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Summary Immunology
- Instelling
- Radboud Universiteit Nijmegen (RU)
This is an extensive summary of the lectures of Theme 1-12.
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ImmunologyThe immune system is a war zone
,Theme 1: introduction immune system
Biological aspects of immunology:
Cell-cell interactions and communication.
Cell proliferation and (programmed) cell death.
Activation of cells via receptors and signal transduction.
Medical aspects of immunology:
Diseases due to a failing immune system:
Immunodeficiencies (e.g. AIDS).
Allergic reactions (hypersensitivity reactions).
Autoimmune diseases.
Health by manipulating the immune system:
Vaccination against infectious diseases.
Immunotherapy against cancer.
Immunosuppression after organ transplantation.
Innate immune system: cells that respond directly to a trigger.
Cells & soluble factors take action first.
Rapid response (seconds) based on recognition of global patterns present
on pathogens.
Cells from the innate IS are descended from the myeloid progenitor.
Except natural killer cells.
Acquired immune system:
T and B
Innate immune Acquired immune lymphocytes
system system recognize
Cellula Macrophages T lymphocytes certain
r Granulocytes B lymphocytes antigens on
Humora Complement Antibodies pathogens
l Cytokines Cytokines very
specifically.
Construction of memory.
Lymphoid organs:
Organs that contain cells in the acquired IS.
Organized accordingly to their function to increase efficiency.
Primary organs (thymus, bone marrow): development and maturation
of lymphocytes.
Secondary organs (lymph nodes, tonsils, spleen): activation of
mature lymphocytes in response to antigens.
Lymphocytes
B cells: produce immunoglobulins, which can recognize intact proteins or
carbohydrates.
T cells: cannot recognize intact proteins, only linear fragments of proteins.
, Clonal selection of lymphocytes: only cells that have specific receptors for
the pathogen are activated and will proliferate.
Lymphocyte clones mature in lymphoid organs, in the absence of
antigens.
Clones of mature lymphocytes specific for diverse antigens enter the
lymphoid tissues; they are still naïve.
Antigens activate antigen-specific clones → antigen specific immune
response.
Naïve cells = cells that have not encountered an antigen yet.
They travel through the body from node to node looking for an
antigen.
When they encounter an antigen, they proliferate and adapt.
Three signals for activation of a naïve B or T cell:
1. Antigen-receptor binding.
2. Co-stimulation.
3. Cytokines.
Naïve lymphocytes become effector
lymphocytes.
Activation leads to proliferation,
differentiation and a biological effect.
Trafficking of B and T cells from primary
lymphoid organs to secondary lymphoid organs.
Immune response
Recognition phase:
The lymphoid organs recognize the antigens and collect them.
Induction phase: induction of an immune response or tolerance?
Migration of naïve lymphocytes to the lymphoid organs
Activation of naïve lymphocytes and initiation of adaptive immune
responses.
Effector phase:
The effector cells travel via the blood to the site of infection.
Activation of effector T cells in infected tissues.
Immune response should be terminated because the B cells are the fastest to
proliferate and it costs a lot of energy.
Induction phase part II: effector cells and
mediators
,Theme 2: innate immunity
In order to cause a disease, the pathogen has to first gain access to the body.
Then it has to attach itself to, and/or enter cells of its host. The receptors on the
pathogen must fit lock and key, with receptor sites on the host cell. Then it has to
reproduce while avoiding the hosts’ immune system long enough to produce
harmful charges.
Inflammation = response to a harmful stimulus characterized by redness,
swelling, warmth and pain.
Harmful stimuli can be physical, chemical, immunological and microbial.
Infection = contamination of an organism with pathogens, followed by
multiplication of pathogen.
→ Every infection causes inflammation, not every inflammation is based on an
infection!
Cells and components of both the innate and acquired IS influence each other:
Innate → acquired:
Inflammation causes an increased efflux of antigens and an
increased influx of lymphocytes.
