IMMUNOLOGY
IMMUNOLOGY describe
• Macroscopic entities = lymphatic system (organs,
which are active in filtration of lymph and blood,
pathogen capture or immune-cell generation in body)
• Microscopic entities (Immune Cells and
macromolecules IMMUNOGLOBLINS, cytokines
andothger moelcules)
• Macroscopic entities : Anatomy of the lymph system, showing the lymph vessels and lymph organs
including lymph nodes, tonsils, thymus, spleen, and bone marrow. Lymph (clear fluid) and
lymphocytes travel through the lymph vessels and into the lymph nodes where the lymphocytes
destroy harmful substances. The lymph enters the blood through a large vein near the heart.
Macroscopic entities :
How lympfatic system is designed?
The fluid and proteins within the tissues begin their journey back to the bloodstreamby passing into tiny lymphaticcapillariesthat
infuse almost every tissue of the body. Only a few regions, including the epidermis of the skin, the mucous membranes, the bone
marrow,and the central nervous system, are free of lymphaticcapillaries,whereasregions such as the lungs, gut, genitourinary
system, and dermis of the skin are densely packed with these vessels. Once within the lymphaticsystem, the extracellularfluid,
which is now called lymph, drains into larger vessels called the lymphatics. These vessels converge to form one of two large vessels
called lymphatic trunks, which are connected to veins at the base of the neck. One of these trunks, the right lymphatic duct, drains
the upper right portionof the body, returning lymph to the bloodstreamvia the right subclavian vein. The other trunk,the thoracic
duct, drains the rest of the body into the left subclavian vein. Lymph is transportedalong the system of vessels
by muscle contractions,and valves prevent lymph from flowing backward.The lymphatic vessels are punctuatedat intervals by
small masses of lymph tissue, called lymph nodes, that remove foreign materialssuch as infectious microorganismsfrom the
lymph filtering throughthem.
Role in immunity
• In addition to serving as a drainage network,the lymphatic system helps protectthe body against infection by
producingwhite blood cells called lymphocytes,which help rid the body of disease-causing microorganisms.The organsand
tissues of the lymphatic system are the major sites of production,differentiation, and proliferation of two types of
lymphocytes—theT lymphocytesand B lymphocytes,also called T cells and B cells. Althoughlymphocytesare distributed
throughout thebody, it is within the lymphatic system that they are most likely to encounter foreign microorganisms.
Microscopicentities
(ImmuneCells)
Starting overview
• Specific and unspecific Immunity
What is Nonspecific Immunity?
Non-specific immunity, as the name suggests, is not
specific to a certain group of micro-organisms. These
defense mechanisms act against each and every invader
of the body. It is very important to understand that this
non-specific immune response is so formidable that only
a minute amount of infections penetrates this first line of
defense.
Skin is the first barrier and the first mechanism of nonspecific
defense. Skin is a multilayered structure that
contains dead cells on the outer surface and live cells in
deeper layers. Thus, many organisms find it impossible to
penetrate this physical barrier. Skin cells are made by cell
division at the deep basal layer. As cells reach the outer
surface, they lose their vitality and finally detach
themselves and shed. This outward migration of cells
acts against the influx of invasive organisms. Skin
contains various glands. Sebaceous glands secrete
sebum which has antibacterial properties. Moreover,
sweat washes infections off as the high salt content of
sweat dries micro-organismsoff.
Tears and saliva are secretions that wash
the cornea and mouth continuously.
Many epithelial surfaces in the body
contain cilia. These cilia beat rhythmically
to transport matter out of the body
(respiratory epithelium). Saliva contains
anti-bacterial properties due to
lysozymes. Some epithelia produce
mucus which also acts as a barrier
against infections. If and when microorganisms
penetrate these defense
systems they meet the lymphocytes,
macrophages which phagocytose foreign
matter non-specifically. This may or may
not lead to the generation of a specific
immune response.
• What is Specific Immunity?
When a foreign substance is phagocytozed by a macrophage, a white blood cell, or an
antigen presenting cell, it gets processed inside the host cell. There are antigen binding
receptors called major histocompatibility complexes (MHC type 1 and 2). MHC 1 crosslinks
with CD8 type lymphocytes while MHC 2 crosslinks with CD4 type lymphocytes. There is an
enormous variation among antigen receptors in both T cells and B cells. CD4 T
Lymphocytes get activated by this receptor cross-linkage, and they produce cytokines
which promote proliferation of selected lymphocytes, the formation of new lymphocytes
with selected receptor types, and activation of B cells to form antibodies. These
mechanisms culminate in the destruction of the foreign organisms phagocytozed
previously.
Erythropoiesis (from Greek 'erythro' meaning "red" and 'poiesis'
"to make") is the process which produces blood cells
The similar scheme with details of lymphocyte subset:
HOW to eliminate the
pathological entities ?
(bacteria, virus, cancer-cell,
infected-cell)
neutralizating or killing
neutralisating killing
B-lymphocyte
has ability to produce
IgM and IgG
to
T-lymphocyte
has ability to switch CELL DEATH
Phagocytic cell has ability to
uptake of bacteria and kill
(desintegrate in lysosome)
Some detail
definition…
Phagocytic cells of the immune system consist
predominantly of macrophages and neutrophils.
These cells represent the major cellular effectors of
nonspecific host defense and inflammation.
• T cells are one of the important white blood cells of the immune system and play a central
role in the adaptive immune response. T cells can be distinguished from other lymphocytes by
the presence of a T-cell receptor (TCR) on their cell surface.
