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Voorbeeld van de inhoud
Hoofdstuk 1: Elements of the immune system and their roles in defense 2Hoofdstuk 2: Innate immunity the immediate response to infection 11
Hoofdstuk 3: The induced response to infection 18
Hoofdstuk 4: Antibody structure and the generation of B-cell diversity 29
Hoofdstuk 5: Antigen recognition by T lymphocytes 36
Hoofdstuk 7: The development of T lymphocytes 43
Hoofdstuk 8: T cell-mediated immunity 48
Hoofdstuk 6: The development of B lymphocytes 55
Hoofdstuk 9: Immunity mediated by B cells and antibodies 67
Hoofdstuk 11 73
Hoofdstuk 12: Coevolution of innate and adaptive immunity 75
Hoofdstuk 13: Failures of the body’s defenses 85
Hoofdstuk 17: Cancer, immunity, and immunotherapy 89
Diversity of the immune system (Computer exercise I) 96
Sequence Analysis in Immunology: Age of NK cells 100
Viral and T cell dynamics in HIV infection (Computer exercise IV) 102
HIV-I Gag responses (Computer Exercise V) 113
Gastcollege TCR sequencing 119
Gastcollege labelling studies 122
Gastcollege: A selective sweep in chimpanzees: Is SIV the culprit? 125
,Hoofdstuk 1: Elements of the immune system and their roles in
defense
Immunology is the study of physiological mechanisms that humans and other animals use to
defend their bodies from invasion by other organisms. Immune is being resistant to infection
because of previous infection.
The host invest heavily in cells dedicated to defense, which collectively form the immune
system. The immune system is the tissues, cells, and molecules involved in the defense of
the body against infectious agents.
Bumblebee put in poor environment. It was found that during starvation the immune response
has almost disappeared. This shows that the immune system costs a lot of energy. The
immune system is very inefficient because a lot of T-cells are made but almost half of them
die by self-recognition.
A way to help the immune system is by vaccination which is the deliberate induction of
protective immunity to a pathogen by the administration of killed or nonpathogenic forms of
the pathogen or its antigens to induce an immune response.
1.1 numerous commensal microorganisms inhabit healthy human bodies
The healthy human body contains many microbial species which do not harm us in any way,
and sometimes even help us. They are called commensal microorganisms which are
organisms that habitually live on or in the human body. An entire community of microbial
species on/in the human body is the microbiota. Commensal organisms enhance human
nutrition by processing digested food and making some essential vitamins. They can also
protect against disease because their presence helps to prevent colonization by other
microorganisms. Antibiotics can kill of all these commensal organisms and increase the risk
of infection by pathogens.
1.2 Pathogens are infectious organisms that cause disease
Any microorganism that causes disease is a pathogen. There are also opportunistic
pathogens which cause disease only in individuals whose immune systems are compromised.
There are four kinds of pathogens
- Viruses: submicroscopic pathogen composed of a nucleic acid genome enclosed in a
protein coat. Viruses replicate only inside living cells because they do not possess all
the metabolic machinery required for independent life. A viral particle is called a
virion.
- Bacteria: diverse prokaryotic microorganisms that are responsible for many infectious
diseases of humans and other animals. Some bacterial pathogens live only
extracellularly, colonizing tissue surfaces and intercellular spaces; others can invade
cells and live intracellularly.
- Fungi: a group of single-celled and multicellular eukaryotic organisms, including the
yeasts and molds, that cause a variety of diseases. Immunity to fungi involves both
antibody-mediated and cell-mediated responses
- Parasites: general name for the unicellular protozoa and multicellular worms that
infect animals and humans and live within them, causing disease.
,1.3 Skin and mucosal surfaces are barrier defenses against infection
The first line of defense against infection consists of
- Epithelium: epithelium is found on the skin but also lining the lungs and internal
organs. It is composed of epithelium cells bound tightly together by tight junctions. It
physically blocks out any pathogens.
- Mucus: mucus is produces by mucosae (mucus-secreting epithelium). Mucus is a
thick fluid layer which contains glycoproteins, proteoglycans, and enzymes that
protect the epithelial cells from damage. In the respiratory tract mucus is moved by
cilia which removes the pathogen filled mucus. Respiratory mucus is replenished by
goblet cells, the mucus is continually removed which removed unwanted material.
- Antimicrobial peptides: all epithelia produce antimicrobial peptides which kills
bacteria, fungi and enveloped viruses by perturbing their membranes.
- Lysozyme: tears and saliva contain lysozyme which kills bacteria by degrading their
cell wall.
- Acidic environment: the stomach, vagina and skin have a low pH with will destroy
microorganisms.
1.4 The innate immune response produces a state of inflammation at sites of infection
The innate immune system is the first line of defense. It is initiated immediately on infection
and does not depend on lymphocytes of adaptive immunity. It depends on host defenses such
as complement, neutrophils, macrophages, and natural killer (NK) cells, which provide
nonspecific defense against a wide range of pathogens. This response does not generate
immunological memory. This response consists of two phases
- Recognition: soluble proteins and cell-surface receptors can bind either to the
pathogen or to human cells and plasma proteins that have been altered by the
pathogen’s presence.
- Response: after recognition effector mechanisms are recruited. Effector mechanisms
are mediated by effector cells which are responsible for killing pathogens or removing
them from the body. In the innate immune response these are mainly neutrophils,
natural killer cells, and innate lymphocytes. The effector cells are guided by the
complement system which is a collection of plasma proteins that act in a cascade of
reactions to attack extracellular forms of pathogens in extracellular spaces and the
blood. Pathogens become coated with complement proteins (molecular flags), which
can either kill the pathogen directly or facilitate its engulfment and destruction by
phagocytes.
, When the skin is damaged bacteria can enter and infect the body. This will activate effector
cells which will secrete cytokines which are any of many small proteins secreted by cells that
act locally to change the behavior of neighboring cells. Cytokines act by binding to specific
receptors on their target cells, which will attract other cells from the bloodstream. This will
cause inflammation (= induced innate immunity) which is local accumulation of fluid,
plasma proteins, and white blood cells. Cytokines also induce vasodilation which increases
blood flow and permeability of the capillary wall. The recruitment of cells and fluids can
cause edema (increase in fluids) which will cause discomfort.
1.5 The adaptive immune response builds on the innate immune response
Adaptive immune system is the response of antigen-specific B and T lymphocytes to
antigen, including the development of immunological memory. Adaptive immunity is
powerful, long lasting, and specific. Lymphocytes of the adaptive immune system recognize
pathogens using only one type of receptor, this receptor is made in billions of different
versions.
Not all species have adaptive immune response. Most vertebrates (like jawed vertebrates)
have adaptive immune system
Jawless vertebrates have an adaptive immune system, however it differences from the jawed
vertebrates.
During infection only the lymphocytes with the receptors for the pathogen are recruited. They
will proliferate and differentiate to form many pathogen-specific effector cells (= clonal
selection). This process takes 7-10 days to complete.
After a successful adaptive immune response some lymphocytes remain in the body and
provide a long-term immunological memory. The memory cells will be able to elicit a
stronger and faster immune response after a second encounter with the same pathogen.
After a first encounter with a pathogen a primary immune response is made,
during which memory is formed. During a second encounter a secondary immune
response is made which will be much faster and stronger.
The innate and adaptive immunity are complimentary. The innate immunity on its
own can control an infection, this can activate the adaptive immune system. When
you have innate immune deficiency, you will not be able to control an infection.
The innate immunity is needed to start the adaptive immunity. Vaccinations work
by activating the innate and primary adaptive immune system to create memory
cells.
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