1. The Immune System
An organisms’ protection from Pathogens
Video

2. Pathogen Any infectious agent that causes disease Bacteria Viruses
Fungi
Protists/parasites
Fungi are parasites or saprophytes Mycoses=fungal infection i.e. they live off living or dead organic matter. Rarely penetrate below the skin but can infect the lungs (serious) Particular species of fungi cause infections of the skin such as athletes foot, ring worm, jock itch, yeast infections, in lungs yeast and Aspergillosis

3. 2 Divisions of Immunity in Humans and Other Mammals
I. Innate Immunity – “Non-Specific”
This defense is not concerned with ‘what’ the pathogen is. This system merely prevents the pathogen from entering the body or destroys it before identifying it.
It shoots first and asks questions later
Innate Immunity involves several layers of defense:
Barrier Defenses B. Inflammatory Response
C. Cellular Defenses D. Natural Killer Cells
E. Antimicrobial Defenses

4. A. Barrier Defenses Epidermis – impenetrable barrier
Oil and Sweat have low pH
Resident Flora – your own bacteria
Mucous Membrane – mucus and cilia
Lysozyme

5. Skin Epidermis an impenetrable barrier to pathogens
Oil and Sweat have a low pH that reduces pathogen growth
Resident Flora your own colonies of bacteria that live on your skin out-- competes with harmful bacteria for space

6. Mucous Membranes
Un-keritonized skin of the mocous membranes have a different layer of defense
MUCUS and CILIA
Lysozyme

7. B. Cellular Defenses Leukocytes – phagocytic
Microbes/antigens
PHAGOCYTIC CELL
Leukocytes – phagocytic
white blood cells have surface
receptors that detect typical
pathogen compounds called
antigens.
Vacuole
Lysosome
containing
enzymes

8. Groups of pathogens are recognized by TLR, Toll-like receptors
EXTRACELLULAR
FLUID
Lipopolysaccharide
Helper
protein
Flagellin
TLR4
Groups of pathogens are recognized by TLR, Toll-like receptors
WHITE
BLOOD
CELL
TLR5
VESICLE
TLR9
CpG DNA
Inflammatory
responses
TLR3
A white blood cell engulfs a microbe, then fuses with a lysosome to destroy the microbe

9. There are different types of phagocytic cells:
Neutrophils engulf and destroy microbes
Macrophages are part of the lymphatic system and are found throughout the body
Eosinophils discharge destructive enzymes
Dendritic cells stimulate development of acquired immunity

10. Interstitial fluid Adenoid Adenoid Tonsil Tonsil Blood capillary Lymph
Fig. 43-7
Interstitial fluid
Adenoid
Adenoid
Tonsil
Tonsil
Blood
capillary
Lymph
nodes
Blood
capillary
Lymph
nodes
Spleen
Tissue
cells
Lymphatic
vessel
Spleen
Tissue
cells
Lymphatic
vessel
Peyer’s patches
(small intestine)
Peyer’s patches
(small intestine)
Appendix
Appendix
Figure 43.7 The human lymphatic system
Lymphatic
vessels
Lymph
node
Masses of
defensive cells
Lymph
node
Masses of
defensive cells

11. C. Antimicrobial Proteins
Peptides and proteins function in innate defense by attacking microbes directly or impeding their reproduction
Interferon proteins provide innate defense against viruses and help activate macrophages
About 30 proteins make up the complement system, which causes lysis of invading cells and helps trigger inflammation

12. D. Inflammatory Responses
Following an injury, mast cells release histamine, which promotes changes in blood vessels; this is part of the inflammatory response
These changes increase local blood supply and allow more phagocytes and antimicrobial proteins to enter tissues
Pus, a fluid rich in white blood cells, dead microbes, and cell debris, accumulates at the site of inflammation

13. D. Inflammatory Responses
Fig
D. Inflammatory Responses
Pathogen
Splinter
Chemical
Signals
(Ligand)
Macrophage
Fluid
Mast cell
Capillary
Phagocytosis
Figure 43.8 Major events in a local inflammatory response
For the Cell Biology Video Chemotaxis of a Neutrophil, go to Animation and Video Files.
Red blood cells
Phagocytic cell

