1. 3m
The Immune System
Fighting Off Invaders

2. Non Specific Defenses 1. Non-specific: General Response
Skin and Mucous Membranes:
first line of defense: physical barrier
skin: barrier of squamous epithelial cells
- secretions: sweat – some antimicrobial properties (lysosyme) – pH 3-5
Mucous membranes: secretes mucous – traps microbes

3. 2. Phagocytosis :
consumption of invaders by white blood cells
Types:
Neutrophils: travel to areas that have cellular damage (such as a cut) due to chemotaxis
damaged cells release chemical signals that attract neutrophils which engulf microbes in the damaged area preventing infection

4. Macrophages (big eaters): long lived – eat and digest microbes forming a food vacuole which combines with a lysosome which kills the microbe by exposing it to an oxygen superoxide and nitrogen oxide
Macrophages either migrate through the body or reside in organs such as the liver, kidney, lung and brain

5. 3. Eosinophils: attack larger parasites (blood flukes) by releasing destructive enzymes that attack the outside of the invader
4. Natural Killer Cells: Attack and lyse cells that have been infected by a virus or abnormal body cells (cancer)

6. 5. Inflammatory Response:
response of tissues around an area with tissue damage and/or microbe invasion
Ex: Splinter
Damaged tissue releases HISTAMINE which stimulate Basophils (WBC) and Mast Cells to release more histamine

7. Result of increased blood flow:
Histamine Response:
1. Vasodilation of pre-capillary arterioles: increases blood flow to area
2. Vasoconstriction of post-capillary venules: decreases blood loss from area
Result of increased blood flow:
Rubor = redness
Calor = heat
Tumor = swelling
Dalor = pain

8. Pathogen Pin Blood clot Macrophage Blood clotting elements
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

9. Release of Chemokines: chemical signal
Increased migration of phagocytotic cells
action of macrophages results in the accumulation of pus
– dead phagocytotic cells and extracellular fluid and proteins

10. 6. Larger Scale Infection:
stimulation of neutrophil production by bone marrow
stimulation of the secretion of pyrogens = fever
7. Secretion of Interferons:
secreted by cells ALREADY infected by viruses
signal nearby cells to produce chemicals that inhibit viral reproduction
limits the spread of the virus and can stimulate phagocyte production
CRASH COURSE

11. Specific Immune Response
Carried out by two classes of lymphocytes – found in the blood and tissues
Classes of lymphocytes:
B Lymphocytes: originate and mature in the Bone – carry out the humoral response – secretion of antibodies
T Lymphocytes: originate in the Bone and mature in the Thymus – carry out cell mediated response

12. Function: attack specific Antigens (Anti-body Gen - erator) (molecules that elicit an immune response)
Ex: proteins on the cell surfaces of viruses, bacteria, fungi etc, Pollen and foreign organisms or organs

13. Specific areas (epitopes) of the Antigens are recognized by specific sites on Antibodies – proteins secreted by B cells giving a very specific response

14. Antigen-
binding
sites
Antibody A
Antigen
Antibody B
Antibody C
Epitopes
(antigenic
determinants)

15. Antibody Structure and Formation: Immunoglobulins (Igs)
Y-shaped proteins comprised of two inner heavy chains and two outer light chains. Chains are held together by di-sulfide bridges.

17. Both types of chains have a constant region and a variable region.
The variable regions are determined by random genetic deletions that occur during embryonic development.
This results in a wide variety of antibody formation and is why identical twins will have different immune systems.
Space between the heavy and light chains is what binds to the epitope of the antigen and is substrate specific.

18. Light-chain polypeptide
DNA of
undifferentiated
B cell
DNA of differentiated
pre-mRNA
mRNA
Cap
B cell receptor
Light-chain polypeptide
Intron
Variable
region
Constant V1 V2 V3
V4–V39
V40 J1 J2 J3 J4 J5 V C
Poly (A)
Figure 43.11

19. V C Figure 43.8a Antigen- binding site binding site Disulfide bridge
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

20. 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

21. Actions that enhance Phagocytosis
Antibody Actions:
Actions that enhance Phagocytosis
Neutralization – antibodies bind to antigen and blocks its activity
Ex: antibody binds to a virus and prevents it from infecting a cell
Agglutination – a large, multi sided antibody binds multiple antigens together
Precipitation – antibody binds to soluble proteins making them insoluble

22. Figure 43.19 Binding of antibodies to antigens inactivates antigens by
Viral neutralization
(blocks binding to host)
and opsonization (increases
phagocytosis)
Agglutination of
antigen-bearing particles,
such as microbes
Precipitation of
soluble antigens
Activation of complement system
and pore formation
Bacterium
Virus
Bacteria
Soluble
antigens
Foreign cell
Complement
proteins
MAC
Pore
Enhances
Phagocytosis
Leads to
Cell lysis
Macrophage
Figure 43.19

