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Immunity - Human Immune

System

IMMUNE SYSTEM
The immune system can be divided into innate and adaptive immunity.

Innate immunity is composed of defences that are always active, but that
cannot target aspecific invader and cannot maintain immunologic memory. It is
also called nonspecific immunity.

Adaptive immunity is composed of defences that take time to activate, but that
target aspecific invader and can maintain immunologic memory; also called
specific immunity.

The immune system is dispersed in the body.

Immune cells come from the bone marrow.

The spleen and lymph nodes are sites where immune responses can be
mounted, and inwhich B-cells are activated.

The thymus is the site of T-cell maturation.

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 Secondary lymphoid tissue provides the environment for the foreign or
(antigens) to interact with the lymphocytes. It is exemplified by the lymph
nodes, and the lymphoid follicles in tonsils, Peyer's
patches, spleen, adenoids, skin, etc. that are associated with the mucosa-
associated lymphoid tissue (MALT).

In the gastrointestinal wallthe appendix has mucosa resembling that of the

colon, but here it is heavily infiltrated with lymphocytes.

HEMATOPOIESIS

INNATE IMMUNE SYSTEM

Many of the nonspecific defenses are noncellular.

Innate immune system consists of two lines of defences.

First Line of Defence

The skin acts as a physical barrier and secretes antimicrobial compounds, like
defensins.

Mucus on mucous membranes traps pathogens; in the respiratory system, the

mucus ispropelled upward by cilia and can be swallowed or expelled.

Tears and saliva contain lysozyme, an antibacterial compound.

The stomach produces acid, killing most pathogens. Colonization of the gut
helps preventovergrowth by pathogenic bacteria through competition.

Second Line of Defence

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 It consists of phagocytes, antimicrobial proteins and inflammatory response.
1) Phagocytes

Macrophages ingest pathogens and present them on major histocompatibility

complex(MHC) molecules. They also secrete cytokines.

MHC class I (MHC-I) is present in all nucleated cells and displays

endogenous antigen(proteins from within the cell) to cytotoxic T-cells
(CD8 cells).

MHC class II (MHC-II) is present in professional antigen-presenting cells

(macrophages,dendritic cells, some B-cells, and certain activated
epithelial cells) and displaysexogenous antigen (proteins from outside the
cell) to helper T-cells (CD4 cells).

Dendritic cells are antigen-presenting cells in the skin.

Natural killer cells attack cells not presenting MHC molecules, including virally
infectedcells and cancer cells. They do not phagocytise the target cells.

Granulocytes include neutrophils, eosinophils, and basophils.

Neutrophilsingest bacteria, particularly opsonized bacteria (those marked

withantibodies). They can follow bacteria using chemotaxis.

Eosinophilsare used in allergic reactions and invasive parasitic infections.

They releasehistamine, causing an inflammatory response.

Basophilsare used in allergic reactions. Mast cells are related cells found
in the skin.

2) Antimicrobial proteins

Blood and interstitial fluids contain three main types of antimicrobial proteins that
discourage microbial growth.

Interferons (IFN's): Lymphocytes, macrophages and fibroblasts infected with

viruses produce proteins called interferons. Once released from virus-infected
cells, IFN's diffuse to uninfected neighbouring cells and bind to surface receptors
where they induce synthesis of antiviral proteins that interfere with viral
replication.

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 Complement System: A group of normally inactive proteins in blood plasma and
on plasma membranes make up the complement system. When activated, these
proteins "complement" or enhance certain immune, allergic and inflammatory
reactions. They cause lysis of bacteria, serve as chemoattractant for
macrophages and promote phagocytosis.

Transferrins are iron-binding proteins inhibit the growth of certain bacteria by

reducing the amount of of available iron.

3) Inflammatory Response

Inflammation is the body’s reaction to an injury or by the entry of micro organisms.

It is characterized by redness, heat, swelling and pain in the injured tissue.

When injured basophils and mast cells release the substance called histamine
which causes increase in the permeability of the adjacent capillaries local
vasodilation and also makes capillary leaky.

