1. Human Biology Immune system
Senior Lecturer
Talib F. Abbas
Collage of Pharmacy
University of Muthana

2. The Immune System
The immune system identifies specific foreign agents, contains and attacks them. The word we use for foreign agents (anything that is non-self) is antigen. Every cell has antigens; antigens are markers on the surface of cells that the immune system can recognize. Self antigens are antigens in individual to which the immune system is tolerant (the immune system does not try to attach).

4. Acquired immunity 
The Acquired immunity is extremely specific; the body produces antibodies that work against a specific antigen. Ex. The antibodies that kill the polio virus will not affect any other organism. You make antibodies in response to every antigen that you come into contact. The antigen is usually of sufficient size to contain a specific marker that triggers antibody production. Small substances that can't be recognized by the immune system are called haptens; when join with a protein the immune system can recognize them. Also it is very important to remember that the immune system can distinguish between self and non-self.

5. Primary versus Secondary Immune Response
The Primary Immune:
The first contact with antigen.
Take time ( 2 weeks)
IgM is the main antibodies
The secondary Immune :
The second contact with antigen.
Less time ( 3,4 second)
IgG and IgA is the main antibodies
Titers of antibody refer to the amount of antibody you find in the blood.

6. Adaptive or Specific Immune System
History : experiments in the late 1800s found that there were protective factors in the blood that defended against future infection by the same pathogen
a. protective factors are proteins called antibodies
b. these factors could be transferred to other organisms that were not exposed to the antigen
2. important findings about the adaptive immune response
a. antigen-specific
b. systemic
c. has “memory”

8. General Characteristics
Specific so that it can eliminate with equal precision almost any type of pathogen
2. Functional System
a. can eliminate specific foreign substances as well as abnormal body cells
b. can magnify the inflammatory response
i. responsible for most complement activation
3. Must be primed by an initial exposure to a specific foreign substance called an antigen
a. takes time

9. General Characteristics
Two branches of adaptive immunity
1. Humoral immunity or antibody-mediated immunity consists of antibodies circulating in the fluids of the body
a. produced by lymphocytes or their offspring
2. Cellular or cell-mediated immunity – lymphocytes themselves
a. Targets – virus or parasite-infected tissue cells, cancer cells, foreign graft cells
b. can act directly by lysing foreign cells or indirectly by releasing chemicals that enhance the inflammatory response or activate other lymphocytes or macrophages.

10. classes of lymphocytes
There are three major classes of lymphocytes
B-cells (10-20%) that ultimately differentiate to plasma cell
Humeral immunity is important in eliminating bacteria, neutralizing bacterial toxins, and preventing viral reinfection and hypersensitivity.
T-cells (60%) which differentiate along two lines
CD4 cells (helper cells)
CD8 cells (suppressor cells or cytotoxic T-cells)
Null cells (natural killer cells)
These cells can attack any antigen but must be directed by the T cell.

11. B-cells
In order for a B cell to differentiate into a plasma cell, it must de introduced to the antigen by the macrophage.
The macrophages are also called an antigen-presenting cell (APC). There are other APCs in the body such as the Langerhans’ cells in the skin and Dendritic cells in the lymph nodes
The production of antibody is usually under the influence of T helper cells. Thus when the T cells are not working properly, antibody production is effected.

12. ANTIBODIES OR IMMUNOGLOBULINS
Made of four protein chains, two heavy and two light.
Heavy chains identify the class of antibody (G, A, M, E or D).
Each chain has a constant region (C) and a variable (V) region.
Antigen reacts to the variable region.
The variable region can change in response to the antigen.
The macrophage introduces antigen to the variable region.

13. TYPES OF ANTIBODY IgM, (Mu)
First immunoglobulin to appear after exposure to antigen.
Indicates new infection.
Activates Complement
Big, can not cross placenta
Naturally occurring IgMs against A and B blood antigens

14. TYPES OF ANTIBODY IgG, (gammaglobulin) Most common
Small in molecular weight
Only produced in large amount during the secondary immune response.
(The secondary immune response is after immunological memory has taken place)
The more exposure to antigen, the more IgG.
Crosses the placenta.
Acts as an opsin (coats the bacteria so it is easily phagocytized.

15. TYPES OF ANTIBODY IgA, (alpha)
Found in secretions (mucous, milk, eyes, sweat, etc.).
Offers primary protection
Is protected from digestive enzymes.
Is proceeded by IgM.

