1. Immune System
Chapter 35

2. Immune System Functions Protection from pathogens and cancer
Viruses
Bacteria
Parasites
Toxins
Innate Immunity – nonspecific defenses
1st line of defense
2nd line of defense
Acquired immunity – specific defenses
3rd line of defense
Humoral immune response
B-cell response
Cell mediated immune response
T-cell response

3. broad range of microbes
INNATE IMMUNITY
Rapid responses to a
broad range of microbes
ACQUIRED IMMUNITY
Slower responses to
specific microbes
External defenses
Internal defenses
Skin
Mucous membranes
Secretions
Phagocytic cells
Antimicrobial proteins
Inflammatory response
Natural killer cells
Humoral response
(antibodies)
Cell-mediated response
(cytotoxic
lymphocytes)
Invading
microbes
(pathogens)

4. Immune System Structures Skin Mucous Membranes Bone Marrow
WBC’s - leukocytes
Neutrophils – attack pathogens in the blood and tissues
Monocytes  macrophages – in body tissues
Eosinophils – attack parasites
Basophils – allergies and parasites
Dendritic cells  Lymphocytes
B-cells
T-cells
Lymph nodes
Spleen
Lymph vessels
Thymus

5. Innate Immunity – Non Specific Defense
1st lines of defense
Skin
Barrier to pathogens
Sebaceous (oil) and sweat glands secrete lysozyme which destroys bacteria
pH of 3-5 – acidic
Mucous Membranes
Line the respiratory, digestive, and urinary tracts
Mucus and cilia trap and expel pathogens
Secretions
Stomach – gastric juice – pH 2
Saliva, tears, and mucous all contain lysozyme proteins

6. Innate Immunity – Non Specific Defenses
2nd lines of defense
Only activated if the 1st line fails
Phagocytes – Phagocytic WBC’s
Attach to microbes (pathogens)  ingest them  lysosome destroys them
Nitric oxide and lysozyme in lysosomes
Tuberculosis is resistant to lysosome destruction
Neutrophils
Engulf pathogens traveling in the blood and self destruct  killing the pathogen
Macrophages (monocytes)
Reside in tissues and organs and attack pathogens that enter or begin to infect
Eosinophils
Attack parasites
Dendritic cells
Attack like macrophages and stimulate acquired immunity (3rd line of defense)
lymphocytes

8. Innate Immunity – Non Specific Defenses
Antimicrobial proteins – impede pathogen reproduction
Complement system
Lyses microbes and triggers inflammation (inflammatory response)
Interferon
Inhibit viral reproduction
Natural Killer Cells
Attack virus infected body cells and cancer cells  apoptosis
Programmed cell death
Fever
Stimulate WBC production and tissue repair

9. Inflammatory Response
Pathogen
Pin
Macrophage
Chemical signals
Capillary
Phagocytic cells
Red blood cell
Blood
clotting
elements
Blood clot
Phagocytosis
Fluid, antimicrobial proteins,
and clotting elements move
from the blood to the site.
Clotting begins. 2
Chemical signals released
by activated macrophages
and mast cells at the injury
site cause nearby capillaries
to widen and become more
permeable. 1
Chemokines released by various
kinds of cells attract more
phagocytic cells from the blood
to the injury site. 3
Neutrophils and macrophages
phagocytose pathogens and
cell debris at the site, and the
tissue heals. 4

10. Innate Immunity – Non Specific Defenses
Inflammatory Response
1. Skin is punctured and pathogens enter
2. Mast cells in connective tissue release histamine increasing permeability and dilation of capillaries to injured site
3. WBC’s and blood clotting factors move from the blood to the infection
4. Clot forms a scab
5. Neutrophils and macrophages attack pathogens
6. WBC’s release chemokines which attract more phagocytes to attack the pathogen
Positive feedback
7. Redness, swelling, and soreness are side effects

