A&P 300 -- chapter 22 (Lymphatic system) Flashcards
what is lymphatic system
..
consists of
Lymphatic vessels
liquid CT called lymph
Lymphatic organs and tissues
(immune response)
what systems are closely integrated with lymphatic system
cardiovascular and gastrointestinal systems
major functions of lymphatic system
1) Draining excess interstitial fluid (vessels)
2) Carries out immune responses (organs/nodes/tissues)
3) Transporting dietary lipids absorbed by the gastrointestinal tract to the blood (lacteals/vessels)
1) Draining excess interstitial fluid (vessels)
HOW MUCH (litres)
what other component does lymphatic system return to blood?
Approximately 3.5 L per day
Returns lost PLASMA PROTEINS to bloodstream
2) Carries out immune responses (organs/nodes/tissues)
which immune response type?
Adaptive immune response (lymphocytes)
3) Transporting dietary lipids absorbed by the gastrointestinal tract to the blood (lacteals/vessels)
INCLUDING WHICH VITAMINS
Fat soluble vitamins (A, D, E & K)
ADEK
components of lymphatic system
1) Lymph
2) Lymphatic vessels
3) Lymphatic tissues
4) Lymphocytes
what does lymph resemble
closely resembles interstitial fluid
lymph vs isf
Lymphatic fluid contains lymphocytes, while interstitial fluid contains phagocytes (both are types of white blood cells).
lymph/isf vs plasma
Both lymph and interstitial fluid have relatively less protein than plasma. This is because the lymph mainly consists of leaked interstitial fluid. This leak consists of water, cells, smaller proteins but the larger proteins do not leak through.
isf vs plasma
Plasma has a much higher protein concentration than interstitial fluid due to the presence of albumin, globulins, and fibrinogen.
Additionally, plasma oxygen levels are significantly higher than those of interstitial fluid, which is largely due to the presence of red blood cells carrying oxygen in the plasma.
lymphatic vessels consist of
capillaries, vessels, trunks, ducts
two types of lymphatic tissues
Primary and secondary lymphatic tissues
lymphocytes are
Cells of the lymphatic system (T-cells and B-cells)
1) lymphatic fluid (lymph)
Liquid connective tissue
Formed when excess interstitial fluid enters lymphatic capillaries
Usually clear (exception is in GIT when it appears milky due to absorbed dietary lipids, “lacteal”)
what does lymph contain
Contains immune cells
“Lymphatic fluid contains lymphocytes” (?)
2) LYMPHATIC VESSELS ****
Often called lymphatics
Carry lymph from peripheral tissues to venous system
Found in close association
with blood vessels
Network begins with lymphatic capillaries (smallest vessels)
lymph vessels: capillaries
Differ from blood capillaries:
i) Closed at one end (blind-ended)
ii) Have larger diameters
iii) Have thinner walls —> Basement membrane is incomplete or absent
iv) Typically have a flattened or irregular outline in sectional view
lymph vessels – what is unique about endothelial cells
Have overlapping endothelial cells:
i) Region of overlap acts as a one-way valve
ii) Permits entry of fluid and solutes (including proteins)
—-> Also allows entry of viruses, bacteria, cell debris
—-> Prevents return of these materials to the intercellular space
note “one-way flow” of lymphatic vessel wall
(via endothelial cell alignment/structure)
“Prevents return of these materials to the intercellular space”
“Pressure changes between the interstitial fluid and lymph cause opening or closing of the endothelial “doors””
I.e.
—> materials can go in, but not back out (?)
note “anchoring filament” of endothelial cells of lymph vessels
anchor vessels to surround ISF/cells structures
Lacteals
“the lymphatic vessels of the small intestine which absorb digested fats.”
Specialized lymphatic capillaries Located in small intestine
Carry dietary lipids into lymphatic vessels
Chyle
Lymph in lacteals appears creamy white because of fat; referred to as CHYLE
Chyle:
“a milky fluid consisting of fat droplets and lymph. It drains from the lacteals of the small intestine into the lymphatic system during digestion.”
where does lymph go from the lymphatic capillaries
Lymph from capillaries flow into larger lymphatic vessels that lead toward the body’s trunk
VALVES of lymphatic vessels
Vessel bulges at each valve
—> “Series of bulges makes vessel resemble string of pearls”
what feature of lymphatic vessels necessitates presence of valves
Low pressure in lymphatic vessels
—> Valves prevent backflow of lymph
what other feature helps movement of lymph in the vessels
Contraction of surrounding skeletal muscles aids flow of lymph
superficial vs deep lymphatics
..
superficial lymphatics – where?
i) Subcutaneous layer deep to skin
ii) Areolar tissues of mucous membranes
(digestive, respiratory, urinary, and reproductive tracts)
iii) Areolar tissues of serous membranes
(pleural, pericardial, and peritoneal cavities)
deep lymphatics – where?
Accompany deep arteries and veins supplying skeletal muscles and other organs of the neck, limbs, and trunk, and wall of visceral organs
which direction is lymphatic flow ?
