Immune/Lymphatic System

I. Brief history of disease

• A. Disease: any change, other than injury, that disrupts the normal functions of the body.– 1. Inherited– 2. Environmental– 3. Infectious agents (pathogens- “sickness maker”)

B. Spread & the Fight Against

• 1. Fight a disease by avoiding it• 2. Understand disease so you are better able

to prevent it.• 3. Remove vectors: organisms that carry

disease causing agents.– a. Ex: mosquito & spray insecticides

• 4. New Drug Treatments: Antibiotics-work by killing bacteria BUT not the host cells.

• C. For thousands of years people did not know what caused illness– 1. Curses, evil spirits, etc– 2. Mid 19th century Louis Pasteur & Robert Koch

concluded that disease was caused by microorganisms or germs called “Germ Theory of Disease”

II. Body Defenses

• A. The body is constantly in contact with bacteria, fungi, and viruses

• B. Because of our two defense systems– 1. Nonspecific defense system– 2. Specific defense system

C. Nonspecific Body Defenses

• 1. 1st line of defense– a. Intact skin & production of sweat, body oils &

Mucous – b. Chemicals produced by the body (very low pH

in the stomach, slightly lower pH in urine and female reproductive tract.)

• 2. 2nd line of defense• a. Defensive Cells- cells that

roam the body engulfing (phagocytosis) intruder cells– Neutrophils– Phagocytes-> macrophages

• b. Natural Killer Cells– i. can recognize invader cells

based on chemicals on cell membrane (cancer and viral cells) before specific defense kicks in.

– Use perforin, not phagocytosis

Figure 12.7a

• c. Inflammatory Response– i. Triggered when body tissues are injured– ii. Produces 4 cardinal signs

• Redness• Heat• Swelling• Pain

– iii. chain of events which lead to protection and healing

Steps in the Inflammatory Response• histamine

– Allow: Blood vessels to dilate, become more permeable & allow more Defense cells to the wound area

• 3 parts of the inflammation responses?

• 1. Blood Vessels dilate– heat

• 2. leaky capillaries:– Pain & Swelling (aka: edema)

• 3. NEUTROPHILS ENTER BLOOD FROM BONE MARROW AND GO TOWARDS CHEMICAL “SCENT”– SQUEEZE THROUGH THE

CAPILLARY WALL (DIAPEDESIS)– NEUTROPHILS GATHER AT SPOT

OF TISSUE INJURY. EAT FOREIGN MATERIALS

– PHAGOCYTES COME LATER- turn into MACROPHAGES (eating machines)

• Pus indicates a possible problem.Figure 12.8

Complement proteins

• ENHANCE THE INNATE DEFENSES EITHER BY– ATTACKING MICROORGANISMS– OR HINDER THEIR ABILITY TO REPRODUCE.

• COMPLEMENT FLOAT AROUND INNATE UNTIL ACTIVATED BY FOREIGN MATERIAL THROUGH COMPLEMENT FIXATION (THEY ATTACH TO MATERIAL).– ALSO ACTIVATE INFLAMMATION.

• Interferon. CHEMICAL RELEASED BY INFECTED CELLS TO “TELL” HEALTHY CELLS INCREASE DEFENSE PROTEINS.

Fever

• Caused by pyrogens activating the hypothalamus.

• Allows the liver and spleen to pull in iron & zinc, taking it away form invaders use.

• Increases metabolism.• if too high it can be detrimental…denatures

proteins and can kill you if too high.

Understanding Specific Immune

• 1800’s scientists determined–Antigen specific- acts against particular

pathogens/foreign substances–Systemic- full body not just sight of

initial infection–Memory- amounts a stronger attack

upon 2nd exposure

Specific defense system– Humoral-makes the antibodies (memory)– Cellular immunity- lymphocytes (white blood cells)

defend directly with lysing or indirect with chemicals

– a. A.K.A. “immune system”

Types of Immunity

• 1. Antibody-mediated immunity (HUMMORAL)

– a. Cells (lymphocytes) produce chemicals (anti-bodies) to mark antigens for disposal.

• 2. Cell-mediated immunity– a. Cells target virus

infected cells directly

Antigens (Nonself)

• 1. Any substance capable of activating the immune system and provoking an immune response

• 2. Examples of common antigens– a. Foreign proteins – b. Pollen grains– c. Microorganisms

Self-Antigens• 1. Our cells have many surface proteins thus

our system can recognize itself• 2. Our immune cells typically do not attack our

own cells (If it did that would be a homeostatic imbalance!)

