Overview of the Immune System

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YOU MUST KNOW:

*Elements of INNATE immune response.*Differences between B & T cells (how activated & actions of each)*How antigens are recognized by immune system cells.*Differences in humoral and cell-mediated immunity.*Why Helper T cells are central to immune response.

What is its function?

• PROTECTION FROM INVADERS!• Three Lines of Defense:• Innate Immunity- born with it!• 1. Barrier Defenses – NONSPECIFIC• 2. Internal Cellular Defenses - NONSPECIFIC

• 3. Acquired Immunity –develops only after exposure to a SPECIFIC pathogen!

Barrier Defenses / 1st line of defense• The Skin and Mucous Membranes• Physical barriers; trap microbes• Secrete substances (oil, sweat, etc.) that makes

the skin too acidic (pH= 3-5) for microbes to live there• Also secrete lysozyme, an enzyme that can

destroy bacterial cell walls (in saliva, mucous secretions, & tears.)• INNATE=you’re born with it!

Internal Cellular Defenses• If an invader gets inside the body, the internal

defenses (2nd line of defense!) take over• Phagocytes (“to eat”/”cell”)• White blood cells that “eat”/engulf

invaders• NEUTROPHILS• most numerous phagocyte (60-70%)• Attracted to infected tissue• Tend to destroy self with pathogen• Short-lived

• MONOCYTES• Become macrophages• Long-lived

Internal Cellular Defenses• MACROPHAGES• Can patrol lymphatic system/ spleen, lymph

nodes for pathogens• Only about 5% of phagocytes• Does not self-destruct after destroying

pathogen• EOSINOPHILS• Phagocytize parasitic invaders• They do not engulf parasites, but instead

release destructive enzymes• DENDRITIC CELLS• Still act as phagocytic cell, but also• Activates acquired immune system

• Invaders (bacteria/virus/etc) are then digested by lysosomes.

Internal Cellular Defenses

• Antimicrobial Proteins• Complement System- 30 serum

proteins w/ variety of functions. Many lyse invaders.• Interferon = “Warning Protein”

sent out by virus infected cells. • Other body cells then make other

substances to inhibit viral replication.

Internal Cellular Defenses• Inflammatory Response• Damage to tissue (from physical injury or the entry of

pathogens) leads to inflammation• Histamine (signal molecule) is released by

basophyls & mast cells (leukocytes).• This causes increased vasodilation & increased

permeability of capillaries. • Increases blood flow to site of injury• Carries clotting factors, platelets, phagocytes,

etc. • Diffuse into interstitial fluid to help REPAIR • Causes redness, edema (swelling caused by fluid),

& increased temperature occur.• The purpose is to limit infection and repair damaged

tissue

Internal Cellular Defenses

•Example of how to activate the inflammatory response

Internal Cellular Defenses

• Natural Killer (NK) Cells- Patrol the body and attack virus-infected cells and cancer cells• Surface receptors (“nametags”) identify these

infected/damaged cells• NK cells release chemicals that cause cells to kill

themselves, apoptosis (programmed cell death)• Indiscriminate . . . can damage surrounding healthy

cells• All 4 of these internal defenses (phagocytes, interferons,

inflammatory response, and natural killer cells) occur INNATELY.

Acquired Immunity

• Acquired immunity is the third line of defense.• Acquired immunity only comes after

EXPOSURE to a specific pathogen.• Receptor proteins in cell membrane

provide pathogen-specific recognition.• Acquired immunity occurs more slowly

than innate immunity.

Acquired Immunity

• Acquired immunity is performed by lymphocytes• Made from stem cells in

the bone marrow• B-cells: • mature in the bone

marrow• T-cells: • mature in the thymus

Acquired Immunity• Antigen = foreign molecule that is

recognized by lymphocytes and causes them to respond• Other phagocytic cells release

cytokines (chemical proteins) that activate acquired immunity

• An antigen is usually a surface marker (“nametag”) that is “presented” by another phagocyte

• Lymphocytes• Have antigen receptors (100,000 on

each cell!) that recognize a SPECIFIC portion of the antigen (epitope) by shape

• VERY SPECIFIC!!!

