Immune System Ch 31

Advanced Placement Biology in Brandon High School 2013-2014

Teacher: Mrs. Radjewski; Room 224;Upstairs next to Mrs. Spezia in Room 222Diagonal from the Social Studies Office, otherwise known as the Social Studies

Cave with the nasty microwave.

Defense against Pathogens

• Pathogens– Harmful organisms and viruses that can cause

disease– Animals have 2 defensive mechanisms against

them to provide immunity• The ability to avoid disease when invaded by

a pathogen

1. Innate immunity2. Adaptive immunity

Innate Immunity

• Nonspecific – used against a wide variety of invasive organisms

• Includes barriers such as the skin, which is a 1st line of defense for the body

• Also includes phagocytic cells (phagocytes) as a 2nd line of defense for the body– They ingest foreign cells (phagocytosis)

• These defenses may be presented all the time, or activated in response from an injury or invasion by a pathogen (if activated, it is rapid)

• Most animals have innate immunity

Adaptive Immunity

• Specific• Distinguishes between substances made by the

organism (self) and substances that are not part of the organism (nonself)

• Involves antibody proteins that recognize, bind to, and aid in the destruction of specific viruses and bacteria

• Typically slow to develop, but long lasting• Only found in vertebrate animals

White Blood Cells (WBC’s)

• Blood contains 5 billion RBC’s and 7 million WBC’s

• Also called leukocytes• Play major role in immune system• Two major kinds

1. Phagocytes – large cells that engulf pathogens by phagocytosis (involves in innate and adaptive)• Example: macrophages

2. Lymphocytes – only involved in adaptive• Example: B cells and T cells

4 Major Components of Immune System

1. Antibodies – proteins that bind specifically to substances identified by immune system as nonself– Binding inactivates and destroys microorganisms

and toxins– Can act as a tag on nonself cells, making them

easier for immune system to attack– Produced by B cells (type of lymphocyte)

2. Major Histocompatibility Complex (MHC)

• Proteins that are self-identifying cells• Play a major role in coordinating interactions

between lymphocytes and macrophages (type of phagocyte)

• Two classes– MHCI – found on surface on most mammalian

cells– MHCII – found on most immune system cells

3. T Cell Receptors

• Integral membrane proteins on the surfaces of T cells (type of lymphocyte)

• Recognize and bind to nonself substances

4. Cytokines

• Soluble signaling proteins released by many cells

• Bind to cell surface receptors and alter the behavior of their target cells

• They can– Activate and inactivate B cells– Activate and inactivate macrophages– Activate and inactivate T cells

31.2 Innate Defenses are Nonspecific

Suppose a bacteria lands on human skin….challenges the bacteria faces:

• Physical barrier of the skin– Bacteria can

rarely penetrate intact skin

– Broken skin increases the risk of infection

More challenges…

• Saltiness of skin– Bacteria will have a hard time growing

• Presence of normal flora– Competition for space and nutrients

Pathogen lands on inside nose or another internal organ….defenses it will encounter are:

• Mucus– Slippery secretion produced by mucous

membranes, which lines various body cavities– Traps microorganisms and will be removed by cilia

• Lysozyme– Enzyme made by mucous membranes, that cleave

the cell wall of bacteria causing them to burst open

More defenses inside nose….

• Defensins – Made by mucous membranes– Peptides of amino acids containing hydrophobic

portions that are toxic to bacteria and other pathogens

– Insert themselves in plasma membranes of these organisms and make membranes freely permeable to water and all solutes, thus killing the invaders

If Bacteria gets into body, 2nd line of defense will begin…

• Phagocytes– Recognizes

pathogenic cells and then ingest them by phagocytosis

2nd Line of Defense continued…

• Natural Killer Cells– Lymphocytes– Can distinguish between healthy cells and those

who are infected by viruses or are cancerous– Can initiate apoptosis (programmed cell death) in

the target cells

2nd Line of Defense continued…

• Complement Proteins– 20 different proteins– Once activated, a cascade occurs

1. One complement protein binds to components on the surface of the invading cell. This binding helps phagocytes recognize and destroy the invading cell

