The Immune SystemThe Immune System

AP BiologyUnit 6

Types of Immunity

• Innate Immunity = non-specific protection against many different microbes

• Acquired Immunity = specific protection against microbes

Nonspecific Defenses

• Target a wide range of pathogens (non-specific foreign body) – Examples include: skin, mucous membranes,

inflammatory response, phagocytic cells

Nonspecific Defenses: Lymphatic System

• “filters” interstitial fluid and blood continually

• immune system cells in the lymph (in lymph nodes) take care of foreign particles and microbes

Phagocytosis

• phagocytes are white blood cells (leukocytes) that ingest microbes

• neutrophils and macrophages are the most common

Antimicrobial Proteins

• Complement System– Series of 30 proteins that are usually present in

the blood (inactive)– Activated when microbes are present (by

molecules on the surface of microbes)– Creates a cascade of reactions results in the

microbe cells bursting– May also trigger inflammatory response (by

attracting phagocytes)

Antimicrobial Proteins: Interferons

• Secreted by cells infected by viruses

• Causes nearby cells to inhibit viral reproduction/replication

• Not virus-specific

• Because of these, you aren’t as likely to get 2 viral diseases at the same time

Inflammatory Response

• A non-specific way to protect tissues from possible infection by destroying invading bacteria

Signs of Inflammation

• Redness– Due to the dilation of blood vessels

• Swelling– Due to extra fluid in the area

• Heat– Due to dilation of blood vessels (increased

blood flow)

• Pain– Extra fluid presses on nerves

Inflammatory Response

• Chemokines are small proteins that guide macrophages and signal them to increase lysosome contents

Natural Killer Cells

• Recognize virus-infected cells and cancer cells

• They directly release lethal chemicals, leading to apoptosis

Image taken without permission from http://www.news.utoronto.ca/images3/killercells.jpg

Specific Defenses

• Antigen = foreign body recognized by acquired immune system

• Examples of antigens include viruses and bacterial toxins

• Antibodies in the immune system bind antigens

Half way through day 1 lecture…

Specific Defenses

• B cells and T cells are lymphocytes with receptors that each recognize a specific antigen. – Ex. Specific B and T cells recognize the cold

virus, but not the chicken pox virus.

• After recognizing the specific antigen, certain cells are activated to eliminate the antigen or infected cells

B and T Cell Receptors

• The receptors on B and T cells and antibodies are formed from the random rearrangement of gene segments– Like different

combinations of the letters in the alphabet make different words

Humoral Immune Response

• Involves the actions of antibodies

• Antibodies– Proteins also known as Immunoglobulins – Tremendous Diversity—there are thought to be

millions (1015) of different specific antibodies

B cells

• Each B cell has a different antigen receptor on it

• Mature in the bone marrow

• Differentiate to become Memory cells or Plasma (Antibody-Secreting) cells after binding to the appropriate antigen

B cells

• “Anti-self” cells are destroyed before fully differentiating (Clonal Selection) – This has to occur since the antigen receptors are

formed from RANDOM gene rearrangements could accidentally produce a receptor that recognizes a body cell/molecule

– Autoimmune diseases result when clonal selection fails

Steps of the Humoral Response

1. Macrophage presents antigen on Class II MHC and binds to Helper T Cell

– MHC proteins are on the surface of cells and bind antigens

Steps of the Humoral Response

2. Helper T Cell secretes cytokines

Cytokines activate other Helper T Cells

Steps of the Humoral Response3. B cell with specific antibody binds to antigen (at the

same time Helper T cells are being activated)

4. Cytokines activate B cell to divide and differentiate into: Plasma Cells and Memory B cells

5. Antibodies combine with antigens all over body and help to facilitate phagocytosis

Plasma Cells

• Secrete loose antibodies into the bloodstream– Like antibody factories

• Plasma cells have a lot of ribosomes and Rough ER– WHY?– Antibodies are proteins these are the

organelles needed for protein synthesis

Image taken without permission from http://bcs.whfreeman.com/thelifewire/default.asp?s=&n=&i=&v=&o=&ns=0&uid=0&rau=0

Actions of Loose Antibodies

• Surround virus/bacteria prevent it from binding to and infecting cells

• Antibodies can bring together multiple bacteria or antigens, making them much larger and hence more noticeable for destruction by macrophages or phagocytes – clumps them together

End of Day 1 Lecture

Cell-Mediated Response

• Involves the action of Cytotoxic T Cells

• Eliminates infected cells, cancer cells, and transplanted cells

T cells

• Arise from lymphocytes maturing in the thymus gland

• Differentiate to become Cytotoxic T Cell or Helper T Cell – Helper T cells also participate in Humoral

