INTS 3: Innate and Acquired Immunity Flashcards
(42 cards)
1
Q
What are leukocytes?
A
- Any nucleated white blood cells within the peripheral blood.
- Leukocytes include both mononuclear cells (lymphocytes and monocytes) and granulocytes (neutrophils, basophils, and eosinophils).
2
Q
What are the lymphocytes?
A
- The general name used to identify the most common mononuclear cell in the blood.
- Lymphocytes mature in the bone marrow and later populate the lymphoid tissues and the peripheral blood.
- They also circulate through the lymphatic system which is separate from the blood system.
3
Q
What are T cells?
A
- These are lymphoid cells called T cells as they are derived from the thymus.
- These form a subtype of lymphocytes representing the majority of lymphocytes (approximately 80%).
- They are indistinguishable from B lymphocytes based on morphology, and flow cytometry is needed to distinguish T and B cells on the ground of the expression of T-specific surface antigens.
4
Q
What are B cells?
A
- Called B cells as they are bone marrow-derived.
- These are a subtype of lymphocytes representing a minority of the lymphocytes ( <20%).
- They are indistinguishable from T lymphocytes based on morphology, and flow cytometry is needed to identify them on the ground of expression of B cell surface antigens.
5
Q
What is the innate immune system?
A
- A system comprising the cells and processes developed to defend the host from infection caused by external organisms.
- These include physical barriers such as skin, chemicals in the blood, and cells that attack foreign cells in the body.
- As opposed to the adaptive immune system, the innate system does not provide long-lasting immunity and unless there are genetic defects preventing its development it is present in all individuals at birth.
6
Q
What is the adaptive or acquired immune system?
A
- A system of highly specialized cells and processes that provide an antigen-specific immune response targetted to specific viral or bacterial infections.
- This takes time to develop (at least days or weeks).
- Unlike the innate immune system, the adaptive immune system is highly specific to a particular pathogen.
- Adaptive immunity can also provide long-lasting protection and can be provided by vaccinations.
7
Q
What is an antibody?
A
- A large Y-shaped protein used by the immune system to recognise and neutralize foreign pathogens like bacteria and viruses.
- Antibodies are generally produced against specific epitopes of a virus (protein particles) rather than against the whole viral pathogen.
8
Q
What is an antigen?
A
- A molecule capable of inducing an immune response (to stimulate the production of an antibody) in the host organism.
- Some antigens are more immunogenic than others and they refer to specific protein sequences in the viral coat or part of a bacterial able to be recognised by the host as a non-self.
9
Q
What is the Immunoglobulin gene (IG)?
A
- A gene encoding the complete immunoglobulin protein.
- There are heavy and light chain types based on the structure and type of the constant region.
- The heavy chain type is made of different segments (variable, diversity, joining, and constant), whereas the light chain type does not have diversity segments.
- The type of chain, H or L and M, D, E, A and G is based on the sequence of the CONSTANT region, while the Variable region identifies the ability to recognise the antigens
- because there are missions of different ones, there can be millions of V regions produced.
10
Q
What is immunoglobin gene rearrangement?
A
- The process that leads to the formation of functional immunoglobulin through the joining of all the different segments that form the Ig gene.
11
Q
What is an IG class switch?
A
- The process by which a B cell production of immunoglobulin changes from one type to another, based on the segment encoding the constant region.
- An Ig can switch class (but retain the same antigen recognition specificity).
12
Q
Define innate immunity
A
- the nonspecific defense mechanism that come into play immediately or within hours of foreign invasion by a bacteria or virus and an antigen appearing in the body
13
Q
What are the four different components of the innate immune system?
A
- Anatomical barriers:
- skin, gastric barriers (gastric acid, bile acids, digestive enzyme, gut flora), respiratory tracts (mucociliary elevator), nasopharynx (mucus and saliva), and eyes (tears). - Inflammation:
- occurs when tissues are injured by bacteria, trauma, toxins, heat, or any other cause.
- The damaged cells release chemicals including histamine, bradykinin, and prostaglandins.
- These chemicals cause blood vessels to leak fluid into the tissues, causing swelling. - Complement:
- The complement system enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism
- it promotes inflammation and attacks the pathogen’s plasma membrane.
- It can be activated by certain polysaccharides found on the surface of bacteria.
- This can occur immediately and does not require prior exposure to the molecules. - Cells:
- they include mast cells, neutrophils and macrophages, whose major function is to attack the invading agent, phagocyte and digest it.
