strategies involve dendritic cells, one of which is pictured here in an artist’s rendering. Dendritic cells share information to coach the adaptive system’s cells about which pathogens or pathogen-infected cells to hunt and how to destroy them. This involves exchanging information parcels called exosomes. But there’s a problem: cancer cells can hijack these communications to weaken the immune response. Using computer models, researchers have revealed that exosome exchanges between cancer and immune cells create three different cancer states. The intermediate state, with a moderate cancer load and an immune system on high alert, could potentially provide a window for combination treatments involving alternate cycles of immune-boosting therapies and cancer-killing chemotherapy.

Written by Daniel Cossins

Image by Don Bliss and Sriram Subramaniam
National Cancer Institute
This image is in the public domain and can be freely reused
Research published in PNAS, September 2014

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