Introduction To clinical Immunology

Dr. Dalia Galal Hamouda

Definition

• Immunity: This is a protective or defense mechanism of our body, which leads us to a healthy life.

First line of defense First line of defense

Barriers to EntryBarriers to Entry•The skin is the main barrier preventing the entry of foreign organismsThe skin is the main barrier preventing the entry of foreign organisms

•Skin oils weaken or kill bacteria.Skin oils weaken or kill bacteria.

•Cilia lining the respiratory tract Cilia lining the respiratory tract trapped trapped mucus and particles to the throat to mucus and particles to the throat to be swallowedbe swallowed

•The low pH of the stomach kills microorganisms.The low pH of the stomach kills microorganisms.

•Tears wash the eyes.Tears wash the eyes.

•Saliva helps clean teeth, preventing dental caries.Saliva helps clean teeth, preventing dental caries.

•Urine flow prevents colonization of the urinary tract.Urine flow prevents colonization of the urinary tract.

•The normal bacterial colonists of the skin and gut prevent harmful The normal bacterial colonists of the skin and gut prevent harmful microorganisms from colonizing the areas.microorganisms from colonizing the areas.

• Inborn or innate immunity (non specific): 1. It is present at birth.2. This is our First Line Of Defense.3. It is generally effective against a variety of infections.

• Acquired (adaptive) or specific immunity: 1. It is not present at birth but generally acquired after

exposure to the infecting particles or cells.2. Specific for one type of infection

Second line of defenseSecond line of defense

Third line of defenseThird line of defense

Cells Involved in Immunity

Natural Natural

killerkiller

Denderitic cells Denderitic cells B cells B cells T cells T cells

Important components of innate immunityFactors that limit entry of microorganisms into the body

Factor Mode Of Action

-Keratin layer of intact skin -Acts as mechanical barrier-Lysozyme in tears and other secretions -Degrades peptidoglycan in bacteria cell wall -Respiratory cilia -Elevate mucus containing trapped organisms-Low pH in stomach and vagina; -Retards growth of microbes fatty acids in skin-Surface phagocytes -Ingest and destroy microbes (eg. alveolar macrophages)-Defensins (cationic peptides) -Create pores in microbial membrane-Normal flora of throat, colon -Occupy receptors which prevent and vagina colonization by pathogens

Important components of innate immunityFactors that limit growth of microorganisms within the body

• Natural killer cells• Neutrophils• Macrophages and dendritic

cells• Inferons• Complement

• Transferrin and lactoferrin

• Fever

• Inflammatory response • APOBEC3G (apolypoprotein is RNA

editing enzyme)

• Kill virus infected cells• Ingest and destroy microbes• Ingest and destroy microbes, and present

antigen to helper T-cells• Inhibit viral replication • C3b is an opsonin, membrane attack

complex creates holes in bacterial membranes

• Sequester iron required for bacterial growth

• Elevated temperature retards bacterial growth

• Limits spread of microbes• Causes hypermutation in retroviral DNA

and mRNA

B Lymphocytes and T lymphocytesB Lymphocytes and T lymphocytes

B lymphocytes (B cells) mature in the bone marrow.B lymphocytes have receptors (antibodies) attached to their surface which function to detect antigens.

There is only one specific kind of receptor on the surface of a lymphocyte. A single B lymphocyte can therefore detect only one kind of antigen. Our bodies have millions of different kinds of B lymphocytes.

T lymphocytes (T-cells) are lymphocytes that mature in the thymus.This type of immunity is used to fight cells such as cancer cells, virus-infected cells, single-celled fungi, parasites, and cells of an organ transplant.

