The innate immune system Flashcards
what is the innate immune system?
The innate immune system is a fast, non-specific initial response to any foreign invader. It steps in if pathogens are able to ‘break in’ past the physical and chemical barriers that protect the body from harm
what cells are involved in the innate immune response?
the highlighted ones
The major functions of the innate immune system include what?
antigen recognition
inflammation
the recruitment of immune cells
natural killer cell cytotoxicity
phagocytosis
the opsonisation of pathogens
and activation of the complement cascade
The innate immune system is the first line of defense against invading pathogens and relies on what in order to recognise invading pathogens?
relies on a large family of pattern recognition receptors (or PRRs) in order to recognise invading pathogens
Pattern recognition receptors can be located on the cell surface membrane, in cytosol and on the endosomal membrane
Some examples of PRRs include what?
Toll-like receptors (TLRs) and C-type lectin receptors (CLRs)
Toll-like receptors are most commonly found on monocytes, macrophages and dendritic cells
Pattern recognition receptors are able to detect distinct molecular ‘motifs’ that are common amongst groups of different pathogens, but absent from host cells. One group of molecular motifs recognized by pattern recognition receptors are called pathogen-associated molecular patterns (or PAMPs)
what is the functions of PAMPs and an example of it?
Different micro-organisms display different PAMPs, with these molecular structures that form pathogen-associated molecular patterns often found to be vital to the pathogen’s survival
One example of a pathogen-associated molecular pattern is bacterial lipopolysacharride (or LPS), found on the cell membrane of all gram negative bacteria.
Another group of molecular motifs recognised by PRRs are called damage-associated molecular patterns (or DAMPs)
what is it?
When host cells die as a result of tissue injury, contents of the cell that are normally safely stored within the cell membrane and nucleus are released into the extracellular environment
Release of specific intracellular proteins and components alerts the immune system that unscheduled cell damage is occurring
Examples of these DAMPs include DNA, histones, and ATP
Recognition of PAMPs and DAMPs by the innate immune system induces an ___________ ________, which is one of the first responses to a foreign invasion
inflammatory response
Upon pathogen recognition by resident macrophages within the affected tissues, what is released by these macrophages?
pro-inflammatory cytokines such as interleukin 1 (IL-1) and tumour necrosis factor-alpha (TNF-α) are released by these macrophages
what do cytokines cause?
These cytokines increase vascular permeability and cause endothelial cells of neighbouring blood vessels to express cellular adhesion molecules (or CAMs), such as selectins and ICAM-1
what do adhesion molecules cause?
These adhesion molecules enable leukocytes to adhere to and migrate through the endothelium to reach affected tissues
Chemokines are also released in response to inflammation
what are they?
act as chemical ‘attractors’ to recruit or attract immune cells to the point of inflammation
The process of attracting a cell down a chemical gradient is known as chemotaxis
An example of a chemokine is CXCL-8, released by macrophages and endothelial cells to attract neutrophils and other granulocytes to sites of infection
In order to reach the site of infection, the neutrophil has to be able to leave the bloodstream and enter the affected tissue
The process by which a leukocyte migrates and moves through the endothelium into a site of tissue infection or inflammation is called diapedesis, or leukocyte extravasation
how is it done?
In response to inflammation, specific receptors on the neutrophil cell membrane binds onto selectin receptors on the surface of the endothelium
This slows down the progress of the neutrophil within the blood stream and causes it to ‘roll’ against the inner surface of the blood vessel wall
Chemokines on the endothelium of the inflamed tissue enable neutrophils that are weakly bound to the endothelium to express integrins on their cell membrane
Integrins in turn bind to CAMs such as ICAM-1 receptors on the endothelial cells and this causes a tighter bond between the neutrophil and endothelium
Vasodilators such as histamine and bradykinin loosen the junctions between the neighbouring endothelial cells. This enables the bound neutrophils to ‘crawl’ along the endothelial surface, until they can squeeze through a gap junction between two endothelial cells and passage out of the bloodstream into the inflamed tissues
Effects of bradykinin and histamine:
Some of these chemical mediators are also responsible for some of the cardinal signs of inflammation
whata re the cardina signs of inflammation and how are they caused?
The pain, or ‘dolor’, associated with inflammation is due to this release of bradykinin and histamine from mast cells, which stimulate surrounding nerve endings
The vasodilation and increased vascular permeability they also produce are the causative factors of calor (meaning heat), rubor (meaning redness) and tumor (meaning swelling).
important group of cells within the innate immune system are the antigen-presenting cells (or APCs)
Antigen-presenting cells process and present antigens to T helper lymphocytes via their MHC II molecules, and so provide a useful link between the innate and adaptive immune responses
whata re some professional and some atypical APCs?
