Natural Defense Against Disease

How many TLRs to humans have?

13 Total.

CD8 protein

Also binds to helper t cell along with MHC. Makes the connection stronger.

How are T Cell receptors similar and different to antibodies?

Also have constant and variable regions. Differnent because T cell receptors bind only to an antigenic determinant in the context of MHC molecules.

IgD

B cell surface receptor and important for B cell activation

Where are TLRs found?

Both on the cell surface and within the cell b/c during viral infection viruses want to enter the cell

Where are T Cells made and matured?

Bone marrow and they leave when they are immature to finish maturing in the thymus.

4. Immunological Memory

Once exposed to a pathogen, the immune system remembers it and mounts future responses much more rapidly

Where are all blood cells derived from?

Stem cells in the bone marrow.

Where are B Cells made and matured?

They are both made and matured in the bone marrow.

What happens if clonal deletion fails?

"Forbidden Clones" of B and T cells are made and an autoimmune disease can occur. EX: -Systemic lupus erythematosis: chronic systemic inflammatory disorder. The entire body is inflamed. -Rheumatoid arthritis-inflammation directed at the joints -Multiple sclerosis -insulin-dependent (type-1) diabetes

Interferons

"warning signal to other cells". Signaling glycoproteins consisting about 160 amino acids, they increase resistance of neighboring cells to infection by the same or other viruses by increasing the expression of protein kinase R (PKR)

Blood

(closed circulatory system) includes red and white blood cells and platelets

What are the two general types of defense mechanisms?

-NONSPECIFIC DFENSE: innate, inherited mechanisms that protect the body from many different pathogens. Ex: skin -SPECIFIC DEFENSE: adaptive mechanisms that protect against specific targets Ex: body makes antibodies to bind to specific pathogens

What do Myeloid progenitor cells give rise to?

-Red Blood cells: (erythrocytes) transport O2 and CO2 -Platelets: (cell fragments) initiate blood clotting -White Blood cells: (leukocytes) Granular Cells and Agranular Cells

Poliomyelitis

-acute viral infectious disease -spread by oral-fecal route -asymptomatic *no symptoms! - in 1% of cases virus destroys motor neurons, weakens muscles, iron lung machines -predominantly affects children -outbreaks in summer

Why do pathogens like us?

-we have lots of nutrients and H2O -we have a constant temperature and pH levels

How do we make sure antigens in vaccinations will provoke an immune response but not cause disease?

1. Inactivation-kill the pathogen with heat or chemicals, this makes sure the virus is not alive but its antigenicy is retained and allows the body to fight it 2. Attenuation-reducing the toxicity of the antigenic molecule or organism. LIVE viral vaccines. (e.g adaptation of a virus for growth in nonhuman cells) 3. Biotechnology-produces recombinant antigenic fragments of pathogens that activate lymphocytes but are harmless by themselves. Only inject in the proteins that will activate lymphocytes

What are the four characteristics of the adaptive immune system?

1. Specificity 2. Diversity 3. Distinguish self from nonself 4. Immunological memory

T Cells binding in the presence of MHC

1. The antigen-presenting cell takes up an antigen by phagocytosis 2. The cell breaks down the antigen into fragments in the phagosome 3. A class II MHC protein binds an antigen fragment 4. The MHC presents the antigen to a Th cell

Clonal Selection of B Cells (similar process for T cells)

1. The body makes an antibody that binds the specific antigen *each naive B cell makes a different, specific antibody and displays it on its cell surface 2. This binding along with signals from T helper cells stimulates B cell to divide resulting in cell clones. 3. Differentiation into plasma cells that secrete antibodies OR into memory ells *plasma cells work hard and die quickly *Memory cells divide at a low rate, their job is to perpetuate the clone, they hang around and survive for decades

How does binding of PAMPs to TLR activate immune system/bring about expression of defensive proteins?

1. fragment of a bacterium (PAMP) binds to the toll-like receptor 2.Protein kinase cascade occurs (phosphoralation) 3.The shape of the transcription factor NFxB is altered so it is now able to enter nucleus 4. NFxB enters the nucleus and binds to promotors 5. Genes encoding defensive proteins are transcribed

immune system

A set of mechanisms that protect organisms from infection by identifying and killing pathogens.

Protein Kinase R (PKR)

Activated by viral dsRNA. Inhibit all protein synthesis.

Secondary Immune Response

Activated when the antigen reappears. Is much more rapid because of immunological memory. *little to no lag phase

Primary immune response

Activated when the body encounters an antigen for the FIRST time *long initial lag phase

What is another name for white blood cells? What are they important for?