11. Acquired Immunity – Specific Defense
3rd line of defense
Lymphocytes
Humoral Immune Response
B-Cells  Antibodies
Made and matured in bone marrow
Cell Mediated Immune Response
T- Cells  attack infected body cells
Made in bone marrow and matured in the thymus
Bone marrow
Lymphoid
stem cell
B cell
Blood, lymph, and lymphoid tissues
(lymph nodes, spleen, and others)
T cell
Thymus

12. Triggering a lymphocyte response
Antigen Presentation - Dendritic cells engulf and display antigens activating Helper T-Cells
Antigen displayed on class II MHC
MHC = Major Histocompatability Complex
Helper T-Cells activate B-Cells AND secrete cytokines which activate Cytotoxic T-Cells
Cell-mediated
immunity
(attack on
infected cells)
Humoral
(secretion of
antibodies by
plasma cells)
Dendritic
cell
Bacterium
Peptide antigen
Class II MHC
molecule
TCR
CD4
Helper T cell
Cytokines
Cytotoxic T cell
B cell 1 2 3

13. Triggering a lymphocyte response
Humoral Response – B-Cell
Cell Mediated Response – T-Cell
B-Cells are also activated by intact antigens on pathogens
B-Cells give rise to Plasma cells and Memory Cells
Plasma Cells make antibodies to trap pathogens and mark them for destruction
Memory cells “remember” antigens so antibodies can be made quickly upon second exposure.
43_18CytotoxicTCells_A.swf
Cytotoxic T-Cells are also activated by antigens displayed on infected body cells
Antigen displayed in Class I MHC
Cytotoxic T-Cells give rise to Active Cytotoxic T-Cells and Memory Cytotoxic T-Cells
Active Cytotoxic T-Cells kill infected body cells, cancer cells, and transplant tissues
Memory Cytotoxoic T-Cell “remember” the antigen so infected cells can be killed quickly upon second exposure.

14. Humoral immune response Cell-mediated immune response
First exposure to antigen
Intact antigens
Antigens engulfed and displayed by dendritic cells
Antigens displayed by infected cells
Activate
Gives rise to
B cell
Helper T cell
Cytotoxic T cell
Plasma cells
Memory B cells
Active and memory helper T cells
Memory cytotoxic T cells
Active cytotoxic T cells
Secrete antibodies that defend against pathogens and toxins in extracellular fluid
Defend against infected cells, cancer cells, and transplanted tissues
Secreted
cytokines
activate

15. Antigen Recognition
Memory B-Cells and T-Cells recognize antigens by antigen specific receptors
Both have constant and variable regions
Variable regions have antigen binding sites and vary from cell to cell for specificity
B-Cell Receptors – recognize intact antigens
Y shaped
2 identical heavy chains
2 identical light chains
Linked by disulfide bridges
T-Cell Receptors – recognize fragments of antigens presented by infected body cells or macrophages or dendritic cells
2 non identical chains
Alpha and beta
43_09bTCellReceptors_VT.swf

16. V C Antigen- Binding site b chain Disulfide bridge a chain T cell
Light
chain
Heavy chains
Cytoplasm of B cell V
A B cell receptor consists of two identical heavy
chains and two identical light chains linked by
several disulfide bridges.
(a)
Variable
regions
Constant
Transmembrane
region
Plasma
membrane
B cell C
Antigen-
Binding site
b chain
Disulfide bridge
a chain
T cell
A T cell receptor consists of one
chain and one b chain linked by
a disulfide bridge.
(b)
Variable
regions
Constant
Transmembrane
region
Plasma
membrane
Cytoplasm of T cell

17. 43_21Antibodies_A.swf Antigen- binding sites Epitopes (antigenic
Antibody A
Antigen
Antibody B
Antibody C
Epitopes
(antigenic
determinants)