Acquired Immunity

• B-lymphocytes are responsible for the humoral immune response• They are responsible for

pathogens OUTSIDE of cells (in body fluids, etc.)

• B-lymphocyte is “activated” when specific antigen binds to its receptors.

• Activated B-lymphocytes reproduce using clonal selection in order to destroy the invader (the clones are able to specifically bind to antigens)

Acquired Immunity• These B-lymphocytes produce

two types of cloned cells:• Effector cells (Plasma Cells)• Make antibodies!• Special proteins that bind onto

the ANTIGENS of the “invaders,” which flags them for destruction (usually by macrophages)

• Memory cells• These cells live a long time, and

can respond quickly if this same antigen is seen again

Types of Antibodies• IgM• First of the antibodies produced• Responsible for agglutination of antigens• Activates complement

• IgG• Most abundant antibody• This is the only antibody that can cross placenta to fetus (discuss

later)• Agglutinates and neutralizes antigens

• IgA• Found in tears, saliva, mucus, and breast milk• Gives localized defense of mucous membranes by antigen

agglutination• Gives passive immunity to nursing infants through breast milk

Types of Antibodies• IgE• Triggered release form mast cells and basophils• Responsible for agglutination of parasites• Also responsible for allergic reactions

• IgD• Present on surface of non-differentiated B cells• Acts as an antigen receptor and stimulates the differentiation of

and proliferation of B cells (clonal selection)

Primary vs. Secondary Response

• Primary Immune Response• When an individual is

first exposed to an antigen, it takes time to activate the immune system

• Must do a series of recombinant changes in protein synthesis to create the correct antibody that binds to a specific epitope

• Secondary Immune Response• After an initial exposure, the

memory cells that remain are able to recognize the SAME antigen

• Subsequent exposures allow the immune system to RAPIDLY respond to the antigen and create the necessary immune cells

• Individual doesn’t fell symptoms and is considered immune

Acquired Immunity

• T-lymphocytes are responsible for the cell-mediated immune response• Guard against invaders hiding out inside infected cells • Cytotoxic T cells • They are the effectors (“hit men”) of the cell-mediated immune

response by lysing infected cells or “punching holes” in the membrane

• They kill infected body cells (present foreign antigens on major histocompatability complex (MHC) or other cells that don’t belong (like tumors) at the cell membrane• Class I MHCs = on almost all body cells except RBCs.• Class II MHCs= made by dendritic cells, macrophages, & B cells.

• Some of these cells will become memory cells, so they can be reactivated if the pathogen “strikes again.”

Acquired Immunity

• Helper T Cells• When activated by binding to MHC protein of an

antigen presenting cell, Helper T-cells secrete cytokines (like interleukin) which stimulate & activate B cells & Cytotoxic-T cells.

• “Master Switch of acquired immunity”• HIV destroys Helper T cells, and shuts down both

humoral & cell-mediated immunity!

Cytotoxic T Cells & MHC

The Immune System

• Key Features of the Immune System• Specificity• Recognizes SPECIFIC invaders – species of

bacteria, for example• Due to ANTIGENS displayed on the MHC

(Major Histocompatibility Complex)• Diversity• The immune system can respond to millions

of different invaders because it has so many different lymphocytes “on reserve”

The Immune System

• Key Features of the Immune System• Memory• The immune system can “remember” antigens it’s

seen before and react more quickly the second, third, etc. time it sees them• Acquired immunity• Because of memory cells (B & T cells)!

• Self/Nonself Recognition• The immune system can distinguish between the

body’s own molecules from foreign molecules• Autoimmune disorders (example: lupus, MS,

rheumatoid arthritis) means that this part of the immune system is not working – the immune system destroys the body’s own tissues

Passive vs. Active Immunity

• Passive Immunity• Transferring antibodies from one person to

another, without the B-lymphocytes having to make them!• The person will already have the memory cells

and antibodies, so the next response will be quicker!• Example: • Pregnant mother passes antibodies to her fetus through

the placenta• Antibodies in breast milk• Immunoglobulins (antibodies) may be given to a person

who is exposed to a disease to prevent them from getting the disease.