Professional antigen-presenting cells include dendritic cells and macrophages, as well as B lymphocytes in the adaptive response
Other atypical antigen-presenting cells include mast cells and basophils. They are referred to as ‘atypical’ because they do not always express their MHC II molecules
As described in the introductory module, all nucleated cells contain MHC I on their cell surface
What is an exception to this rule?
platelets
Although platelets do not have a nucleus, they do express MHC I molecules on their cell surface. MHC I molecules process and present endogenous, or intracellular antigens
where are MHC 2 molecules found and what is their function?
MHC II molecules, found on antigen presenting cells, process and present exogenous, or extracellular antigens.
This diagram illustrates the processes involved in antigen processing and presentation via MHC I and MHC II molecules:
When antigens such as viral proteins or damaged DNA are found within the cell, they are processed by proteasomes into small peptides. These peptides are then transported into the endoplasmic reticulum, where they bind to newly produced class I MHC molecules, before migrating to the cell surface for antigen presentation
In contrast, exogenous antigens are engulfed via a process called endocytosis into professional antigen presenting cells, which then break down the antigens into peptides. These peptides are then bound to class II MHC molecules for antigen presentation on their cell surface.
Natural killer, or NK cells, develop from lymphoid progenitors, but play an important role in the innate immune system
what is their function?
the action is similar to that of cytotoxic T lymphocytes in that they target viral-infected host cells, or host cells that have become damaged or malignant
differ from T lymphocytes in that they produce a rapid response, they lack immunological memory and they do not require priming by an antigen in order to initiate a response
Natural killer cells are primarily involved in recognising and targeting host cells that have a reduced or absent MHC I signal
This is useful, as sometimes viruses and malignant cells can try to evade the immune system by reducing the MHC I signal expressed on the surface of host cell membranes
whata re phagocytes?
Phagocytes, highlighted here, are immune cells responsible for the “clear up” of cells and antigens through phagocytosis
Phagocytosis involves engulfing a pathogenic invader or antigenic material in order to digest and neutralise the threat they pose to the host
Examples of phagocytes include macrophages, neutrophils, monocytes, mast cells and dendritic cells.
how does a phagocyte destroy a pathogen?
This allows the phagocyte to engulf the pathogen into a vesicle called a phagosome. The phagosome then fuses with a lysosome containing enzymes to form a phagolysosome, which can generate toxic reactive oxygen and nitrogen species such as nitric oxide. The phagolysosome degrades and destroys the pathogen, and any leftover waste products are expelled out of the phagocyte into the surrounding tissues.
what is opsonisation?
“to prepare for eating”
Opsonisation within the immune system refers to the binding of an opsonin, or ‘tag’, to an invading cell or organism
The binding of an opsonin to the chosen target (especially C3b) enhances the efficiency of phagocytosis, by increasing the likelihood of binding occurring between a phagocyte and a pathogen. This is achieved by increasing the number of binding sites available to the phagocyte, and also by reducing the repellent negative charge that exists at the surface of all cells
Another way the immune system can “target” a foreign pathogen for destruction is via the complement system
what is it?
The complement system is a biochemical cascade of plasma proteins that become activated in a sequential fashion
This means that the activation of one protein acts enzymically to activate the next protein in the cascade
Complement proteins are able to help trigger the recruitment of immune cells, to opsonize pathogens, and aggregate to form the membrane attack complex which causes the lysis of target cells.
The complement cascade can be initiated, or activated, via three different pathways; the classical pathway, the lectin pathway, and the alternative pathway.
what are they?
- The classical pathway is activated by immune complexes
- The alternative pathway is activated by the direct binding of complement proteins to a pathogen
- The lectin pathway is activated by the binding of microbial polysaccharides, like mannose, to circulating lectins, such as mannose binding lectin
Activation of all three of the pathways leads to the formation of C3 convertase by the amalgamation of various complement proteins. Once C3 convertase is activated, a common pathway of downstream complement effects and functions are initiated.
Match the activation signal to each complement pathway.
- Classical
- Alternative
- Lectin
a. Direct binding of complement proteins to a microbe/antigen
b. Immune complexes
c. Binding of microbial polysaccharides, like mannose, to circulating lectins, such as mannose binding lectin
- b
- a
- c
List 3 types of opsonin
Antibody
Complement proteins - C3b, C1q, C4b
Plasma proteins, such as mannose binding lectin
Cytokines released in response to inflammation induce endothelial cells to express integrin for leukocyte adhesion.
The answer is False, it causes endothelium to produce selectin on its surface. Integrin is found on the surface of leukocytes, such as neutrophils.
Mast cell degranulation is dependent upon the cross-linking of IgM antibodies bound to FC receptors on the mast cell membrane
true or false?
The answer is False, Mast cell degranulation is dependent upon the cross-linking of IgE antibodies bound FC receptors on the mast cell membrane.
what makes up the membrane attack complex??
C5b
C6
C7
C8
C9
