IMMUNOLOGY
Chapter 1
Elements of the Immune system and their roles in defense.
Immunology – study of the physiological mechanisms that humans and other animals use to
defend their bodies from invasion by all sorts of other organisms. When some has become
immune to infection, it means that people who survived the ravages of epidemic disease were
untouched when faced with that same disease again. Infectious diseases are caused by
microorganisms, which have the advantage of reproducing and evolving much more rapidly than
their human hosts. All humans suffer from infectious diseases because the IS takes time to build
up its strongest response to an invading microorganism.
Vaccination or immunization – a procedure whereby severe disease is prevented by prior
exposure to the infectious agent in a form that cannot cause disease. Vaccination was first used
against smallpox in 1796 by Edward Jenner, a doctor in rural England, who showed how
inoculation with cowpox virus offered protection against the related smallpox virus with less risk
than the earlier methods.
Almost all infectious diseases of humans are caused by microorganisms smaller than a single
human cell. For both benign and dangerous microorganisms alike, the human body constitutes a
vast resource-rich environment in which to live, feed, and reproduce. Commensal species –
more than 1000 different microbial species live in the healthy adult human gut and contribute
about 10 pounds or 4.5 kilograms to the body’s weight. Microbiota – the community of
microbial species that inhabits a particular niche in the human body like skin, mouth, gut etc.
Commensal organisms enhance human nutrition by processing digested food, making several
vitamins, protecting against disease, because their presence helps to prevent colonization by
dangerous, disease-causing microorganisms. Escherichia coli, a major bacterial component of
the normal mammalian gut flora, secretes antibacterial proteins called colicins that incapacitate
other bacteria and prevent them from colonizing the gut. Clostridium difficile can sometimes
establish themselves, causing further disease and sometimes death by producing a toxin that
causes diarrhea and, in some cases, an even more serious gastrointestinal condition called
pseudomembranous colitis.
Pathogen – any organism with the potential to cause disease. Pathogens can be of four kinds:
bacteria, viruses, fungi and parasites. Human populations evolve a degree of built-in genetic
resistance to common disease-causing organisms, as well as acquiring lifetime immunity to
endemic diseases. Endemic diseases – such as measles, chickenpox, and malaria, that are
ubiquitous in a given population and to which most people are exposed in childhood. Influenza is
,an example of a common viral disease that, although severe in its symptoms, is usually overcome
successfully by the immune system.
Skin is the human body’s first defense against infection because it forms a touch, impenetrable
barrier of epithelium protected by layers of keratinized layers. Mucosal surfaces are the internal
surfaces secreting mucus in which impermeable skin gives way to tissues specialized for
communication with their environment and are more vulnerable to microbial invasion. Mucus is
the thick fluid that contains glycoproteins, proteoglycans and enzymes that protect the epithelial
cells from damage and help to limit infection. In the respiratory tract, mucus is continuously
removed through the action of epithelial cells that bear beating cilia and is replenished by
mucus-secreting goblet cells. It is thus continually cleansed of unwanted material, including
infectious microorganisms that have been inhaled. All epithelial surfaces secrete antimicrobial
peptides that kill bacteria, fungi and enveloped viruses by perturbing their membranes: sebum
secreted by sebaceous glands associated with hair follicles contains fatty acids and lactic acids,
both of which inhibit bacterial growth on the surface of the skin. Tears and saliva contain
lysozyme, an enzyme that kills bacteria by degrading their cell walls.
Innate immunity – set of responses that can be mobilized immediately an infection occurs.
Innate immune response – is the one that controls such infections that are highly localized and
are extinguished within a few days without illness. It consists of two parts:
● Pathogen-recognition mechanism which involves soluble proteins and cell-surface
receptors that bind either to the pathogen and its products or to human cells and serum
proteins that become altered in the presence of the pathogen.
● Recruitment of destructive effector mechanisms which are provided by effector cells
that engulf bacteria, kill virus-infected cells, attack protozoan parasites and eliminate the
pathogen. Complement – battery of serum (plasma) proteins that help the effector cells
by marking pathogens with molecular flags but also make them more susceptible to
phagocytosis by neutrophils and macrophages.
Cytokines – are the soluble proteins that are sent out by cells in the damaged tissue, that interact
with other cells to trigger the innate immune response. Innate immune response induces
inflammation in the infected tissue. Cytokines induce the local dilation of blood capillaries,
which by increasing the blood flow causes the skin to warm and redden. Vascular dilation
introduces gaps between the cells of the endothelium making it permeable and increases the
leakage of blood plasma into the connective tissue. Expansion of the local fluid causes
edema/swelling putting pressure on nerve ending and causing pain. Cytokines also change the
adhesive properties of the vascular epithelium, inviting white blood cells to attach to it and move
from the blood into the inflamed tissues and release inflammatory cells.