Pattern recognition by TLR leads to initiation of adaptive immune
response.
Acquired → innate:
Antibodies make pathogens susceptible for destruction by
cells/components of innate IS.
T cells produce cytokines that activate macrophages.
The first line of defence are physical barriers that viruses and other pathogens
must cross, such as the skin and mucous membranes.
Damage to tissue triggers local non-specific inflammatory response:
Release chemical signals: histamines and prostaglandins.
Capillaries dilate, become more permeable (leaky).
Delivers macrophages, RBCs, platelets, and clotting factors to fight
the pathogens and to clot.
Increases temperature to decrease the bacterial growth, to stimulate the
phagocytosis, and to speed up the repair of tissues.
The function of the innate immune system:
Prevents, controls, or eliminates invading microbes.
Elimination of damaged cells and initiation of the process of tissue repair.
Activation of the adaptive immune system.
Components of the innate immune system:
Patrolling cells: attack pathogens, but do not remember for the next
time.
Phagocytes and NK cells.
Innate immune receptors: recognizes features common to many
pathogens.
Proteins: complement proteins, acute phase proteins, and cytokines.
Leukocytes
Leukocytes recruitment to the cells:
Leukocytes = white blood cells (WBCs).
, Includes: basophils, eosinophils, neutrophils, lymphocytes, and
monocytes.
They are all derived from a common progenitor in the bone marrow.
They are involved in protecting the body from infections.
A site of inflammation secretes cytokines → the endothelial cells get activated
→ they express selectins → the neutrophils that travel through the vessel bind to
them → they start to slow down and adhere to the cells → they travel through the
vessel wall to the site of inflammation.
Neutrophils:
Specialized in capturing, phagocytizing and killing microorganisms.
Short life span, it dies at the site of infection where it will form pus.
Most common leukocyte in blood.
Phagocytes
Macrophages:
Monocytes become macrophages when they enter tissues.
They perform phagocytosis on pathogens by using cytoplasmic
extensions.
Phagosome = vesicle with the pathogen.
The phagosome will fuse with the lysosome, which contains many
enzymes.
These enzymes will destroy the pathogen.
Activation of other cells of the Innate IS by producing cytokines
and chemokines.
Dendritic cells:
Phagocytosis of pathogens → migrates to lymph nodes → presents
peptides to T cells.
Crucial for initiation of the adaptive immune response.
Innate immune receptors
Recognition of microbes and infected cells occur via: PAMPs and
DAMPs.
PAMPs = pathogen-associated molecular patterns → expressed by the
pathogen.
Shared by a large group of pathogens (general patterns & non-
specific).
Conserved and not subject to antigenic variability.
Pathogens cannot change them because they are essential for the survival
or pathogenicity.
Distinct from self-antigens.
DAMPs = damage-associated molecular patterns.
Released from damaged or dying cells due to trauma or an infection due to
a pathogen.
PRRs = pattern-recognition receptors → recognize the signals from the pathogen (PAMPs).
Toll-like receptors (TLRs): TLRs appear to be one of the most ancient,
conserved components of the IS. Its pathway is required for innate defence in
flies.
There are about ten known TLRs that all recognize different types of
pathogens.
Cell surface TLRs recognize bacterial cell wall structures.
, Intracellular TLRs recognize pathogen nucleic acids.
Location likely aids discrimination of viral vs. host nucleic acids.
TLR recognition of microbial ligands results in the activation of several signalling
pathways and ultimately transcription factors. These TFs induce the expression of
genes whose products are import for inflammatory and antiviral responses.
The complement system
Function is complementary to that of antibodies.
Activated by binding of certain antibodies to the surface of a bacterium.
Activation triggers a cascade of proteolytic processes.
It is a set of circulating proteins and cell surface proteins acting in a cascade that
leads to:
1. Opsonisation: make microbes more susceptible to phagocytosis.
2. Local inflammation: promote recruitment of phagocytes.
3. Lysis of bacteria: to attack and kill extracellular pathogens.
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