The Immune System Flashcards
innate immunity
- defences always active against infection
- lacks ability to target specific invaders
- nonspecific immunity
adaptive or specific immunity
- defences that target a specific pathogen
- slower to act but maintains immunological memory of an infection to mount a faster attack in subsequent infections
What constitutes the innate immune system?
- antimicrobal molecules
- phagocytes - cells that ingest and destroy pathogens
- includes: macrophages, dendritic cells (trigger inflammatory response by secreting cytokines that trigger an influx of immune cells), monocytes and neutrophils
What constitutes the adaptive immune system?
- B-cells (activated B-cells secrete antibody molecules that bind to antigens that destroy invaders directly or mark them for attack)
- T-cells (recognize antigens displayed on other cells and either help activate B-cells or other T-cells or directly attack infected cells)
- T-cells and B-cells spawn memory cells that promptly eliminate invaders encountered before
Bone marrow
- produces all of the leukocytes that participate in the immune system
- site of hematopoiesis
Spleen
- location of blood storage
- location of activation of B-cells
(where B-cells turn into plasma cells that produce antibodies - dissolve and act in the blood in a form of adaptive immunity called humoral immunity) - when B-cells leave bone marrow, they are mature but naive (lack antigen exposure)
Thymus
- small gland in front of the pericardium (sac that protects the heart)
- site of T-cell maturation
- agents of cell-mediated immunity because they coordinate the immune system and directly kill virally infected cells
Lymph nodes
- major component of the lymphatic system
- place for immune cells to communicate and mount an attack
- B-cells can also mature here
Gut-associated lymphoid tissure (GALT)
- close proximity to lymphatic system
- include tonsil and adenoids in the head
- Peyer’s patches in small intestine
- lymphoid aggregates in appendix
Skin
- first line of defence
- physical barrier between the outside world and our internal organs
- antibacterial enzymes - defensins found on skin
The Gastrointestinal Tract
- stomach acid eliminates most pathogens
- large bacterial population makes it hard for potential invaders to compete
complement
- number of proteins in the blood that act as nonspecific defense (cannot be modified to target a specific organism)
- can be activated through classical pathway (with antibodies) or alternative pathway (without antibodies)
- proteins punch holes in cell walls of bacteria –> makes them osmotically unstable
interferons
- proteins prevent viral replication and dispersion
- cause nearby cells to:
- decrease viral and cellular protein production
- decrease permeability of cells to make it harder for viruses to infect them
- upregulate MHC class I and II molecules to increase antigen presentation and allow for better detection of infected cells by the immune system
- responsible for many flu-like smptoms
macrophages
- derive from blood-borne monocytes and can become a permanent resident population
- activated when bacterial invader enters a tissure
- phagocytizes invader through endocytosis then digests invader using enzymes and presents little pieces (peptides) of invader to other cells using a protein called the major histocompatibility complex (MHC)
- MHC binds to pathogenic peptides (antigens) and carries them to the cell surface where they are recognized by cells of the adaptive immune system
- release cytokines - chemical substances that stimulate inflammation and recruit other immune cells to the area
MHC class I molecules
- all nucleated cells display MHC class I molecules
- any protein produced within the cell can be loaded onto a MHC-I molecule and presented on the cell surface
- allows the immune system to monitor cell health and determine if the cell has been ivaded
- endogenous pathway - binds antigens from inside the cell
- invaded cells can be killed by cytotoxic T-lymphocytes
MHC class II molecules
- displayed on antigen-presenting cells
- include: macrophages, dendritic cells, some B-cells and certain activated epithelial cells
- pick up pathogens from environment –> process them –> present them on MHC-II
- exogenous pathway
Pattern-recognition receptors
- macrophages and dendritic cells can also have special receptors called pattern-recognition receptors (PRR) or toll-like receptors (TLR)
- recognize category of pathogen and production of proper cytokine to recruit the right type of immune cells
natural killer cells
- nonspecific lymphocytes detect downregulation of MHC by viruses and cancer and induce apoptosis in these virally infected cells
neutrophils
- most populous leukocyte in the blood
- short-lived (about 5 days)
- phagocytic and target bacteria
- follow bacteria by chemotaxis (sensing certain products given off by bacteria and following products back to their source)
- opsonized bacteria - marked with antibodies- can be detected
- dead neutrophils form pus
eosinophils
- contain bright red-orange granules
- involved in allergic reactions and invasive parasitic infections
- upon activation, release large amounts of histamines (inflammatory mediator - vasodilation and increases leakiness to allow macrophages and neutrophils into tissues)
inflammation
particularly useful against extracellular pathogens
basophils
- contain large purple granules and are involved in allergic responses
- least populous
- mast cells are similar but they have smaller granules and are present in tissues, mucosa and epithelium
Where do B-cells mature?
- bone marrow
Where do T-cells mature?
- thymus
humoral immunity
- production of antibodies by B-cells
- may take up to a week to become fully effective after initial infection
- antibodies specific to antigens of invading microbe
immunoglobulins
- can be present in body fluids or the surfaces of cells
How do antibodies in body fluid act?
- can bind to specific antigens and attract other leukocytes to phagocytize these antigens immediately
- can cause pathogens to agglutinate and form large insoluble complexes that can be phagocytized
- can block ability of pathogen to invade tissues - neutralization
How do antibodies at the cell surface act?