2. Another protein activates the inflammation response and attracts phagocytes to the site of infection

3. Finally, other proteins lyse the invading cell

2nd Line of Defense continued…

• Interferons– Signalling proteins (cytokines)– Help increase the resistance of neighboring cells

to infection– Can bind to receptors on the plasma membrane of

uninfected cells, stimulating a signaling pathway that inhibits viral reproduction if the cell near it are infected

Inflammation

• Response when tissue is damaged because of infection or injury

• Redness, swelling, and heat near damaged site• Can be painful• Is important– It isolates the area to stop the spread of the

damage– It recruits cells to the location to kill any pathogens– It promotes healing

Response to Inflammation

• Mast Cells– Adhere to the skin and linings of organs and

release numerous chemical signals• Tumor necrosis factor – a cytokine protein that kills

target cells and activates immune cells• Prostaglandins – fatty acid derivative that initiates

inflammation in nearby tissues• Histamine – amino acid derivative that increases the

permeability of blood vessels to white blood cells so they can act in nearby tissues

OH NO! A Splinter!!

• Damaged tissue attract mast cells, which release histamine that diffuses into the blood vessels

• Also tumor necrosis factor is released that diffuses to phagocytes

• Histamine causes the vessels to dilate and become leaky

• Complement proteins leave the blood vessels and attract and activate phagocytes

• Tumor necrosis factor stimulates phagocytosis

• Blood plasma and phagocytes move into infected tissue from the blood vessels

• Phagocytosis engulfs bacteria and dead cells

• Histamine and complement signaling cease; phagocytes are no longer attracted

• A growth factor from platelets stimulates epithelial cell division, healing the wound

Following Inflammation

• Pus– Mixture of leaked fluid and dead cells (bacteria,

WBC’s, and damaged body cells– Normal result of body’s fighting a disease or

inflammation– Gradually removed by macrophages

Inflammation can cause medical problems

• Allergic Reaction– Nonself molecule that is normally harmless, could

bind to a mast cell causing the release of histamine and subsequent inflammation (along with itchy, watery eyes and possible rash)

– The nonself molecule could come from food or from the environment

Inflammation can cause medical problems

• Autoimmune Disease– Immune system fails to distinguish between self

and nonself – Ends up attacking tissues in own organism’s body

• Sepsis– Inflammation does not remain local and extends

throughout the body with the dilation of blood vessels

– If bp drops during this, it could be lethal

• In most cases Innate immunity is good enough• But in some cases, when the pathogen is in

large numbers, adaptive immunity must take over.

31.3 Adaptive Immunity Response in Specific

Key features of Adaptive Immunity

• Specific – allows it to focus its responses on pathogens that are actually present

• Diverse – enables it to respond to a variety of pathogens

• Distinguishes self from nonself – prevents it from destroying self cells

• Immunological memory – allows it to respond more effectively in later exposures to the same pathogen

Specificity

• Reason why its specific is because of B and T lymphocytes

• T cell receptors and the antibodies produces by B cells recognize and bind to specific nonself substances called antigens.

• This interaction initiates a specific immune response

• Each T cell and each antibody-producing B cell is specific for a single antigen

Antigens

• Have sites that the immune system (antibodies) recognizes called antigenic determinants or epitopes

• Usually proteins or polysaccharides

• A bacterium can have multiple antigens on them

An antigenic determinant is a specific portion of the antigen, like a certain sequence of amino acids

Diversity

• Pathogens can be:– Viruses– Bacteria– Protists– Fungi– Multicellular parasites– Toxins made by these organisms

• Human can respond specifically to 10 million different antigens – by activating lymphocytes– So humans need to generate a vast diversity of lymphocytes

that are specific for different antigens

Diversity Continued…

• Diversity is generated primarily by DNA changes

• Each B cell is able to produce only one kind of antibody; thus there are millions of different B cells

• There are also millions of different T cells with specific T cell receptors

Diversity continued…

• Antigen binding “selects” a particular B or T cell for proliferation (growth/spreading)

• For example, when an antigen fits the surface receptor on a B cell and bind to it, the B cell is activated. It divides to form a clone of cells, (clonal selection) all of which produce and /or secrete antibodies with the same specificity as the receptor