23. Compliment Fixation: Antibodies bind to a pathogen or infected cell and begin a series of events that leads to the lysing of the pathogen or cell
- antibodies bring in compliment proteins that are released and form a pore in the cell membrane causing it to lyse

24. Figure 43.19 Binding of antibodies to antigens inactivates antigens by
Viral neutralization
(blocks binding to host)
and opsonization (increases
phagocytosis)
Agglutination of
antigen-bearing particles,
such as microbes
Precipitation of
soluble antigens
Activation of complement system
and pore formation
Bacterium
Virus
Bacteria
Soluble
antigens
Foreign cell
Complement
proteins
MAC
Pore
Enhances
Phagocytosis
Leads to
Cell lysis
Macrophage
Figure 43.19

25. Specific Cell Response:
1. Exposure to Antigen activates either B or T Lymphocyte
2. Lymphocyte divides into two types of cells:
a. Effector Cells – combat the antigen
B Cell Effector cells are called plasma cells because they generate large amounts of antibodies that are released into the plasma.
HelperT Cells activate B Cell plasma cells, Cytotoxic T cells kill infected cells
b. Memory Cells – Cells that remain in the body and mount a greater and faster response in the case of reinfection by the same pathogen
Immune System Video General

26. Self-Tolerance: Preventing Immune Response to Self Tissues
Self Code of Tissues = Major Histocompatability Complex (MHC)
MHC is the collection of surface proteins (part of ECM) on the outside of the cell
Two Types of MHC:
MHC I: Regular body tissues
MHC II: B and T Cells

27. Role of the MHC I:
An infected cell takes a portion of a protein from the virus places it in a surface protein in the MHC
– this is called Antigen Presentation
- Cytotoxic T Cells Bind to these cells and destroy them

28. Figure 43.9a
Infected cell
Antigen
fragment
Class I MHC
molecule
T cell
receptor
(a) Cytotoxic T cell
A fragment of
foreign protein
(antigen) inside the
cell associates with
an MHC molecule
and is transported
to the cell surface. 1
The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection. 2

29. Role of the MHC II of Macrophages:
Macrophages eat an antigen (bacterium, infected cell) and then incorporate some of the proteins in the MHC becoming an Antigen Presenting Cell.
These bind to Helper T-cells which then activate other cells to target the antigen.

30. Microbe
Antigen-
presenting
cell
Antigen
fragment
Class II MHC
molecule
T cell
receptor
Helper T cell
A fragment of
foreign protein
(antigen) inside the
cell associates with
an MHC molecule
and is transported
to the cell surface. 1
The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection. 2
(b)

31. Difference between Antigen Presentation and Antigen Presenting Cells.
Infected Cells have Antigen Presentation which are then killed by Cytotoxic T-cells.
These beg to be killed.
Antigen Presenting Cells are Macrophages that have ingested antigens (they are not infected) and activate Helper T-cells
These alert the immune system to the foreign antigen.
MHC I: Presentation = Infection = Destruction
MHC II: Presenting = Warning = Helping

32. Humoral Response: B Cells
targets antigens that are floating in the blood, toxins, free moving bacteria and viruses
Process:
1. Antigen encounters the correct Antibody on the surface of B Cell
2. B Cell becomes active and divides into Effector Cells (Plasma Cells) and Memory Cells.

33. 3. Plasma Cells generate copious amounts of the correct antibody which circulate in the body and bind to the remaining antigens.
4. Macrophages destroy the antibody bound antigen and can become Antigen Presenting Cells linking it to the Cell Mediated Response (T cells)
5. Memory cells remain in the body in case of reinfection (acquired immunity).
Crash Course #2

34. Figure 43.12 bind to the antigen Antigen molecules
receptor
B cells that
differ in
antigen
specificity
Antibody
molecules
Clone of memory cells
Clone of plasma cells
bind to the antigen
receptors of only one
of the three B cells
shown.
The selected B cell
proliferates, forming
a clone of identical
cells bearing
receptors for the
selecting antigen.
Some proliferating
cells develop into
short-lived plasma
cells that secrete
antibodies specific
for the antigen.
Some proliferating cells
develop into long-lived
memory cells that can
respond rapidly upon
subsequent exposure
to the same antigen.

35. Cell Mediated Response: T Cells
- targets infected cells (bacteria, virus), fungi, protozoans and parasites
Two Types: Helper T Cell and Cytotoxic T Cell
Helper T Cell
1. A macrophage eats an antigen and becomes an Antigen Presenting Cell (APC) and secretes the Cytokine (protein) Interleukin I. Interleukin I attracts Helper T Cells to the APC.
2. The MHC II of the APC binds to the Helper T Cell and activates it.