Another name for them is Leukocytes and they are important for defense.

Immunoglobulins

Antibody molecules made of

What are the sites on antigens that are recognized by the immune system?

Antigenic determinants aka Epitopes. These occupy small portions of antigens that are actually bound to antibodies. -each antigen typically has several antigenic determinants -the host creates Tcells and/or antibodies that are specific to the antigenic determinants

Normal Flora

Any infecting flora have to compete with our normal floor for space and nutrients

What do Lymphoid progenitor cells give rise to?

B-Cells-differentiate to form antibody-producing cells and memory cells(live for a long time) ----Plasma Cells: secrete antibodies (live for a short time but quickly release antibodies) -T-Cells: Kill virus infected cells (cytotoxic T-Cells); regulate activities of other white blood cells (helper T-Cells) -Natural Killer Cells: attack and lyse virus-infected or cancerous body cells * part of nonspecific immune

Why don't antibodies and T cells attack and destroy our own cells?

Based on clonal deletion

Why do red blood cells lose all their organelles?

Because their main function is to carry hemoglobin and oxygen. Without their organelles they can carry more hemoglobin.

Lymphatic system

Branching system of tiny capillaries connecting larger vessels. These lymph ducts eventually lead to a large lymph duct that connects to a major vein near the heart. Resembles a drainage system.

T helper cell

Can release chemicals to stimulate both B and T cells and thus regulates both humoral immunity and cellular immunity. *Both T Helper cell and B cell must recognize the same determinants *don't actually participate in killing anything

How are the correct B and T cells selected to mount an immune response?

Clonal Selection

Lymph/Lymph Fluid

Consists of fluids that accumulate outside the closed circulatory system in the lymphatic system. Lymph fluid is the fluid derived from the blood, it is the fluid from tissues, it accumulates in the intercellular spaces throughout the body. The lymphatic system slowly moves this fluid around and it eventually ends up back in the blood.

Granular Cells

Cytoplasm is full of secretory granuals. They release poisons into their surroundings and kill the micro organisms around them. Basophils-release histamine; may promote T-Cell development Eosinophils-Kill antibody coated parasites Mast Cells-release histamine when damaged

Activated T cells give rise to two types of effector cells.

Cytotoxic Tc cells "killer T cells"-recognize virus-infected or mutated cells and kill them by causing them to apoptose Helper Th cells- assist both the cellular and humoral immune systems, activated by the antigen presenting cells *activated helper T cells proliferate and stimulate both B and Tc Cells

Humoral Immune response

Deals with extracellular pathogens, based on B cells that produce specific antibodies. Antibodies recognize pathogens in extracellular spaces: blood/lymph/tissue fluids. *humor is latin for "fluids"

Proteasome

Degrades unwanted, excess, or weird proteins. Allows cell to control its protein concentration.

What do mast cells do?

Degranulate releasing tumor necrosis factor (signaling protein that activates immune cells and kill target cells by making the apoptose), prostaglandins (chemicals that interact with nerve endings, cause pain/itching/vessal dialation) and histamine (vessel dialation and leaky blood vessels allowing white blood cells to go into tissue of infected area) which trigger inflammation

Cellular immune response

Detect antigens that reside within body cells. Destroys virus infected or mutated (cancerous) cells. Based on cytotoxic T-cells. T cells express T cell receptors that recognize and bind to specific antigenic determinants.

Polio Vaccines

Dropped polio cases by 85%-90%

3. Distinguishing self from nonself

Each normal cell in the body bears a tremendous number of antigenic determinants. It is crucial that the immune system leaves these alone. Ex of disease where the body attacks it self (auto-immune disease): diabetes, multiple sclerosis.

An active lymphocyte (either B or T cells) produces two types of daughter cells.

Effector and memory cells. Effector B Cells- plasma cells that produce antibodies Effector T cells- release cytokines and activate other immune cells Memory cells-live longer and retain the ability to divide quickly to produce more effect and memory cells

What happens if lymphatic system does not function properly?

Elephantiasis-a parasitic worm destroys the lymphatic system, excess fluid does not get returned to the blood system but accumulates in the lower part of the body.

Clonal deletion

Eliminates B or T cells from the immune system during their differentiation. -In bone marrow , 90% of all B cells made are removed because they react against self antigens -In thymus the smae results appear for T cells -Elimination is accomplished by apoptosis (suicide)

How do the phagocytes kill the pathogens the engulf?