Always from periphery to central vasculature
steps in lymphatic flow
- Begins as interstitial fluid
- Enters lymphatic capillaries (forms lymph)
- Travels in lymphatic vessels to regional lymph nodes
- Enters lymphatic trunks
- Drains into either left or right lymphatic ducts
- Ducts return lymph to blood stream at subclavian veins
capillaries –> vessels (?) –> trunks –> ducts
?
about lymphatic trunks
Formed by confluence of many efferent lymph vessels
node meaning of efferent vs afferent in the context of lymphatic vessels
Afferent (toward) lymphatic vessels convey unfiltered lymphatic fluid from the body tissues to the lymph nodes,
and efferent (away) lymphatic vessels convey filtered lymphatic fluid from lymph nodes to subsequent lymph nodes or into the venous system.
named lymphatic trunks
R/L Lumbar trunks
R/L Intestinal trunks
R/L bronchomediastinal trunks
R/L subclavian trunks
R/L jugular trunks
R/L Lumbar trunks
Drain the lower limbs, the wall and viscera of the pelvis, kidneys, adrenal glands and abdominal wall
R/L Intestinal trunks
Drain the stomach, intestines, pancreas, spleen, part of the liver
R/L bronchomediastinal trunks
Drain the thoracic wall, lung, heart
R/L subclavian trunks
Drain upper limbs
R/L jugular trunks
Drain head and neck
WHERE DO TRUNKS DRAIN INTO?
they drain into
A) THE THORACIC DUCT (Aka Left Lymphatic Duct)
B) RIGHT LYMPHATIC DUCT
which duct drains from most of the body?
THORACIC DUCT (LEFT LYMPHATIC DUCT)
1) Thoracic Duct
(Aka left lymphatic duct)
Collects lymph from:
—> Entire body inferior to the diaphragm
—> The left side of the body superior to the diaphragm
where does thoracic duct drain?
Drains into the left subclavian vein
2) Right Lymphatic Duct
Collects lymph from:
—> The right side of the body superior to the diaphragm
where does right lymphatic duct drain?
Drains into the right subclavian vein
where does Thoracic (left lymphatic) duct begin?
Begins as a dilation called cisterna chyli
@ LEVEL OF L2
(anterior to “)
which trunks does thoracic duct receive lymph from?
Right and left lumbar trunks
Right and left intestinal trunks
Left bronchomediastinal trunk
Left subclavian trunk
Left jugular trunk
where exactly does thoracic duct drain lymph into?
Drains lymph into venous blood
—> at the junction of the left INTERNAL JUGULAR and left SUBCLAVIAN veins
where does right lymphatic duct receive lymph from?
Right bronchiomediastinal trunk
Right subclavian trunk
Right jugular trunk
where does right lymphatic duct drain lymph into
Drains lymph into venous blood
—> at the junction of the right internal jugular and right subclavian veins
recap of lymphatic flow
Blood capillaries interstitial space lymphatic capillaries lymphatic vessels lymphatic trunks lymphatic ducts subclavian veins
= —>
recall – mechanisms of lymph movement
recall lymph vessels themselves don’t have much pressure
(no/ very little smooth muscle)
1) Pressure in the interstitial space
2) ‘Milking’ action of skeletal muscle contractions
3) Pressure changes during inhalation and exhalation (respiratory pump)
recall respiratory pump
“The respiratory pump is a mechanism to pump blood back to the heart using inspiration. It aids blood flow through the veins of the thorax and abdomen.”
“During inhalation, the volume of the thorax increases, largely through the contraction of the diaphragm, which moves downward and compresses the abdominal cavity.”
what happens if lymph flow does not occur?
Obstruction or malfunction of lymph flow => lymphedema
lymphedema
Caused by blocked lymphatic drainage:
—> Interstitial fluids accumulate
—> Affected area becomes swollen and distended
where is lymphedema most often seen?
Most often seen in limbs but can
affect other areas
what permanent changes can take place in the CT with excessive / long-term lymphedema?
Swelling may become permanent
—> Connective tissue loses elasticity
what other immune-related issues can take place with stagnant ISF that is not being filtered properly??
Stagnant interstitial fluids may
accumulate toxins and pathogens
—> Local immune defenses
overwhelmed
3) LYMPHOID TISSUES ****
..
lymphoid tissues can either be …
A) Lymphoid nodules
B) Lymphoid organs
a) lymphoid nodules
Densely packed lymphocytes in an area of areolar tissue
Nodules may cluster together and form larger masses
No fibrous capsule surrounds the masses
lymphoid nodules vs nodes
Lymph nodules form in regions of frequent exposure to microorganisms or foreign materials and contribute to the defense against them.
The nodule differs from a lymph node in that it is much smaller and does not have a well-defined connective-tissue capsule as a boundary.
b) lymphoid organs
Separated from surrounding tissues by fibrous connective tissue capsule
another way of classifying lymphoid tissues
primary vs secondary lymphatic tissues
two ways of classifying?
nodules vs organs
primary vs secondary
(?)
primary lymphatic tissues =
Red bone marrow and thymus
—> Sites where lymphocytes are made and/or become immunocompetent (mature)
secondary lymphatic tissues =
Lymph nodes, spleen, lymphatic nodules
—> Where lymphocytes are activated and cloned
—> Site of most immune responses
SO LYMPHOID NODULES (vs organs) are always (?)
Secondary lymphatic tissues
(?)
about red bone marrow
(Primary lymphatic tissue)
and lymphatic organ
= PRIMARY LYMPHOID ORGAN
Pluripotent stem cells in red bone marrow give rise to:
—> Mature immunocompetent B cells
—> Pre-T cells
(Migrate to the thymus where they become immunocompetent T cells)
about thymus
(primary lymphatic tissue,
and lymphoid organ)
= PRIMARY LYMPHOID ORGAN
..
thymus size/function
The thymus is a lymphoid organ that produces functional T cells
Produces several hormones (thymosins) important in functional T cell development
what happens to thymus with age?