- See the section INTS02 for further information on granulocytes.
14
Q
How does skin contribute to innate immunity?
A
- it functions as a physical obstacle
- an unfriendly environment for many microbes
- the skin’s surface is slightly acidic
- some areas are quite dry
- also the skin has ‘good’ bacteria already present
15
Q
What are dendritic cells?
How do they evolve?
A
- they ‘guard’ the immune system and test their surroundings for danger
- they evolve from BM cells that have a monocyte-type structure
- when they receive a stimulus (mainly in the form of cytokine production) they evolve from immature to mature cells and grow dendrites
16
Q
Describe the function of dendritic cells
A
- when they are activated, they migrate to the lymph nodes where they interact with their main targets
- which are T lymphocytes: a signal is transmitted that the body needs to defend itself
- therefore, they represent the ‘link’ between the innate and acquired immune system
- depending on the type of interaction they have will T cells they will trigger different responses (see image)
17
Q
What are natural killer cells?
What is their major function?
A
- NK cells are a type of cytotoxic lymphocyte
- a major component of the innate immune system
- play a major role in the rejection of tumors and cells infected by viruses
- the cells kill by releasing small cytoplasmic granules of proteins
- perforin and granzyme: target cell to die by apoptosis
18
Q
What well-established pattern do natural killer cells work on?
A
- via the Major Histo-Compatibility (MHC) Molecules
- if they recognise a cell with MHC class I, then it won’t be killed, if not it will be killed
19
Q
Describe how NK cells kill
A
- they perforate cells
- by releasing perforin protein
- into the membrane of the target cells
- forming a pore allowing fluid to flow in and out of the cell
- cell ruptures (lysis)
- causing the cell to die via apoptosis
20
Q
What are the two types of acquired (adaptive) immunity responses?
A
- Cellular Response:
- involves the lymphocytes and cells known as antigen-presenting cells (APC)
- the co-op between APCs and lymphocytes will eventually lead to the production of : - Humoral Response:
- the production of specific antibodies against individual antigens or part of a pathogen
21
Q
Observe the image of the major components/sites of the immune system
A
- thymus and bone marrow are primary tissues
- remaining parts of secondary tissues
22
Q
Describe the two primary lymphatic organs (function, structure)
- bone marrow
- thymus
A
- bone marrow: look at INTS 2
- thymus:
- a specialised primary lymphoid organ of the immune system. - Within the thymus, T cells or T lymphocytes, which are critical to the acquired/adaptive immune system, mature
- The thymus is composed of two identical lobes and is located anatomically in front of the heart behind the sternum and just below the thyroid (see the figure below).
- The structure is mainly formed of follicles that are enclosed into a capsule. The thymus is a large organ in children but progressively it involves and reduces in size especially after the age of 25 in adults
23
Q
Describe the function of the secondary lymphatic tissue, spleen
A
- The spleen is the largest of all secondary lymphatic tissues.
- It plays multiple supporting roles in the body.
- It acts as a filter for blood as part of the immune system.
- it fights to invade germs in the blood (the spleen contains infection-fighting white blood cells)
- it controls the level of blood cells (white blood cells, red blood cells, and platelets) i
- it filters the blood and removes any old or damaged red blood cells.
- The spleen also helps fight certain kinds of bacteria that cause pneumonia and meningitis.
24
Q
Describe the function of the secondary lymphatic tissue, the lymph nodes
A
- A lymph node or lymph gland is an ovoid or kidney-shaped organ of the lymphatic system (a few millimeters to about 1–2 cm long) and of the adaptive immune system, that is widely present throughout the body.
- They are linked by the lymphatic vessels as a part of the circulatory system.
- The primary function of lymph nodes is the filtering of lymph to identify and fight infection.
- Lymph nodes act as filters for foreign particles and cancer cells.
- Lymph nodes are major sites of B and T lymphocytes, and other white blood cells.
- Lymph nodes are present throughout the body, are more concentrated near and within the trunk, and are divided in the study of anatomy into groups, like cervical, axillary, mediastinal, inguinal, etc.
