Dr. Chhaya Sawant

Immunological Disorders

Our bodies are constantly at war and are under Our bodies are constantly at war and are under attack,attack, 24-hours a day from infection and toxins. 24-hours a day from infection and toxins.

Crossing the barriersCrossing the barriers

•skin

•mucosal membranes

If physical & chemical barrier is broken If physical & chemical barrier is broken down by:down by:- trauma - as result of infection on surface

invading microorganisms can enter body, invading microorganisms can enter body, blood stream & lymphatic system.blood stream & lymphatic system.

Inside the body, pathogens can find a Inside the body, pathogens can find a niche in body tissue to multiply and niche in body tissue to multiply and causes diseases.causes diseases.

That we survive at all, is due to That we survive at all, is due to our immune system. our immune system.

- a network of chemicals & cells - a network of chemicals & cells that protect the body.that protect the body.

In humans, the immune system begins to develop in the embryo. The immune system starts with hematopoietic (from Greek, "blood-making") stem cells.

What is Immunity?

The immune system is localized in several parts of the body

Immune cells develop in the primary organs - bone marrow and thymus (yellow)

Immune responses occur in the secondary organs (blue)

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ANATOMY OF THE IMMUNE SYSTEM• Thymus – glandular organ near the heart – where T cells learn

their jobs

• Bone marrow – blood-producing tissue located inside certain bones– blood stem cells give rise to all of the different types of blood cells

• Spleen – serves as a filter for the blood– removes old and damaged red blood cells – removes infectious agents and uses them to activate cells called

lymphocytes

• Lymph nodes – small organs that filter out dead cells, antigens, and other “stuff” to present to lymphocytes

• Lymphatic vessels – collect fluid (lymph) that has “leaked” out from the blood into the tissues and returns it to circulation

Humans have three types of immunity

– Innate, non-specific

– Adaptive• Humoral• Cell-mediated

– Helper T

– Cytotoxic T

– Passive

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YOUR ACTIVE IMMUNE DEFENSES

Innate Immunity- invariant (generalized)- early, limited specificity- the first line of defense

Adaptive Immunity- variable (custom)- later, highly specific- ‘‘remembers’’ infection

1. Barriers - skin, tears

2. Phagocytes - neutrophils, macrophages3. NK cells and mast cells

4. Complement and other proteins

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PASSIVE IMMUNITY

Antibodies (Y) are also found in breast milk.

The antibodies received through passive immunity last only several weeks.

While your immune system was developing, you were protected by immune defenses called antibodies. These antibodies traveled across the placenta from the maternal blood to the fetal blood.

Major Principles of Immunity• Elimination of many microbial agents through the

nonspecific protective mechanisms of the innate immune system

• Highly specific recognition of foreign antigens coupled with potent mechanisms for elimination of microbes bearing such antigens

• A vast universe of distinct antigenic specificities and a comparably vast capacity for the recognition of these antigens

• The capacity of the system to display immunologic memory

• Tolerance of self-antigens

Function of Immune System is PROTECTION against:

1. Bacteria

2. Virus

3. Fungus/ multicellular parasites

4. Cancer

5. Toxins

6. ( 5,000 daltons--protein/lipid/CHO/nucleic acids)

Normally our bodies are fit enough to Normally our bodies are fit enough to fight an infection with all the parts of fight an infection with all the parts of

our immune system.our immune system.

Sometimes we need help fighting infection.

B cells and T cells are the main types of lymphocytes.

B-Cells: stored and mature in spleenLymphocytes

LymphoidStem Cell

Y

YY

YYY

Y

Y

Y

Pre-B Cell

Plasma Cell

Pro-B Cell

MemoryB Cell

MatureB Cell

ImmatureB Cell

Antigen Dependent

ActivatedB Cell

Antigen Independent

Bone Marrow PeripheryBone Marrow Periphery

YIgM

IgM IgDAntigen

Primary Lymphoid Organ Secondary Lymphoid Organs

IgM

• secrete highly specific Ab to bind foreign substance (antigen: Ag), form Ab-Ag complex

• responsible for humoral response• perform antigen processing and presentation• differentiate into plasma cells (large Ab secretion)

Overview of B-Cell Development

T cells: stored & mature in thymus-migrate throughout the body-Helper Cells

Enhance T killer or B cell activity-Killer Cells Perform lysis (infected cells)Cell mediated immune response

-Supressor Cells Reduce/suppress immune activity May help prevent auto immune disease

Lymphocytes

ORGAN AND T-CELL DEVELOPMENT YOLK SAC

LIVER - (4 Weeks)

BONE MARROW - (4-5 Weeks )

THYMUS - (7-10 Weeks)

BLOOD LYMPH - (14 Weeks) SPLEEN - (16 Weeks) 

• Phagocytes include - Monocytes, which circulate in the blood; 

- Macrophages, which are found in tissues throughout the body; 

- Dendritic cells, which are more stationary, monitoring their environment from one spot such as the skin

- Neutrophils, cells that circulate in the blood but move into tissues when they are needed.

• Cytokines

2. Neutrophils (Phagocytes)- found throughout body, in blood - phagocytosis of Ab-Ag CX

3. Macrophages- throughout body, blood, lymphatics-phagocytose non-specifically (non Ab coated Ag)-phagocytose specifically Ab-Ag CX-have large number of lysosomes (degradative enzyme)-perform Ag processing and presentation-present Ag to T helper cell-secrete lymphokines/ cytokines to stimulate T helper

cells and immune activity

4. Natural Killer Cells- in blood throughout body-destroy cancer cells-stimulated by interferons

IgG, the major immunoglobulin in the blood, is also able to enter tissue spaces; cross placental barrier, fix complement, induce macrophage engulfment 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, fix complement, induce macrophage engulfment, primary immune response

Antibodies belong to a family of large protein molecules known as immunoglobulins. Different classes play different roles in the immune defense strategy.

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.

The complement system

A series of about 25 proteins that work to "complement" the work of antibodies in destroying bacteria.

ComplementSeries of enzymes which are sequentially

activated and result in lysis of cell membrane of infected cell of bacterium

Permeablizes membrane leaky

Complement binding and activation

~35 enzymes and factors involved in cascade

Activation of B Cells

Things That Can Go Wrong With the Immune System

Disorders of the immune system can be broken down into four main categories:

• Immunodeficiency disorders (primary or acquired)• Autoimmune disorders (in which the body's own immune system attacks

its own tissue as Foreign matter)• Allergic disorders (in which the immune system overreacts in response to

an antigen)• Cancers of the immune system

The immune response to an antigen is potentially a "two-edged sword“

May either protect or harm the host.