,Adaptive immune response – it is organized around an ongoing infection and adapts to the
nuances of the infecting pathogen. Adaptive immunity – develops against one pathogen and
provides a highly specialized defense, only evolved in vertebrates. The difference in the effector
mechanisms in the AIR than IIR is the way lymphocytes recognize pathogens. In the IIR, each
receptor recognizes features shared by groups of pathogens and are not specific for a particular
pathogen. In contrast, lymphocytes recognize pathogens by using cell-surface receptors of just
one molecular type but can be made in billions of different versions, each capable of binding a
different ligand. Meaning, AIR can be made specific for a particular pathogen by using only
those lymphocytes receptors that bind to the infecting pathogen and that are not encoded by
conventional genes but by genes that are cut, spliced and modified during lymphocyte
development.
During infection, only those lymphocytes bearing receptors that recognize the infecting pathogen
are selected to participate, which then proliferate (cell selection) and differentiate (clonal
expansion) to produce a large number of effector lymphocytes.
Immunological memory – when an adaptive immune response persists in the body, the memory
cells allow subsequent encounters with the same pathogen to elicit a stronger and faster AIR
which terminates infection with minimal illness (also called acquired or protective immunity).
Primary immune response – first time that an AIR is made to a given pathogen. Secondary
immune response – the second and subsequent times and when immunological memory applies.
Vaccination is used to induce immunological memory to a pathogen so that subsequent infection
with the pathogen elicits a strong adaptive response.
Hematopoiesis – developmental process that generates blood cells in the body. Leukocytes
(white blood cells), erythrocytes (red blood cells), megakaryocytes and platelets derive from a
common progenitor pluripotent hematopoietic stem cell. In the early embryo, blood cells are first
produced in the yolk sac and later in the fetal liver. From the 3-7 months of fetal life, the spleen
is the major site of hematopoiesis. As the bones develop during the 4-5 months of fetal growth,
hematopoiesis begins to shift to the bone marrow and by birth this is where practically all
hematopoiesis takes place. In adults, hematopoiesis occurs mainly in the bone marrow of the
, skull, ribs, sternum, vertebral column, pelvis, and femurs. Because blood cells are short-lived,
they have to be continually renewed, and hematopoiesis is active throughout life. Hematopoietic
stem cells divide through self renewal – daughter cells become more mature stem cells that
commit to one of three lineages: the erythroid, myeloid and lymphoid.
● Erythroid progenitor gives rise to the oxygen-carrying erythrocytes and
platelet-producing megakaryocytes. Megakaryocytes are giant cells that arise from the
fusion of multiple precursor cells and have nuclei containing multiple sets of
chromosomes, also known as permanent residents of the bone marrow. Platelets are
small packets of membrane-enclosed cytoplasm that break off from these cells, are
non-nucleated and function to maintain the integrity of blood vessels. They also initiate
and participate in the clotting reactions that block badly damaged blood vessels to
prevent blood loss.
● Myeloid progenitor gives rise to the myeloid lineage of cells: the granulocytes, which
have prominent cytoplasmic granules containing reactive substances that kill
microorganisms and enhance inflammation; monocytes, macrophages, dendritic cells
and mast cells. Because granulocytes have irregularly shaped nuclei with two to five
lobes, they are also called polymorphonuclear leukocytes. Most abundant of the
granulocytes, and of all white blood cells, is the neutrophil, which is specialized in the
capture, engulfment and killing of microorganisms. Cells with this function are called
phagocytes, of which neutrophils are the most numerous and most lethal. Neutrophils are
effector cells of IIR that are rapidly mobilized to enter sites of infection and can work in
the anaerobic conditions that often prevail in damaged tissue. They are short-lived and
die at the site of infection, forming pus (pyogenic). The second most abundant
granulocyte is the eosinophil, which defends against helminth worms and other intestinal
parasites. The least abundant granulocyte, the basophil, is also implicated in regulating
the immune response to parasites, but is so rare that relatively little is known of its
contribution to immune defense.The eosinophil’s granules contain basic substances that
bind the acidic stain eosin, the basophil’s granules contain acidic substances that bind
basic stains such as hematoxylin, and the contents of the neutrophil’s granules bind to
neither acidic nor basic stains. Monocytes are leukocytes that circulate in the blood. They
are distinguished from the granulocytes by being bigger, by having a distinctive indented
nucleus, and by all looking the same. Monocytes are the mobile progenitors of sedentary
tissue cells called macrophages traveling in the blood to tissues, where they mature into
macrophages and take up residence and like the neutrophil, the macrophage is well
equipped for phagocytosis. Tissue macrophages are large, irregularly shaped cells
characterized by an extensive cytoplasm with numerous vacuoles, often containing
engulfed material. Macrophages respond to the pathogen by secreting the cytokines that
recruit neutrophils and other leukocytes into the infected area. Dendritic cells have a