Response

• Differentiate to become Memory cells or Effector cells– Effector cells will act immediately, memory

cells act later if the microbe returns

T Cells

• The receptors on each T cell are specific to an antigen

• T cell receptors can also recognize antigen fragments

Steps of the Cell Mediated Response

1. Infected cell presents antigen on Class I MHC

2. Cytotoxic T Cell recognizes antigen and binds to it

Steps of the Cell Mediated Response

3. Cytotoxic T Cell reproduces (clones itself)

4. Cytotoxic T Cells bind to antigen bound to infected cells and release perforin to lyse infected cells

Primary versus Secondary Response

• Primary Response = initial immune response to antigen

• Secondary Response = immune response when exposed the same antigen a second time (carried out by Memory cells)

Primary vs. Secondary Response

• The secondary response is much faster than the primary response– More antibody & T cell production in a shorter

amount of time

Primary response

Secondary Response

Helper T cells

• Participate in both the Humoral and Cell-Mediated Immune Responses

• the HIV virus attacks Helper T cells

Immunizations

• Active immunity = immunity due to exposure to an antigen (produces memory cells)

• Immunizations (vaccinations) allow an individual to develop active immunity to an antigen without actually getting “sick” during initial exposure

• Vaccines are usually made up of weakened viruses or microbes

Immune Responses to Donor Tissue• There are 3 kinds of antigens associated

with blood: A, B, and Rh – Antibodies are produced that react to the wrong

blood type (Anti A and Anti B)– This causes agglutination (clumping of RBCs)

and lysis (bursting) of RBCs which can lead to serious conditions

Blood Donors and Recipients

• What blood type is the Universal donor? – Type O does not have any surface antigens

(A or B) so the donor’s body will not attack it

• What is the blood type of the Universal recipient? – Type AB no anti A or B, so it won’t attack

any of the other blood cells

Rh factor

• The Rh factor is another surface protein that is found on the surface of red blood cells

• An individual either has the Rh factor on RBC (+) or doesn’t (-) – genetically determined

• Individuals who are Rh- will produce antibodies that attack Rh+ cells– This is particularly dangerous if a mother is Rh-

and her fetus is Rh+ (she produces antibodies against Rh)

Tissue Donors

• In tissues, the body looks at MHC molecules to identify self from non-self.

• What is the best host of tissue you might need for a transplant? – Yourself or someone very closely related to

you (identical twin would be ideal)

Allergies

• When the immune system “overreacts” or becomes hypersensitive to certain antigens

• Most allergies involve the actions of IgE antibodies – This causes mast cells to release histamine

Allergies

• Histamine triggers inflammatory responses leads to allergy symptoms such as runny nose, tearing eyes, etc.

• Many allergy medicines are antihistamines to block the receptors for histamine

Autoimmune Disorders• When the immune system fails to recognize

a body cell as a self cell and attacks it – Could be due to a failure in clonal selection

• Examples include: – Lupus (attacks a variety of body cells) – Rheumatoid Arthritis (attacks cartilage and

joints between bones) – Type I Diabetes (attacks beta cells in pancreas

that produce insulin) – Multiple Sclerosis (attacks myelin sheaths on

nerves)

HIV: the Basics

• The Human Immunodeficiency Virus attacks Helper T Cells

• HIV progresses to AIDS when white blood cell counts reach a certain low

• HIV is a retrovirus (RNA is the nucleic acid inside)

HIV: the Basics

• Mutations to the HIV surface antigen occur each time the virus replicates, which is why finding a cure is difficult.

• Drugs can help slow HIV reproduction but some drug resistant strains have now been generated from mutations during viral replication

ELISA

• ELISA = Enzyme Linked Immunosorbent Assay

• This is a test that detects the presence of specific antibodies in the blood to determine if an individual has a certain condition

• The same principles are used in home pregnancy tests

ELISA• The ELISA plate is coated

with antigens specific to the antigen being tested for (ex. Chicken pox)

• Blood is added that may contain the antibodies (present only if the person has the disorder)– Only the specific antibody

will bind to the antigen on the plate

antigens

ELISA

• Unbound antibodies are washed away

• A secondary antibody (anti antibody) is added that will bind to the antibody already bound to the antigen

• The secondary antibody has an enzyme attached to it

After washing

Secondary Antibody

ELISA• After washing away unbound

secondary antibody, a substrate is added

• If there is secondary antibody in the well (bound to the antibody), there will also be enzyme present to break apart rhe substrate

• Breaking apart the substrate causes a color change antibody present

ELISA and Pregnancy tests

• Home Pregnancy tests use the same principles as home pregnancy tests.