The Immune System

Chapter 43

The Immune System

The Immune System

Consists of cells and substances secreted by cells

Cells All arise from stem cells (self renewing) that give rise to progenitor cells programmed to differentiate into particular type of specialized cells

The Lymphatic SystemConsists of

Branching net work of vesselsLymph nodes (sac like organs packed with lymphocytes)

The thymus, tonsils, appendix, spleen & bone marrow

Lymphatic Vessels Carry a fluid called lymph, similar to

interstitial fluid but w/ few nutrients & O2

Functions:Return tissue fluid to the circ.

SystemTo fight infection1% of fluid that enters tissues from

blood, does not reenter returned via lymphatic vessels

Fluid Lymphatic syst. into tiny dead end capillaries drains into large cap. reenters via 2 large vessels

The Immune ResponseBody must deal with invasion of bacteria, viruses, other pathogens in air & water and also abnormal body cell that cause cancer

Three co-op lines of defense have evolved

Defense

A. Non Specific B. Specific

A. Non Specific Defense

1. First line of defense Skin Mucous membranes Secretion of skin & mucous

membranes2. Second line of defense

Phagocytes Antimicrobial proteins The inflammatory response

B. Specific Defense

Third line of defense

LymphocytesAntibodies

First Line of Defense Intact skin, Mucous Membranes of the

digestive, genitourinary& respiratory tract act as barriers

Sweat pH 3-5 acidic Tears washing action Saliva & mucous secretions Lysozyme Mucous traps microbes Microbes in food killed by acidic stomach

Exception Hepatitis A, survives gastric acidity & enters body via the digestive tract

Second Line of Defense

Microbes that penetrate the 1st line face the 2nd line Phagocytes

Phagocytes

Phagocytes are large white cells that can engulf and digest foreign invaders

Phagocytes

Phagocytes/ Neutrophils/ PMNs 60-70% of WBCSelf destructAverage life span few daysCirc. & move into tissues when needed

PhagocytesNeutrophils also

granulocytes, contain granules filled with potent chemicals.

Chemicals destroy microorganisms, play a key role in acute inflammatory reactions.

Other types of granulocytes are eosinophils and basophils. Mast cells are granule-containing cells in tissue.

Phagocytes

Cells damaged by microbes Release chemical factors attract phagocytes phagocytes engulf microbes

Phagocytes contd.Monocytes5%

of WBCMore effective

than the PMNScirculate in the

blood enter tissues

Macrophages

Are found in tissues throughout the body Fixed liver, spleen, lymph nodes

Wandering interstitial fluid

Largest , long lived & very effective

Macrophages Act as scavengers Extend pseudopodia engulf

microbe destroyed by lysozyme Secrete a wide variety of

chemicals & activate T-cells

Exception Encapsulated bacteria M. tuberculosis resistant to lysozyme

Natural Killer

Soldiers of the immune system, most aggressive of all cells

1st line of defense against virus infected cells & abnormal cells (SARS & West Nile)

Mode: Normal cells have markers NK looks for these & does not Kill attaches to other cells & lyses the membranes

The Inflammatory Response

Damage to tissue localized response

1. Tissue Injury2. Dilation & Increased permeability3. Phagocyte migration4. Engulfment of microbe

Tissue Injury Tissue Injury, Release of Chemical

signals

Dilation & Increased Permeability

Dilation & increased permeability of cap.

Blood flow increases, brings clotting factors, begins repair, prevents spread of microbe

Phagocyte Migration

Phagocytes attracted become macrophages

Engulfment of microbe Phagocyte

consumes pathogen & damaged tissue

Pus accm.= dead phagocytes, protein leaked from cap. clean up in a few days

Antimicrobial Proteins

Complement Proteins Interferon

Complement Proteins

Set of 20 Proteins Carries out a cascade of steps that

leads to lyses of microbes Part of specific and non specific

defense Some complement components work

with chemokines to attract phagocytic cells to sites of infection.

Interferons

A set of proteins that provides nonspecific defenses

Are secreted by virus-infected cells When produced in response to one

virus may confer short-term resistance to unrelated viruses.