Engulf the pathogen inside the cell and then fuses with a lysosome (acidic). Some bacteria are resistant to the lysosomes acidic conditions. They can also kill by "respiratory or oxidative burst": rapid release of active oxygen species which causes oxidative damage within the pathogen. In the phagosome the superoxide can be converted into hyrdogen peroxide which is converted into bleach (HOCl) or hydroxyl radical (.OH).

Lymphoid Tissue

Essential parts of the defense system. (thymus, bone marrow, spleen, lymph nodes)

IgG

Found free in blood, about 80% of circulating antibodies. Most abundant antigen in both primary and secondary response. Can cross placenta and give immunity to the fetus.

Where are red blood cells found?

Found in the closed circulatory system (they never leave the blood vessels)

Where are white blood cells found?

Found in the closed circulatory system AND in the lymphatic system. Move into tissues and spaces to fight infection

IgM

Found on surface of B cell and free in blood. Antigen receptor on B cell membrane; first class of antibodies released by B cells during primary response.

MHC (major histocompatibility complex)

Gene products are plasma membrane glycoproteins. Display/present antigens to helper t cells. Enable immune system to determine between different between self and nonself cells. There are 3 classes of MHC proteins but we only talk about two.

How do vaccinations/immunizations work?

Gives you artificial immunity by purposely introducing antigenic determinants into the body. Stimulate immune system to produce memory cells and save them to be used when the person is actually under attack.

What are the adaptive immune system's two responses against invaders?

Humoral immune response and cellular immune response. They operate together and share mechanisms.

Appearance and composition of of white blood cells.

They are clear and have a nucleus and organelles.

Antibody Classes

IgG- monomer IgM-pentamer IgD-monomer IgA-dimer IgE-monomer

What causes lymph nodes to increase in size?

Immune cells are activated and are proliferating.

HCl and proteases

In the stomach

Fever

Increased temp makes immune cells more active, and certain pathogens are inhibited by high temps

pathogen

Infectious biological agent. "Germs"

What happens during an inflammatory response? Use splinter example.

Inflammation is triggered by the release of histamine which diffuses into the blood vessels. Induce mast cells to degranualte and release their signalin chemicals-histomines and prostoglandins. These cause blood vessels to dialate.

Inflammation

Innate Immune System. Used by the body when dealing with infection or tissue damage. Isolate damaged area to stop spread of infection and recruit new white blood cells into the area to fight invader and to promote healing.

Phagocytes

Involved in innate immunity. Engulf and digest foreign materials. Remove dead and dying cells. Also have important signalinf function, release chemicals into their surrounding when they come in contact with pathogens. They cause inflammation which calls more white blood cells to come. Motile, follow their target via chemotaxis,

Lymphocytes

Involved in specific immunity. Two types: -T Cells: migrate from the circulation to the thymus, where they mature -B Cells: circulate and also collect in lymph nodes and make antibodies

Class I MHC

Is a "kill me" protein. Present on the surface of every nucleated cell in vertebrates. When cellular proteins are degraded in the proteasome an MHC I protein may bind a fragment and travel to the plasma membrane to present it outside on the cell's plasma membrane. *discovered in transplantation rejection

When PKR inhibits protein synthesis of the cell what happens?

It inhibits ALL protein synthesis within the cell. Thus it kills both the virus and the host cell if this response is active for sufficient time.

2. Diversity

It is estimated that the human immune system can distinguish and respond to 10 million different antigenic determinants.

What are two major traits a functioning immune system should have?

It should be SPECIFIC so it does not attack normal cells and tissues. It should be ADAPTIVE because pathogens are constantly evolving new ways to avoid detection.

What role do complement proteins play in inflammation?

Large family of proteins that cleave each other and cause the release of chemo attractant signals that recruit phagocytes.

What can white blood cells do that red ones cannot?

Leave the circulatory system and proliferate in response to invading pathogens. Look round.

Physical T Cell Receptor

Made of two chains: alpha and beta. Have a variable and constant region. Variable-must bind to the apitote and the MHC molecule

What is the first responder to an injury?

Mast cells.

Agranular Cells (phagocytes)

Monocytes-develop into macrophages and DC. Live longer and consumer larger numbers of pathogens than do neutrophils. Some roam and others are stationary in lymph nodes/lymph tissues. Macrophages-Engulf and digest microorganisms; activate T-Cells Dendritic Cells-present antigens to T Cells. Have highly folded plasma membranes that can capture invading pathogens. *both of the above can carry out several phagocytosis

Which white blood cell is both granular and agranular?