18. Antigen Presentation Class I MHC Class II MHC
Found on all nucleated body cells
Identify self from non-self
Display antigens from pathogens by becoming infected
Display antigens to Cytotoxic T-Cells which contain a CD8 protein which recognizes and binds Class I MHC
Found on antigen presenting cells - dendritic cells, macrophages and B-cells
Bind antigens that have been ingested through phagocytosis
Display antigens to Helper T-Cells which contain a CD4 surface protein which recognizes and binds the Class II MHC

19. Antigen Presentation Antigen- Microbe Infected cell presenting cell 1
fragment
Class I MHC
molecule
T cell
receptor
(a) Cytotoxic T cell 1
Microbe
Antigen-
presenting
cell
Antigen
fragment
Class II MHC
molecule
T cell
receptor
Helper T cell
(b)

20. Active vs. Passive Immunity
Active Immunity
Passive Immunity
Lasts a lifetime
Exposure to an infectious agent (pathogen)
3rd line of defense
Specific immune response
Immunizations – vaccines
Inactive pathogen that stimulates the immune response producing memory cells
Lasts a few weeks
Antibodies are transferred from one person to another
Pregnant women  fetus
placenta
Mother  baby
breast milk

21. Primary vs. Secondary Response
1st exposure to antigen
Takes days to produce antibodies
Slow
2nd or more exposure to the same antigen
Memory cells produce antibodies
Quick

22. Antibody concentration
(arbitrary units)
104
103
102
101
100 7 14 21 28 35 42 49 56
Time (days)
Antibodies
to A
to B
Primary
response to
antigen A
produces anti-
bodies to A 2
Day 1: First
exposure to 1
Day 28:
Second exposure
to antigen A; first
antigen B 3
Secondary response to anti-
gen A produces antibodies
to A; primary response to anti-
gen B produces antibodies to B 4

23. Blood Groups Blood Type Antigen(s) Antibodies Produced Can Receive A B
A antigens
B antigens
A and B antigens
NONE
Anti - B
Anti - A
NONE
Anti – A and Anti - B
A and O Blood
B and O Blood
A, B, AB, and O Blood
Universal recipient
O only
Universal donor

25. Rhesus Factor and Blood
Rh factor – blood antigen
Can be problematic in pregnancy if the mom is Rh- (lacks the antigen) and the baby is Rh+ (has the antigen)
If blood mixes during delivery mom will produce antibodies for the Rh antigen
If mom has a 2nd child that is Rh+ her antibodies will attack the fetus during late pregnancy and child birth
Mom is injected with anti-Rh antibodies to prevent this

26. Transplants
No two people except identical twins have identical MHC molecules
% matches are made in a transplant to minimize rejection
Transplant recipients take medicine to suppress the immune response to the transplant
Leaves the recipient susceptible to other infections
Bone Marrow Transplant
Graft vs. Host
Graft is bone marrow – unless matched carefully could cause the new blood cells produced in the bone marrow to reject the host, most hosts reject because they’re immune system is working well. Use anti-rejection medications

27. Autoimmune Diseases
Immune system does not recognize body cells as self and creates antibodies against them
Lupus – attack histones and DNA
Arthritis – attack cartilage and joints
Insulin dependent Diabetes – attack beta cells of the pancreas which secretes insulin
Multiple Sclerosis – attacks myelin sheath on neurons

28. AIDS
People with AIDS are susceptible to opportunistic infections that the immune system cannot fight off.
HIV (RNA Virus)  AIDS
Retrovirus – uses the enzyme reverse transcriptase
HIV invades and destroys Helper T-Cells impairing both the Humoral and Cell Mediated Responses

30. Systems Approach to Vaccine Development
Old Method:
Use a control group and an experimental group
Give control group a placebo
Give experimental group an experimental drug
Monitor to determine effectiveness of the vaccine
Systems Method:
Give experimental subject a vaccine
Measure protein levels, DNA activity, cellular components
The vaccine that produces a result closest to “normal” will be the most effective