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Summary Immunology

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Summary of the lectures, question hours, lab class and from the book 'Cellular and molecular immunology'

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Innate Immunity .................................................................................................................................. 3
Adaptive immune response .................................................................................................................. 10
Lymphocyte development..................................................................................................................... 11
T-cell development, and T-cell receptor and signaling ......................................................................... 18
B-cell development, B-cell receptor and signaling antibodies .............................................................. 24
The Major Histocompatibility Complex ................................................................................................. 28
Leukocyte circulation and migration into tissues.................................................................................. 31
Cellular immunity .................................................................................................................................. 33
Humoural immunity .............................................................................................................................. 37
Antibodies and antigens ........................................................................................................................ 39
Infections and immunodefiencies ......................................................................................................... 41
Bacteria.......................................................................................................................................... 41
Viruses ........................................................................................................................................... 42
Fungi .............................................................................................................................................. 43
Protozoa ........................................................................................................................................ 43
Helminths ...................................................................................................................................... 43
Tumor immunology ............................................................................................................................... 44
Tolerance and autoimmunity ................................................................................................................ 49
Types of auto-immune diseases .................................................................................................... 49
Characteristics associated with auto-immunity ............................................................................ 54
Transplantation immunology ................................................................................................................ 56
Modulation of the immune response ................................................................................................... 61
Vaccination .................................................................................................................................... 61
Farmacotherapy ............................................................................................................................ 64

,https://www.youtube.com/watch?v=JKqFOwudwEI

,Innate Immunity
As you have seen, the various components of the innate immune system use the same basic
mechanisms:
- Activation by recognition of molecular patterns
- Removing pathogens by phagocytosis
- Secretion of soluble factors (cytokines, chemokines, complement factors) to mobilize
other cells
- Presenting antigens to the adaptive immune system
- The recognition of pathogen associated molecular patterns (PAMPs) by Toll-like
receptors (TLRs) is crucial.
- Cells descend from the myeloid progenitor: Monocytes/macrophages, granulocytes
(neutrophilic granulocytes, basophilic granulocytes, eosinophilic granulocytes) mast
cells
- Cells descend from the lymphoid origin: natural killer cells
https://www.youtube.com/watch?v=kKqKOUGFVjU




https://www.youtube.com/watch?v=kKqKOUGFVjU

Functions of the innate immune system:
- Maintains physical and chemical defenses and epithelial barriers to block microbe entry
- Prevent control and eliminate infections by many pathogens
- Eliminating damaged cells and initiate tissue repair
- Stimulate adaptive immune responses
- Inflammation and antiviral defense are major types of protection
The innate immune system is evolutionarily seen, the oldest immune system. Some components of
mammalian innate immune system are similar to those in plants and insects. Toll-like receptors are
crucial for the innate immune system. The major signal transduction pathway that is linked to these
receptors is the NF-kB pathway. An adaptive immune system is found only in vertebrates.

- Recognition and phagocytosis mediated by PAMPs and PRRs
- Different bacteria express different features and can be recognized (LTA, PGN, lipoproteins,
DNA, flagellin, LPS)

, Innate immune cells are often stimulated by PAMPs (Pathogen Associated
Molecular Patterns). This can for example be double stranded RNA,
features of proteins like N-formylmethionine, and complex lipids and
carbohydrates like lipopolysaccharide (LPS). The innate immune system is
thus focused on recognizing features that are shared by most microbes,
whereas the adaptive immune system aims to recognize features specific
to one microbe. Stimulation can also be elicited by DAMPs (Damage
Associated Molecular Patterns), which are substances that are produced
by damaged or dying cells. DAMPs are not excreted by cells dying from
apoptosis.
Damage-associated molecular patterns (DAMPs) are endogenous danger
molecules that are released from damaged or dying cells and activate the
innate immune system by interacting with pattern recognition receptors
(PRRs). Although DAMPs contribute to the host's defense, they promote
pathological inflammatory responses.

During an infection, several molecules might be recognized and used to
initially activate the innate immune system. These can be classified as
pathogen-associated molecular or damage-associated patterns (PAMPs
and DAMPs, respectively) (5, 6). These molecules will be recognized by
pattern recognition receptors (PRRs) -expressed in most innate cells-,
among which Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), and NOD-like receptors (NLRs) are
included. The interaction between PAMPs and PRRs promotes the release of cytokines, chemokines,
and other chemical mediators that induce the inflammation of the infected tissue.

There are many types of Toll-like receptors, some are expressed on the surface of the cell and others
are expressed inside endosomes. The TLRs expressed on the surface are mainly used for recognition
of lipopeptides, peptidoglycan, LPS and the flagellum, whereas the receptors on the inside recognize
different aspects of microbial DNA/RNA (unmethylated, high amount of U and G).
When a ligand binds the TLR, it will induce dimerization of the TLRs, resulting in the fact that the
cytoplasmic parts of the receptors with (TIRs) are brought together and leads to recruitment of
several kinases. This ultimately leads to the activation of NF-kB, which leads to the stimulation of
gene expression of genes coding for molecules for inflammatory responses (TNF, IL-1, chemokines
and E-selectin) RIG-like receptors are cytosolic sensors of viral RNA, that upon activation, lead to
production of type 1 interferons.
- Depending on the type of activated TLR → different pathways are
activated.
- Pattern recognition receptors: TLRs, NLRs, RLRs, CDSs, CLRs, N-Formyl
receptors, Pentraxins, Collections, Ficolins, Complement.


Epithelial barriers
Intact epithelial surfaces form a physical barrier to protect the organism from microbe infection. In
the skin, dying keratinocytes cause a layer of keratin to originate blocks microbes from entering.
Epithelial cells can produce several antimicrobial molecules as well, like defensins and cathelidicin.
Some epithelia contain a certain amount of T-lymphocytes.

Innate lymphoid cells
Innate lymphoid cells are bone marrow derived cells that express the same cytokines as T-cells do,
but lack the TCR.

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