36. 3. Activated Helper T Cell divides into more Activated Helper T Cells and Memory Cells
4. Activated Helper T Cells secrete Cytokines (Interleukin II) that stimulate other lymphocytes (B and T Cells) into action.
Ex: Interleukin II activates B cells to become plasma cells and Cytotoxic T cells to become Active Killer Cells.
5. Memory Cells remain incase of reinfection.

37. Helper T Cell B cell Figure 43.15
After a dendritic cell engulfs and degrades a bacterium, it displays
bacterial antigen fragments (peptides) complexed with a class II
MHC molecule on the cell surface. A specific helper T cell binds
to the displayed complex via its TCR with the aid of CD4. This
interaction promotes secretion of cytokines by the dendritic cell.
Proliferation of the T cell, stimulated
by cytokines from both the dendritic
cell and the T cell itself, gives rise to
a clone of activated helper T cells
(not shown), all with receptors for the
same MHC–antigen complex.
The cells in this clone
secrete other cytokines
that help activate B cells
and 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

38. Cytotoxic T Cell:
1. Infected cells carry out Antigen Presentation.
2. Cytotoxic T Cells bind to the MHC I of an infected cell and becomes active (Active Killer Cell). This Cytotoxic T cell is also stimulated into action by Interleukin II.
3. The Active Killer Cell releases perforin proteins that bind to the infected cell making large pores in the cell membrane

39. 4. Ions and water flow into the cell causing it to lyse.
5. Infection particles are then marked with antibodies and destroyed.
6. Killer T Cell moves onto the next victim
Crash Course #3

40. Cytotoxic T Cell Figure 43.16 Cytotoxic T cell Perforin Granzymes CD8
TCR
Class I MHC
molecule
Target
cell
Peptide
antigen
Pore
Released
cytotoxic
T cell
Apoptotic
target cell
Cancer
Cytotoxic
A specific cytotoxic T cell binds to a
class I MHC–antigen complex on a
target cell via its TCR with the aid of
CD8. This interaction, along with
cytokines from helper T cells, leads to
the activation of the cytotoxic cell. 1
The activated T cell releases perforin
molecules, which form pores in the
target cell membrane, and proteolytic
enzymes (granzymes), which enter the
target cell by endocytosis. 2
The granzymes initiate apoptosis within the
target cells, leading to fragmentation of the
nucleus, release of small apoptotic bodies,
and eventual cell death. The released
cytotoxic T cell can attack other target cells. 3
Figure 43.16

41. Humoral immune response Cell-mediated immune response
Figure 43.14
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

42. 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)
Figure 43.2

43. Purpose of Antibodies
Bombard invaders and neutralize them.

44. Immunity and Health
1. Immunization/Vaccinations: expose a person to a dead or weakened antigen that allows for the primary immune response to occur without the major symptoms.
- allows for the production of memory cells to prevent/limit effects of secondary exposure

45. 2. ABO Blood: Immunoglobulin of one type produce antibodies for the other as a response to exposure to bacteria with similar epitopes.
Type A produces anti B
Type B produces anti A
Type O produces anti A and B
Type AB produces no antibodies

46. 3. Transplants: MHC are matched as closely as possible so the host does not reject the transplant (graft vs. host disease)
- patient is given immunosuppressant drugs to help prevent rejection

47. 4. Allergies: abnormal response to harmless environmental antigen (allergen)
- presence of the allergen causes Mast Cells to secrete large amounts of histamine which triggers the inflammatory response (swelling, excess liquids)
- take antihistamines to block the action of histamine

48. Allergies – Ted Ed Figure 43.20 IgE antibodies produced in
response to initial exposure
to an allergen bind to
receptors or mast cells. 1
On subsequent exposure to the
same allergen, IgE molecules
attached to a mast cell recog-
nize and bind the allergen. 2
Degranulation of the cell,
triggered by cross-linking of
adjacent IgE molecules,
releases histamine and other
chemicals, leading to allergy
symptoms. 3
Allergen
IgE
Histamine
Granule
Mast cell

49. 5. Autoimmune Disease:
- body begins to recognize itself as non-self and attacks its own tissues
Ex: Rheumatoid arthritis, Lupus, Multiple Sclerosis, Insulin Dependent Diabetes Mellitus

50. Figure 43.21

51. 6. Immunodeficiency : decreased immune function
- Genetics
- Result of other illnesses such as cancer
- Treatments for cancer
- Stress : stress causes the production of steroids which suppress the immune system
- AIDS: Acquired Immune Deficiency Syndrome caused by the Human Immunodeficiency Virus (HIV) – HIV attacks the white blood cells making the person immune compromised

52. Body Snatchers – The Flu
Ebola
Measles
Secret Life of Cell
Antibiotic Apocolypse