Immune system 6-3 and 11-1

The Immune SystemTopics 6.3 and 11.1

Immunity• Immunity

– The ability of the body to fight infection and/or foreign invaders by producing antibodies or killing infected cells.

• Immune System– The system in the body responsible for maintaining

homeostasis by recognizing harmful from non-harmful organisms and produces an appropriate response.

• Highly specific recognition of foreign antigens • Mechanisms for elimination of microbes bearing such

antigens• A vast universe of distinct antigenic specifies• Immunologic memory• Tolerance of self-antigens

Key attributes of immune system

• 4 attributes that characterize the immune system as a whole– specificity

• antigen-antibody specificity

– diversity• react to millions of antigens

– memory• rapid 2° response

– ability to distinguish self vs. non-self• maturation & training process to reduce auto-

immune disease

Foreign Invaders• Called Pathogens

– Viruses, bacteria or other living thing that causes disease/immune response.

• Antigens– Toxins that pathogens

produce that cause harm to an organism.

Avenues of attack

• Points of entry– digestive system– respiratory system– urogenital tract– break in skin

• Routes of attack– circulatory system– lymph system

Parts of the Immune System

1. Blood - White Blood Cells in particular.

2. Lymph nodes

3. Thymus Gland – Produces T Lymphocytes

4. Bone Marrow – Produces B Lymphocytes

Lymph system Production & transport of leukocytes

Traps foreign invaders

lymph node

lymph vessels(intertwined amongst blood vessels)

Lines of Defense

How does the body fight infection/foreign invaders?

First Line of Defense – The Skin• Provides Physical and Chemical barriers

• Physical – hard to penetrate, made of indigestible keratin• Chemical – tears, sweat

1st line: Chemical barriers on epithelium

Skin & mucous membrane secretions– Sweat -pH 3-5

– Tears- washing action, lysozyme

– Mucus- traps microbes

– Saliva- anti-bacterial = “lick your wounds”

– Stomach acid- pH 2

– Anti-microbial proteins• lysozyme enzyme

– digests bacterial cell walls

2nd Line – Nonspecific Immune Response

These are defenses the body uses no matter what the invader may be. These defenses include:

– Phagocytosis – done by Macrophages

– Natural Cell Killers– Inflammation - caused by release of Histamine from

leukocytes– Fever – caused by histamines. The fever (high temp) kills

invaders by denaturing their proteins.

2nd line: Internal, broad range patrol

leukocytesleukocytes• Innate, general defense– rapid response

• Patrolling cells & proteins– attack invaders that penetrate

body’s outer barriers

• leukocytes– phagocytic white blood cells

• complement system– anti-microbial proteins

• inflammatory response

Leukocytes: Phagocytic white blood cells (WBCs)

• Attracted by chemical signals released by damaged cells – enter infected tissue, engulf & ingest microbes

• lysosomes

• Neutrophils– most abundant WBC (~70%)– ~ 3 day lifespan

• Macrophages– “big eater”, long-lived

• Natural Killer Cells– destroy virus-infected cells

& cancer cells

Phagocytes

yeastmacrophage

• Natural Killer Cells perforate cells– release perforin protein– insert into membrane of target cell– forms pore allowing fluid to

flow into cell– cell ruptures (lysis)

• apoptosis

Destroying cells gone bad!

perforin puncturescell membrane

cell membrane

natural killer cell

cell membrane

virus-infected cell

vesicle

perforin

Anti-microbial proteins

• Complement system– ~20 proteins circulating in blood plasma– attack bacterial & fungal cells