• This also applies to T lymphocytes

Distinguish self from nonself

• The human body contains thousands of different molecules, each with a specific 3D structure capable of generating immune responses

• Thus every cell in the body bears a tremendous number of antigens

• Hopefully the individuals immune system can recognize it’s own body’s antigens and not attack them

Clonal Deletion

• Any immature B or T cell that shows the potential to mount a strong immune response against self-antigens undergoes apoptosis within a short time

• A failure of clonal delection leads to an immune response or autoimmunity

Autoimmune Diseases

• SLE – Systemic Lupus erythrematosis– Their antibodies can cause serious damage when

they bind to normal tissue antigens and form large circulating antigen-antibody complexes

– They become stuck in tissues and provoke inflammation

• Hashimoto’s thyroiditis– Most common in women over 50– Immune cells attack thyroid tissue, resulting in

fatigue, depression, weight gain, and other symptoms

Immunological Memory

• After responding to a particular type of pathogen once, it will remember that pathogen and will respond faster to same threat in the future

• Saves us from repeats of childhood infectious diseases

• First exposure – primary immune response• Second exposure – secondary immune

response

Primary Immune Response

• Activated lymphocytes divide and differentiate to produce 2 types of daughter cells1. Effector cells – carry out the attack on the

antigen• Effector B cells (plasma cells) secrete antibodies• Effector T cells release cytokines • Live only a few days

2. Memory cells – long lived cells that retain the ability to start dividing on short notice to produce more effector and more memory cells• Memory B and T cells may survive decades

Secondary Immune Response

• More rapid and more powerful• The memory cells that bind with that antigen

proliferate and launch a huge army of plasma cells and effector T cells

The principle behind vaccination is to trigger the primary immune response that prepares the body to mount a stronger, quicker secondary response if it encounters the actual pathogen again.

3 phases to adaptive immune response

1. Recognition – organism discriminates between self and nonself to detect pathogen

2. Activation – The recognition event leads to a mobilization of cells and molecules to fight the invader

3. Effector phase – mobilized cells and molecules destroy the invader

A T cell with a specific receptor binds to an antigen presenting cell. The T cell then makes cytokines, which stimulate other cells to divide

T cell that binds to the antigen on the antigen presenting cell is stimulated to form a clone

The specific B cell that binds the antigen is stimulated to form a clone.

T cells bind to and destroy cells bearing the antigen

B cells form specific antibodies that bind to free antigens

31.4 Adaptive Humoral Response involves specific antibodies

Humoral Response

• Basis is B cells• Billions of B cells survive the test of clonal deletion

and are released from the bone marrow into the circulatory system

• Remember it has a receptor protein on its cell surface that is specific for a particular antigen

• It gets activated by antigen binding to this receptor and then after stimulation from a T cell, it produces a clone of plasma cells that make antibodies as well as memory cells

Each B cell makes a different specific antibody and displays it on its cell surface

This B cell makes an antibody that binds this specific antigen

The specific antigen also binds to a T cell, which stimulates the B cell to divide, resulting in a clone of cells

Primary immune response – some cells develop into plasma cells (effector B cells) that secrete the same antibody as the parent cell

Potential Secondary Immune Response – a few cells develop into non-secreting memory cells that divide at a low rate.

Antibodies

• Also called immunoglobulins• Two of the polypeptides are identical light chains and

two are identical heavy chains• Held together by disulfide bonds• Each chain has a

– Constant region – amino acid sequence determines the general structure and function (class) of the immunoglobulin

– Variable region – amino acid sequence is different for each specific immunoglobulin.

• There are 2 antigen binding sites, making the antibody bivalent. – This allows the antibodies to form large complexes with the antigens

5 Classes of Immunoglobulins (Ig)

• Differ in function and in the type of heavy chain• IgG – secreted by B cells and constitutes about

80% of circulating antibodies• IgD – cell surface receptor on a B cell• IgM – initial surface and circulating antibody

released by a B cell• IgA – protects mucosa on epithelia exposed to the

environment• IgE – binds to mast cells and is involved with

inflammation

Antibodies have 2 roles in B cells

1. Acts as a receptor for an antigen in the recognition phase of the humoral response

2. In the effector phase, they can be produced in large amounts by a clone of B cells– They are then secreted and enter the

bloodstream– Can then do 2 actions

2 actions of antibodies in bloodstream

1. Bind to antigen that is expressed on the surface of a pathogen – this stimulates macrophages to ingest, or natural killer cells to destroy the pathogen