- antigen binds to B-cell –> activation –> proliferation and formation of plasma and memory cells
- binding to mast cell –> degranulation - exocytosis of granule contents (release of histamine –> inflammatory allergic reaction)
antibody
- Y-shaped molecule
- has a constant region and variable region
- has two heavy chains (inner) and two light chains (outer) held together by disulphide bonds or noncovalent interactions
- B-cell undergoes hypermutation of its antigen-binding region until best match is found –> high affinity binding cells survive –> clonal selection
constant region
natural killer cells, macrophages and eosinophils have receptors for this
- can initiate complement cascade
How many types of antibodies does each B-cell make?
1
What are the different isotypes of antibodies?
IgM, IgA, IgG, IgE, IgD
- different types are used at different times,/ for different pathogens/ different locations
isotype switching
-cells can change which isotype of antibody they produce when stimulated by specific cytokines
How does B-cell maturation occur?
- naive B-cells wait in the lymph nodes until the particular antigen arrives
- after, B-cells proliferate to produce plasma cells - produce large amounts of antibodies and memory cells - stay in the lymph nodes, awaiting rexposure
primary response
- initial activation
- takes 7 to 10 days to become fully effective against antigen
- plasma cells eventually die
- memory cells may last a lifetime
secondary response
- rapid and robust
- memory cells jump into action and produce antibodies specific to pathogen
- basis of vaccination
positive selection
- maturing only cells that can respond to the presentation of antigens on MHC
negative selection
- causing apoptosis in cells that are self-reactive
How are T-cells activated?
- once T-cells leave the thymus, they are mature but naive until exposure to antigens
- clonal selection - only those with a high affinity for a given antigen proliferate
helper T-cells
- also called CD4+ T-cells
- coordinate immune response by secreting lymphokines
- recruit other immune cells (plasma cells, cytotoxic T-cells, macrophages) and increase their activity
autoimmune deficiency syndrome
- advanced HIV infection
What is HIV?
- loss of Th cells (human immunodeficiency virus) prevents immune system from mounting an adequate response to infection
What type of molecules do CD4+ cells respond to?
- CD4+ T-cells respond to antigens presented on MHC-II molecules
- most effective against bacterial, fungal and parasitic infections
cytotoxic T-cells or CTL
- CD8+ T-cell
- capable of directly killing virally infected cells by injecting toxic chemicals that promote apoptosis into the infected cell
- respond to antigens presented on MHC-I molecules
- most effective against viral (an intracellular bacterial or fungal infections)
suppressor or regulatory T-cells
- express CD4
- can be differentiated from CD4+ by protein Foxp3 - tones down the immune system when the infection has been contained and turns off self-reactive lymphocytes to prevent autoimmune disease
memory T-cells
- similar to memory B-cells
What happens during a bacterial (extracellular) infection?
- macrophages (and other antigen-presenting cells) engulf the bacteria, digest it and present antigens via MHC-II and release inflammatory mediators
- cytokines attract inflammatory cells (neutrophils and macrophages)
- mast cells activated by inflammation degranulate - release histamines that increase capillary leakiness
- immune cells travel to affected tissue
- dendritic cell leave affected tissue and travels to nearest lymph node -> presents antigen to B-cell
- B-cells that produce correct antibody proliferate through clonal selection –> plasma and memory B-cells
- antibodies travel through bloodstream to affected tissue and tag bacteria for destruction
- dendritic cells present to T-cells –> activate T-cell response (particularly CD4+)
- Th1 - release interferon gamma which activates macrophages and increases their ability to kill bacteria
- Th2 - activates B-cells
What happens during a viral (intracellular pathogen) infection?
- virally-infected cell will release interferons
- infected cells will present intracellular proteins (some are viral) on MHC-I
- CD8+ T-cells recognize MHC and antigens as foreign and inject toxins -> apoptosis
- viruses downregulate production and presentation of MHC-I –> natural killer cells cause apoptosis
- memory T-cells will be generated after pathogen elimination
self-antigens
- proteins and carbohydrates that are present on every body cell
- signal to the immune system that cell is non-threatening
autoimmunity
- immune system attacks cells expressing self-antigens
hypersensitivity
allergies and autoimmunity
active immunity
- immune system stimulated to produce antibodies against a specific pathogen
- natural exposure - antibodies generated by B-cells after infection
- artificial exposure - vaccines without infection
passive immunity
- transfer of antibodies to an individual
- includes: transfer across the placenta or through breast milk or transfer of IV immunoglobulins when exposed to rabies virus or tetanus
What is the structure of the lymphatic system?
- one-way vessels that become larger as they move towards the body’s center
- vessels carry lymphatic fluid - lymph- and join to comprise a large thoracic duct in the posterior chest to deliver fluid to the left subclavian vein
lymph nodes
- small bean-shaped structures along the lymphatic vessels
- contain a lymphatic channel, artery and vein
- allow immune cells to be exposed to possible pathogens
What are the functions of the lymphatic system?
- fluid leaves bloodstream –> tissues
- quantity of fluid leaving depends on Starling forces
- lymphatic vessels drain tissues and then return it to the bloodstream- only when lymphatics are overwhelmed does edema occur
- transports fat from digestive system into bloodstream via lacteals
- fats are packaged into chylomicrons by intestinal mucosal cells and enter lacteals
- lymphatic fluid with many chylomicrons takes on a milky white appearance - chyle
- lymph nodes are places for the lymphocytes and antigen-presenting cells to interact
- B-cells proliferate and mature in the lymph nodes in collections called germinal centers