Physiology Exam 3 (Immune and urinary)

Immune system

Protect against disease-causing agents called pathogens

Innate immunity

This is inherited. Innate immunity is non-specific, so it can function to protect against numerous different types of pathogens

Adaptive immunity

This is learned from exposure to specific pathogens. It is specific, meaning the white blood cells and antibodies target specific antibodies.

Complement System

Integrates the innate and adaptive immune responses. Consists of proteins floating in the plasma as well as other bodily fluids that become activated when antibodies bind to their specific antigens

Complement Proteins

Promote phagocytosis, local inflammation and lysis of target cells

Innate Immunity barriers

internal and external defenses that serve as a first line of defense against pathogens as well as the toxins they produce

Chemical barriers of innate immunity

including antimicrobial peptides and the acidity in the stomach

Physical barriers of innate immunity

including the skin and mucous membranes

Activation of innate immunity

System is activated when the body recognizes something as foreign. It does this by distinguishing “self” from “non-self” by using pathogen-associated molecular patterns (PAMPs)

Pathogen-associated molecular patterns (PAMPs)

Distinguishing “self” from “non-self” in innate immune system. Examples include lipopolysaccharides and peptidoglycan

Innate immunity: phagocytic cells

Three types: Neutrophils, Mononuclear, Tissue/ Organ-specific phagocytes

Neutrophils

First to arrive at the site of infection (Innate immunity). In blood and tissues.

Mononuclear phagocytic cell

arrive later (Innate immunity)

Tissue/ Organ-specific phagocytes

Many of these are fixed within the specific tissues and cannot migrate

Langerhans

in the epidermis (Tissue/ Organ-specific phagocytes of innate immune system)

Kupffer cells

In the liver, spleen and lymph nodes (Tissue/ Organ-specific phagocytes of innate immune system)

Microglia

In the central nervous system (Tissue/ Organ-specific phagocytes of innate immune system)

Monocytes

In blood (Tissue/ Organ-specific phagocytes of innate immune system)

Alveolar macrophages

In the lungs (Tissue/ Organ-specific phagocytes of innate immune system)

Innate immunity: diapedesis

Tissue specific phagocytes migrate to their final destinations by traveling in the bloodstream. They are attracted to their target tissues via a process called chemotaxis. Cytokines and chemokines are secreted by the tissues, thus attracting the tissue specific pathogens. Once in their tissues, these cells can be activated because they have specific receptors on their membranes that can bind to microbial molecules, complement proteins and antibodies

Cytokines and chemokines are secreted by…

tissues in response to infection, trauma, or other forms of tissue damage (called chemotaxis)

Innate Immunity: Phagocytosis in tissues

Phagocyte engulfs the pathogen by reaching out pseudopods. Pathogen is surrounded in a vacuole and the vacuole contains lysosomal enzymes and this vacuole allows the cell to digest the pathogen without damaging itself (In some cases, the lysosomal enzymes are released during phagocytosis. The enzymes are released into the cell, killing it. This contributes to local inflammation.)

What do Macrophages do in innate immune system

Reduce inflammation and they remove the remnants of cells after apoptosis

Phosphatidylserine

Cell that has undergone apoptosis display this extracellular surface molecule and signals to macrophage to engulf in dead cell. When this happens, the inflammatory responses of macrophages are suppressed

Hypothalamus and innate immune system

Regulates body temperature, so it is also responsible for creating a fever. Triggers an increase in metabolism, breaking down brown adipose tissue to increase body temperature. Blood vessels constrict to keep body heat in.

Innate Immunity: Interferons

Antiviral proteins made by infected cells that cause non-specific resistance to viruses for a short period of time (Nucleic acids from the pathogen stimulates the expression of STING genes, stimulator of interferon genes. These stimulate the production of interferons)

Alpha Interferons

Inhibit the replication of virus

Beta Interferons

Inhibit the replication of the virus

Gamma Interferons

Stimulates the production of chemokines and antimicrobial molecules. Also triggers phagocytosis

How is adaptive immunity gained

Acquired after exposure to these pathogens

White blood cells of adaptive immunity…

Are lymphocytes and phagocytes, and they work tougher to give the adaptive immune process four important characteristics: Self/ non self recognition,  Specificity of antibodies for antigens, Diversity of antibodies, Memory gives us the ability to fight the antigen more effectively after a second exposure

ADAPTIVE IMMUNITY: ANTIGENS

Molecules on the cell’s surface that help other cells determine which cell type they are. Help us to determine “self” from “non-self”

ADAPTIVE IMMUNITY: IMMUNOASSAYS

Tests that use specific antibodies to identify whether a person has been exposed to a certain antigen. If the antigen is present, it binds to the antibody and causes agglutination (clumping of the blood)

Primary lymphoid organs of adaptive immune system

bone marrow and thymus - they produce t lymphocytes

Secondary lymphoid organs of adaptive immune system

tonsils, peyer’s patches (in the mucosa of the intestine), lymph nodes

Lymphocytes

Made by stem cells in the bone marrow, They are stem cells themselves and seed the thymus. This means that the lymphocytes go to the thymus, mature and can then seed other organs (during childhood, goes to secondary organs in adulthood)

T lymphocytes

Made in the thymus seed the blood, lymph nodes and spleen.