2. If the antigen is free in the bloodstream, then antibodies may bind to it to form large, insoluble antibody-antigen complexes, which are then ingested and destroyed by phagocytic cells

31.5 Cellular Immune Response involves T cells

and their receptors

T Cells

• Like B Cells, also possess specific membrane receptors

• Not a immunoglobulin• Glycoprotein made up of 2

polypeptide chains– Each chain has a constant and a

variable region• Variable region provides the site

for specific binding to antigens

Two types of T Cells

• TH is a T-helper cell• When they bind to an

antigen, it results in the activation of the adaptive immune response

• Tc is a cytotoxic T cell• When they bind to an

antigen, it results in death of the cell

The MHC proteins form complexes with antigens on cell surfaces and assist with the recognition by the T cells, so that the appropriate type of T cell binds. There are 2 types of MHC proteins.

2 Types of MHC Proteins

1. Class 1 MHC – on the surface of every nucleated cells in the mammalian body– Present antigens to Tc cells– These antigens can be fragments of viral proteins

or abnormal proteins made by cancer cells

2. Class 2 MHC – on the surface of macrophages, B cells, and dendritic cells– Present antigens to TH cells

Death of target cells

• TC cells can produce perforin, which lyses the bound target cell

• TC cells stimulate apoptosis in the target cell

Infected Cell

A Tcell receptor recognizes an antigenic fragment bound to a class I MHC protein

T cell releases perforin

Perforin lyses the infected cell before the viruses can multiply!

Regulatory T Cells (Tregs)

• Third class of T cells• Ensures that the immune response does not

spiral out of control• Similar to other T cells in that– It is made in the thymus gland– It expresses the T cell receptor– It becomes activated if they bind to antigen-MHC

complexes

Tregs continued…

• Different than other T cells in that– The antigens they recognize are self antigens

• The activation of Tregs causes them to secrete cytokine interleukin-10, which blocks T cell activation and leads to apoptosis of the TC and TH cells that are bound to it

• Main role is to mediate tolerance to self antigens

A T cell has the T cell receptor for the self antigenA self antigen binds to MHC

and is exposed on the cell surface

A Treg cell binds to the antigen-MHC complex

Binding stimulates Treg to make interleuken-10, which suppresses the TH or TC cell and causes it to undergo apoptosis

2 Experimental Evidence for the role of Tregs

1. If Tregs are experimentally destroyed during development in the thymus of a mouse, then the mouse grows up with an out-of-control immune system – autoimmunity.

2. IPEX – rare x linked disease in infants mounts an immune response that attacks the pancreas, thyroid, and intestine. Most affected individuals die within the first few years of life

AIDS

• Acquired Immune Deficiency Syndrome• Results from HIV – human immunodeficiency

virus• Transmitted from person to person in blood,

semen, vaginal fluid or breast milk• Initially infects macrophages, TH cells, and

antigen presenting dendritic cells in blood and tissues

AIDS continued..

• At first there is an immune response to the viral infection, and some TH cells are activated

• But because HIV infects the TH cells, they are killed both by HIV itself and by TC cells that lyse infected TH cells

• So TH cell numbers decline after the first month or so of infection

• Meanwhile, the humoral immune response is activated due the extensive production of HIV by infected cells

AIDS cont…

• Antibodies bind to HIV and the complexes are removed by phagocytes

• HIV level in blood goes down• During this dormant stage, people carrying HIV feel

fine, and their TH cell levels are adequate for them to mount immune responses against other infections

• Eventually the virus destroys the TH cells and their numbers fall to the point where they are susceptible to infections that the TH cells would normally eliminate

AIDS continued…

• Infections that result now are:– Kaposi’s sarcoma – skin tumor– Pneumonia caused by a fungus– Lymphona tumors – caused by Epstein-Barr virus

• These are opportunistic infections because the pathogens are taking advantage of the crippled immune system of the host

• Once this happens, death is within a year or 2