• 3. BUT each persons surface proteins are unique so, our cells in another person’s body can trigger an immune response because they are foreign

– a. Restricts donors for transplants– b. Can cause miscarriage

Cells of the Immune System

• 1. Lymphocytes– a. from stem cells in the red bone marrow– b. B lymphocytes create antibodies & memory cells

(hummoral)– c. T lymphocytes specialized in the thymus gland

(cell Mediated)• 2. Macrophages (cell mediated)

– a. Large cells that eat other invader cells– b. Become widely distributed in lymphoid organs

Immunocompetance

• All of your immune cells need to mature before they can do their job. Being immunocompetant means that the immune cell is able to bind to its specific antigen.

• B cells in bone marrow• T cells in thymus• 1 receptor for 1 antigen so each immune cell

is immunocompetent is for 1 specific antigen!

Self-Tolerance• The immune system need to be trained to go after

antigens and avoid “self” cells.• T cells go through this in the thymus.• The T cells with the best ability to identify antigens

survive. • T cells that strongly identify with SELF antigens are

destroyed!• B cells go through this in the bone marrow but little

is known about that…• Autoimmune diseases are an issue with this process

• Your GENES determine what specific foreign substances our immune system will be able to recognize and resist.

• Ebola is “new” to our immune system so it does not have a receptor for it in our bodies.

antigen-presenting cells

• Engulf antigens and present fragments of them on the outside of their cell. So they can activate T cells.

• A big part of activating the immune system– Dendritic cells– Macrophages- stay in the lymph nodes– B lymphocytes

Antibody-Mediated Immune Response (HUMMORAL)

• 1. B lymphocytes with specific receptors bind to a specific antigen

• 2. activates the lymphocyte to clone itself– A large number of clones are

produced with same receptor.

• 3. most clones become plasma cells– Make antibodies at 2000 per

minute!!!Other B cells become Memory cells

Secondary Response to an

invader• 1. Memory cells are

long-lived• 2. A second exposure

causes a rapid response• 3. The secondary

response is stronger (w/i hours) and longer lasting (weeks to months)

• Gives you life-long immunity

Figure 12.13

Immunity

• 1. Active:• a. Your B cells actively encountered antigens

and produce antibodies• b. usually life-long immunity• 2. Passive:• a. Antibodies are obtained from “other” source.• b. B cell memory does not occur because your

body did not create the antibodies

Antibodies (Immunoglobulins)

• 1. proteins secreted by cloned plasma cells

• 2. Carried in blood• 3. Bind to specific

antigens to inactivate them…

Cell-Mediated Immune Response

• 1. Antigen presenting cells directly attack invaders.

• 2. “eat” invaders & displayed bits of antigen on surface. – APC Essential in activating T

cells!

• 3. Helper T ( the managers)cells bind to these macrophages antigens and release cytokines (attract more lymphocytes)

T cell activation and interactions with other cells of the immune response.

Antigen “Presented” antigen

T cell antigenreceptor

Cytotoxic(killer)T cell

Cell-mediatedimmunity(attack oninfected cells)

Humoralimmunity(secretion ofantibodies byplasma cells)

B cell

Cytokines

HelperT cell

Self-protein

Antigenprocessing

Dendritic cell

Cytokines

• 4. Cytokines: attract Killer T, B cells & other phagocytic WBC.

• A. B cells are activated by Helper T cells.

• B. Killer T Cells (cytotoxic T) are very effective in killing. Because they actively seek out the specific invader.– a. Killer T makes organ

transplant difficult

• 1. Regulatory T cells– a. Once the invader has been removed chemicals

are released to suppress the activity of T and B cells

– b. Stop the immune response to prevent uncontrolled activity

• 2. Memory T– Again, respond quickly to later invasions.

Other T Cells

Figure 12.19 A summary of the adaptive

immune responses.

• Immune game: log onto a desktop and go to the HW website for the link. Play the game reading all of the information as you go Take notes on any NEW information

• http://biomanbio.com/GamesandLabs/Physiogames/conflictimmunity.html

• If there is time we’ll watch the flu video.• HW: wp #4 & review worksheets

Transplant

• 4 types of grafts• Auto- self to self, like a skin graft for a burn.• Iso- twin to self grafts, this would be best…but if

doesn’t exist…• Allo- other person to self, family member possible

or donor list. This is the most common transplant from a donor who has recently died.

• Xeno- animal to self, mostly pig heart valves

Allograft Success• Check: ABO, other blood group antigens and membrane

antigens. – minimal 75% match of above

• Difficult to find– Immunosuppressive therapy

• Reduce rejection• Drugs and therapy kill rapidly dividing cells like WBC• All have severe side effects

–Biggest issue is body not protected from infection as well

• 50% rejection of organ by 10 years–New look at teaching the body tolerance vs

current drugs.

