The Immune System Dr. Ammar ALMOFTI

Anatomy of the Immune system

Leukocytes

Granulocytes

NeutrophilsEosinophilsbasophils

Agranulocytes

Monocyteslymphocytes

Lymphoid tissues

Neutrophils Eosinophils Monocytes

Macrophages Dendritic cells

Phagocytes

50 ~ 80 % of all leukocytes.

An elevation in the number of neutrophils in blood is used clinically as a determinant of infection.

Neutrophils release cytokines.

Neutrophils

1 ~ 4 % of all leukocytes

Release toxic substances against parasites.

Eosinophils

2 ~ 8 % of all leukocytes.

Monocytes in blood can be developed into Macrophages in tissues.

Eg:◦ Microglia : Nervous tissue◦ Kupffer cells : Liver◦ Histiocytes: connective tissue

Monocytes in blood

Dendritic cells: ◦ activate T-cells.◦ they are formed in bone marrow from

hematopoietic stem cells

One Additional phagocytic cell

secrete chemical mediators (Histamine…) in inflammation and allergic reaction.

( < 1% of all leukocytes)

Release toxic substances against larger parasites.

Basophils

Secrete histamine and other substances.

They are found in skin and mucosal epithelial tissue.

They are formed in bone marrow from hematopoietic stem cells

Mast cells

Provide:◦ Diversity◦ Specificity◦ Memory◦ Distinguish between self nonself

Lymphocytes Types:◦ B- Lymphocytes◦ T- Lymphocytes◦ Null cells

Lymphocytes

Contact antigens and develop to plasma cells.

Plasma cells secrete antibodies (Immunoglobulins) that mark Ags only.

B-Lymphocytes

Contact infected, mutant and transplanted cells and develop to cytotoxic T-cells.

They kill abnormal cells by secreting perforines; molecules form pores in the membrane causing burst.

T-Lymphocytes

No cell membrane component.

Mostly called Natural Killers (NK).

Contact virus infected cells and kill them.

Null cells

1. Central Lymphoid tissues1. Bone marrow.2. Thymus

2. Peripheral lymphoid tissues1. Spleen.2. Lymph nodes3. Tonsils4. Adenoids5. Appendix6. Lymph nodules of the gastrointestinal tract.

Lymphoid Tissues

Spleen: filter blood .

Lymph nodes: filter lymph.

Tonsils and adenoids: filter inhaled particles.

Appendix, lymph nodules and Peyer’s patches: filter substanses in ingested food and water.

Filteration

1. Nonspecific defenses:1. Physical barriers: skin (sebaceous glands,

sebum)2. Inflammation3. Interferons4. Complement system

2. Specific defenses

Organization of Body’s Defenses

1. Phagocytosis by nearby macrophages.

2. Dilation and permeability of capillary: induced by histamine released by mast cells (basophils) -> redness, swelling, heat, pain.

3. Containment of foreign matter: ◦ heparin suspends blood clotting temporarily.◦ Access of leukocytes to injured area.◦ Clot formation.

4. Leukocyte migration and proliferation after injury.

5. Continued clearing of infection by recruited leukocytes.

Inflammation

Neutrophils: 1 hour after injury accumulate.

Monocytes: 10 hours after injury accumulate and develop.

Transit regulation of leukocytes:1. Margination.2. Diapedesis.3. Attachment.4. Chemotaxis.

Cont.

1. Attachment.2. Internalization.3. Degradation.4. Exocytosis.

Steps of Phagocytosis

Attachment is enhanced by opsonins.

Opsonins are proteins (including antibodies) that bind tightly to the foreign material and make it easier for phagocytosis.

Opsonization for attachment

1. Interleukin-1 (IL-1).2. Interleukin-6 (IL-6).3. Tumor necrosis factor – alpha (TNF- α).

Cytokines secreted by macrophages

1. Synthesis of more adhesion molecules by blood vessel endothelial cells.

2. Release of more neutrophils from bone marrow.3. Action on the hypothalamus to raise body

temperature by releasing prostaglandins.4. Stimulation of liver cells to produce acute phase

proteins, antibacterial proteins such as C-reactive protein which acts as an opsonin.

5. IL-1 helps in proliferation and differentiation of B and T lymphocytes.

Functions of cytokines

Interferons are a group of proteins interfere with virus replication.

Interferon-α and Interferon-β are secreted from virus-infected cells and their function is to induce resistance to the surrounding cells.

Interferon-γ is secreted by active T cells and NK cells. Its function is to inhibit viral replication, enhance phagocytosis, boost antibody production, activate NK and cytotoxic T cells, finally suppress growth of tumor.

Interferons

Its so named because it completes the actions of specific antibodies, but this system acts in the absence of antibodies.

The system consists of about 30 plasma proteins as a cascade of activation steps to destroy invading microorganisms by development of a membrane attack complex (MAC) which forms a pore in bacterial membrane and so bacteria will burst.

The Complement System

1. Some complement proteins act in chemotaxis, guiding phagocytes into the area.

2. Others bind to nearby mast cells and induce them to release histamine.

3. One specific protein, called C3b, coats bacterial surfaces were it acts as an opsonin.

Other functions of complement system

It is a specific immune response generated by B lymphocytes and conferred by antibodies that circulate in the blood and lymph.