Neutrophils-Phagocytose antibody coated pathogens. Most abundant type of white blood cells in the body (70%). Attack pathogens in infected tissue. They react fast. Average half life of a non-activated neutrophil is 4-10hrs. *Can only go through ONE phagocytic event

Leukocytes

Only adhere to veins, not arteries, and slip out of veins when the sense the chemicals released by damaged cells. They move toward the wound with purpose, they don't just randomly leave veins.

What are the two major groups of white blood cells?

Phagocytes and Lymphocytes

What are the different types of Innate Immunity?

Physical-skin, mucous Chemical-HCl in stomach Cell-mediated-white blood cells (except b and t cells), phagocytosis, complement proteins, interferons, inflammation, fever

IgA

Present in saliva, tears, milk, secretions. Mucosal immunity.

Structure of antibody (immunoglobulin)

Proteins made of 4 polypeptide chains, 2 heavy and 2 light, held together by disulfide bonds. Both the light and heavy chains on each peptide have variable and constant regions. Constant regions-theses amino acid sequences are similar to each other, determines the antibodies destination/function. Variable regions-on the tip. Unique amino acid sequences, contribute to the specificity of antibodies.

Antigens

Proteins/peptides or molecules that are specifically recognized by T cell receptors and antibodies (expressed on surface of B cells)

1. Specificity

Reactions to specific antigens.

Does the body make more white blood cells or more red blood cells?

Red

Symptoms of inflammation

Redness Swelling-histamines and prostaglandens dialate blood vessels (make them larger), accumulation of plasma outside the blood vessels Heat Pain

What are plasma cells full of?

Rough Endoplasmic Reticulum! B/c their job is to secrete proteins.

IgE

Secreted by plasma cells in skin. Fc region has a high affinity for mast cells, causes them to degranulate and cause inflammation. *Allergies!

Cytokines

Signal proteins produced by phagocytes, activate and recruit other immune cells and may signal brain to produce a fever

Lymph nodes

Sites along the lymph vessels that are small and roundish. Packed with white blood cells that filter and inspect the lymph fluid as it goes through the node.

Physical barriers to infection.

Skin and mucous. Mucous lines various body cavities exposed to the external environment (GI, respiratory, urinary, reproductive). It helps to trap pathogens and contains antiseptic substances like lysozyme.

When cells are infected by viruses what does the cell produce?

Small amounts of interferons

Definsins

Small cation polypeptides that are 18-45 aa in length. Produced by mucus membranes. Have a hydrophobic domain. Insert themselves into pathogens plasma membrane and create holes in the membrane allowing the cytoplasm to leak out and the invading cell dies.

Appearance and composition or red blood cells.

Smaller and lose their nuclei and organelles before they become functional. Look Biconcave.

What is the only disease to be considered completely eradicated?

Smallpox

Skin Defense

The skin is salty and dry and is thus inhospitable for microorganisms to live on.

Where do B and T cells collect?

The lymph nodes and the spleen.

Chemotaxis

The movement of a cell towards or away from some chemical in their environment

Antigen binding sites

There are two identical binding sites on every antibody (bivalent). The heavy and light chain variable regions align and form the Ag binding sites.

How are components of the defense system organized?

They are distributed throughout the body because infection can happen anywhere!

AIDS

This virus attacks the T helper cells. Therefore people with AIDS have very poor immune systems.

How is an invading pathogen recognized?

Toll-like receptors (TLRs)-innate immune-molecules that alert the immune system to the presence of microbial infection. They recognize "pathogen associated molecular patterns" (PAMPs) that are highly conserved among classes of pathogens and do not occur in the host. *present in vertebrates and invertebrates *discovered in toll genes of drosophila *one of the most ancient conserved components in the immune system *TLRs are only expressed by pathogens

Mucus and Cilia in respiratory system

Trap pathogens and remove them

Possible Pathogens

Viruses/bacteria/single-cell eukaryotic parasites (yeast)/parasitic worms/maggots *not lions

Tears, mucus, and saliva

contain enzyme lysozome that attacks the cell walls of many bacteria

How exactly do antibodies work?

cross link bacteria together to prevent them from dispersing, increasing efficiency for phagocytosis. Can neutralize toxins and prevent them from binding to target cells.

Percipitation

for large particles

Glutenation

for small particles

Innate Immune System

nonspecific response, exposure leads to immediate maximal response (it's on all the time), cell mediated and humoral components, no immunological memory, found in nearly all forms of life

Adaptive Immune System

pathogen and antigen specific response, lag time between exposure and maximal response, cell-mediated and humoral components, exposure leads to immunological memory, found only in jawed vertebrates