• form a membrane attack complex• perforate target cell• apoptosis

plasma membrane of invading microbe

complement proteinsform cellular lesion

extracellular fluid

complement proteins

bacterial cell

Inflammatory response 1

• Damage to tissue triggers local non-specific inflammatory response– release histamines & prostaglandins – capillaries dilate,

more permeable (leaky)• increase blood supply

• delivers WBC, RBC, platelets, clotting factors

• fight pathogens

• clot formation

• accounts for swelling, redness & heat of inflammation & infection

Fever

• When a local response is not enough– systemic response to infection

– activated macrophages release interleukin-1 (IL-1)• triggers hypothalamus in brain to readjust body thermostat to raise

body temperature

– higher temperature helps defense• inhibits bacterial growth

• stimulates phagocytosis

• speeds up repair of tissues

• causes liver & spleen to store iron, reducing blood iron levels

– bacteria need large amounts of iron to grow

The Inflammatory Response• 1- Tissue injury; release of chemical signals~ • histamine (basophils/mast cells):

causes Step 2... • prostaglandins: increases blood flow & vessel permeability• 2/3- Dilation and increased permeability of capillary~ • chemokines: secreted by blood

vessel endothelial cells mediates phagocytotic migration of WBCs• 4- Phagocytosis of pathogens~ • fever & pyrogens: leukocyte-

released molecules increase body temperature

• Specific defense – lymphocytes

• B lymphocytes (B cells)• T lymphocytes (T cells)

– antibodies • immunoglobulins

• Responds to…– antigens

• specific pathogens • specific toxins• abnormal body cells

(cancer)

3rd line: Acquired (active) Immunity

This is a specific response to a specific pathogen/antigen.

The response involves the creation of Antibodies.

3rd Line – Specific Immune Response

Antibodies

• Y-shaped protein molecule.

• Made up of variable and constant regions.

• Made up of Heavy and Light chains.

• Produced by B-Lymphocytes

• Function: Recognize antigens, bind to and deactivate them.– Note: Variable region

recognizes the anitgens.

“self” “foreign”

Antigens- recognition of invaders

• Antigens– proteins that serve as cellular name tags

• foreign antigens cause response from WBCs– viruses, bacteria, protozoa, parasitic worms, fungi, toxins – non-pathogens: pollen & transplanted tissue

• B cells & T cells respond to different antigens– B cells recognize intact antigens

• pathogens in blood & lymph

– T cells recognize antigen fragments• pathogens which have already infected cells

How an antibody operates/works?

Deactivation of a bacterium by an antibody.

How are cells tagged with antigens?

• Major histocompatibility (MHC) proteins – antigen glycoproteins– MHC I – on all nucleated cells– MHC II – on macrophages, B-Ly, activated T-Ly

• MHC proteins constantly carry bits of cellular material from the cytosol to the cell surface– “snapshot” of what is going on inside cell– give the surface of cells a unique label or “fingerprint”

MHC proteinsdisplaying self-antigens

T cell

The Pathway of Specific Immune Response

Pathogens

Pathogens eaten by Macrophage

Displays portion of Pathogen on surface

Helper-T cell recognizes Pathogen

Step 1

Step 2

Step 3

Activates B- CellActivates Cytotoxic

T- Cell

Memory B-CellMemory T-Cell

Kills Infected CellsAntibodies

Cellular Immunity vs. Antibody Immunity

• Carried out by T-Cells• Infected cells are killed by

Cytotoxic T –Cells.

• Carried out by B-cells• Antibodies are produced

and dumped into blood stream.

• Antibodies bind to antigens and deactivate them.

Cellular Immunity Antibody or Humoral Immunity

Immune Response Explained

1. Antigen infects cells.2. Macrophage ingests antigen and displays portion on its surface.3. Helper T- Cell recognizes antigen on the surface of the

macrophage and becomes active.4. Active Helper T-Cell activates Cytotoxic T-Cells and B-Cells.5. Cytotoxic T-Cells divide into Active Cytotoxic T-cells and Memory

T – Cells.6. Active Cytotoxic T-Cells kill infected cells.7. At the same time, B-Cells divide into Plasma Cells and Memory

B- Cells.8. Plasma cells produce antibodies that deactivate pathogen.9. Memory T and Memory B cells remain in the body to speed up

the response if the same antigen reappears.10. Supressor T-Cells stop the immune response when all antigens

have been destroyed.

