Chapter 6 Diseases of the Immune system: Normal Response Flashcards
The Normal Immune Response
- INNATE IMMUNITY
- ADAPTIVE IMMUNITY
The normal immune response is best understood in the context of defense against infectious
pathogens, the classical definition of immunity.
The mechanisms of protection against infections
fall into two broad categories.
- Innate immunity (also called natural, or native, immunity) refers to defense mechanisms that are present even before infection and that have evolved to specifically recognize microbes and protect individuals against infections.
- Adaptive immunity (also called acquired, or specific, immunity) consists of mechanisms that are stimulated by
(“adapt to”) microbes and are capable of recognizing microbial and nonmicrobial substances.
I
What are the major components of innate immunity?
The major components of innate immunity are:
- epithelial barriers that block entry of microbes,
- phagocytic cells (mainly neutrophils and macrophages),
- dendritic cells,
- natural killer (NK) cells,
- and several plasma proteins, including the proteins of the complement system.
What are the two most important cellular reacitons of innate immunity?
The two most
important cellular reactions of innate immunity are:
- inflammation, the process in which phagocytic leukocytes are recruited and activated to kill microbes,
- and anti-viral defense, mediated by dendritic cells and NK cells.
.What is pathogen associated molecular patterns?
Leukocytes and epithelial cells that participate in
innate immunity are capable of recognizing components of microbes that are shared among
related microbes and are often essential for the infectivity of these pathogens (and thus cannot
be mutated to allow the microbes to evade the defense mechanisms). These microbial
structures are called pathogenassociated molecular patterns
What is danger associated molecular patterns?
Leukocytes also recognize
molecules released by injured and necrotic cells, which are sometimes called dangerassociated
molecular patterns.
What are recognition receptors?
The cellular receptors that recognize these dangerassociated
molecular patterns molecules are often
called pattern recognition receptors.
What is the best defined pattern recognition receptor?
The best-defined pattern recognition receptors are a
family of proteins called Toll-like receptors (TLRs) [1] that are homologous to the Drosophila
protein Toll. Different TLRs are specific for components of different bacteria and viruses.
Wher are TLRs located?
TLRs
are located on the cell surface and in endosomes, so they are able to recognize and initiate
cellular responses to extracellular and ingested microbes.
Other microbial sensors are located
in the _______, where they recognize bacteria and viruses that may have colonized cells.
cytoplasm
What does NF-κB (nuclear factor κB) do?
Upon recognition of microbes, the TLRs and other sensors signal by a common pathway that
leads to the activation of transcription factors, notably NF-κB (nuclear factor κB).
NF-κB turns
on the production of cytokines and proteins that stimulate the microbicidal activities of various
cells, notably the phagocytes.
Other cellular receptors bind microbes for phagocytosis; these
include receptors for mannose residues, which are typical of microbial but not host
glycoproteins, and receptors for opsonins such as antibodies and complement proteins that coat microbes.
How does the epithelium provide innate immunity?
Epithelia of the skin and gastrointestinal and respiratory tracts provide mechanical barriers to
the entry of microbes from the external environment. Epithelial cells also produce anti-microbial
molecules such as defensins, and lymphocytes located in the epithelia combat microbes at
these sites. If microbes do breach epithelial boundaries, other defense mechanisms are called
in.
Monocytes and neutrophils are phagocytes in the blood that can rapidly be recruited to any site
of infection; monocytes that enter the tissues and mature are called macrophages ( Chapter 2
). Dendritic cells produce type I interferons, anti-viral cytokines that inhibit viral infection and
replication; these cells are described below, in the context of antigen display to lymphocytes.
Natural killer cells provide early protection against many viruses and intracellular bacteria; their
properties and functions are also described below.
What are dendritic cells?
Dendritic cells produce type I interferons, anti-viral cytokines that inhibit viral infection and
replication; these cells are described below, in the context of antigen display to lymphocytes.
How does Natural Killer cells providei innate immunity?
Natural killer cells provide early protection against many viruses and intracellular bacteria; their
properties and functions are also described below.
How does complement system provide innate immunity?
The proteins of the complement system, which were described in Chapter 2 , are some of the
most important plasma proteins of the innate immune system. Recall that in innate immunity the
complement system is activated by microbes using the alternative and lectin pathways; in
adaptive immunity it is activated by antibodies using the classical pathway. Other circulating
proteins of innate immunity are mannose-binding lectin and C-reactive protein, both of which
coat microbes for phagocytosis. Lung surfactant is also a component of innate immunity,
providing protection against inhaled microbes.
