Module 4 - Immunity & Immune Disorders Flashcards
What is “immunity”?
Immunity is the body’s defense mechanism against ‘foreign’ invaders (e.g. infectious microorganisms, allergens, foreign tissues, i.e. transplanted tissues/organs).
- The immune system is the collection of cells and molecules that are responsible for defending the body against the countless pathogens that individuals encounter.
- Pathogens include viruses, bacteria, mycobacteria, parasites, and fungi.
What happens if there are defects in the immune system? What is the immune system capable of doing to itself?
Defects in the immune system render individuals easy prey to infections and are the cause of immunodeficiency diseases
- But the immune system is itself capable of causing tissue injury and disease, which are often referred to as hypersensitivity disorders
What is “immunology”?
Immunology is the science that examines the structure and function of the immune systems.
What is the major function of the immune system?
The major functions of the immune system are defense and surveillance
What does the immune system need to:
- Carry out defense and surveillance?
- Function efficiently?
CARRY OUT:
1) Recognition:
- The ability to distinguish between normal self, altered (damaged) self and non-self (foreign material).
2) Specificity:
- The ability to inactivate, destroy and remove the “offending” material, without damaging normal tissues in the vicinity of the reaction, i.e. the reaction must be target-specific.
FUNCTION EFFICIENTLY:
3) Regulation:
- The immune system is able to control the type, intensity and duration of the reaction and has the ability to prevent immune reaction (suppression).
4) Amplification:
- The effector (attack) phase of the immune reaction is mediated through multiple pathways which act synergistically for optimal effect
- Each pathway has built-in amplification systems, too
- All these systems have different triggering points and each may be triggered independently, but eventually involve the other systems.
- Examples of such interacting systems are: the complement system, coagulation system and fibrinolytic system - All these may interact with the immune system.
5) Memory:
- The identity of the foreign material (antigen) which led to the first (primary) immune response is remembered so that the next episode involving the same antigen will result in an accelerated reaction (secondary immune response), which by-passes several initial steps that the primary immune response has to go through. Immunological memory is what confers long-term immunity againstinfections.
What are two key features of the immune system?
Defence against pathogens consists of two types of reactions; during evolution, mammals acquired a complex immune system consisting of:
1) Natural or innate immunity and;
2) Specific adaptive (acquired) immunity.
What is innate immunity mediated by?
Innate immunity (also called natural, or native, immunity) is mediated by cells and proteins that are always present (hence the term innate), poised to react against infectious pathogens (or other foreign substances). - These mechanisms are called into action immediately in response to infection, and thus provide the first line of defense. A major reaction of innate immunity is inflammation (review acute inflammation from Module 3).
Does the innate immune systems require prior expose to a microbe or offending agents?
Our innate immune system does not require prior exposure to a microbe or offending agent (antigen) to mount an immune response – it is always present and ready to attack.
- Acquired immunity is a more advanced system requiring previous exposure to an antigen in order to become active against microbes which have evaded the innate system.
- Response is enhanced by subsequent exposure to the antigen.
What are 4 characteristics of the innate immune system?
- Exposure leads to immediate maximal response.
- It is non-specific.
- It does not require a previous exposure to an offending agent (antigen).
- Found in nearly all forms of life
What are 5 characteristics of the adaptive immunity?
- Pathogen and antigen specific response.
- Lag time between exposure and maximal response.
- Cell-mediated (primarily lymphocytes) and humoral (antibody) components.
- Exposure leads to immunological memory.
- Found only in jawed vertebrates.
When does innate immunity take place?
What stimulates the inflammatory response?
How do cells recognize the components that are preserved among broad groups of micro-organisms?
The innate immune response takes place when a microorganism is able to break through the normal epithelial barriers of the skin, GI and respiratory tract.
Phagocytes ingest microbes and secrete cytokines which stimulate the inflammatory response.
Cells have various receptors (pattern recognition receptors) that are able to recognize components that are preserved among broad groups of microorganisms.
What are two components of innate immunity?
- Surface barriers
a. Mechanical, such as skin
b. Chemical, such as enzymes in saliva, vaginal secretions and tears
c. Biological, such as bacterial flora in different organs - Humoral and chemical barriers:
a. Inflammation: is one of the first responses of the immune system to infection - It is produced as a result of release of:
- Cytokines (such as interleukins) released by infected or injured cells
- Prostaglandins
- Leukotrienes
- Chemokines
- Interferons
*Additionally we have Dendritic cells (phagocyte) and Natural killer cells (lymphocyte).