Made in these secondary lymph organs attack host cells that have become infected with a fungus or virus. They can also attack unrecognized transplanted cells as well as cancer cells

What kind of process does T lymphocytes use

Cell mediated immunity, which requires the T lymphocytes to be close by to attack a host cell (NO ANTIBODIES). Produced in the thymus and make up 75-80% of all white blood cells. Examples include: Cytotoxic T cells, Helper T cells and regulatory T cells

Cytotoxic T Cells

Killer T cells that destroy cells that harbor antigens via cell mediated immunity (must touch)

Helper T cells

Help B lymphocytes become plasma cells, which secrete antibodies to enhance the ability of killer T cells to kill targets

Regulatory T lymphocytes

(Suppressor T lymphocytes)
Inhibit the response of B lymphocytes and killer T lymphocytes. Activated by specific antigens. Suppress allergic reactions by preventing inappropriate immune responses. Can have an overactive response that results in disease

Lymphokines/interleukins

A cytokine produced by lymphocytes that act upon other cells of the immune system via autocrine regulation

Autocrine regulators

Cell releases something that binds to itself and changes its own function (paracrine means the cell releases something that nearby cells can use)

Interleukin-1 (IL-1)

Proliferation and activation of T lymphocytes

Interleukin-2 (IL-2)

Proliferation of activated T lymphocytes

Interleukin-3 (IL-3)

Proliferation of bone marrow stem cells and mast cells

Interleukin-4 (IL-4)

Proliferation of activated B cells; promotes production of IgE antibodies; increases activity of cytotoxic T cells

Interleukin-5 (IL-5)

Induces activation of cytotoxic T cells; promotes eosinophil differentiation and serves as chemokine for eosinophils

Interleukin-6 (IL-6)

Proliferation and activation of T and B lymphocytes

Granulocyte/ Monocyte macrophage colony stimulating factor (GMCSF)

Proliferation and differentiation of neutrophils, eosinophils, monocytes, and macrophages

T cell receptor proteins

These cannot bind directly to antigens. as they require antigen-presenting cells to present the antigen to them

Dendritic cells

Originate in the bone marrow and migrate to most tissues. Engulf protein antigens, partially digest them and display their fragments on the cell surface for T cells to recognize. Once activated, they divide to form either effector T cells or memory T cells

B Lymphocytes

Utilize a process called antibody-mediated immunity (humoral immunity). This requires them to secrete antibodies to fight bacterial and viral infections. This means that B lymphocytes can fight infection from far away and do not travel toward the site of infection. They come directly from the bone marrow and make up 10-15% of all white blood cells. Examples include: Memory B cells and plasma cells

Steps of B LYMPHOCYTES

Pathogens enter the blood stream and activate the B lymphocyte. The activated B lymphocyte enters a secondary lymphoid organ. The cell divides several times (cloning). Some become memory cells, which are used to fight the same infection if infected again in the future. Others become plasma cells, which can produce 2,000 antibodies per second

Albumin

Plasma protein class that accounts for about 55% of plasma

Alpha-1 globulin

Plasma protein class that inhibits some blood proteases

Alpha-2 globulin

Plasma protein class that inhibits some blood proteases

Beta globulin

Plasma protein class that transports iron

Gamma globulin (immunoglobulins)

Plasma protein class that includes antibodies

Antibodies

Plasma proteins made by B lymphocytes (Gamma globulins: immunoglobulins) and are specific to antigens

IgG Antibody

Main form of antibodies in circulation. The production is increased after vaccinations

IgA Antibody

Main form of antibodies in external secretions like mother’s milk and saliva

IgE Antibody

Responsible for allergic reactions

IgM Antibody

Function as antigen receptors on the surface of lymphocytes before immunization; involved in the primary response (first exposure)