The early innate immune response not only provides the initial defense against infections but is
also involved in triggering the subsequent, more powerful adaptive immune response.
The adaptive immune system consists of :
The adaptive immune system consists of:
lymphocytes and their products, including antibodies.The receptors of lymphocytes are much more diverse than those of the innate immune system, but lymphocytes are not inherently specific for microbes, and they are capable of recognizing a vast array of foreign substances. In the remainder of this introductory section we focus on
lymphocytes and the reactions of the adaptive immune system
What are the two types of adagptive immunity?
There are two types of adaptive immunity:
- humoral immunity
- cellular immunity
What is humoral immunity?
humoral immunity, which protects against
extracellular microbesandtheir toxins,
What is cell mediated immunity?
cell-mediated (or cellular) immunity,
which is responsible for defense against intracellular microbes
Humoral immunity is mediated by ________
B (bone marrow–derived) lymphocytes and their secreted products, antibodies (also called
immunoglobulins, Ig),
What mediates cellular immunity?
cellular immunity is mediated by T (thymus-derived) lymphocytes.
CT
What are antigens?
Both classes of lymphocytes express highly specific receptors for a wide variety of substances,
called antigens.
What are the COMPONENTS OF THE IMMUNE SYSTEM:
COMPONENTS OF THE IMMUNE SYSTEM:
- CELLS,
- TISSUES,
- AND SELECTED MOLECULES
Although lymphocytes appear morphologically unimpressive and similar to one another, they
are actually remarkably heterogeneous and specialized in molecular properties and functions.
T or F
True
Lymphocytes and other cells involved in immune responses are not fixed in
- *particular tissues** (as are cells in most of the organs of the body) but are capable of migrating
- *among lymphoid and other tissues and the vascular and lymphatic circulations**
True
What are naivee lymphocytes?
In lymphoid organs, different classes of
lymphocytes are anatomically segregated in such a way that they interact with one another only
when stimulated to do so by encounter with antigens and other stimuli. Mature lymphocytes that
have not encountered the antigen for which they are specific are said to be naive (immunologically inexperienced).
What are effector cells?
After they are activated by recognition of antigens and other signals described later, lymphocytes differentiate into effector cells, which perform the function
of eliminating microbes, and memory cells, which live in a state of heightened awareness and
are better able to combat the microbe in case it returns. The process of lymphocyte
differentiation into effector and memory cells is summarized below.
The principal classes of lymphocytes and their functions in adaptive immunity
- B- lymphocyte: Antibody secretion
- CD4 T helper cells:
- Activation of macrophage
- inflammation
- Stimulation of B lymphocyte
- CD8 Cytotoxic T cell: Killing of infected cell
Where do T lymphocytes develop?
T lymphocytes develop from precursors in the thymus
T T
Where can you find mature T cells and it constitute by how much?
- Mature T cells are found in the blood, where they constitute 60% to 70% of lymphocytes,
- and in T-cell zones of peripheral lymphoid organs (described below)
Each T cell recognizes a specific cell-bound antigen by means of an
antigen-specific T-cell receptor (TCR)
In approximately 95% of T cells the TCR consists of a
________________________-
disulfide-linked heterodimer made up of an α and a β polypeptide chain ( Fig. 6-2 ), each
having a variable (antigen-binding) region and a constant region
The αβ TCR recognizes
peptide antigens that are displayed by __
major histocompatibility complex (MHC) molecules on
the surfaces of antigen-presenting cells (APCs).
What is MHC restriction?
By limiting the specificity of T cells for peptides displayed by cell surface MHC molecules,
called MHC restriction, the immune system ensures that T cells see only cell-associated
antigens (
The T-cell receptor (TCR) complex and other molecules involved in T-cell
activation.
- The TCR heterodimer, consisting of an α and a β chain, recognizes antigen (in
the form of peptide-MHC complexes expressed on antigen-presenting cells, or APCs),
- and the linked CD3 complex and ζ chains initiate activating signals.
- CD4 and CD28 are also involved in T-cell activation. (
Note that some T cells express CD8 and not CD4; these
molecules serve analogous roles.)
The sizes of the molecules are not drawn to scale. MHC,
major histocompatibility complex.
TCR diversity is generated by __________ of the genes that encode the TCR α and
β chains.
All cells of the body, including lymphocyte progenitors, contain TCR genes in the
germ-line configuration, which cannot be expressed as TCR proteins
somatic rearrangement
What is RAG-1 and RAG2
During T cell
development in the thymus, the TCR genes rearrange to form many different combinations that
can be transcribed and translated into functional antigen receptors.