• B lymphocytes – two mains type:
• Memory B cell – Dormant B cell arising from B cell differentiation.[1] Their function is to circulate through the body and initia
a stronger, more rapid antibody response (known as the anamnestic secondary antibody response) if they detect the antige
that had activated their parent B cell (memory B cells and their parent B cells share the same BCR, thus they detect the sa
antigen).[23] Memory B cells can be generated from T cell-dependent activation through both the extrafollicular response an
the germinal center reaction as well as from T cell-independent activation of B1 cells.[23]
• Plasma cell – A long-lived, non-proliferating antibody-secreting cell arising from B cell
differentiation.[1] There is evidence that B cells first differentiate into a plasmablast-like cell, the
differentiate into a plasma cell.[14] Plasma cells are generated later in an infection and,
compared to plasmablasts, have antibodies with a higher affinity towards their target antigen
due to affinity maturation in the germinal center (GC) and produce more antibodies.[14] Plasma
cells typically result from the germinal center reaction from T cell-dependent activation of B
cells, however they can also result from T cell-independent activation of B cells.[21]
Natural killer cells (CD57 cells) and are developer from of T cell progenitor,
representing a significant componentof the innateimmune system.
They do not produceantibodiesagainst a foreign pathogen,but rather, are
activated by chemical messenger molecules derived from macrophagesincluding:
interleukin-2, 12, 15 and 18, and interferon. Natural killer cells circulatein the
blood and possess cytotoxic properties whereby their primary
responsibility is to “kill” viral and bacterial pathogens.
B cell
IgM antigen
Final fight of IgM against bacteria (and other xenogenobiotica or
pathogen)
Example FOR SARS-virus neutralization see
file:///C:/Users/229576/Downloads/pathogens-10-00751-v3.pdf
Complex summary of main 2
types of B-Cells and activities
T cell
T-cells developerinto two different group:
CD4 POSITIVE CELLS (so called Th or HELPER cell)
CD 8 POSITIVE CELL (so called CYTOTOXIC CELL)
HELPER T lymphocytehave this role in the immune action:
CYTOTOXIC T lymphocytehave this role in the immune action:
Cytotoxic T Cells and T Helper Cells - Bing video
No killing by TC cell
Imunity and memmory (cell production of
ANTIBODY at first and second invasion
of patogen)
Exist only one type of
antibodies?
No! Two most common are IgM and IgG.
T
Their activation time-schedule in patient after pathogen invasion is there:
Example FOR SARS-virus neutralization see
file:///C:/Users/229576/Downloads/pathogens-10-00751-v3.pdf
Summary of pathogen elimination
(not only by Tcell and B cell)
Figure 2: Phagocytosis in main innate immune cells
The innate immune cells include mast cells and naturalkiller cells, phagocytes(monocytes,macrophagesand dendritic cells),
and the granulocytes (neutrophils,eosinophils and basophils).Each cell type is equipped with different mechanisms to attackand
eliminate pathogens from the host, but these innate immune cells could synergistically function to combat microbial entry.
COMPLEMENT
(additional type of immune reaction, where only molecule without blood cell play role)
• The complement system helps antibodies and phagocytic cells clear pathogens from an organism.
• The complement system consists of a number of small proteins produced by the acute phase
reaction in the liver during inflammation.
• Complement was discovered many years ago as a heat-labile component of normal plasma that augments the opsonization of bacteria by antibodies
and allows antibodies to kill some bacteria. This activity was said to ‘complement’ the antibacterial activity of antibody, hence the name. Although
first discovered as an effector arm of the antibody response, complement can also be activated early in infection in the absence of antibodies. Indeed, it
now seems clear that complement first evolved as part of the innate immune system, where it still plays an important role.
• The complement system is made up of a large number of distinct plasma proteins that react with one another to opsonize pathogens and induce a
series of inflammatory responses that help to fight infection. A number of complement proteins are proteases that are themselves activated by
proteolytic cleavage. Such enzymes are called zymogens and were first found in the gut. The digestive enzyme pepsin, for example, is stored inside
cells and secreted as an inactive precursor enzyme, pepsinogen, which is only cleaved to pepsin in the acid environment of the stomach. The
advantage to the host of not being autodigested is obvious.
• The classical complement pathway starts with antibody binding, which causes a cascade
reaction of complement proteins that gradually form a membrane attack complex.
• The alternative complement pathway is usually stimulated by pathogen antigens or toxins rather than
antibodies, and cleaves C3 until there is enough to continue the steps of the classical complement pathway from
the C5 convertase step.
• The lectin pathway is homologous to the classical pathway, but with the opsonin, mannose-binding lectin (MBL),
and ficolins, instead of C1 from the antibody. This pathway uses proteases on the MBL to form C3 convertase,
which continues the steps of the classical complement pathway from the C3 convertase step.
• The complement system is regulated by complement control proteins, such as decay accelerating pathway, which
prevent complement proteins from forming MAC on the body’s cells.
remember:
C1
C2 andC4
C3
C5
C6 –C9
-basic picture scheme-
Summary of effect of classical and another
COMPLEMENT pathways
TIME interval of immune action
(compare NK-cell vs. T-cell)
Described problem of decreased or
increased imuno-reaction
Odkazy
• Slide 1 (vscht.cz)
• Figure 2.7, Schematic overview of the
complement cascade - Immunobiology NCBI
Bookshelf (nih.gov)