One type activates phagocytes

Action of Interferon

Virus infected cells cells stimulated to make interferon infected cell dies, interferon diffuses to other cells viral reproduction is inhibited

B. Specific Immunity

Third line of defense Kicks in when 1st & 2nd lines have

failedAntigen: a molecule that elicits an

immune responseAntibody: a protein found in plasma

that attaches to a particular kind of antigen & helps counter its effects

Immunity Resistance to specific invaders Can be

Acquire by natural infectionAchieved by vaccination stimulates IS to mount defenses & immunological memory

TypesActive exposed to disease

/vaccinationPassive fetus gets Ab from mother,

travelers get Ab shot

Immunity contd

Body Invaded by Microbes2 types of attack

Humoral Provided by Abs Bcells

Can be passively transferred

Cell mediatedProvided by T-Cells

T-cells circ. & attack infected cellsattacks own cancerous cells

Immunity contd

Body has about 100 X 106 -100 X 109 T & B Cells

Can recognize virtually any kind of antigen

Antigen ReceptorsSurface proteins on the cells can mount an IR

Dual Defense by Lymphocytes

Lymphocytes originate from stem cell

Can differentiate into B-Cells & T-Cells

Both can mount an immune response

Antibodies

Recognize & bind to Ags, & assist in neutralizing Ag.

Participates in general effector rxnsComplement activationStimulates macrophagesTriggers mast cells

Antibody Structure

Y Shaped4 Polypeptide Chains2 Heavy Chains

2 Light Chains

Antibody Function

Neutralization Promotes Phagocytosis Agglutination Complement Activation

Abs mark Ag for Destruction

Classes of Antibody

Ag- Ab reactions

AntigenProtein or large PS on surfaces of viruses or foreign cells

Protein coat of viruses, parts of capsule or CW, macromolecules on surface of cells protozoans & worms

Blood cells & Tissues antigenic molecules rejection of transplants

Antigenic Determinant & Binding Site

Ag Determinant Localized regions that Abs identify and react with

Ag Binding Site specific region on the Ab molecule that recognizes the Ag determinant & binds to it

Ag binding Site & Ag determinant have complementary shapes

Clonal Selection Production of a line of genetically

identical cells that recognize & attack a specific Ag that stimulated its production

Steps-Ag enters body-Stimulates lymphocytes-Lymphocytes proliferate clone of effector cells produce Abs & memory cells

Clonal Selection

Memory & Effector Cells

Effector Cells produce antibodies , survive for only few days

Memory Cells last for decades, 2nd exposure produces more Abs, can confer life long immunity

Immunological Memory

T – Cell Mediated Immunity

T – Cells Battle pathogens that already have entered body cells

Respond to Ag present on the surface of the body’s own cells

2 kinds of T- cells

T – Cells

Cytotoxic T-Cells attack body cells that are infected

Helper T- Cells Activate TC & MØ & stimulate B- Cells to produce Abs

Macrophages MØ Function as APC Have special proteins on surface

known as major histocompatibility complex (MHC)

MHC 2 Classes MHC I on all nucleated cells MHC II on B, Act T & MØ

Helper T- Cells

Helper T – binds to Ag & MHC

Cytotoxic T Cell

Cytotoxic T Cell Attack cancer cells changes on

surface of cancer cell Tc recognizes as foreign lyses cancer cells

Tumor developshed surface markersSecrete substances that suppress the IS

Cytotoxic T - Cell

Cytotoxic T -Cells

Allergies & Hypersensitivity

Allergies abnormal sensitivity to Ags in the environment ( Immune Disorder)

Allergens Ags that cause allergies

Origins Of AllergiesHypothesis• That they are evolutionary

remnants of the immune system’s response to parasitic worms.

• The humoral mechanism that fights worms is similar to the allergic response that causes such disorders as hay fever and allergic asthma.

Common Allergies Involve IgE

Histamines & other inflammatory agents High levels of histamines cause dilation

and increased permeability of small blood vessels.Lead to typical allergy symptoms:

sneezing, runny nose, tearing eyes, and smooth muscle contractions that can result in breathing difficulty.

Antihistamines diminish allergy symptoms by blocking receptors for histamine.