14. Fever is a systemic inflammatory response triggered by pyrogens released by macrophages, and toxins from pathogens
Septic shock is a life-threatening condition caused by an overwhelming inflammatory response

15. II. Acquired immunity lymphocyte receptors provide pathogen-specific recognition
Lymphocytes- are white blood cells that recognize and respond to antigens, foreign molecules.
Lymphocytes that mature in the thymus above the heart are called T cells, and those that mature in bone marrow are called B cells
Lymphocytes have immunological memory.

16. Fig. 43-9
B cells and T cells have receptor proteins that can recognize and bind to antigens
Antigen-
binding
site
Antigen-
binding site
Antigen-
binding
site
Plasma
membrane
Figure 43.9 Antigen receptors on lymphocytes
B cell
Cytoplasm of B cell
Cytoplasm of T cell
T cell
(a) B cell receptor
(b) T cell receptor

17. Antibody Genes V D J V D C J C
Heavy chain
Light chain V D J C
Antigen-binding region
Constant region
Rearranged gene components encoding a heavy chain
Assembled antibody molecule
Scientists long wondered how all the genetic information needed to make millions of different antibodies could fit in a limited number of genes.
The answer is that antibody genes are spliced together from widely scattered bits of DNA located in two different chromosomes. Each antibody molecule is made up of two separate chains, a heavy chain and a light chain. The heavy chain is where the binding of antigens occurs, so much genetic variation is involved in its assembly. For example, to form a heavy chain, 1 of 400 possible variable gene segments (V) combines with 1 out of 15 diversity segments (D) and 1 out of 4 joining (J) segments. This makes 24,000 possible combinations for the DNA encoding the heavy chain alone. As this part of the gene assembles, it joins the variable coding segments with those for the constant-C segments of the heavy-chain molecule.
Gene components scattered through one chromosome

18. Markers of Self: Major Histocompatibility Complex
Antigenic peptide
Antigenic peptide
Antigenic peptide
Viral infection
MHC Class I
MHC Class I
MHC Class II
Antigen-presenting cell uses MHC Class I or II
Infected cell
Cell membrane
Your immune cells recognize major histocompatibility complex proteins(MHC) when they distinguish between self and non-self. An MHC protein serves as a recognizable scaffold that presents pieces (peptides) of a foreign protein (antigenic) to immune cells.
An empty “foreign” MHC scaffold itself can act as an antigen when donor organs or cells are introduced into a patient’s body. These MHC self-marker scaffolds are also known as a patient’s “tissue type” or as human leukocyte antigens (HLA) when a patient’s white blood cells are being characterized.
For example, when the immune system of a patient receiving a kidney transplant detects a non-self “tissue type,” the patient’s body may rally its own immune cells to attack.
Every cell in your body is covered with these MHC self-marker proteins, and—except for identical twins—individuals carry different sets. MHC marker proteins are as distinct as blood types and come in two categories—MHC Class I: humans bear 6 markers out of 200 possible variations; and MHC Class II: humans display 8 out of about 230 possibilities.
Antigen presentation- the display of an antigen fragment by a cell’s MHC on the infected cell’s surface.
Body Cell with “Self-Markers called MHC