Due to chemotaxis, phagocytes and macrophages are attracted at the injured

site. The phagocytes literally eat up micro organisms who escape away from
the inflammatory response to infect some large part of the body, trigger fever.
It is usually caused by certain WBCs that release substance called ‘pyrogen’. It
sets the temperature of the body higher than normal.

Very high fever is dangerous but moderate fever contributes to the defense of
the body .it inhibits the growth of some microorganisms, facilitates
phagocytosis, increase the production of interferon, and may speed up repair
of damage tissues.

ADAPTIVE IMMUNE SYSTEM:

The adaptive immune system consists mainly of two types of lymphocytes, B-

cells and T-cells. B-cells govern the humoral response, while T-cells mount
the cell-mediated response.

All cells of theimmune system are created in the bone marrow, but B- and T-
cells mature in different locations.

B-cells mature in the bone marrow (although the B in their name originally
stood for the bursa ofFabricius, an organ found in birds), and T-cells mature in
the thymus.

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 Humoral Immunity

Humoral immunity, which involves the production of antibodies.

An antigen is a substance that is foreign to the body and stimulates an immune

response.

An antibody is a glycoprotein (immunoglobulin) made by plasma cells derived

from B-lymphocytes, secreted in response to an antigen; the variable region of
the antibody molecule is complementary in shape to its specific antigen.

Antibodies target a particular antigen. They contain two heavy chains and two
light chains.

They have a constant region and a variable region; the tip of the variable
region is theantigen-binding region.

When activated, the antigen-binding region undergoes hypermutation to

improve thespecificity of the antibody produced. Cells may be given signals to
switch isotypes ofantibody (IgM, IgD, IgG, IgE, IgA).

Circulating antibodies can opsonize pathogens (mark them for destruction),

causeagglutination (clumping) into insoluble complexes that are ingested by
phagocytes, orneutralize pathogens.

Cell-surface antibodies can activate immune cells or mediate allergic

reactions.

Memory B-cells lie in wait for a second exposure to a pathogen and can then
mounta morerapid and vigorous immune response (secondary response).

Cell Mediated Immunity

Cell-mediated (cytotoxic) immunity is centered on the functions of T-cells.

The peptide hormone thymosin promotes T-celldevelopment.

Helper T-cells (Th or CD4 ) respond to antigen on MHC-II and coordinate the
rest of theimmune system, secreting lymphokines that are capable of
recruiting other immune cells(such as plasma cells, cytotoxic T-cells, and
macrophages) and increasing their activity. Because MHC-II presents
exogenous antigens, CD4 T-cells are most effective againstbacterial, fungal,
and parasitic infections.

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 Th1 cells secrete interferon gamma, which activates macrophages.

Th2 cells activate B-cells.

Cytotoxic T-cells (Tc , CTL, or CD8 ) respond to antigen on MHC-I and kill
virallyinfected cells.by injecting toxic chemicals that promote apoptosis into
theinfected cell. CD8 T-cells respond to antigens presented on MHC-I
molecules.

Suppressor (regulatory) T-cells tone down the immune response after an

infectionand promote self-tolerance.

Memory T-cells serve a similar function to memory B-cells.

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 IMMUNIZATION

Immunization can be achieved in an active or passive fashion.

Active Immunity is immunity gained when an antigen enters the body, an immune
response occurs and antibodies are produced by plasma cells.This can be natural
or artificial.

Through natural exposure, antibodies are generated by B-cells once an

individual becomes infected. As this activation occurs naturally during an
infection it is called natural active immunity.

The immune response can also be activated artificially by injecting antigens

into the body. This is artificial active immunity, more commonly known as
vaccination.

Passive Immunity is immunity gained without an immune response.

The immunity is transient because only the antibodies, and not the plasma cells
that produce them, are given to the individual.

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 Natural examples are the transfer of antibodies across the placenta during
pregnancy to protect the foetus and the transfer of antibodies from a mother
to her nursing infant through breast milk.

Antibodies are injected in the form of antisera, to make a person immune

against a disease. This is artificial immunity.

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