16. TYPES OF ANTIBODY IgE, (epsilon) Only a small amount in serum.
Usually found in tissue attached to Mast cells.
Mediates allergic reactions.
Important in fighting parasites.
Systemic release can cause anaphylactic shock.

17. TYPES OF ANTIBODY IgD, (delta) Not released into serum or body fluids.
Found on B-cell.
Helps the B cell become antigentically active.

18.  T-LYMPHOCYTES
Also known as thymus derived lymphocytes or cellular immunity.
In the blood, T-cells make up 60-70% of peripheral lymphocytes.
Also found in lymph nodes and spleen.
Each T-cell is programmed to recognize a specific cell-bound antigen by means of an antigen-specific receptor site on the T-cell. It is like antibody that is attached to a cell Vs antibody that circulates freely (as in humeral immunity).

19.  T-LYMPHOCYTES
All T-cells have CD3 sites. CD3 sites do not bind antigen, but they send a signal into the nucleus of the cell after antigen is bound to the cell. The CD3 cite is just one of many T-cell receptor cites (TCR).
T-cells have a number of other receptor sites that enable scientist to distinguish different types of T-cell with different functions. The two you have heard the most about are CD4 and CD8, but there are many more TRCs.

20.  T-LYMPHOCYTES
CD4 (helper, the conductor of the orchestra, the master regulator) is expressed on about 60% of mature CD3 T-cells. When antigen if presented to the CD4 cell, the CD4 site binds to the antigen presenting cell (class II major histocompatibility complex (MHC)), often a macrophage. CD4 cells secrete cytokines that influence every type of cell in the immune system (other T-cell, B-cell, macrophages, and natural killer cells). There are two major subsets of CD4 cells that secrete different types of cytokines.
T1-facilitaes delayed hypersensitivity, macrophage activation, and IgG antibodies.
T2-facilitaes other classes of antibodies
CD8 (cytotoxic) expressed on about 30% of T-cells. CD8 T-cells bind to class I MHC molecules.

21.  T-LYMPHOCYTES
Secrete cytokines similar to the T1 type but they mostly act as cytotoxic cells.
T-cells need two signals for activation. Signal 1 occurs when TCR comes together with MHC bound antigen. Coreceptors CD4 and CD8 enhance the signal.
Signal 2 occurs when another site (CD28) on the T-cell is activated.
When there is NO signal 2, T cells undergo apoptosis.

22. NATURAL KILLER CELLS (NK)
10-15% of blood lymphocytes. Do not have T-cell receptors or surface immunoglobulin. Have the ability to lyse many tumor cells, virally infected cells without previous sensitization. CD16 and CD56 are surface markers that are used to identify NK cells. NK cells have the ability to lyse antigen coated target cells (antibody-dependent cell-mediated cytotoxicity). NK cells do not kill normal cells because all nucleated normal cells express class I MHC and these cells send inhibitory impulses to the NK. If the cells in changed by a virus or a tumor, the inhibitory signals are blocked and the NK cells begin the attack.

23. CYTOKINES (messenger molecules) also called lymphokines
Can be produced by different types of cells.
Wide spectrum of effects
Many different types
Five categories
Cytokines that mediate natural immunity, protect against viruses
Cytokines that regulate lymphocyte growth, activation and differentiation.
Cytokines that activate inflammatory cells.
Cytokines that effect lymphocyte movement. Also called chemokines.
Cytokines that stimulate hematopoiesis. Colony-stimulating factors..

24. MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)
In humans also known as HUMAN LYMPHOCYTE ANTIGEN (HLA). MHC is really a group of genes that code for antigens. All cells contain antigens. Because the antigens on your cells are slightly different from the antigens on someone else’s cells, you are distinctly different from everyone else in the world. The immune system has to be able to determine between you and someone else; it has to recognize self from non-self. In order to understand graft rejection and autoimmune diseases, you have to know something about the MHC.

25.   Autoimmune disease
A- Multiple sclerosis (MS) – destroys the white matter of the brain and spinal cord
b. Myasthenia gravis – impairs communication between nerves and skeletal muscle
c. Graves’ disease – prompts the thyroid gland to produce excessive amounts of thyroxine
d. Type I diabetes mellitus – destroys pancreatic beta cells resulting in a deficit of insulin and the inability to use carbohydrates
e. systemic lupus erythematosus (SLE) – systemic disease that affects the kidneys, heart, lungs, and skin.
f. Glomerulonephritis – severe impairment of renal function
g. rheumatoid arthritis (RA) – systematically destroys joints