IgD Antibody

Function as antigen receptors on the surface of lymphocytes before immunization

Structure of antibodies

Y shaped protein. The bottom part is constant for every antibody. The top parts are specific to each antigen. (B lymphocytes have antibodies on their membranes for that act like receptors for antigens. When the antigen binds, it activates the B lymphocyte, which divides and produces more antibodies)

Why are antibodies so diverse

A large portion of our genome is dedicated to making antibodies, Genetic recombination during cell division, Recombination of genes during cell division in secondary lymphoid organs

CLONAL SELECTION THEORY for antibodies

During antibody production, a number of different antibodies are made, but only the antibodies with the highest affinity for the antigen are selected for

FAS protein

Surface protein that active T cells have and used as a way to target t cell after infection for destruction

Primary response for active immunity

After infection it takes 5-10 days before antibodies are made in large enough amounts to be detected in the blood (The individual will get sick)

Secondary response for active immunity

Later exposure to the same antigen results in maximum antibody production in less than two hours after exposure (The individual likely will never get sick)

VACCINATIONS and active immunity

Stimulate a primary response without getting the person sick

Killed virus vaccine

Salk polio vaccine

Live but attenuated virus vaccine

Sabin polio vaccine, MMR vaccine

mRNA that codes for the virus vaccine

COVID-19 vaccine

SYMPTOMS OF INFLAMMATION

Redness and warmth, swelling, pain, and pus

Redness and warmth

Caused by histamine which causes vasodilation, which brings the blood vessels closer to the surface of the skin. This results in redness and the loss of heat.

Swelling

An increase of blood flow to the area and fluid build up

Pain

caused by the release of prostaglandins

Pus

Result of apoptotic cells, bacteria and digestive enzymes. This actually helps fight the infection because it builds pressure in the area to close capillaries and prevent the spread of bacteria

Immunological tolerance

continued recognition of self-cells

Immunological competence

ability to mount an immune response

Autoreactive lymphocytes

immune system does not recognize the “self” cells and begins to create autoantibodies that attack these cells

Clonal deletion

lymphocytes are destroyed via apoptosis

Clonal anergy

regulatory T lymphocytes prevent these autoreactive lymphocytes from becoming active

Common autoimmune diseases:

rheumatoid arthritis, multiple sclerosis, Grave’s disease, thyroiditis, psoriasis and lupus

REASONS WHY SELF-TOLERANCE MAY FAIL

An antigen not normally exposed to the immune system has become exposed • (Hashimoto’s Hypothyroiditis)

A normally tolerated antigen is combined with a foreign hapten (a small molecule that binds to another molecule). Can happen after taking medications like aspirin • (Thrombocytopenia)

Antibodies that attack other antibodies are made (Rheumatoid arthritis)

Antibodies for foreign antibodies cross react with self antigens (Glomerulonephritis)

Abnormal response to allergens (also called hyper sensitivity)

Allergies

Hypersensitivity reactions

Immediate hypersensitivity

Abnormal B cell response. Effects seen within seconds to minutes. Can be caused by foods, bee stings, etc. Symptoms caused by histamine. These antibodies stay locally and don’t circulate in the blood. Conditions caused: allergic rhinitis, conjunctivitis, asthma, atopic dermatitis, food allergies

Delayed hypersensitivity

Abnormal T cell response. Effects seen hours to days after exposure. Symptoms caused by lymphokines. Conditions caused: contact dermatitis, poison ivy, oak or sumac

PASSIVE IMMUNITY

passing of antibodies from one individual to another which provides temporary protection. Examples: From mother to fetus, From mother to child (breast milk) Artificially via immunization (Blood plasma is collected from thousands of people and mixed together to give a huge variety of IgG, This is used to treat immunocompromised individuals)

TUMOR IMMUNOLOGY

Abnormal cells that continue to clone themselves and can de-differentiate to an embryonic state

Benign tumors

not cancerous, they are slow growing and limited to a specific area of the body

Malignant tumors

fast growing and can spread to other parts of the body (metastasize)

Cancerous tumors

Begin when there is a change in the expression of specific genes (oncogenes and tumor suppressor genes). Additionally, the immune system fails to stop the spread of the tumors

What provided protection against cancer

Lymphocytes

Humanized monoclonal antibodies

Type of cancer treatment where antibodies are biologically engineered to target cancer cells. They’re grown in mice and the binding site is then grafted onto a human antibody.

Adoptive cell transfer

Type of cancer treatment where the patient’s T cells are harvested and activated, then injected into the tumor site (their immune system has been suppressed by the regulatory T cells)

Chemotherapy and radiation

Type of cancer treatment that don’t rely on the immune system

Surface Barriers

Billions of helpful microorganisms live on our external surfaces. They fight off bacteria that would be harmful to us.