Passive vs. Active Immunity

• Active Immunity• Immunity to a specific pathogen that

comes after having come in contact with the pathogen.

• Can come naturally• Been sick with the pathogen before• Example: had measles before, 2nd

time won’t take as long to respond• Can come artificially

• Immunization (weakened or dead form of the pathogen is used to induce immune response.)

• Edward Jenner - smallpox• Stimulates B-lymphocytes to make

antibodies AND memory cells

Problems associated with the immune system

Blood Groups and Transfusions• When we discussed Genetics, we discussed blood groups (A,B,O)• The A and B represent different protein markers on the surface

of blood cells• If you have an A protein on your blood cell, you have Type A

blood• If you have a B protein on your blood cell, you have Type B

blood• If you have an A protein and a B protein on your blood cell, you

have Type AB blood• If you have neither an A protein or a B protein on your blood

cell, you have Type O blood• There is also a factor called the Rh factor• If you have the Rh factor, you are considered “+”• If you don’t have the Rh factor, you are considered “-”

Blood Groups and Transfusions• Your bodies’ immune system is able to “recognize” your

blood type• If you get a transfusion that has a surface protein your

blood cells are lacking, your immune system will mount a reaction• Example: You have type A blood. If you get a

transfusion of type B or type AB, your immune system will attack the blood as a foreign antigen• This is why type O blood is the universal donor, it

doesn’t have any surface proteins to activate the immune system

Rh Factor and a Fetus

• The Rh Factor can cause some problems for pregnant mother• Take the following scenario:• Rh Factor is dominant to no Rh Factor• Mother is homozygous recessive for Rh

factor• Father is homozygous dominant for Rh

Factor• Do a Punnett square to determine the Rh

Factor phenotype for the infant

Erythroblastosis Fetalis• Blood does transfer from mother to fetus (through placenta)• During child birth, the mother is exposed to blood of child• After 1st child, mother has been exposed to Rh factor• For all other fetuses that are Rh+ (does have the Rh factor), the mother, who

is Rh- (does not have the Rh factor), has produced antibodies against the Rh factor

• REMINDER: IgG antibodies can pass through the placenta• End result, the antibodies produced by the mother will attack the blood of

infant• This is called Erythroblastosis Fetalis

• NOWADAYS: There are ways to prevent death of fetus through transfusions• Also, the mother can be given a shot of anti-Rh antibodies to destroy any

baby blood cells that the mother becomes exposed to . . . prevents the mother form developing memory cells

Organ and Tissue Transplants• MHC markers on cells are unique to everyone

(except identical twins)• Therefore when looking for donors, they must

have a majority of these markers that “match”• Otherwise, body will recognize the

transplant/graft as a foreign antigen and the organ/tissue will be destroyed• Many individuals that have transplants must take

immunosuppressive drugs to prevent a “graft vs. host reaction” . . . rejection of the transplant/graft

Allergies• Allergies are hypersensitivies of the immune system to an

environmental molecule because of its ANTIGENS• Allergic reactions are caused by the release of IgE

antibodies . . . an over-reaction to nonharmful stimuli• Anaphylactic shock• Life-threatening allergic reactions to ingested or injected

allergens• Peanuts, shellfish, bee stings, etc.

Autoimmune Diseases

• Sometimes a body loses the ability to recognize “self” cells• As a result, the immune system attacks these self

cells• Rheumatoid arthritis: immune system attacks

cartilage and bone of joints• Insulin-dependent diabetes mellitus: Cytotoxic

T cells attack the insulin-producing beta cells in the pancreas

HIV/AIDS• We have already discussed the action of HIV (human

immunodeficiency virus) and how it affects cells (retroviruses)• What makes HIV so dangerous is that is targets and eventually

destroys the T helper cells• Since the T helper cells are key to activating both cell-

mediated and humoral immune responses (through the release of cytokines), the acquired immune system is effectively shut down

• HIV does not kill the individual, it is subsequent diseases• Since the host doesn’t have an immune system, they cannot fight

off the infection• The condition of a compromised immune system is given the

name of the disease, AIDS (acquired immunodeficiency syndrome)