Abstract (English) Immunology Biomedische wetenschappen Universiteit Leiden jaar 2. Samenvatting van het boek The immune System, Parham, 5th edition. Onderverdeeld in 2 documenten.
Immunology is the study of the physiological mechanisms that humans and other mammals use to
defend their bodies from invasion by other organisms. The remit of the immune system is to protect
the human body from infectious disease.
Commensal microorganisms are present in the healthy human gut, and ‘eat at the same table’.
Microbiota are microbial species that inhabits the human body (skin, mouth, gut, or vagina).
Any microorganism that causes disease is termed pathogen. Pathogens are of four kinds:
• Viruses
• Bacteria
• Fungi
• Parasites
Skin and mucosal surfaces are barrier defenses against infection. The skin is an epithelium protected
layer. Internal surfaces are respiratory, gastro-intestinal, and urogenital tracts which are mucosal
surfaces. This thick flued layer contains glycoproteins, proteoglycans, and enzymes that protect the
epithelial cells. The mucus bathing the epithelium is replenished by goblet cells, specialized in the
synthesis and secretion of mucus (constantly cleansed from unwanted material). All epithelia
produce antimicrobial peptides that kill pathogens by perturbing their membranes.
Two immune systems:
• Adaptive (acquired) immune system: composed of specialized, systemic cells and processes
that eliminate pathogens or prevent their growth.
• Innate immune system: the body's first line of defense against germs entering the body.
Recognition mechanisms of innate immunity
• Fast (hours)
• Fixed
• Limited number of specificities
• Constant during response, doesn’t change
Common effector mechanisms for the
destruction of pathogenesis
Recognition mechanisms of adaptive immunity
• Slow (days to weeks)
• Variable
• Numerous highly selective specificities
• Improve during response, getting better
Innate cells can distinguish ‘self’ and ‘non-self’.
Macrophage receptors recognize the cell-surface carbohydrates of bacterial cells but not those of
human cells. Natural killer cell receptors recognize changes at the surface of human cells that are
caused by viral infection.
The innate immune response consists of two phases:
1. Recognition that a pathogen is present (soluble proteins and cell-surface receptors).
2. Effector mechanisms (kill or eliminate pathogen with effector cells).
Guiding effector cells is complement, a system of plasma proteins that commands the effector cells
by tagging pathogens with molecular flags. Complement can also kill pathogens without effector cells
(perturbing the integrity).
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,The receptors of cells in the damaged tissue detect bacteria, and the cells send out small messenger
proteins called cytokines that bind receptors on the effector cells to trigger the innate immune
response. Inflammation is part of the process by which the immune system defends the body against
pathogens (reaction of the body cells).
Cytokines induce dilation of nearby blood capillaries, which increases the blood flow (warm and red
skin). Vascular dilation creates gaps between endothelium cells. White blood cells leave the blood
and enter the inflamed tissue (lymphocytes).
During infection, only lymphocytes bearing receptors that recognize the infecting pathogen are
recruited to the adaptive immune response. The processes that select pathogen-specific
lymphocytes for proliferation and differentiation are called clonal selection and clonal expansion.
Memory cells are lymphocytes that contributed to a successful adaptive immune response which
provide long-term immunological memory of the pathogen. Adaptive immunity based on
immunological memory is called
acquired immunity or protective
immunity.
Primary immune response: first time
adaptive immune response to a
pathogen.
Secondary immune response: faster and
stronger response to the same pathogen.
All the cellular elements of blood
ultimately derive from the
hematopoietic stem cell of the bone
marrow. The hematopoietic stem cell
give rise to common lymphoid precursor
and common myeloid precursor.
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,Lymphoid cells become:
• B cell (plasma cell)
• T cell (effector T cell)
• NK cell
Myeloid cells become:
• Granulocyte
o Macrophage and dendritic
o Neutrophil
o Eosinophil
o Basophil
o Mast cell
• Megakaryocyte
o Megakaryocyte → Platelets
o Erythroblast → Erythrocyte
Neutrophils kill by phagocytosis, are short lived, and die within infected tissue (forming pus).
Eosinophil defends the body against parasites (worms).
Basophil initiates the anti-parasites response → more regulatory cell than effector cell.
Macrophages are large phagocytic cells.
Macrophage receptors that recognize components of the microbial surfaces:
• Dectin-1
• Complement receptors
• SR-A, MARCO
• SR-B
Microorganisms are bound by phagocytic receptors on the macrophage surface. Binding of bacteria
to phagocytic receptors on macrophages induces their engulfment and degradation.
Signaling:
The cell is maturing and starts to become different, acquiring different functions like Toll-like
receptors. Once the pathogen is taken up, and a signal has been gone through Toll-like receptors, the
cell will start digesting it better and will start presenting it to T cells. Binding of bacterial components
to signaling receptors on macrophages induces the synthesis of inflammatory cytokines.
Monocytes are leukocytes that circulate in the blood. Macrophage recruite monocyte to infected
tissue.
Dendritic cells are residents of the body’s tissues. DC’s are the bridge between innate and adaptive
immunity → determine when and where the innate immune response needs reinforcement with an
adaptive immune response.
NK cells (Natural killer) are cytotoxic lymphocytes of innate immunity that respond to viral infections.
M cells are found in the Gut-associated lymphoid tissue (GALT) of Peyer’s patcher. They deliver
pathogens from the gut lumen to the lymphoid tissue within the gut wall.
Immunoglobulins and T-cell receptors are the antigen receptors of adaptive immunity, also called B-
cells and T-cells.
Teffector cells (cytokines)
T cells and B cells → antigen recognition → effector cells
Plasma cells (antibodies)
Immunoglobulins are composed of two identical heavy chains and two identical light chains. T-cell
receptors are composed of two protein chains, an 𝑎 chain and a β chain.
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, B lymphocytes (bone marrow) and T lymphocytes (thymus).
Both have specificity antigen receptors (different for each
lymphocyte). The receptors on individual lymphocytes are
identical.
Antibody structure (symmetrical molecule):
• Fab region (light chain), antigen binding
• Fc region (heavy chain), effector function (immune cells express FC receptors
→ antibody link immune cell with pathogen
• Hinge region, couple together
The part of the outer surface of an antigenic
macromolecule that interacts directly with an antibody
or B-cell receptor is called the epitope.
T cells recognize antigenic peptides and HLA (MHC).
Major Histocompatibility Complex (MHC) (human
Leukocyte Antigens HLA)
• MHC I (HLA I)
• MHC II (HLA II)
MCHI and II molecules present peptides from different cellular
compartments.
MHC I: cytosol → ER → Golgi → lysosomes (green)
MHC II: phagosomes → lysosomes → Class II compartment (red)
Variations in MHC allotypes at sites that bind peptide and T cell receptor
MHC class I variability→ a2, a3, a1
MHC class II variability → B1, B2, a1, a2
T cell activation → CD8 MHCI → CD4 MHCII. T cells expressing the CD8 co-receptor are cytotoxic T
cells that kill cells infected with a virus or bacterium. T cells expressing the CD4 co-receptor are
helper T cells (secrete cytokines that enable other cells to become fully activated effector cells).
The immunity conferred by antibodies is called humoral immunity. Humors are the body fluids.
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