1. Immune System - 1

2. Defense Mechanisms Two types:
Innate (nonspecific) immunity - inherited
Adaptive (specific) immunity – learned from exposure to specific pathogens; function of lymphocytes
Serves as a first line of defense against pathogens
Examples: epithelial membranes, high acidity in stomach, cells that can engulf/kill pathogens, fever

3. Activation of Innate Immunity
Cells distinguish “self” from “nonself” using pathogen- associated molecular patterns (PAMPs) unique to the pathogens.
Immune cells have pathogen recognition receptors, such as toll-like receptors for PAMPs on their surface.
So far, 10 distinct toll-like receptors have been identified.
These cells respond by secreting chemokines to recruit more immune cells or activate specific immune cells.

4. DAMPS Tissue damage that causes necrosis (tissue death)
Immune system exposed to DAMPs – danger associated molecular patterns
-- AKA “damage-associated molecular patterns”
DAMPS stimulate innate immune responses and inflammation

5. Phagocytosis Three types of phagocytic cells:
Neutrophils are the first to arrive at an infection.
Mononuclear phagocytic cells (monocytes in the blood and macrophages and dendritic cells in the tissues) arrive later.
There are organ-specific phagocytes in the liver, spleen, lymph nodes, lungs, and brain.
Some of these, called fixed phagocytes, are immobile in the walls of these organs.

6. Phagocytosis in Tissues
Neutrophils and monocytes squeeze through gaps in post- capillary venule walls to enter tissue in a process called extravasation, or diapedesis.
Attracted to site by a process called chemotaxis by cytokines called chemokines
The pathogen becomes engulfed by pseudopods.
The vacuole containing the pathogen fuses with a lysosome.
The pathogen is digested.

7. Migration of white blood cells
Extravasation, or diapedesis.

8. Phagocytosis by a neutrophil or macrophage

9. Fever Regulated by hypothalamus
A chemical called an endogenous pyrogen sets the body temperature higher.
Produced as a cytokine by leukocytes
Endotoxins from some bacteria stimulate leukocytes to produce these cytokines.
Along with fever, they also induce sleepiness and a fall in plasma iron concentration (which limits bacterial activity).

10. Interferons Antiviral polypeptides produced by infected cells
Three types identified
Alpha and beta – inhibit viral replication and assembly
Gamma – helps fight infections and cancer
New antiviral drugs are being developed using interferons.

11. Mediated by antigens and antibodies
Adaptive Immunity
The acquired ability to defend against specific pathogens after exposure to these pathogens
Mediated by antigens and antibodies

12. Antigens
Foreign molecules that illicit an immune response, a fight of the body’s cells.
They are recognized specifically by antibodies
A large molecule can have several antigens (termed “antigenic determinant sites” or epitopes), that stimulate the production of and binding to antibodies.

13. Haptens
Smaller, non-antigenic molecules that can become antigens when bound to other proteins
These are useful for creating antigens for research and diagnosis.

14. Immunoassays using the agglutination technique:
Tests that use specific antibodies to identify specific antigens
Binding causes agglutination, which can be seen.
Used to determine blood type and detect pregnancy

15. Lymphocytes: B cells and T cells
a. Derived from stem cells in the bone marrow.
b. These stem cells seed the thymus, spleen, and lymph nodes.
The thymus is the site of new T lymphocytes through late childhood. It degenerates in adulthood, and new T lymphocytes are made through mitosis in secondary lymphoid organs.
The bone marrow and thymus are considered primary lymphoid organs.

16. B Lymphocytes
Lymphocytes that come directly from bone marrow to seed other organs (not the thymus) are called B lymphocytes.
They combat bacterial and some viral infections.
They secrete antibodies into blood and lymph so can be far from the victim.
This is called humoral immunity or antibody-mediated immunity.
Humor means “fluid”

17. T Lymphocytes
T lymphocytes attack host cells that have become infected with a virus or fungus, transplanted human cells, and cancer cells.
T lymphocytes do not produce antibodies.
They must be in close proximity to the victim cell in order to destroy it.
This is called cell-mediated immunity.

18. THYMUS Grows during childhood; regresses after puberty
Transform bone marrow stem cels into T-cells
In adulthood T- lymphocytes seem to come from spleen and lymph nodes directly.

20. Events of Local Inflammation
Occurs when bacteria enter a break in the skin
Initiated by nonspecific mechanisms of phagocytosis by toll-like receptors
Macrophages and mast cells release cytokines and chemokines to attract phagocytic neutrophils.
Complement proteins are activated, which also attract phagocytic cells.
More phagocytic cells arrive via diapedesis from nearby venules. T lymphocytes are the last to arrive. Mast cells degranulate and secrete heparin, histamine, prostaglandins, leukotrienes, cytokines, and TNF-α.
These produce warmth, swelling, and pain (classic symptoms).
They also recruit more leukocytes. Neutrophils
Kill microorganisms through phagocytosis
Release NETS (neutrophil extracellular traps) to trap pathogens
Undergo programmed cell death and spill protein-digesting enzymes into the surrounding tissues, causing pus
Release granule proteins that draw monocytes to the area Monocytes
Enlarge into macrophages
Phagocytose apoptotic neutrophils and release growth factors and other agents that will end inflammation and promote repair.
As inflammation progresses, B lymphocytes produce antibodies against bacterial antigens.
Formation of antigen-antibody complexes amplifies phagocytosis by neutrophils, monocytes, and macrophages, a process called opsonization. Symptoms of inflammation
Redness and warmth due to histamine stimulated vasodilation
Swelling – vasodilation
Pain – release of PGE2
Pus - phagocytosis

21. Infiltration of an inflamed site by leukocytes

22. FUNCTIONS OF B-LYMPHOCYTES

23. B Lymphocytes Become Plasma & Memory Cells
B cell displays Ab on its surface
Antigen binds to Ab
Causes clones to form
Clones that produce antibodies are called plasma cells
Clones also form memory cells

24. Antibodies (Immunoglobulins)
Five classes:
IgG (induced in secondary response)
IgA, found in mother’s milk, saliva, intestinal mucosa
IgM, secreted during primary response
IgD, unknown
IgE, responsible for allergies

25. Antibodies bind to antigens on bacteria

26. Antibody Structure
Y-shaped protein; heavy chains and light chains held together by S-S bonds.
variable and constant regions
Antigen binding sites

27. An antibody is a receptor for an antigen
B lymphocytes have antibodies on the plasma membranes that are receptors for antigens. When the antigen binds to the antibody, the B cell is stimulated to divide and produce more antibodies

28. Diversity of Antibodies
Mechanisms for antibody diversity
A large percentage of our genetic code is dedicated to making antibodies. Some genes code for light chains and some for heavy chains
Antigen-independent genetic recombination in the bone marrow – different combinations of light and heavy chains, gene recombinations
Antigen-dependent cell division of lymphocytes in secondary lymphoid organs, somatic hypermutation, class switch recombination

29. VDJ Recombination