Anaphylactic Shock A life threatening reaction to injected

or ingested allergens widespread mast cell degranulation

triggers abrupt dilation of peripheral blood vessels, causing a drop in blood pressure.Death may occur within

minutes Triggers bee venom, penicillin, or

foods such as peanuts or fish Epinephrine counteracts this allergic

response (epi-pen)

Self and Non Self

It will not only attack pathogens but will also attack cell from other individuals

Skin graft from one person looks fine initially, but is destroyed after a day or two

Fetus not destroyed by mother as foreign Structure of Placenta is the key to acceptance

Blood Transfusions One potential problem is immune

reaction from individuals with incompatible blood groups

Blood group antigens are polysaccharides and elicit no memoryResponse is like a primary one

generates IgM anti-blood-group Ab not Ig G

IgM does not cross placenta, fetus is protected if blood group ids different

Blood Groups

ABO blood groupsType A Ag A on RBC can be recognized as foreign if placed in the body of another individual

Type B Ag B on RBCType AB have both Ag A & Ag B on RBC

Type O No Ag (A or B) on RBC

Blood Groups

Type AntigenPlasma

AntibodiesCan Receive Blood From

A A Anti -B A,O

B B Anti-A B,O

AB AB NoneA, B, AB, O universal recipient

O noneAnti-A & Anti-

BO universal donor

The Rh Group

Discovered in the 1930s, when working w/ Rhesus monkeys

Ag Present on both human & monkey RBC Ag named Rh Factor

85% of the popln Have Ag & are Rh+

15% lack this Ag on RBC Rh-

Rh-no Abs in serum but exposure to Ag can produce anti-Rh antibodies

Can cause Mother fetus problems b/c Abs are IgG

Rh Factor /Mother-Fetus problems

Arises when Rh- mother carries a fetus that is Rh + (inherited from father)

Small amts of fetal blood crosses placenta, late in pregnancy or during delivery mother makes anti Rh antibodies

Subsequent pregnancy, mother has memory B cells makes Abs that destroy fetal RBCS

Prevention of Rh Factor /Mother-Fetus problems

Mother is injected with anti Rh Ab after 1st delivery of Rh+ baby

She is passively immunized to eliminate the Rh antigen before her body can mount an immune response.

Grafts & Organ Transplants MHC is responsible for stimulating

rejection Foreign MHCs are antigenic & induce an

IR To minimize rejection MHC is matched as

closely as possible In absence of identical twins siblings

provide closest match Nevertheless recipient immune

suppressive drugs susceptible to infection

Graft Versus Host Reaction

In bone marrow transplants Recipient’s bone marrow cells are

irradiated so that there is little chance of graft rejection

But, donated bone marrow lymphocytes may react against recipient Graft versus Host reaction

Autoimmune Disorders

The immune system attacks some components of one’s own body

Immune system loses tolerance for self and turns against certain molecules of the body

Mechanism is not fully understood, likely to arise from failure in the immune regulation

Autoimmune DisordersInsulin Dependent Diabetes (juvenile

onset) ► T-cells attack & destroy the

insulin producing cells of the pancreas (β-cells)

► Develops before the age of 15yrs

► Patients require regular supplements of insulin

Rheumatoid ArthritisT-cells accumulate in joints & react

against body proteinsT-cells and Ab complexes

accumulate in joints, cause inflammation of the joints & damage to bone & cartilage

Rheumatic Feverpreceded by a strep. Infection, self

proteins closely related to strep AgsAbs react to self proteins fever

inflammation of joint & damage to the heart

Multiple Sclerosis T cells are reactive against the myelin

of the CNS & destroy the myelinLeads to a number of serious

neurological disorders

SLE ( lupus)Immune rxn to body’s nucleic acidsAb-nucleic acids complexes accm.in

the joints & kidneys inflammationDrugs suppress the IS & inflam. But

can cause kidney damage

Immunodeficiency Diseases

Individuals lacks one or more components of the IS

More susceptible to infections May be congenital or develop later in

life

Severe Combined Immunodefeciency “Bubble Boy” disease Both T-cells & B –Cells are absent or lacking Child may survive fetal life & 1st few months

of life gets Abs from mother Once this immunity is lost small infectios

become fatal Treated withBone marrow transplant, Abs

produced expt, genetically engineered bone marrow

AIDS 1st recognized in 1981 UCLA Medical Center man with fungal

infect. in throat got a rare form of pneumonia following a series of opportunistic infections he died

In 1983 a retrovirus now called human immunodeficiency virus HIV was identified as the causative agent of AIDS

AIDS

The most common & devastating immunodeficiency diseases

2 viruses HIV -1 & HIV 2 cause AIDS by destroying the TH cells (TH stimulate bothe humoral & cell mediated IR)

TH declines & patients become prone to other diseases

Mortality is close to 100% HIV most lethal pathogen

encountered

AIDS patients produce Abs to HIV basis for blood test

Abs do little to prevent progression of infection

Hypothesis virus spends most of its life inside

the cell seldom exposed to the Abs

**No vaccine yet