Size and secretory abilities decline with age:
—> Size is largest (40 g) before puberty
—> Diminishes in size and becomes increasingly fibrous (involution)
—> By age 50, size can be <12 g
—> Correlated with increased susceptibility to disease
Thymus description
Located in the mediastinum
—> Posterior to the sternum
(anterior mediastinum)
—> Covered in a capsule that divides it into left and right lobes
Fibrous partitions (septa) divide the lobes into lobules
—-> Each lobule is about 2 mm in diameter
thymus histology
Each lobule consists of:
i) Dark outer cortex
ii) Lighter central medulla
i) Dark outer cortex
Contains dividing lymphocytes arranged in clusters surrounded by epithelial reticular cells (ERCs)
—> Regulate T cell development and function
Blood vessels in the cortex are also surrounded by epithelial cells
—> Maintain the BLOOD THYMUS BARRIER
epithelial reticular cells
“Besides the role of providing a structural support for lymphocytes, epithelial reticular cells are responsible for the secretion of thymic hormones which promote lymphocyte proliferation and maturation.”
blood thymus barrier
“The main purpose of the blood thymus barrier is to prevent cortical T lymphocytes from interacting with foreign macromolecules.”
what are the cells of the DARK OUTER CORTEX
(of lobules of thymus)
Pre-T cells from red bone marrow
Dendritic cells
—> Assist T cell maturation
Epithelial cells
—> Help educate pre-T cells in a process known as positive selection, produce thymic hormones thought to aid in T cell maturation
Macrophages
—> Help to clear out the debris of dead and dying cells
recall dendritic cells
“A dendritic cell is a type of phagocyte and a type of antigen-presenting cell (APC).”
“A special type of immune cell that is found in tissues, such as the skin, and boosts immune responses by showing antigens on its surface to other cells of the immune system.”
what percentage of developing T cells survive?
Only about 2% of the developing T cells survive – the remaining cells die via apoptosis
where do the surviving T cells go?
The surviving T cells then enter the inner medulla
how long does it take survivng T cells to go to inner medulla of lobules?
Developing T cells leave the cortex after about 3 weeks and enter the medulla
NOTE***
No blood thymus barrier in medulla
what are the cells inside the inner medulla?
Mature T cells
Dendritic cells
Epithelial cells
—> Create clusters called thymic (Hassall’s) corpuscles
—> Role unknown – may serve as a site of T cell death in the medulla
Macrophages
So what is the major difference between cells of dark outer cortex and light inner medulla of the LOBULES of the thymus?
maturity of T cells
outer cortex = pre-T cells
inner medula = mature “
where do T cells go after leaving the thymus?
T cells that leave the thymus via the blood travel to
lymph nodes, spleen and other lymphatic tissue.
Thymic (Hassall’s) Corpuscles
“one of the small usually concentrically striated bodies in the thymus body representing remains of the epithelial tissue found in early stages of development.”
“Hassall’s corpuscles (also known as thymic bodies) are structures found in the medulla of the human thymus, formed from eosinophilic type VI thymic epithelial cells arranged concentrically.”
LYMPH NODES
SECONDARY (tissue)
Lymphoid organ
Small lymphoid organs surrounded by fibrous connective tissue capsule
Shape resembles a kidney bean
Diameter range 1–25 mm (about 1 in.)
large lymph nodes – aka
Large lymph nodes (lymph glands) located in neck, groin, axillae
what is function of lymph nodes
Function as filters, removing 99 percent of pathogens from lymph before fluid returns to bloodstream
superficial vs deep
Superficial and deep lymph nodes
important lymph nodes (HEAD AND NECK)
Submental and submandibular lymph nodes
Anterior and posterior cervical lymph nodes
Supraclavicular lymph nodes
important lymph nodes (ARMS)
Axillary lymph nodes
important lymph nodes (LEGS)
Inguinal lymph nodes
Femoral lymph nodes
lymph node structure
Covered by a capsule of dense CT
Capsular extensions (EXTENDING INWAR) called trabeculae
—> Divide the node into compartments
—> Provide support
—> Provide a route for blood vessels
Stroma of lymph node
Composed of the capsule, trabeculae, reticular fibers (inside node) and fibroblasts
parenchyma vs stroma
a parenchyma is a structure involved directly in the function of a given organ or organelle.
Stroma, on the other hand, is tissue acting as structural support for these parenchyma.
Parenchyma of lymph node
i) Cortex
ii) Medulla
Cortex of lymph node (parenchyma)
Outer cortex
—> Consists mostly of B cells
Inner cortex
—> Consists mainly of T cells and dendritic cells that enter a lymph node from other tissue
Medulla of lymph node (parenchyma)
Contains B cells, plasma cells and macrophages
lymph nodes general function
Type of filter:
Foreign substances are trapped by the reticular fibers within the sinuses
—> Macrophages destroy by phagocytosis
—> Lymphocytes create immune responses
Path of lymph through a lymph node
(afferent vessels/lymphatics)
Afferent (afferens, to bring to) lymphatics bring lymph into the node on the opposite side
from the hilum (indentation)
hilum
“another term for hilus.”
