Immunology

• Immunity and Immunology

• Related lingoes

• Types of Immunity

• Lymphoid organs

• Types of Immune responses

• Cells of Immune System

TopicsTopics

What is Immunity????

( Latin: Immunis = "to make safe“)

The resistance of the host body towards the pathogenic microbe and its toxin is

called as Immunity!!!!!

Immunology

•It is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms.• It deals with–

the physiological functioning of the immune system in states of both health and disease;

malfunctions of the immune system in immunological disorders;

the physical, chemical and physiological characteristics of the components of the immune

system in vitro, in situ, and in vivo. 

Father of Immunology

Edward Jenner!!!!!He was an English country doctor who pioneered vaccination. Jenner's discovery in 1796 that inoculation with cowpox gave immunity to smallpox, was an immense medical breakthrough and has saved countless lives.

Related Lingoes

Pathogen vs. Antigen

• Pathogen- Microorganism that can cause disease.

• Antigen- (Foreign substances; Non-self materials) It is not an organism, but rather, a molecule attached to a foreign organism that activates an antibody response.Organic compounds with high molecular weight.

• Interferons – Polypeptides synthesized upon viral infection of a cell and act as a messengers that protect normal cells in the vicinity of infected cells from becoming infected.

3 major categories- IFN- alpha , beta, gamma.• Cytokine/Lymphokine/Chemokine – Growth

factors specialized to control cell division and differentiation in the immune system.

• TCR(T cell receptor) – Membrane bound antigen receptor on T-cells that can only recognize the antigen being presented by a cell membrane bound protein called MHC (Major histocompatibility complex).

• CD- stands for cluster of differentiation, which indicates a defined subset of cellular surface receptors (epitopes) that identify cell type and stage of differentiation, and which are recognized by antibodies.More than 250 identified clusters, coating the surface of B lymphocytes and T lymphocytes.

• Monoclonal antibodies – are homogenous immunological reagents of defined specificity ,so that these can be utilized for diagnosis and screening with ease and certainty .

Complement System• Paul Ehrlich coined the term and defined it as

“the activity of blood serum that completes the action of the antibody”.

• It is a major triggered enzyme plasma system. • It coats microbes with molecules that make them

more susceptible to engulfment by phagocytes.• Affects both innate and adaptive immunity.• Based on recognition of pathogen-associated

molecular patterns or PAMPs.

• Vascular permeability mediators increase the permeability of the capillaries to allow more plasma and complement fluid to flow to the site of infection.

• The principle actors in this system are 11 proteins designated C1 to C9.

Immune systemImmune system

Innate (non-specific) immunity

• Anatomic barriers (Skin,mucous membranes)

• Physological barriers (temperature, pH)

• Phagocytic Barriers (cells that eat invaders)

• Inflammatory barriers (redness, swelling, heat and pain)

Adaptive (specific) immunity

• Antigen specificity

• Diversity

• Immunological memory

• Self/nonself recognition

Fluid systems in body

There are two main fluid systems in the body:

•blood

•lymph.

• Blood - The fluid consisting of plasma, blood cells, and platelets that is circulated by the heart through the vertebrate vascular system, carrying oxygen and nutrients to and waste materials away from all body tissues.

• Lymph – Blood – RBCs….. Prominent among the constituents of lymph

are lymphocytes and macrophages, the primary cells of the immune system with which the body defends itself from invasion by foreign microorganisms.

Lymph is conveyed from the tissues to the venous bloodstream via the lymphatic vessels. On the way, it is filtered through the lymphatic organs (spleen and thymus) and lymph nodes.

Lymphoid Organs

Lymphoid Organs

Primary Provide appropriate

environment for lymphocyte maturation.

Thymus and Bone marrow.

Secondary Trap antigens and make

it available for mature lymphocytes.

Lymph nodes, and lymphoid follicles in tonsils, Peyer's patches, spleen, adenoids,etc. associated with the mucosa-associated lymphoid tissue (MALT).

Thymus• Situated in the center of the

upper chest just behind the sternum.

• Bilobed structure.• Zonated into many lobules,

seperated from each other by connective tissue strands called trabeculae.

• Each lobule consists of inner medulla and outer cortex.

•Develops in embryonic life as an outgrowth of a structure known as the 3rd branchial pouch invaded by lymphoid stem cells.

•Thymocytes (T-cells) mature in medulla.

•The majority of lymphocyte production happens early in life, so the thymus gland deteriorates with age. In youth, the thymus will reach the size of an apple, but it is reduced to the size of a small marble in the elderly.

Bone Marrow• Bone marrow is the flexible tissue

found in the hollow interior of bones. In adults, marrow in large bones produces new blood cells. It constitutes 4% of total body weight, i.e. approximately 2.6 kg (5.7 lbs.) in adults.

• Marrow types-There are two types of bone marrow: red marrow (consisting mainly of hematopoietic tissue) and yellow marrow (consisting mainly of fat cells). Red blood cells, platelets and most white blood cells arise in red marrow. Both types of bone marrow contain numerous blood vessels and capillaries.

• Hematopoietic stem cells give rise to the three classes of blood cells that are found in the circulation: white blood cells (leukocytes), red blood cells (erythrocytes), and platelets (thrombocytes).

• Mesenchymal stem cells are found arrayed around the central sinus in the bone marrow. They have the capability to differentiate into osteoblasts, chondrocytes, myocytes, and many other types of cells. They also function as "gatekeeper" cells of the bone marrow.

Immune system Immune system express their specific express their specific activity in two main activity in two main

ways………….ways………….

Humoral immune response

Lymphocyte produce antibodies in response

to certain specific antigens

Antibody binds to antigen and destroy by variety of mechanism

B-cells are responsible!