19. B Cells Antigen-specific B cell receptor
Class II MHC and processed antigen are displayed
Antigen
Antibodies
(Immunoglobins)
B cell
Cytokines (Lymphokines)
LIGAND
Plasma cell
B cells work chiefly by secreting soluble substances known as antibodies. They mill around a lymph node, waiting for a macrophage to bring an antigen or for an invader such as a bacteria to arrive. When an antigen-specific antibody on a B cell matches up with an antigen, a remarkable transformation occurs.
The antigen binds to the antibody receptor, the B cell engulfs it, and, after a special helper T cell joins the action, the B cell becomes a large plasma cell factory that produces identical copies of specific antibody molecules at an astonishing pace--up to 10 million copies an hour.
Antibodies belong to a family of large protein molecules known as immunoglobulins.
Scientists have identified nine chemically distinct classes of human immunoglobulins, four kinds of IgG and two kinds of IgA, plus IgM, IgE, and IgD.
Immunoglobulins G, D, and E are similar in appearance. IgG, the major immunoglobulin in the blood, is also able to enter tissue spaces; it works efficiently to coat microorganisms, speeding their destruction by other cells in the immune system. IgD is almost exclusively found inserted into the membrane of B cells, where it somehow regulates the cell’s activation. IgE is normally present in only trace amounts, but it is responsible for the symptoms of allergy.
IgA--a doublet--guards the entrance to the body. It concentrates in body fluids such as tears, saliva, and secretions of the respiratory and gastrointestinal tracts.
IgM usually combines in star-shaped clusters. It tends to remain in the bloodstream, where it is very effective in killing bacteria.
bacteria
Activated helper T cell

20. Resting cytotoxic T cell Activated helper T cell
T Cells
Resting helper T cell
Resting cytotoxic T cell
Activated when they encounter infected cells that are presenting antigens
Cytokines
Released by
Helper T-Cells
Granule w/
destructive
enzymes
T cells contribute to your immune defenses in two major ways. Some help regulate the complex workings of the overall immune response, while others are cytotoxic and directly contact infected cells and destroy them.
Chief among the regulatory T cells are helper T cells. They are needed to activate many immune cells, including B cells and other T cells.
Cytotoxic T cells (sometimes called killer T cells) help rid your body of cells that have been infected by viruses as well as cells that have been transformed by cancer but have not yet adapted to evade the immune detection system. They are also responsible for the rejection of tissue and organ grafts.
Activated helper T cell
Activated killer cell

21. Killer Cells: Cytotoxic Ts
Target cell
Target-oriented granules
Surface contact
At least two types of lymphocytes are killer cells--cytotoxic T cells and natural killer cells. Both types contain granules filled with potent chemicals. Both types kill on contact. They bind their targets, aim their weapons, and deliver bursts of lethal chemicals.
To attack, cytotoxic T cells need to recognize a specific antigen bound to self-MHC markers, whereas natural killer (NK) cells will recognize and attack cells lacking these. This gives NK cells the potential to attack many types of foreign cells.

22. T cells bind to antigen fragments presented on a host cell
These antigen fragments are bound to cell-surface proteins called MHC molecules
MHC molecules are so named because they are encoded by a family of genes called the major histocompatibility complex

23. The Role of the MHC
In infected cells, MHC molecules bind and transport antigen fragments to the cell surface, a process called antigen presentation
A nearby T cell can then detect the antigen fragment displayed on the cell’s surface
Depending on their source, peptide antigens are handled by different classes of MHC molecules

24. Infected cell Microbe Antigen- presenting cell 1 Antigen associates
Fig
Infected cell
Microbe
Antigen-
presenting
cell 1
Antigen
associates
with MHC
molecule
Antigen
fragment
Antigen
fragment 1 1
Class I MHC
molecule
Class II MHC
molecule 2 2
T cell
receptor
T cell
receptor 2
T cell
recognizes
combination
(a)
Cytotoxic T cell
(b)
Helper T cell

25. Activation of B Cells to Make Antibody Antigen-presenting cell
Circulating antibody
Antigen
Antigen-specific B cell receptor
Class II MHC and processed antigen are displayed
Antigen-presenting cell
Antigen is processed
Antigen
Class II MHC
The B cell uses its antibody-receptor to bind a matching antigen, which it then engulfs and processes. This triggers the B cell to become a large plasma cell producing millions of copies of the same specific antibody. These antibodies then circulate in the bloodstream in search of more matching antigens. B cell antibodies cannot themselves kill an invading organism, but they can use their antibodies to mark invaders for destruction by other immune cells and by complement.
Cytokines
(LIGAND)
B cell
Antibodies
Antigen-presenting cell
Activated helper T cell
Plasma cell