- there are hundreds of lymph nodes throughout the body. Each lymph node filters the fluid and substances picked up by the vessels that lead to it. Lymph fluid from the fingers, for instance, works its way toward the chest, joining fluid from the arm. This fluid may filter through lymph nodes at the elbow or those under the arm. Fluid from the head, scalp, and face flows down through lymph nodes in the neck. Some lymph nodes are deep inside the body, such as between the lungs or around the bowel, to filter fluid in those areas. The lymph fluid slowly flows in from all around the body, making its way back to the chest. At the end of its journey, the filtered fluid, salts, and proteins are dumped back into the bloodstream
25
Describe the secondary lymphatic tissue, tonsils
- Lymphatic tissue surrounding the arches behind the tongue.
- The wall at the back is part of the pharynx which is an area visible when you open widely your mouth and look at the epiglottis.
- The tonsils remove pathogens entering the pharynx in air or food.
26
What are the two main types of cells involved in acquire immunity?
- mononuclear cells (circular single nucleus with high nuclear : cytoplasm ratio):
- monocytes
- lymphocytes
27
Describe the structure and shape of monocytes
- Monocytes are larger than red cells (15-20μm)
- they have a horseshoe or kidney-shaped nucleus with relatively abundant cytoplasm which does not have granules
- They can be bigger than lymphocytes, but the cytoplasm is more abundant than lymphocytes and the nucleus has a 'kidney-shape'.
28
Describe the function of monocytes
- Do they contribute to innate or acquired immunity?
- What cells are they derived from and from where?
- Monocytes participate in both innate and acquired immunity
- they are bone marrow-derived leukocytes that circulate in the blood and spleen which can function as a reservoir of monocytes ready to migrate to a site of damage or infection
Function:
- they recognize “danger signals” via pattern recognition receptors
- they can phagocytose and present antigens, secrete chemokines, and proliferate in response to infection and injury.
- during bacterial infection, for example, monocytes home to the site of infection, phagocytose pathogens and secrete a distinct set of chemokines that lead to recruitment of other immune cells, and present antigen via class II MHC
- In acquired immunity, they degrade antigens when presented via antigen-presenting cells
- they activate lymphocytes, and by turning into dendritic cells they act as potent antigen-presenting cells.
- they also work as housekeeping cells:
- by removing debris and dead cells from sites of infection or tissue damage
- they destroy old red cells
- they maintain a store of iron necessary for erythropoiesis.
29
Describe the structure, size and shape of lymphocytes
- What are the 3 different types of lymphocytes?
- How are they distinguised?
- Lymphocytes are mononuclear cells with a predominance of a large nucleus and a rim of cytoplasm, generally pale or bluish
- Their size is about 9μm. The image below illustrates a classic example of lymphocytes.
- While studying the image, note the size of lymphocytes which is generally twice the size of red cells.
- By comparison, a monocyte is about 3-4 times the size of a red cell.
- There are 3 types of lymphocytes: B, T, and natural killer (NK) lymphocytes
- Interestingly, there is no way to distinguish them morphologically and other techniques (flow cytometry in particular) must be used to differentiate between them
30
What characteristic do B and T lymphocytes display?
1. Heterogeneity and Specificity:
- millions of different types of cells can be produced (heterogeneity) but they can recognise many foreign antigens with a high level of specificity
2. Memory:
- they can remember an encounter with an antigen and be 'woken up' following a re-encounter
- As a result, more cells of the same type are produced and response to the invasion of the same 'foreign antigen' is more rapid
3. Tolerance:
- they do not react against 'self' antigens unless there is a breakdown of the tolerance process
31
Describe B cells
- what type of cell?
- main function
- what percentage of lymphoid cells in blood
- a type of lymphocyte involved in cellular immunity
- their main function is to produce antibodies
- B lymphocytes represent approximately 3-20% of the lymphoid cells in peripheral blood
32
What are the two types of T cells?
- CD4 cells / 'helper T cells'
- CD8 T cells
33
What are CD4 cells?
- Function
- How they are activated
- they are 'effector' cells
- relatively short-lived cells that defend the body in an immune response
- helper T cells becoming activated when encountering the peptide antigens found on the MHC class II molecules on APCs
- Activated CD4 cells divide rapidly and secrete cytokines that assist the immune response.
- CD4 cells help activate B cells to secrete antibodies and macrophages to digest ingested microbes
- they also help activate cytotoxic T cells to kill infected target cells
34
What are CD8 T cells (cytotoxic T cells)?
Function
Activation
Action
- A cytotoxic T cell is a lymphocyte that kills cancer cells, cells that are infected (particularly with viruses), or cells that are damaged in other ways
- They are activated when an antigen-presenting cell after being infected with, for instance, a virus, expresses a part of the virus through the MHC type I receptor onto its surface.
