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
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