Important components of adaptive immunity

B cells T cells

Major Functions Of T Cells and B cellsMajor Functions Of T Cells and B cells

Antibody-Mediated Immunity (B Cells)Antibody-Mediated Immunity (B Cells)

1) Host defense against infection1) Host defense against infection

2) (Opsonize bacteria, neutralize toxins 2) (Opsonize bacteria, neutralize toxins and viruses)and viruses)

3) Allergy (hypersensitivity) eg, hay fever 3) Allergy (hypersensitivity) eg, hay fever anaphylactic shockanaphylactic shock

4) Autoimmunity4) Autoimmunity

Cell Mediated ImmunityCell Mediated Immunity

1) Host defense against infection 1) Host defense against infection (especially M.tuberculosis, fungi (especially M.tuberculosis, fungi and virus infected cells)and virus infected cells)

2) Allergy (hypersensitivity )eg poison 2) Allergy (hypersensitivity )eg poison oakoak

3) Graft and tumor rejection3) Graft and tumor rejection

4) Regulation of antibody response 4) Regulation of antibody response (help and suppression)(help and suppression)

Antigens and AntibodiesAntigens and AntibodiesAntigens are molecules that stimulate antibodies which are capable of being recognized. They are usually a protein or carbohydrate chain. The body can recognize bacteria and viruses as being foreign because they have antigens on their surface which are different than the bodies "self" antigens.

Antibodies are proteins that protect against foreign invaders, either foreign molecules, viruses, or cells. Antibodies are produced by B lymphocytes..

Antibodies are Y-shaped molecules with a constant region and two binding sites that vary from one antibody to the next.

Antibodies fit together with and bind with antigens like a lock and key.

The body does not produce antibodies that bind to its own (self) antigens. But bound to foreign antigens.

• Cells, particles, or molecules that are marked with antibodies:

1. may be phagocytized (engulfed) by neutrophils or macrophages.

2. may agglutinate (clump together) because each antibody is capable of binding to two antigens. If the antigens are chemicals that are dissolved in the body fluids, the clumps of antibody-bound particles will precipitate. Antigens attached to cells will cause the cells to clump together. The clumps are then phagocytized.

3. may activate the complement system. The complement system is a system of blood proteins that enhances the elimination of foreign cells or particles.

• During our life, we will encounter over 1 million different antigens, so we need at least 1 million different antibodies, one for each kind of antigen.

• There are 5 different classes of antibodies (IgA, IgD, IgG, IgH, IgM). One class contains pentamers, another contains dimers.

Important features Of Innate and Acquired (adaptive) Immunity

Type of Immunity Specificity Effective immediately Improves Type of Immunity Specificity Effective immediately Improves Has Has

after exposure to After after exposure to After Exposure memoryExposure memory

microbemicrobe

Innate Innate Nonspecific Yes in No Nonspecific Yes in No No No

minutesminutes

Acquired Acquired Highly No--requires Yes Highly No--requires Yes Yes Yes

specific several daysspecific several days

before becomingbefore becoming

effective effective

Organs of the Immune System

1. Primary lymphoid organs Bone Marrow• Largest tissue of the body•Main source of hematopoietic cells.•Lymphocyte stem cells released from marrow and travel to primary lymphoid organs for maturation: T cells go to Thymus, B cells mature in bone marrow. Thymus•Ductless gland-like structure located beneath the sternum (breastbone).•Lymphocyte stem cells develop into T lymphocytes under the influence of thymic hormones.

2. Secondary lymphoid tissue

From the primary lymphoid organs, B and T lymphocytes migrate to the peripheral secondary lymphoid organs. 1) They encounter antigens and are transformed into an activated state. 2) They become effectors of the humoral or cell-mediated immunity.

Spleen1.It is the body's largest reservoir of mononuclear-phagocytic cells.2.Both T and B lymphocytes are present but they are segregated.3.The red pulp of the spleen consists of blood vessels lined with macrophages.4.White pulp contains lymphoid tissue.5.Also functions as a filter by removing effete cells from circulation.

Lymph nodes1.Located in several areas of the body, including the neck and those points where the arms and legs join the trunk of the body.2.They serve as a filter for the tissue fluid or lymph.3.Lymph is a collection of tissue fluid flowing from the limbs and tissues through the lymph nodes on its way to the blood stream.

Examples of other Secondary Lymphoid Tissue or organs

•Gut associated lymphoid tissue

•Tonsils

•Bronchus associated lymphoid tissue

•Mammary glands

•Salivary glands

Overview of the Immune Response