“an indentation in the surface of a kidney, spleen, or other organ, where blood vessels, ducts, nerve fibers, etc. enter or leave it.”
Path of lymph through a lymph node —> all the steps
- Afferent (afferens, to bring to) lymphatics bring lymph into the node on the opposite side
from the hilum (indentation) - Through the subcapsular space
—> Network of fibers and dendritic cells (involved in immune response) - Into the outer cortex
—> Contains B cells within germinal centers - Through lymph sinuses in the paracortex
—> Contains T cells - Into the medullary sinus at the core
—> Contains B cells and plasma cells - Out of the lymph node in efferent (efferens, to bring out) lymphatics at the hilum and into venous circulation
path of lymph through lymph node – RECAP
afferent lymphatics
—> Subcapsular space
—> Outer cortex
—> Paracortex
—> Medullary Sinus
—> efferent lymphatics (via hilum)
Spleen
lecondary lymphatic tissue
lymphoid organ
Contains the largest mass of lymphoid tissue in the body
spleen function
Performs same function for blood that lymph nodes do for lymph (filter)
spleen function..
Removes abnormal red blood cells and other blood components by phagocytosis
Stores iron recycled from red blood cells
Initiates immune response by B cells and T cells in response to antigens in circulating blood
liver vs spleen RBC breakdown (???)
““The liver, not the spleen, is the major on-demand site of red blood cell elimination and iron recycling,” according to Filip Swirski, PhD, of the Massachusetts General Hospital Center for Systems Biology, and his colleagues.”
spleen diaphragmatic surface
Smooth and convex
Conforms to the shape of the diaphragm and the body wall
spleen gross anatomy
Lies along the curving lateral border of the stomach on the left side
Attached to lateral border of the stomach by the gastrosplenic ligament (broad band of mesentery)
other gross anatomy facts about spleen
About 12 cm (5 in.) long and weighs ~160 g (5.6 oz.)
Deep red when dissected
(Due to large amounts of blood it contains)
Soft texture
–> Shape molded by structures around it
Visceral (medial) surface has two indentations:
—> Gastric area (near stomach)
—> Renal area (near kidney)
Hilum (indentation where blood and lymphatic vessels communicate)
spleen structure
Outer capsule of collagen and elastic fibers
—> Fairly easily ruptured by impact
—> Spleen tissue too fragile to repair surgically
—> Damage can necessitate removal (splenectomy)
Trabeculae
Fibrous partitions that radiate (INWARD) from the capsule
(similar to nodes)
parenchyma of spleen
Parenchyma is made up of pulp:
Cellular components within the capsule
two types of pulp within spleen (within capsule)
RED pulp
WHITE pulp
Red pulp
Consists of blood filled venous sinuses and cords of splenic tissue called splenic (Billroth’s) cords
—> Consist of many red blood cells and macrophages
Billroth’s cords
“WThe cords of Billroth (also known as splenic cords or red pulp cords) are found in the red pulp of the spleen between the sinusoids, consisting of fibrils and connective tissue cells with a large population of monocytes and macrophages.”
White pulp
Lymphatic tissue: mostly lymphocytes and macrophages
Arranged around branches of the splenic artery called central arteries
function of red pulp
- Removal by macrophages of ruptured, worn out or defective blood cells and platelets
- Storage of platelets (up to 1/3rd of body’s supply)
3.Production of blood cells (hematopoiesis) during fetal life
function of white pulp
Splenic arteries carry blood to central arteries of white pulp
—> B cells and T cells carry out immune functions in white pulp
—> Spleen acts like an ‘immune filter’ of the blood
ruptured spleen
Spleen tears easily and is difficult to repair surgically
Treatment is a splenectomy: removal of spleen
—> Without a spleen, person has increased risk for bacterial infection
—> Liver and bone marrow can take over some functions
Lymphoid nodules
(secondary tissue)
Lymphoid nodules are egg-shaped masses of lymphatic tissue
Differ from lymph nodes because they are NOT surrounded by a capsule (NODULES, not organs)
where are lymphoid nodules
Scattered throughout the lamina propria (CT) of mucous membranes lining the gastrointestinal, urinary and reproductive tracts and respiratory airways
why? (lymphoid nodules)
“Lymph nodules form in regions of frequent exposure to microorganisms or foreign materials and contribute to the defense against them.”
(Lymphoid nodule locations)
Mucosa-associated lymphoid tissue (MALT)
Mucosa-associated lymphoid tissue (MALT)
—> Protect epithelia of digestive, respiratory, urinary, and reproductive tracts from pathogens and toxins
Examples of MALT
E.g.
—> GALT (gut-associated lymphoid tissue)
—> Peyer’s Patches (small intestine)
—> Tonsils
note tonsils
Large lymphoid nodules in the walls of the pharynx
—> Pharyngeal tonsil (or the adenoid)
Located on posterior superior wall of the nasopharynx
—> Palatine tonsils (left and right)
Located at posterior, inferior margin of the oral cavity along the boundary of the pharynx
—> Lingual tonsils
Pair of tonsils located deep to the epithelium covering the base of the tongue
Tonsillitis
inflammation of tonsils
clinical disorders (related to lymphatic nodules)
MALT defends exposed epithelia in multiple tracts exposed to the exterior environment
Infection and/or inflammation of MALT components can cause variety of clinical disorders
*
E.g.
