Immune Defense Mechanisms

• These include; phagocytosis, intracellular killing, fever (increased body

temperature), inflammation and activities of natural killer and lymphokine
activated killer cells.
Phagocytosis and Intracellular Killing;
• Phagocytosis involves ingestion of a particulate matter by cells into the
cytoplasmic vesicles which occurs when phagocytes recognize pathogens.
• Phagocytes are eating cells that engulfs invaders.
• They contain lysozymes (granules containing enzymes) that fuse with vesicles
and destroy invaders
• Phagocytic cell have different kinds of receptors on their cell membrane which
pathogens binds.
• Examples; Fc receptors, Complement receptors, Scavenger receptors and Toll-like
receptors.
Phagocytes receptors
Fc receptors;
• Bacteria with IgG anti body on their surface exposed the Fc region of the antibody to
receptors of phagocytes.
• Antibody must first attached to antigen before the Fc region can bind phagocyte
• Binding of IgG-coated bacteria to Fc receptors enhances phagocytosis and activation of the
metabolic activities of phagocytes.
Complement receptors;
• Phagocytes have a receptor for the third component of complement protein (C3b)
• Binding of C3b-coated bacteria to the complement receptor enhance phagocytosis and
stimulation of the metabolic activities of phagocytes.
Scavenger receptors;
• Binds varieties of polyanions on bacteria surface to cause phagocytosis.
Toll-like receptors ;
• Binding of pathogen to toll-like receptors causes phagocytosis and release of inflammatory
cytokines (eg IL-1, IL-6 and TNF-alpha) by the phagocytes.
Response of Phagocytes to Infection
• Phagocytosis involves four main stages namely chemotaxis, adherence/attachment,
ingestion and digestion
Chemotaxis: is the chemically stimulated movement of phagocytes to a site of
damage/infection. These chemicals that attract phagocytes might come from invading
microbes (bacteria toxins components) antibodies, damaged tissue cells, or activated
complement proteins Chemotaxis begins phagocytosis.
Adherence/Attachment: the attachment of the phagocyte to the microbe or other foreign
material is termed adherence. Binding of complement proteins and antibodies to the
invading pathogen (opsonization) enhances adherence.
Ingestion: This is whereby the phagocyte engulf a pathogen with its pseudopods. When the
pseudopods meet, they fuse and surround the microorganism with a sac called a phagosome.

Digestion: Phagosome enters the cytoplasm and merges with lysosomes to form a single,
larger structure called a phagolysosome. Lysozyme (in lysosome) breaks down microbial cell
walls, whiles other digestive enzymes destroy carbohydrates, proteins, lipids, and nucleic
acids. Residual body (indigestible materials) is formed, and digested microbe is expelled
through exocytosis.
Phagocytosis
• Chemotaxis
• attraction to chemicals from
damaged tissues, complement
proteins, or microbial products
• Adherence
• attachment to plasma
membrane of phagocyte
• Ingestion
• engulf by pseudopods to form
phagosome
• Digestion & killing
• merge with lysosome
containing digestive enzymes &
form lethal oxidants eg
hydrogen peroxide (H2O2)
• exocytosis residual body
The Mechanism of Fever
• Fever is an abnormally high body temperature that occurs because
the hypothalamic thermostat is reset. It commonly occurs during
infection and inflammation.
• Many bacterial toxins elevate body temperature by triggering release
of fever-causing cytokines such as interleukin-1 from macrophages.
• Body temperature falls when IL-1 is eliminated.
• Elevated body temperature intensifies the effects of interferons,
inhibits the growth of some microbes, and speeds up body reactions
that aid repair.
• Fever stimulates phagocytes and cause the liver and spleen to store
iron to reduce blood levels of iron needed in large amount for
bacteria growth
Mechanism of Inflammation

• Inflammation is a nonspecific, defensive response of the body to

tissue damage which may be caused by pathogens, cuts, chemical
irritations and others.
• The objective of inflammation is to localize and eradicate the irritant
and repair the surrounding tissue.
• The four characteristic signs and symptoms of inflammation are
redness, pain, heat, and swelling.
• Inflammatory response has three basic stages: (1) vasodilation and
increased permeability of blood vessels, (2) emigration (movement)
of phagocytes from the blood into interstitial fluid, (3) tissue repair.
• substances that contribute to vasodilation, increased permeability,
and other aspects of the inflammatory response are the following;
histamine, kinins (chemotactic agent), prostaglandins, leukotrienes
Stages of Inflammation
• Vasodilation & increased permeability of vessels
• caused by histamine from mast cells, kinins from protien in the blood,
prostaglandins from damaged cells, and leukotrienes from basophils & mast cells
• occurs within minutes producing heat, redness & edema
• pain can result from injury, pressure from edema or irritation by toxic chemicals
from organisms
• blood-clotting factors leak into tissues trapping microbes
• Phagocyte emigration
• within an hour, neutrophils and then monocytes arrive and leave blood stream
(emigration) via diapedesis
• Diapedesis is whereby phagocytes squeeze themselves between endothelial cells
of blood vessels in order to destroy invading microbe.
• Tissue repair; replacing damaged tissue by forming new collagen.
Inflammation

• Damaged cell initiates

• Signs of inflammation
• redness
• heat
• swelling
• pain
• Function is to trap
microbes, toxins or
foreign material & begin
tissue repair
Natural Killer & Lymphokine Activated Cells
• NK cells attack any body cells that display abnormal plasma membrane
proteins.
• The binding of NK cells to a target cell such as an infected cell, causes the
release of granules containing toxic substances eg perforin and grazymes.
• Perforin creates channels in the target cell membrane for extracellular
fluid to flow into the target cell and the cell bursts, a process called
cytolysis.
• Granzymes are protein-digesting enzymes that induce the target cell to
undergo self-destruction (apoptosis). This type of attack kills infected
cells, but not the microbes inside the cells. The released microbes can
then be destroyed by phagocytes.
• When NK cells are exposed to IL-2 and TNF-gamma, they become
lymphokine-activated killer (LAK) cells which kills cancerous cells.
Features of Adaptive Immunity

• A specific defense is activated by a specific antigen, and the immune

response targets that particular antigen and no others.
• Specificity results from the activation of appropriate lymphocytes and
the production of antibodies with targeted effects.
• Specificity occurs because T cells and B cells respond to the molecular
structure of an antigen. The shape and size of the antigen determine
which lymphocytes will respond to it. Each T cell or B cell has
receptors that will bind to one specific antigen and ignore others.
Tolerance (Recognition of ‘self’ and ‘non-self’)
• The immune system exhibits tolerance toward such self antigens.
• All cells and tissues in the body contain antigens (self antigen) that
normally do not stimulate an immune response.
• Immune response targets foreign antigens but it generally ignores
normal tissues (self antigens)
• Mature B cells and T cells ignore normal antigens, also called self-
antigens, but attack foreign antigens, or nonself antigens.
 Memory
• During the initial response to an antigen, lymphocytes that are sensitive to
it undergo repeated cycles of cell division.
• Immunologic memory exists because those cell divisions produce two
groups of cells. One group attacks the invader immediately. Another group
remains inactive unless it meets the same antigen at a later date.
• This inactive group is made up of memory cells that enable your immune
system to “remember” an antigen it has previously encountered, and to
launch a faster, stronger, and longer-lasting counterattack if such an
antigen appears again.
• Vaccination uses the principle of memory by the injection of avirulent form
of antigen into an animal/human to serve as a stimulus to print memory
cells.
• This causes protection or exemption from second attack of that antigen
disease eg; measles, chicken pox, whooping cough, etc.