Cellular immune response

Lymphocyte and Macrophages cooperate

Direct Destruction of pathogenic organisms

T-cells are responsible!

Cells of Immune system

Mononuclear Phagocytes

•Consists of monocytes and macrophages. •Monocytes circulate in the bloodstream for 8 hrs., during this time they enlarge and migrate into tissue spaces to differentiate into macrophages.•Activity is enhanced by Cytokines.•Activated macrophages serve as antigen presenting cells by expressing higher level of ClassII MHC.•Two types- Fixed and Free/ Wandering Macrophages.

Fixed macrophages-

• Kupffer cells – Liver

• Alveolar macrophages – Lung

• Histiocytes – Connective tissue

• Osteoclasts – Bone

• Mesangial cells – Kidney

• Microglial cells – Brain

Phagocytosis

Types of Mononuclear Phagocytes

1.Granulocytes• Neutrophil- Multilobed

nucleus; phagocytic.• Eosinophil - Resemble

neutrophils; defense against Parasitic organisms; phagocytic

• Basophil – Non-phagocytic; release pharmacologically active mediators found in their granules leading to allergies.

2. Agranulocytes

• Lymphocytes

• Monocytes

Monocytes• Largest corpuscle of blood.

• There are at least three types of monocytes in human blood :

• a) the classical monocyte : CD14++ CD16- monocyte.

• b) the non-classical monocyte : CD14+CD16++ monocyte.

• c) the intermediate monocyte CD14++CD16+ monocytes.

Lymphocytes

• Chief cells of immune system.

• In blood= 20-40% and in lymph=99%.

• Continuously circulate in blood and lymph.

• Capable of migrating into the tissue spaces and lymphoid organs.

• Non-phagocytic, motile cells.

• Three main forms:- T-cells, B-cells, Null cells.

B or T cells that have not come in contact with antigen =Naïve/Resting/Unprunned cells.

Lymphocyte (Naïve cells)

Lymphoblasts

Effector Cells [Plasma (B-cell); TH(T-cells)]

or

Memory Cells

T-cellsT-cells• Derive their name Thymocytes from the

site of maturation i.e. thymus.

• Arise from the hematopoietic stem cells in the bone marrow and later migrate to the thymus gland to mature.

• Three types–

1.T-Helper (TH) 2.T- Cytotoxic(TC)

3.T-Suppressor(Ts)

1. T-Helper (TH) - Display CD4 glycoprotein

Recognise and interact with the antigen presented on ClassII MHC molecule on APC.

TH gets activated and undergoes extensive proliferation

Daughter cells called Effector cells produced

• Specific Cytokines secreted and generate specific immune response

• TH1 Response TH2 Response

Tc ,Macrophages B cells activation activation

2. T-Cytotoxic cells –

• Activated under the influence of cytokines produced by TH cells and antigen interaction presented on Class I MHC.

• Differentiation into an effector cells CTLs/ Cytotoxic T Lymphocytes.

• Possess Cytotoxic activity.

3. T-Suppressor cells –

• Play important role in suppression of humoral and cell-mediated immune response

• But not isolated so far.

B-cellsB-cells• Derived their name from the site of

maturation in birds Bursa of Fabricius.

• Mature in Bone marrow

• Leave bone marrow by expressing a unique antigen binding receptor mIgM.

Naïve B cells + Antigen

Effector B cells Memory B cells

or

Plasma cells

Immunoglobulins (Ig)• Antibodies, also called immunoglobulins or

Igs constitute the gamma globulin part of the blood proteins.

• Soluble proteins secreted by the plasma offspring (clones) B cells.

• The antibodies inactivate antigens by

(a) complement fixation (proteins attach to antigen surface and cause holes to form, i.e., cell lysis), (b) neutralization (binding to specific sites to prevent attachment),

• (c) agglutination (clumping), • (d) precipitation (forcing insolubility and settling out of

solution).

•The upper part or Fab (antigen binding) portion of the antibody molecule attaches to specific proteins [called epitopes] on the antigen. Thus antibody recognizes the epitope and not the entire antigen.

•The Fc region is crystallizable and is responsible for effector functions, i.e., the end to which immune cells can attach.

• Constituents of gamma globulin are: IgG--76%,

IgA--15%,

IgM--8%,

IgD--1%, and

IgE--0.002%

-- IgM is the dominant antibody produced in primary immune responses, First antibody secreted; promotes agglutination and precipitation reactions and activates complement.

-- IgG is the only antibody that can cross the placental barrier and responsible for the 3-6 month immune protection of infants; Major antibody secreted during the secondary response;neutralises antigens and promotes phagocytosis and Activates complement.

-- IgD is present only on surface of B cells, serve as antigen receptor and plays an important role in lymphocyte differentiation.

-- IgA Most abundant form in body secretions; high density in MALT.

-- IgE Fc binds to mast cells and basophils; allergen binding to V regions promotes the release of mediators, which triggers allergic reactions.

Null CellsNull Cells• Cytotoxic.• NK cells belong to this group.• Small granules in their cytoplasm contain

proteins such as perforin and proteases known as granzymes.

• Upon release in close proximity to a cell slated for killing, perforin forms pores in the cell membrane of the target cell, creating an aqueous channel through which the granzymes and associated molecules can enter, inducing either apoptosis or osmotic cell lysis.

• NK cells are activated in response to interferons or macrophage-derived cytokines.

Dendritic cells • Dendritic cells are covered with a maze

of membranous processes that look like nerve cell dendrites.

• Most of them are highly efficient antigen presenting cells.

• There are four basic types: Langerhans cells, interstitial dendritic cells, interdigitating dendritic cells, and circulating dendritic cells.

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