—> Tonsillitis (inflammation of the tonsils)
—> Appendicitis (inflammation of the lymphoid tissue in the appendix)
lecture 2
..
immunity
The ability to fight infection, illness, and disease
two mechanisms – work independently and together
1. Innate (nonspecific) immunity
- Adaptive (specific) immunity
Innate (nonspecific) immunity
Present at birth (innate)
Does not distinguish one type of threat from another (non-specific)
Response is the same regardless of type of invading agent
Prevents the approach, denies the entry, limits the spread of microbes or other environmental hazards
Adaptive (specific) immunity (Acquired immunity)
Utilizes adaptive defenses
Develops over time (acquired)
Protects against particular threats (specific)
Depends on the activities of specific lymphocytes
1st line defense (part of innate IS)
skin
mucous membranes
secretions of skin and MM
2nd line defense
phagocytes
antimicrobial proteins (other than complement & IFNs)
inflammation
fever
3rd line defense
lymphocytes
antibodies
memory cells
cells of innate (MONONUCLEAR PHAGOCYTES)
macrophage (APC)
&monocyte
dendritic cells (APC)
macrophage vs monocyte (recall)
Macrophages are monocytes that have migrated from the bloodstream into any tissue in the body.
cells of innate IS (granulocytes)
basophils
eosinophils
neutrophils
cells of innate IS (lymphocyte?)
NK cells
innate IS other
mast cells?
complement protein system
innate IS
macrophage (APC)
&monocyte
dendritic cells (APC)
basophils
eosinophils
neutrophils
mast cells?
NK cells
complement protein system
component of innate IS
Physical barriers and chemical barriers
Phagocytes
Immune surveillance
Interferons
Complement
Inflammation
Fever
Physical barriers and chemical barriers
skin and mucous membranes
Phagocytes
cells that engulf pathogens and cell debris
Immune surveillance
destruction of abnormal cells by natural killer (NK) cells
Interferons
chemicals against viral infections
Complement
circulating proteins that assist antibodies
Inflammation
localized tissue-level response to limit spread of infection
Fever
elevation of body temperature
interferons??? PROTEINS
A natural substance that helps the body’s immune system fight infection and other diseases, such as cancer.
Interferons are made in the body by white blood cells and other cells
“Interferons are a group of signaling proteins made and released by host cells in response to the presence of several viruses.”
interferon types
There are three types of interferons (IFN), alpha, beta and gamma.
IFN-alpha is produced in the leukocytes infected with virus,
while IFN-beta is from fibroblasts infected with virus.
IFN-gamma is induced by the stimulation of sensitized lymphocytes with antigen
or non-sensitized lymphocytes with mitogens.
mitogen
a substance that induces or stimulates mitosis.
1st line of defense (PHYSICAL)… 1)
1) Integumentary system:
Stratified squamous epithelium
Secretions
Hair
Stratified squamous epithelium
Multiple layers of epithelial cells with keratin that are connected with desmosomes
Secretions
NOTE LYSOZYMES
From sebaceous and sweat glands wash away microorganisms and chemical agents
May also contain bactericidal chemicals, destructive enzymes (lysozymes), and antibodies
Hair
Provides protection from physical abrasion
Prevents hazardous materials or insects from contacting skin
1st line of defense (PHYSICAL)… 2)
2) Mucous Membranes (Line body cavities):
Mucous
Hairs
Cilia
Mucous
A viscous fluid that lubricates, moistens and traps microbes and foreign substances
Hairs
Trap and filter microbes, dust and pollutants
Found in the mucous membrane of nose
Initiate sneezing, coughing and vomiting reflex
Cilia
Waving action helps propel inhaled dust and microbes towards the throat
Found in the mucous membrane of upper and lower respiratory tract
1st line of defense consists of
PHYSICAL barriers
and
CHEMICAL barriers
first line of defense (CHEMICAL) … 1)
Lysozyme
Lacrimal apparatus
Saliva
Flow of urine, vaginal secretions, defecation and vomiting
Sebum
Perspiration
Vaginal secretions
Lysozyme
Enzyme capable of breaking down the cell walls of certain bacteria
where lysozymes found
Found in
tears,
saliva,
perspiration,
nasal secretions,
tissue fluids
Lacrimal apparatus
Found in the eyes
Manufactures and drains away tears in response to irritants
Saliva
Produced by salivary glands in the mouth
Washes microbes from teeth and mucous membranes of mouth
Flow of urine, vaginal secretions, defecation and vomiting
Helps move microbes out of the body
Sebum
From sebaceous (oil) glands
Gastric juices
Very low pH inhospitable to most organisms
Vaginal secretions
Mechanical (trapping and removal),
antimicrobial proteins,
antibodies,
immune cells
about CHEMICAL BARRIERS – what do they all (or most?) have in common?
(physical/chemical feature that discourages bacterial growth)
All are ACIDIC which helps to discourage bacterial growth
SECOND LINE OF DEFENSE: PHAGOCYTES
Phagocytes are specialized cells that perform phagocytosis
Engulf and destroy foreign substance, pathogens, and cellular debris
First line of cellular defense against pathogenic invasion
which cells do phagocytes outpace in quickness to detect pathogens?
Can attack and remove microorganisms even before lymphocytes detect their presence
how can different phagocytes differ?
Different types target different threats
All function in the same basic way
3 major types of phagocytes
Monocytes/macrophages
Neutrophils
Dendritic cells
also?
eosinophils?
basophils?
basophils and eosinophils as phagocytes –
a comparison to 3 major phagocytes
Among the White blood cells (WBCs) four cells have the phagocytic ability. The neutrophils, monocytes, eosionophils and basophils.
