HUMAN DEFENCE MECHANISM

To build up the body & to fight against pathogens or foreign bodies, a defence mechanism is required.

There are 3 lines of defence. 1^st line of defence 2^nd line of defence 3^rd line of defence

The defense mechanism is of two types:

1. Non specific
2. Specific

NON SPECIFIC

The non specific defense system deals with the 1^st line of defense of the body. This does not require antibodies to fight with the invading microorganisms.

The non specific barrier consist of external & internal barrier.

The external barrier consists of  skin and mucosal membrane.

SKIN

The outermost layer of the skin is called stratum corneum which have dead cells present over it which are keratin rich and thus are impermeable to water and thus acts as a physical barrier .

It does not let the entry of the germs into the body via skin.

MUCOSAL MEMBRANE

The mucosal membrane is present where the direct contact of the body is not with the skin like the digestive system, the reproductive system.

The digestive system have mucosal membrane over it or the lining of mucosal membrane is present and thus acts as a internal barrier.

In digestive system

The mucus present in the buccal cavity helps to kill the microorganism that enters via mouth.

The acid secreted via stomach kills the microorganism and thus acts as an internal defense mechanism.

Bile have alkaline ph again helps in killing the bacteria which were able to survive in the acidic content of the stomach.

Thus at every step the fail safe mechanism of the body helps in fighting with the alien species.

In respiratory system

The nasal hairs present at the nasal cavity traps the germs and kill them, or through sneezing they are removed from the nasal cavity.

CHEMICAL BARRIER

The chemical barrier includes those specific organs which secrete enzymes  and thus acts as an internal barrier.

Eyes

The tears secreted by eyes contains lysozyme, lactoferin that is helpful in killing the harmful bacteria.

Mouth

Saliva  contains enzymes lysozymes that kills the harmful bacteria & some other microbes.

VAGINA

It secretes lactic acid thus making the environment bit acidic and thus kills the harmful bacteria & some other microbes.

Skin & mucus membrane sometimes due to any reason may not be able to defend the microorganism and thus lead to failure of 1^st line of defense and thus comes the 2^nd line of defense.

2^nd LINE OF DEFENSE SYSTEM

This is also known as internal defense.

These are carried out by WBCs, Inflammatory reactions, fever

AGRANULOCYTES

As the name suggest they do not have granules in their cytoplasm.

The nucleus do not have lobes

They are formed in the bone marrow.

MONOCYTES

Monocytes are largest of all the WBCs. The nucleus is large and eccentrically placed. They are motile and show phagocytic activity.The monocytes circulate in the blood and enlarges and migrate to the tissue and result in formation of the Macrophage.

The bacteria when enters the body, then the macrophage extends it pseudopodia around it and engulf the microorganism.

After engulfing it is known as phagosome.

The phagosome now fuses with the lysosome and known as phagolysosome

The lysosome digest the internal material and throw the waste through the process of exocytosis.

The macrophage membrane have receptors for certain class of antibody and thus the same process occurs but with the receptor mediated pathway.

KILLING MECHANISM

There are two ways of killing by the macrophage

1. Oxygen dependent killing mechanism

2. Oxygen independent killing mechanism

OXYGEN DEPENDENT KILLING MECHANISM

Activated phagocytosis produces reactive oxygen intermediate & reactive nitrogen intermediate.

During phagocytosis a process RESPIRATORY BURST occurs and this is toxic to microorganisms. This result in oxygen consumption & ATP generation.

NO also has antimicrobial activity, it combines with them and produces toxic substances that kill the microorganisms. When macrophages are activated with the bacteria, they begin to express high level of nitric oxide synthetase (NOS enzyme) that oxidases L-arginine to yield the following product.

OXYGEN INDEPENDENT KILLING MECHANISM

This can be achieved through lysozymes which are synthesised by the macrophages. Macrophages also release defensins which are cytotoxic peptides and they kill the bacteria.

Macrophages also have tumor necrosis factor α that also kills the bacteria.

The granulocytes are of 3 types

Neutrophil

Basophil

Eosinophil

NEUTROPHIL:

They have multilobed nucleus. They stain with both the dyes, acidic as well as basic dyes. They are phagocytic in nature. Occupies 50%-70% in the cell. The bacteria when enters the body, then the neutrophil extends it pseudopodia around it and engulf the microorganism.

After engulfing it is known as phagosome.

The phagosome now fuses with the lysosome and known as phagolysosome

The lysosome digest the internal material and throw the waste through the process of exocytosis.

EOSINOPHIL:

They have Bilobed nucleus. They stain with the Acidic dye (EOSIN RED). They are phagocytic in nature. Occupies 1%-3%. Play an important role against parasitic organism.

BASOPHIL

THEY HAVE LOBED NUCLEUS. They stain basic dyes. Less than 1% population. Responds to allergic reactions.

INFLAMMATION

Due to mechanical, physical or chemical injury of tissue there is another process initiated called  by tissue damage which is called as Inflammation.

The sign of inflammation are pain, redness, swelling and heat.