Innate Immune System
- Humoral and chemical barriers
Where does invasion by microbes usually occur?
What happens once they cross this barrier?
Invasion by microbes usually occurs across the main epithelial barriers.
- Epithelia are a physical barrier to entry.
Once across the epithelium, microbes face attack by phagocytes, including macrophages that reside within the sub-epithelial tissues, and neutrophils which are rapidly recruited to the site.
Innate Immune System
- Humoral and chemical barriers
How do phagocytes recognize microbes?
How do phagocytes kill microbes?
What do phagocytes produce to enhance killing of microbes?
Phagocytes recognize microbes through receptors such as Toll-like receptors (TLRs).
- These are a family of ‘pattern-recognition’ receptors which recognize products of bacteria (endotoxin, etc.), viruses (double stranded RNA), and other pathogens.
The phagocytes kill microbes by ingesting them (phagocytosis) and production of microbiocidal substances.
Phagocytes (and dendritic cells) also produce cytokines which enhance killing of microbes and recruitment and activation of other cells of the immune system.
Innate Immune System
- Humoral and chemical barriers
What to natural killer cells recognize?
What do they express?
- What type of a receptor is it?
- What if the cell is damaged?
- What if they are absent?
How do they function as part of the adaptive immune system?
Natural killer cells recognize class I MHC molecules (see MHC section below), which are present on all healthy cells.
NK cells express inhibitory and activating receptors.
- The receptor for MHC class I is an inhibitory receptor, therefore NK cells will be ‘inhibited’ from attacking normal healthy cells.
- However if a cell is damaged or abnormal (i.e., virally-infected cell, tumor cell), such that MHC I is abnormal or not expressed, NK cells will kill them - In addition, damaged or stressed cells may express molecules that bind to the activating receptors on NK cells.
- In the absence of normal MHC I, NK cells will become activated to kill these cells.
NK cells also function as part of the adaptive immune system by recognizing antibody-coated cells, which they will also kill (antibody-mediated cytotoxicity).
- NK cells also produce the cytokine interferon-y in order to activate macrophages.
Innate Immune System
- Humoral and chemical barriers
What do plasma proteins (i.e. compliment system) recognize?
- What does it consist of?
- Once activated what occurs?
Some plasma proteins, particularly the complement system, recognize components of microbes (endotoxin, mannose residues) and are activated.
- The complement system consists of a group of proteins that are present in plasma in inactive form.
- Once activated via proteolysis they may form complexes with other complement proteins to kill microbes by direct cell lysis (MAC or membrane attack complex) - They may also act as inflammatory mediators to recruit leukocytes, or may act as opsonins (C3b) coating microbes to target them for phagocytosis
Innate Immune System
What is the compliment system?
What is it activated by?
What does it result in?
Complement system: consists of more than 20 proteins and named as such due to its ability to “complement” the killing of a pathogen.
- They are synthesized mainly in the liver and normally circulate in the blood in inactive form.
The complement proteins can be activated by:
- Proteases (damaged cells, bacterial endotoxins), or
- Binding of the complement to antibodies that are attached to microbes, or
- Binding complement to carbohydrates on the microbes’ surfaces
Complement activation results in:
- Cell membrane disruption (lysis of target cell), or
- Opsonization (coat) an organism, marking it for destruction, or
- Attraction of other immune cells through production of peptides.
- Complement activation also results in the release of various factors, e.g. anaphylatoxins and
chemotactic factors which result in acute inflammation.
- Certain products of complement activation can also trigger the coagulation system, kinin system and
fibrinolytic system
What is adaptive immunity?
- How is specificity achieved?
Adaptive immunity is dependent on several cell types (lymphocytes, antigen presenting cells, some phagocytes)
- Specificity is achieved through recognition of specific antigens and expression of MHC molecules on particular cell types.
What does the adaptive immune system allow for?
It allows for stronger immune responses and immunological memory, and requires the recognition of a specific foreign (non-self) antigen.
What are the components of adaptive immunity?