The basophils and the eosinophils have much less phagocytic ability when compared to the phagocytic ability of neutrophils and monocytes.
“Eosinophils and basophils are broadly referred to as non-professional phagocytes, in that they can use phagocytosis, but don’t primarily”
“Basophils, a type of white blood cell, can be phagocytic, but this is not their main function.”
about neutrophils
Neutrophils (in bloodstream and tissues)
Abundant, mobile, fast-acting
Phagocytize cellular debris or bacteria
Monocyte–macrophage system
Macrophages (derived from monocytes)
Fixed macrophages (scattered among connective tissues; immobile within those tissues)
Free macrophages (travel throughout body)
what can macrophages function as
Function as antigen presenting cells (APCs)
3 main APC cell types
dendritic cells
macrophages
B cells
Dendritic cells
foundin tissue that has contact with the outside environment (ie. resp. mucosa, skin, GI tract)
Function as antigen presenting cells (APCs)
Eosinophils (less abundant than neutrophils)
— NOT ONE OF THE 3 MAJOR PHAGOCYTE TYPES
Phagocytize foreign compounds and antibody-coated pathogens
5 steps of phagocytosis
- Chemotaxis
- Adherence
- Ingestion
- Digestion
- Killing
chemotaxis
movement of the phagocyte due to the attraction of chemicals
“Chemotaxis is defined as the unidirectional movement of a cell in response to a chemical gradient in the direction from a low to a high … “
“The ability of somatic cells, bacteria, other single-celled organisms and multicellular organisms to move in a particular direction in response to a chemical stimulus is known as chemotaxis”
“the directed movement of cells in a gradient of chemoattractant—allows leukocytes to seek out sites of inflammation and infection”
- Adherence
attachment of the phagocyte to the target cell
- Ingestion
pseudopods –“false feet” are formed and engulf the target cell forming a phagosome
- Digestion
lysozymes, proteasomes, &/or peroxisomes bind with the phagosome
proteasome
a protein complex in cells containing proteases; it breaks down proteins that have been tagged by ubiquitin.
peroxisome
“Peroxisomes are small, membrane-enclosed organelles (Figure 10.24) that contain enzymes involved in a variety of metabolic reactions, including several aspects of energy metabolism.”
- Killing
death of target cell (or pathogen??) & release of debris
SECOND LINE OF DEFENSE: IMMUNE SURVEILLANCE
Constant monitoring of normal tissues (immune surveillance) by natural killer (NK) cells
Normal cells are generally ignored by immune system
what do cancer cells often contain that is detected by IMMUNE SURVEILLANCE of NK cells
Cancer cells often contain tumor-specific antigens
NK cells recognize as abnormal and destroy
Tumor-specific antigens (TSAs)
A protein or other molecule that is found only on cancer cells and not on normal cells. Tumor-specific antigens can help the body make an immune response
what can NK cells (immune surveillance cells) recognize?
NK cells recognize
bacteria,
foreign cells,
virus-infected cells,
cancer cells
Steps of NK recognition and destruction
- Presence of unusual plasma membrane activates NK cell
- Golgi apparatus moves within NK cell near target cell
- Perforins are released from NK cell and arrive at target cell
- Perforins create pores in target cell membrane
what do NK cells do
NK cell adheres to target cell
what does Golgi apparatus in NK cells produce
Produces many secretory vesicles containing perforins
what happens to target cell after pores are created in its plasma membranes by perforins?
Target cell can no longer maintain its internal environment and disintegrates
SECOND LINE OF DEFENSE: ANTIMICROBIAL SUBSTANCES
Interferons (proteins)
Complement system
Iron-binding proteins
Antimicrobial proteins
1) Interferons (IFNs)
Small proteins released by activated lymphocytes, macrophages, and virus-infected tissues
WHAT CAN RELEASE IFNs
activated lymphocytes,
macrophages,
virus-infected tissues
what can IFNs do when released?
Trigger production of ANTIVIRAL PROTEINS (?) in cytoplasm of nearby cells
—> (Do not prevent entry of viruses but interfere with viral replication)
Also stimulate activities of macrophages and NK cells
IFNs are an example of a broader category of proteins called
Example of a CYTOKINE
CYTOKINES
cytokine define
any of a number of substances, such as interferon, interleukin, and growth factors, which are secreted by certain cells of the immune system and have an effect on other cells.
“Cytokines are a broad and loose category of small proteins important in cell signaling.”
cytokine – class notes
Cytokines are chemicals released by cells to coordinate local activities
2) Complement system
why called complement system
Name refers to the fact that the system complements the action of antibodies
how many proteins in complement system
Over 30 special proteins form this system
what do proteins do – how do they interact w/ each other
Proteins interact with one another in chain reactions or cascades (similar to blood clotting system)
what are three possible pathways of complement system
Classical pathway
Lectin pathway
Alternative pathway
CLASSICAL PATHWAY
Most rapid and effective complement activation method
Complement proteins attach to antibody molecules already bound to a pathogen
Attached protein activates and initiates cascade to activate and attach other complement proteins
Membrane attack complex (MAC)—destroys integrity of target cell
LECTIN PATHWAY
Activated by mannose-binding lectin (MBL) protein
—> Binds to carbohydrates on bacterial surfaces
Activates an inflammatory response
Also enhances phagocytosis (opsonization)
mannose define
a sugar of the hexose class which occurs as a component of many natural polysaccharides.
mannose binding lectin define
Mannose-binding lectin (MBL) is a pattern recognition molecule of the innate immune system.