26. Animation: Role of B Cells
Fig
Antigen molecules
B cells that
differ in
antigen
specificity
Antigen
receptor
Animation: Role of B Cells
Figure Clonal selection of B cells
Antibody
molecules
Clone of memory B cells
Clone of plasma cells

27. Figure 43.16 An overview of the acquired immune response
Humoral (antibody-mediated) immune response
Cell-mediated immune response
Key
Antigen (1st exposure) +
Stimulates
Gives rise to
Engulfed by
Antigen-
presenting cell + + +
B cell
Helper T cell
Cytotoxic T cell + +
Memory
Helper T cells + + +
Figure An overview of the acquired immune response
Antigen (2nd exposure) +
Memory
Cytotoxic T cells
Active
Cytotoxic T cells
Plasma cells
Memory B cells
Secreted
antibodies
Defend against extracellular pathogens by binding to antigens,
thereby neutralizing pathogens or making them better targets
for phagocytes and complement proteins.
Defend against intracellular pathogens
and cancer by binding to and lysing the
infected cells or cancer cells.

28. Animation: Helper T Cells
Fig
Antigen-
presenting
cell
Peptide antigen
Bacterium
Class II MHC molecule
CD4
TCR (T cell receptor)
Cytokines
Helper T cell +
Humoral
immunity
(secretion of
antibodies by
plasma cells) +
Cell-mediated
immunity
(attack on
infected cells)
Figure The central role of helper T cells in humoral and cell-mediated immune responses
Cytokines secreted by Antigen presenting cell – cell signaling molecules
Cytokines released by helper T-Cells + +
B cell
Cytokines
Cytotoxic T cell
Animation: Helper T Cells

29. Cytotoxic T Cells: A Response to Infected Cells
Cytotoxic T cells are the effector cells in cell-mediated immune response
The activated cytotoxic T cell secretes proteins that destroy the infected target cell
Animation: Cytotoxic T Cells

30. Released cytotoxic T cell
Fig
Released cytotoxic T cell
Cytotoxic T cell
Perforin
Granzymes
perforin
CD8
TCR
granzymes
Dying target cell
Class I MHC
molecule
Pore
Figure The killing action of cytotoxic T cells
For the Discovery Video Fighting Cancer, go to Animation and Video Files.
Target
cell
Peptide
antigen

31. B Cells: A Response to Extracellular Pathogens
The humoral response is characterized by secretion of antibodies by B cells
Activation of B cells is aided by cytokines and antigen binding to helper T cells
Clonal selection of B cells generates antibody-secreting plasma cells, the effector cells of humoral immunity

32. Antigen-presenting cell Bacterium
Fig
Antigen-presenting cell
Bacterium
Peptide
antigen
B cell
Class II MHC
molecule +
Clone of plasma cells
Secreted
antibody
molecules
Cytokines
TCR
CD4
Endoplasmic
reticulum of
plasma cell
Activated
helper T cell
Helper T cell
Clone of memory
B cells
Figure B cell activation in the humoral immune response
2 µm

33. The Role of Antibodies in Immunity
Neutralization occurs when a pathogen can no longer infect a host because it is bound to an antibody
Opsonization occurs when antibodies bound to antigens increase phagocytosis
Antibodies together with proteins of the complement system generate a membrane attack complex and cell lysis
Animation: Antibodies

34. Antibodies bound to antigens on viruses can neutralize the virus
Fig
Viral neutralization
Opsonization
Activation of complement system and pore formation
Antibodies bound to antigens on viruses can neutralize the virus
Bacterium
Complement proteins
Virus
Binding of antibodies to bacteria
Promotes phagocytosis of the
Bactria by Macrophages
Formation of
membrane
attack complex
Flow of water
and ions
Macrophage
Pore
Figure Antibody-mediated mechanisms of antigen disposal
Foreign
cell
Following activation the attack complex forms pores in the foreign cell’s membrane , allowing water and ions to rush in.
Binding of antibodies to antigens on the surface of a foreign cell activates a complex system.
The Cell swells and eventually lyses.

35. Evolution and Immunity
VIDEO 1
VIDEO 2