Components of adaptive immunity:
1) Lymphocytes
- T lymphocytes
- B lymphocytes
2) Natural Killer (NK) cells
3) Other cells:
- antigen presenting cells (i.e. dendritic cells, macrophages)
4) Phagocytes
- macrophages
5) Human major histocompatibility complex (MHC)
What are the major functions of the adaptive immune system?
1) The recognition of specific “non-self” antigens during the process of antigen presentation.
2) The generation of responses that are tailored to maximally eliminate specific pathogens or
pathogen infected cells.
3) The development of an immunologic memory, in which a signature antigen in each pathogen is
“remembered” or “recognized”. These memory cells can be recruited to quickly eliminate a pathogen if a subsequent infection occurs.
What cells are a part of the immune system?
The cells of the immune system consist of lymphocytes, most of which have specific receptors for antigens and mount adaptive immune responses; specialized antigen presenting cells (APCs), which capture and display microbial and other antigens to the lymphocytes; and various effector cells, whose function is to eliminate microbes and other antigens
- lymphocytes: B, T, NK (natural killer)
- macrophages (monocytes; histiocytes)
- dendritic cells
- human major histocompatability complex (MHC)
T-Lymphocytes
- Where do they originate from and mature in?
- What percentage do they constitute the peripheral blood lymphocytes?
What are they programmed to recognize?
- What do they do?
What do t-lymphocytes also express?
- They originate from primitive stem cells (yolk sac in embryos and bone marrow after birth), and mature in the thymus gland.
- They constitute 60 to 70% of peripheral blood lymphocytes.
Each cell is programmed to recognize a specific cell-bound antigen by means of an antigen-specific T-Cell Receptor (TCR).
- TCRs are linked to a cluster of five polypeptide chains, called CD3 molecular complex. CD3 molecules do not bind antigen but are involved in the transduction of signals into the T cell after it has bound the antigen.
T- lymphocytes also express a variety other molecules including CD4 or CD8. [CD=cluster of differentiation]
T-lymphocytes
What are CD4 and CD8?
- How do they function?
What are regulatory T-lymphocytes?
CD4 (expressed on ~60 to 65% of mature CD3+ cells) and CD8 (expressed on ~30 to 35% of T cells) are very important.
- They provide the helper/inducer and cytotoxic functions, respectively.
Antigens are presented to T- cells by accessory cells (antigen presenting cells) that carry the appropriate histocompatibility molecule (MHC)
- T cells that function to suppress immune responses are called regulatory T lymphocytes.
T-lymphocytes
What are CD4+ T cells called Why?
What re CD8+ T cells? why?
CD4+ T cells are called helper T cells because they secrete soluble molecules (cytokines) that help B cells to produce antibodies and also help macrophages to destroy phagocytosed microbes.
CD8+ T cells also can secrete cytokines, but their most important role is to directly kill virus-infected cells and tumor cells; hence, they are called cytotoxic T lymphocytes (CTLs).
B-lymphocytes
What percentage do they constitute the peripheral blood lymphocytes?
Where do they arise from and mature?
Constitute 10-20% of peripheral lymphocytes.
Arise from yolk sac in embryos, and bone marrow after birth - They mature in the Bone marrow.
B-lymphocytes
What do immature B-cells contain?
- What do they develop later on?
Immature B-cells (pre-B) contain cytoplasmic heavy-chain immunoglobulins (Ig).
- Later, they develop surface immunoglobulins (Igs).
B-lymphocytes
What are mature B-cells primarily doing and awaiting?
What occurs when they are stimulated?
How do the B-cells recognize antigens?
- What is the major antigen?
- What are the other antigens?
- What constitutes 95% of circulating antibodies?
- What is the major isotope in mucosal secretions?
- Where is IgE present?
- Where is IgD expressed?
Mature B-cells are primarily in a resting state, awaiting activation by foreign antigen.
On antigenic stimulation, they form plasma cells which secrete 5 classes of immunoglobulins (M, G, A, D, E).
Like the T lymphocytes, B- cells recognize antigen via the B-cell antigen receptor complex.
- The major one is IgM antigen receptor complex.
- Other receptors are complement receptors, IgA and IgE, CD40 and Fc receptors. IgG, IgM, and IgA constitute more than 95% of circulating antibodies.
- IgA is the major isotype in mucosal secretions
- IgE is present in the circulation at very low concentrations and also is found attached to the surfaces of tissue mast cells
- IgD is expressed on the surfaces of B cells but is secreted at very low levels.