It belongs to the collectin family of proteins in which lectin (carbohydrate-recognition) domains are found in association with collagenous structures.
ALTERNATIVE PATHWAY
Important defense against bacteria, some parasites, and virus-infected cells
—> Interaction triggered by exposure to foreign substances
End result is attachment of activated complement protein
effect?
enhances phagocytosis?
& induces inflammation?
properdin define
a protein present in the blood, involved in the body’s response to certain kinds of infection.
properdin etymology
properdin etymology:
pro = before
perdere = destroy
ALL THREE PATHWAYS =
Regardless of the pathway, the effects are the same
The split of inactive C3 complement protein into C3a and C3b leads to:
what are the effects of complement protein system
- Pore formation and cell lysis (MAC)
- Enhanced phagocytosis
- Histamine release
- Pore formation and cell lysis (MAC)
Pore formed in cell membrane by many complement proteins
Destroys integrity of target cell
- Enhanced phagocytosis
Attracts phagocytes and makes target cells easier to engulf
Process called OPSONIZATION
- Histamine release
By mast cells and basophils
Increases inflammation and blood flow to region
opsonization
Opsonization is an immune process which uses opsonins to tag foreign pathogens for elimination by phagocytes.
Without an opsonin, such as an antibody, the negatively-charged cell walls of the pathogen and phagocyte repel each other.
3) IRON-BINDING PROTEINS
Inhibit the growth of certain bacteria by reducing the amount of available iron
i.e. transferrin, lactoferrin, ferritin
3) ANTIMICROBIAL PROTEINS
Short peptides that have a broad spectrum of antimicrobial activity
—> Includes killing and assisting other cells in targeting and neutralizing microbes
antimicrobial proteins E.g.
dermicidin, defensins, catherlicidins, thrombocidin
SECOND LINE OF DEFENSE: INFLAMMATION
Localized tissue response to injury, producing the cardinal signs and symptoms of inflammation:
Local redness
Swelling
Heat
Pain
Sometimes lost function
SHARP
Sis for swelling caused by an accumulation of fluids
His for heat which is also due to more blood rushed to the affected area
Ais for altered function or loss of function that results in severe inflammation
Ris for redness because more blood is rushed to the affected area
Pis for pain due to the release of certain chemicals
inflammation caused by
Caused by various stimuli that kill cells, damage connective tissue fibers, or injure tissue
Cause a change in chemical composition of the interstitial fluid
(inflammation) what do damaged cells release
Damaged cells release prostaglandins, proteins, and potassium ions
Foreign proteins or pathogens may have been introduced
—> trigger complex inflammation response
THREE STAGES OF INFLAMMATION RESPONSE
- Vasodilation and increased permeability of blood vessels
- Emigration of phagocytes from the blood to interstitial fluid
- Tissue repair
- Vasodilation and increased permeability of blood vessels
VIA WHICH SUBSTANCES?
vasodilation / permeability of BV
VIA WHICH SUBSTANCES?
KININS
HISTAMINE
PROSTAGLANDINS
LEUKOTRINES (LTs)
COMPLEMENT
histamine – which cells release?
mast cells, basophils and platelets
histamine – which cells STIMULATE its release
Neutrophils and MO (monocytes?)
a) histamine
Histamine:
—> Released by mast cells, basophils and platelets
—> Neutrophils and MO (monocytes?) stimulate its release
—> Causes vasodilation and increased permeability
b) KININS
Polypetides (e.g. bradykinin)
Induce vasodilation and increased permeability
Serve as chemotactic agents for phagocytes
bradykinin define
“a compound released in the blood in some circumstances that causes contraction of smooth muscle and dilation of blood vessels. It is a peptide comprising nine amino-acid residues.”
histamine vs kinins?
The action of the kinins on the microvasculature is similar to that of histamine, that is, potent vasodilatation. =
Kinins are rapidly destroyed by tissue proteases, suggesting their importance is limited to the early inflammatory stage of wound healing.
histamine quicker than kinins (??)
..
c) Prostaglandins (PGs)
Lipids released by damaged cells
Intensify the effects of histamine and kinins
Stimulate emigration of phagocytes (chemotaxis?)
d) Leukotrienes (LTs)
Produced by basophils and mast cells
Cause increased permeability
Adherence of phagocytes to pathogens
Chemotactic agents that attract phagocytes
e) Complement
Stimulate histamine release, attract neutrophils by chemotaxis, promote phagocytosis, same can destroy bacteria
what cells release LTs
basophils and mast cells
what do basophils and mast cells release
LTs
Histamine
(also via platelets)
what stimules HISTAMINE release
Neutrophils
monocytes (?)
complement proteins
which of 5 inflammation substances are CHEMOTACTIC
all?
complement
LTs
PGs
Kinins
histamine (?)
which one enhances effect of histamine/kinins?