Pain results due to increase vascular diameter that results in the increased blood flow and results in  heat and redness.

As the damaged tissue area is occupied by the WBCs that results in the movement of the leucocytes to the injured tissue area and thus result in tenderness.

And all these results in edema i.e. swelling the inflammatory process thus activates a group of proteins known as Acute-phase proteins. The acute phase proteins are kinins and coagulation system i.e. clotting

The kinins acts on smooth muscles and results in muscle contractions.

The coagulation pathway results in blocking of the microorganism into the bloodstreams there is formation of clot.

SPECIFIC DEFENSE MECHANISM

This mechanism provides protection against specific alien particles and this mechanism is known as IMMUNE SYSTEM

The immune system consists of the Lymphocyte with acts as the 3^rd line of defense.

The lymphocytes are agranulocytes and are non-phagocytic in nature and non motile. The nucleus is large and round. The lymphocytes arise from the bone marrow and migrate to the lymphoid organs.

Organs of Immune System

PRIMARY LYMPHOID ORGAN

The organs where T cell and B cell develop.

THYMUS:

This is the site of T- cell development & maturation.Thymus of two lobes thus called as bilobed structure.The lobes have a partition called TRABECULAE which separates them.The lobules have two compartments. The outer compartment is called cortex & is surrounded by immature T-cells which are densely packed.The inner compartment  is called Medulla and contains less T-cells as compared to cortex.

BONE MARROW

This is the site of activation of B & T cells. The B-cells mature in bone marrow. The name B-Cells is derived from – Bursa of Fabricius which is present in birds, mammals do not have bursa of Fabricius. It contains antibody producing B cells. B lymphocytes have antigen specific receptors.

SECONDARY LYMPHOID ORGAN

• These are the main site for the production of antibodies.
• Have high trapping rate for the alien particles.

SPLEEN

Largest secondary lymphoid organ. It is the major organ of the body which results in synthesis of antibodies and also in the circulation of antibodies. Structure: red pulp and white pulp. Red pulp contains numerous RBCs & macrophages. White pulp contains numerous T-cells.

LYMPH NODES

Bean shape structure comprising of reticular network.

Contains macrophages & dendritic cells.Lymph node is divided into 3 parts- cortex, Para-cortex & medulla.Cortex being the outermost layer is rich in B- cells and has Follicular dendritic cells. Para-cortex being the middle part is rich in T- cells.Medulla the innermost is rich in lymphoid lineage cells.

MALT (MUCOSAL- ASSOCIATED LYMPHOID TISSUES)

• These are related with the mucous secreting areas like the linings of respiratory tract, digestive tract, salivary glands.

GALT (GUT ASSOCIATED LYMPHOID TISSUES)

• The lymphoid tissues that have associations with the gut are called GALT.

CALT (Cutaneous associated lymphoid tissue)

This is related with the skin. The skin have different layers out of which the outer layer called epidermis is composed of Keratinocytes and these keratinocytes secretes cytokinesis

• The B cell & T cell cannot be differentiated morphologically.
• The B cells & T cells  which have not yet interacted with antigen are referred to as Naïve cells. These are resting cells in the GO phase of the cell cycle.
• After that the cell enter into G1 phase of cell cycle and this occurs only when the lymphocyte interact with the antigens present in them.
• Diagram of cell cycle
• Lymphocyte  complete their cycle and get enlarge and are called Lymphoblast.
• Lymphoblast differentiate into effector cells & memory cells.
• All the cell arises from the hematopoietic stem cell which have the ability to self renew. The hematopoietic stem cells  are futher divided into two parts, myeloid progenitor and lymphoid progenitor. Progenitor cells are those which have lost the ability to self renew and thus they cannot be renewed again.

LYMPHOID PROGENITOR

B LYMPHOCYTE

Site of maturation is bone marrow in human beings. Have membrane receptor for antigens.The effector B cells eliminate antigens in various ways.The effector cells are called plasma cells.The memory B cells have life long immunity.B cells are capable to bind with soluble antigens.

T LYMPHOCYTE

Site of maturation is Thymus. Do not recognize free antigen.They are restricted to binding to the antigens which are displayed on self cells.T cells are of two types: T_H & T_C cells.TH cells are known as T Helper cells.T_C cells are known as T cytotoxic cells.The T_H cells have MHC II with CD4 binding.  The T_C cells have MHCI with CD8 binding.

NATURAL KILLER CELLS (NK CELLS)

• These cells do not express the membrane molecules.
• They response to Interferon. (glossary:these are signal proteins which are released by the host cells when any foreign body invades the host body)
• They response to tumors.
• Natural Killer cells express CD16

MYELOID PROGENITOR

RED BLOOD CELLS & PLASMA

• Develops in the bone marrow
• The function of RBC is to transport oxygen.
• The cytoplasm of RBC contains Hemoglobin.
• Mature red cells in humans are biconcave.
• Plasma is a part of blood and considers having the proteins of the blood.
• It protects the body from infection.
• RBCs take no part in defense.

White Blood Cells (WBCs)

Already explained in the topic of 2^nd line of defence.