B lymphocytes proliferate and develop into plasma cells and memory B cells. The plasma cells secrete antibodies.

Humoral Immunity

It is the reaction of certain types of T lymphocytes to kill abnormal or infected body cells.

T lymphocytes proliferate and develop into cytotoxic T cells and memory T cells. The cytotoxic T cells kill abnormal or infected body cells.

Cell-Mediated Immunity

When a person is first exposed to an antigen.

The B cells and T cells proliferate and

develop into effector cells and memory cells (clonal selection).

This reaction takes place about 10-17 days after exposure to the antigen.

Primary Immune Response

When a person is subsequently exposed to the same antigen.

It is faster; only 2-7 days. Memory cells quickly proliferate and differentiate into effector cells and again memory cells.

Greater in magnitude.

More prolonged than primary response.

Secondary Immune Response

Helper T cells sometimes influence B cell activation when contact antigens by secreting cytokines (including IL-2). In this case, antigens are called T-dependent antigens.

Some antigens do not need helper T cells. They are called T-independent antigens. In this case, B cells do not develop to memory

B cells and so repeated exposures to the same antigen always cause primary response.

Important Note

IgG IgE IgM IgD IgA

All Igs neutralize and agglutinate antigens

Classes of Antibodies

The most common in the blood produced in secondary responses.

Crosses placenta, so it is important for fetus and newborns.

Other functions of IgG: IgG activates complement. Opsonizes antigens. Enhances NK cell activity.

IgG

Involved in allergies

Binds to mast cells and basophils, causing them to release histamine.

IgE

The most common produced in the primary response.

Activates complement.

IgM

It crosses epithelial cells and it is present in breast milk, so it is important in immunity in newborns.

IgA

1. Helper T cells.2. Cytotoxic T cells.3. Suppressor T cells.

Suppressor T cells are not well-understood.

T lymphocytes

Operate indirectly.

Secrete cytokines to activate B cells, T cells including helper T cells themselves.

Secrete cytokines to activate macrophages and NK cells

Helper T cells

Operate directly.

They kill cells infected by viruses.

They kill abnormal cells (like cancer cells).

Cytotoxic T Cells

TCRs detect antigen only when antigen is associated with molecules called MHC (Major HistoCompatibility).

MHC molecules first bind to antigen (or fragment) within a cell body and then transport it to the surface to be detected by T cells. This process is called antigen presentation.

T cell Receptor (TCRs)

MHC molecules in human are called HLA molecules (human leukocyte antigens).

They are varied enough to various complex antigens but unique to each person.

So, each person has different HLA molecules to recognize a different portion of the antigen.

This diversity of HLA molecules is adaptive to the survival of the human species as a whole.

MHC molecules

1) Class I MHC molecules: are found on the surface of all nucleated cells (every cell of the body).

2) Class II MHC molecules: are found on the surface of some specialized cells as:

o macrophages and dendritic cells.o activated B cells.

Classes of MHC molecules

Class I MHC molecules capture fragments of antigen within an infected cell and transport them to the surface.

A cytotoxic T cell then binds to the infected cell through its TCR and CD8. This cytotoxic T cell is called CD8 cell.

MHC-I molecules & Antigen Presentation

CD8 cells kill virus-infected cells by releasing perforins.

CD8 cells release fragmentins (proteins enter through the pores and cause apoptosis to the infected cells).

CD8 cells kill tumor cells after binding of their TCRs to the distinctive tumor antigens presented by class I molecules existing on tumor cells.

DOES TUMOR INHIBIT (CLASS-I)PRODUCTION?

How do CD8 cells kill?

Class II MHC molecules capture fragments of antigen engulfed by a macrophage and transport them to the surface.

A Helper T cell then binds to the presenting cell through TCR and CD4. This helper T cell is called CD4 cell.

CD4 cells do not kill the antigen-presenting cell but secrete cytokines to activate other immune cells.

MHC-II molecules & antigen presentation

It is called also vaccination.

A safe form of a microorganism (or a collection of its components) is introduced into the body and then stimulates immune response and immunological memory.

It could be artificial or natural after real infection.

Immunization

Both artificial and natural immunization confer a type of protection referred to as active immunity.

Because it depends on the immune system to mount a response.

Active Immunity

Ready-made antibodies to a particular antigen can also be introduced into the body to provide a protection called passive immunity.

Can passive immunity be natural? IgG-IgA?

Passive Immunity

It is called hypersensitivity reaction. It is exaggerated response to certain allergens.

IgE is the most involved antibody.

IgE is produced highly and causes hay fever in restricted area when an individual responds to pollen.

Allergy

It is a life-threatening reaction to injected or ingested allergens.

Widespread degranulation of mast cels. Dilation of peripheral blood vessels. Drop in total peripheral resistance. Drop in pressure. Death may occur within a few minutes.

Anaphylactic shock

Injection of epinephrine (adrenaline) raises blood pressure back toward normal levels.

END

Management of Allergic shock