Immune Response Summary

Antigen

Macrophage

Helper T - Cell

Active Cytotoxic T-Cell Active B - Cell

Kills Infected Cells Memory T- Cell Plasma Cell Memory B-Cell

Antibodies

Deactivates Antigens

Displays copy of antigen on surface of cell

Cellular ImmunityAntibody Immunity

Primary .vs. Secondary Immune Response

• Primary Immune Response– This is a response to an invader the 1st time the

invader infects the body.• No measurable immune response for first few days.• Next 10 – 15 days antibody production grows steadily

• Secondary Immune Response– A more rapid response to an invader the 2nd time it

invades the body.• Antibody production increases dramatically and in a much

shorter time period..

Primary .vs. Secondary Immune Response

Induction of Immune Responses

• Primary immune response: lymphocyte proliferation and differentiation the 1st time the body is exposed to an antigen

• Plasma cells: antibody-producing effector B-cells

• Secondary immune response: immune response if the individual

is exposed to the same antigen at some later time~ Immunological memory

Passive vs. Active Immunity1. Active Immunity

This is immunity where the body is “actively” producing antibodies to fight infection.

Ex: You have a throat infection and you are actively creating antibodies to fight it.

Vaccination:An injection of a weakened strain of an infectious microbe (pathogen) that causes the body to undergo active immunity (produce antibodies).

2. Passive ImmunityThis is immunity where antibodies are given to a person from the blood of another person or animal.This immunity only lasts for a short period of time.

ex: Breastfeeding mothers pass antibodies to their children through the milk.

Autoimmune Disease

• Autoimmune diseases are diseases where the immune system begins to attack itself.– Ex:

• Rheumatoid Arthritis – crippling disease of the joints.

• Lupus – disease of blood and organs.• Multiple Sclerosis – disease of nervous system

• Cause(s): unknown• Cures/Treatments: No known cures.

Allergies

Allergy- An exaggerated response by the immune system to an allergen.

Allergen: a normally harmless substance that causes an allergic reaction.ex: dust, pollen, mould, food, insect stings

Types of Allergic reactionsThere are two types of allergic reactions.

a. Immediate – occurs within seconds and normally lasts for about 30 mins.b. Delayed – takes longer to react and can last for a much longer time.

What happens during an allergic reaction?

• During an allergic reaction antibodies cause histamines to be released from certain cells.

Histamines cause:a. Swelling of tissuesb. Release of fluids (runny noses and eyes)c. muscle spasms (some cases)

Anaphylaxis or anaphylactic shock:This is the sudden and severe allergic reaction to a substance that can cause death.

Treatments for Allergies1. Avoidance of material – especially food.2. Epinephrine – “epi – pen”3. Antihistamines -- benadryl

Abnormal immune function

• Allergies (anaphylactic shock): hypersensitive responses to environmental antigens (allergens); causes dilation and blood vessel permeability (antihistamines); epinephrine

• Autoimmune disease: multiple sclerosis, lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus

• Immunodeficiency disease: SCIDS (bubble-boy); A.I.D.S.

HIV & AIDS

• Human Immunodeficiency Virus– virus infects helper T cells– helper T cells don’t activate rest of immune

system: T cells & B cells• also destroy T cells

• Acquired ImmunoDeficiency Syndrome– infections by opportunistic

diseases– death usually from other

infections• pneumonia, cancer

HIV

• HIV is a virus that specifically attacks the lymphocytes.

• This means the number of lymphocytes decreases.

• Less antibodies are made.• Predict the consequences…

HIV Progression

Transmission of HIV

• Infected blood – blood transfusions, sharing needles,

• Infected semen and vaginal mucus – unprotected sex

• Infected mother’s milk – low risk

• Infected saliva – almost zero risk

AIDS

• Caused by the HIV virus that selectively infects the immune system leaving the body open to infection by removing the specific immunity.

Social implications of AIDS

• Cases of AIDS are not evenly distributed in the world, for example there are severe problems in Africa (some populations with 30% of their people are infected).

• What cultural and economic reasons are there for differences in the prevalence of AIDS?

• Is there a moral obligation of those with the technology and the wealth to help others lacking these things in the fight against AIDS?