Disorders of Immunity:• Autoimmune Diseases: T cells attack its own

tissues– Example: Juvenile diabetes – destroys pancreatic beta

cells that produce insulin

• Self-Tolerance Breakdown?– New “self” antigens appear

• “hidden” in sperm, eye lens, thyroid• New mutations that change the structure of self-proteins• Bacterial or viral damage

– Foreign antigens look like “self”• Antibodies produced during rheumatic fever cross-react with

heart antigens causing damage to the heart muscle, valves, joints and kidneys.

• Allergies (Hypersensitivity) a. Abnormal, vigorous immune responses

hypersensitivity• Immediate/Acute:

– Triggered by histamine from mast cells (a type of WBC)

• Anaphylactic shock: – Rare!– Allergen directly enters the blood and circulates rapidly

or some foods (peanuts)– Same as regular allergy attack but whole body involved.

• Delayed: – Takes 1-3 days– Cytokines cause– Ex: poison ivy, heavy metals, cosmetics, deodorants

Immunodeficencies

• Severe combined immunodificiencie disease (SCID) have all or some of their immune system missing

AIDS

• Acquired Immune Deficiency Syndrome• Caused by HIV (Human Immuno Deficiency

Virus)• Virus attacks helper T. • People die of other infections.• NEWS 2015: HIV has been reclassified as a

chronic life long illness vs. a “death sentence”.

Unique• Incurable but treatable.• Before the development of anti-virals it had:

– high mortality– quickly spread– no vaccine. – **This combination was RARE in this technological age.

• Spread through intimate contact w/ an infected person– THIS is a limiting factor! – UNFORTUNATLY a person can carry and transmit

HIV for years before symptoms arise

How it’s contracted• Unprotected sex (of any kind) is the most

common. You can also be exposed…– Sharing needles– Blood transfusion (rare if blood is tested)– Mother/baby– Breastfeeding

Not transmitted through…• Sweat, saliva, tears • Insects• Environment: HIV is fragile and dies quickly

outside of the body.– Same toilet use– Touching, hugging, hand shaking– Sitting next to or where someone has been

sitting

Life Cycle• HIV attacks the helper T cell which reduces the

number of helper T (hT) cells until the person has AIDS– Usual amount= 1million hT cells in 1 ml pf blood– AIDS= > 200,000 hT cells per 1 ml blood– Takes 2-15 years

• HIV is really good at mutating• No one dies from HIV/AIDS• They die from infections that their body can no

longer fight off. Can be the common cold to a minor infection.

Lymphatic System Anatomy

• Consists of two semi-independent parts–Lymphatic vessels–Lymphoid tissues and organs

• Lymphatic system functions–Transport fluids back to the blood–Play essential roles in body defense and

resistance to disease

Organs of the Immune System

• outside• Skin-• Mucose Membranes-

Inside…

• Lymph System– When the Dr. checks your neck they are feeling

for swollen lymph nodes.

• Lymph system follows the pattern of the circulatory system BUT it is not pressurized, it is passive.– Fluid diffuses into the lymph system and is

“pushed” by normal body and muscle motion to the nodes.

Lymph Fluid?• Clear fluid that bathes the cells in

nutrients. – interstitial fluid & blood plasma are

similar• Also carries away waste and proteins

and random bacteria through the lymph vessels to the lymph Nodes.

Lymphatic Vessels

Figure 12.2

Lymph Nodes

• Filter lymph before it is returned to the blood

• Defense cells within lymph nodes–Macrophages present to B & T cells here

• These nodes swell during some infections due to filtration (full of dead invaders and defense cells)

Lymph Node Structure

Figure 12.4

Most are kidney-shaped, less than 1 inch long

Other Lymphoid Organs

• Several other organs contribute to lymphatic function–Spleen–Thymus–Tonsils–Peyer’s patches

Figure 12.5

The Spleen

• Filters blood & Destroys worn out blood cells

• Forms blood cells in the fetus• An adult can live w/o the spleen, but

you’ll be sick more often

The Thymus

• Located low in the throat, overlying the heart

• Functions at peak levels only during childhood to produce/mature t-cells.

Tonsils• Small masses of lymphoid tissue around the

back of the throat• Trap/remove bacteria and other foreign

materials & give immune system a “heads up”.• Tonsillitis is caused by congestion with bacteria

– They are no longer removed because we now understand their purpose is to become infected (rather than the whole person)

Peyer’s Patches

• Found in the wall of the small intestine

• Resemble tonsils in structure• Capture and destroy bacteria in the

intestine (same idea as tonsils)• Appendix?