- This activates the cytotoxic CD8 cell which then proceeds to kill the infected cell.
35
Describe B-cell receptors
- Location
- Structure
- They are transmembrane receptor proteins located on the outer surface of B cells
- See image: Note that B-cell receptors include both CD79 (a transmembrane protein) and immunoglobulin. See how the receptor extends both outside the cell (above the plasma membrane) and inside the cell (below the membrane)
- The receptor is composed of a membrane-bound antibody that, like all antibodies, has a unique and randomly determined antigen-binding site
- Upon antigen binding to a B cell receptor, a signal is sent into the B cell to turn on immune response.
36
What are T-cell receptors?
Structure
Function
- The T-cell receptor (TCR) is a molecule found on the surface of T cells, or T lymphocytes,
- it is responsible for recognising fragments of antigens as peptides bound to major histocompatibility complex (MHC) molecules
- Unlike B cells, T cells do not directly recognise antigens.
- Instead, they recognise antigens presented through the MHCs that cells use to display which proteins are inside of them
- If a cell is infected, it will present antigenic portions of the infecting pathogen on its MHC for recognition by T cells, which will then mount an appropriate immune response.
- Unlike antibodies, which can typically bind one and only one antigen, T cell receptors have more flexibility in their capacity to recognise antigens presented by MHCs
37
What structures in common do Immunoglobulins (Ig) and T cell receptors (TCR) have?
See image
1. An antigen recognition region (antigen-binding site)
- the most variable part of the protein
- generated by a high combinatorial process (will be explained)
2. Constant region (complement activation or cell membrane interacting region)
- identifies the type of Ig or TCR
- heavy chains (H): μ, delta, gamma, alpha, or epsilon
- light chains (L): lambda, kappa
38
What makes up the constant region of the Immunoglobulin antibody?
- each antibody is made of 2 identical heavy and 2 indentical light chains
- these are randomly chosen, increasing heterogeneity of the Ab (antibody) each cell can produce
- one B cell can only produce one type of antibody
39
What is V-D-J recombination?
On what cells does it occur?
Where?
What is the result of this?
- V-D-J recombination is the unique mechanism of genetic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation
- It involves somatic recombination and results in the highly diverse repertoire of antibodies/immunoglobulins (IGs) and T cell receptors (TCRs) found on B cells and T cells, respectively.
- The process is a defining feature of the adaptive immune system and its development was a key event in the evolution of jawed vertebrates.
- V-D-J recombination occurs in the primary lymphoid organs (bone marrow for B cells and thymus for T cells) and in a nearly random fashion rearranges variable (V), joining (J), and in some cases, diversity (D) gene segments.
- The process ultimately results in novel amino acid sequences in the antigen-binding regions of IGs and TCRs that allow for the recognition of antigens from nearly all pathogens including bacteria, viruses, parasites, and worms as well as 'altered self cells' as seen in cancer.
- The recognition can also be allergic in nature (e.g., to pollen or other allergens) or maybe 'autoreactive' and lead to autoimmunity.
40
What are the two main steps of Immunoglobulin gene rearrangement?
1. The selection of specific segments (V-D-J)
2. The process of deletion of large regions of DNA during the process
- in this process, the region in between the selected segments is deleted and this is an irreversible process
- this is the only process leading to the porduction of a protein where large DNA regions are lost and the process cannot be reversed
41
What happens in the Immunoglobulin class switch?
- as we know mature antibodies are made of 2 identifical heavy and 2 identical light chains
- these can be different types of H chains: mu, delta, gamma, epsilon, alpha
- and L: kappa and lambda
- the first type of H chains is the mu and delta
- and for L chains it is kappa
- the cell, during the process of adapting to recognise better antigen, will then 'switch' to a different type of chain
42
How does the vaccine work?
1. the exposure to a foreign antigen via the breakdown of a barrier which could be a airway or skin etc, the exposure to a virus which is a 'vaccine' is an 'inactivated form'
- i.e. it provides all the peptide component to stimulate the immune response but is attenuated enough to prevent its replication and hence cannot cause a full-blown infection upon exposure.
2. the activation of the innate immune system to the point of educating all the different components (T cells and B cells) to recognise a foreign invader and learn how to defend the body against all the way to the final stage of producing antibodies.
- But most importantly, it generates a population of memory T and B cells ready to come back into action when the body may be 'challenged' again with the same foreign antigen peptide in the future.
- This is diagrammatically shown below.