The enzyme in developing
lymphocytes that mediates rearrangement of antigen receptor genes is the product of RAG-1
and RAG-2(recombination activating genes)
What happens when there is a defect in RAG proteins?
inherited defects in RAG proteins result in a
failure to generate mature lymphocytes.
Whereas each T cell expresses TCR molecules of one specificity, collectively, the full complement of T cells in an individual is capable of recognizing a
very large number of antigens.
T or F
True
Important : It is important to note that unrearranged (germ-line) TCR genes
are present in all non-T cells in the body, but only T cells contain rearranged TCR genes.
Furthermore, because each T cell and its clonal
progeny have a unique DNA rearrangement (and hence a unique TCR), it is possible to
distinguish polyclonal (non-neoplastic) T-cell proliferations from monoclonal (neoplastic) T-cell
proliferations. Thus, analysis of antigen receptor gene rearrangements is a valuable assay for
detecting lymphoid tumors
Each TCR is noncovalently linked to five polypeptide chains, which form the__________(see Fig. 6-2 ). [4]
CD3 complex and
the ζ chain dimer
The CD3 and ζ proteins are invariant (i.e., identical) in all T cells. They are involved in the transduction of signals into the T cell after the TCR has bound
the antigen. Together with the TCR, these proteins form the “TCR complex.”
A small population of mature T cells expresses another type of TCR composed of______
polypeptide chains.
γ and δ
What does γδ TCR recognizes?
The γδ TCR recognizes peptides, lipids, and small molecules, without a
requirement for display by MHC proteins.
γδ T cells tend to aggregate at epithelial surfaces,
such as the skin and mucosa of the gastrointestinal and urogenital tracts, suggesting that these
cells are sentinels that protect against microbes that try to enter through epithelia. However, the
functions of γδ T cells are not known.
What are NKT cells?
Another small subset of T cells expresses markers that
are found on NK cells; these cells are called NK-T cells. [6]
NK-T cells express a very limited
diversity of TCRs, and they recognize glycolipids that are displayed by the MHC-like molecule
CD1.
The functions of NK-T cells are also not well defined.
In addition to CD3 and ζ proteins, T cells express several other proteins that assist the TCR
complex in functional responses. These include
- CD4,
- CD8,
- CD2,
- integrins,
- and CD28
___________ are expressed on two mutually exclusive subsets of αβ T cells
CD4 and CD8
Where is CD4 secreted and what is the function?
CD4 is expressed on approximately 60% of mature CD3+ T cells, which function as cytokine-secreting helper cells
that help macrophages and B lymphocytes to combatinfections
Where is CD8 expressed and what is the function?
CD8 is expressed on
about 30% of T cells, which function as cytotoxic (killer) T lymphocytes (CTLs) to destroy host
cells harboring microbes
Why is CD4 and CD8 are co receptors?
CD4 and CD8 serve as “coreceptors” in T-cell activation, so called because they work with the antigen receptor in responses to antigen.
During antigen presentation, **CD4 molecules bind to class II MHC** molecules that are displaying antigen (see Fig. 6-2 ), and **CD8 molecules bind to class I MHC** molecules.
When the antigen receptor of a T
cell recognizes antigen, the CD4 or CD8 coreceptor initiates signals that are necessary for
activation of the T cells. Because of this requirement for co-receptors, CD4+ helper T cells can
recognize and respond to antigen displayed only by class II MHC molecules, whereas CD8+
cytotoxic T cells recognize cell-bound antigens only in association with class I MHC molecules;
this segregation is described below.
During antigen presentation, CD4 binds to where?
During antigen
presentation, CD4 molecules bind to class II MHC molecules that are displaying antigen (see
Fig. 6-2 )
4-2
Where does CD8 binds during antigen presentation?
CD8 molecules bind to class I MHC molecules
Batch 81
To respond, T cells have to recognize not only antigen-MHC complexes but additional signals
provided by APCs. We will describe these later, when we summarize the steps in cell-mediated
immune responses
B lymphocytes develop from precursors in the _____________-
bone marrow.
Mature B cells constitute _________- of the circulating peripheral lymphocyte population and are also present in peripheral
lymphoid tissues such as lymph nodes, spleen, and mucosa-associated lymphoid tissues
10% to 20%
T cell > B cell
T for tantamount
How do B cells recognize antigen?
B-cell antigen receptor complex.