PGs
INFLAMMATION
- EMIGRATION OF PHAGOCYTES
A process, dependent on chemotaxis, in which phagocytes migrate to the area of tissue damage and squeeze through holes in the endothelium of the blood vessel wall
NOTE THAT SAME SUBSTANCES THAT INCREASE BV PERMEABILITY/DILATION
ALSO ARE CHEMOTACIC (trigger emigration of phagocytes)
..
leukocytosis
Increased production and release of WBCs in red bone marrow
“Leukocytosis is a high white blood cell count. It can occur when you have infection or inflammation in your body.”
INFLAMMATION
- TISSUE REPAIR
Once the inflammation & edema subsides, fibroblasts bring in ground substance that contains protein aggregates to help with tissue repair
New collagen, elastin, & fibrin are brought in, and new blood vessels and neuronal synapses are formed
**SECOND LINE OF DEFENSE: FEVER
Body temperature > 37.8ºC (100ºF)
—> 38 C
—> either 100.0 F (37.8 C) or 100.4 F (38 C).
37ºC is normal body temperature
—> (36.4 C) to 99.6 F (37.6 C)
—> between 97 F (36.1 C) and 99 F (37.2 C)
low vs moderate vs high fever
low = to 38.0 C
moderate = 38.1 to 39.0
high = 39.1 to 41 C
Pyrogens
Circulating fever-inducing proteins
Reset temperature thermostat in hypothalamus
—> Raise body temperature
what is function of fever
Can be beneficial within limits
—> May inhibit some viruses and bacteria
—> Increases metabolic rate, which may accelerate tissue defenses and repair process
SUMMARY OF INNATE IMMUNITY
Physical barriers and chemical barriers
—> Prevent approach of pathogens and deny them access
Phagocytes
—> Remove debris and pathogens
Immune surveillance
—> Destroys abnormal cells
Interferons
—> Increase resistance of cells to viral infections
—> Slow the spread of disease
Complement system
—> Attacks and breaks down surfaces of cells, bacteria, and viruses
—> Attracts phagocytes
—> Stimulates inflammation
Fever
—> Mobilizes defenses
—> Accelerates repairs
—> Inhibits pathogens
adaptive (specific) immunity
Not present at birth
Specific response to a particular antigen
Exposure to antigen (natural or vaccine)
—> Active immunity
Receiving antibodies
—> Passive immunity
passive immunity
receiving antibodies (injection?)
adaptive immunity coordinated and produced by
Coordinated and produced by T cells and B cells
acitve immunity
1) Naturally acquired
2) artificially induced
naturally acquired active immunity
Develops after natural exposure to antigens in the environment
Example: contracting the measles gives immunity against future infection by that specific pathogen
artificially induced active immunity
Develops after administration of an antigen
Example: vaccination (immunization)
vaccines
Vaccines contain dead or inactive pathogens, antigens derived from those pathogens, or simulated antigens
Stimulate immune response to produce antibodies against that specific pathogen
passive immunity tpes
1) Naturally acquired
2) Artificially induced
naturally acquired passive immunity
Example: transfer of maternal antibodies across placenta or breast milk
artificially induced passive immunity
Example: administration of antibodies to a patient
properties of adaptive immunity
1) Specificity
2) Versatility
3) Memory
4) Tolerance
1) Specificity
T cells and B cells have receptors for only one specific antigen
Responses of activated T cell or B cell are also specific (do not affect any other antigens)
2) Versatility
Millions of lymphocytes, each sensitive to a different antigen
When activated, a lymphocyte divides
Produces more lymphocytes with same specificity
All cells produced by the division of an activated lymphocyte constitute a clone
3) Memory
Activated lymphocytes produce two groups of cells
a) Groups that attack invaders immediately
b) Group that remains inactive unless exposed to the same antigen later
—> These memory cells “remember” antigens, making future attacks faster, stronger, and longer lasting
4) Tolerance
Immune response ignores “self” but targets abnormal and foreign “nonself” cells and toxins
Can develop over time in response to chronic exposure to an antigen
Types of Adaptive Immune Cells
The adaptive immune response is produced and coordinated by lymphocytes (T cells and B cells)
Types of B cells:
Plasma cells: create antibodies
Memory B cells
Types of T cells:
a) Cytotoxic (suppressor) T cells (CD8+ cells)
—> Kill infected cells
b) Helper T cells (CD4+ cells)
—> Help activate immune cells (T and B)
c) Regulatory T cells
d) Memory T cells
CD marker define
CD is an abbreviation “for cluster of differentiation”. CD molecules are cell surface markers which are very useful for the identification and characterization of leukocytes and the different subpopulations of leukocytes.
The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophenotyping of cells
T Cell CD markers
Membrane proteins
involved in antigen
recognition
CD stands for “cluster of differentiation”
Two classes associated with T cell:
CD4 & CD8
Two classes associated with T cell:
CD8 markers
(on CD8 T cells: cytotoxic and regulatory T cells)
CD4 markers
(on CD4 T cells: helper T cells)
Overview of the immune response
Antigens either infect cells or are “processed” by phagocytes
Antigens or antigenic fragments are then displayed on the plasma membrane
Called antigenic presentation
—> (PHAGOCYTE, DENDRITIC CELLS, B CELLS)
Triggers an immune response
presentation of specific antigens stimulates
a) Cell-mediated immunity (T cells)
b) Antibody-mediated immunity (B cells)
2 types both triggered by antigens
Both of these types of responses are aided by helper T cells
a) Cell-mediated immunity
Cytotoxic T cells directly attack cells
b) Antibody-mediated immunity
Activated B cells transform into plasma cells, which synthesize and secrete specific proteins called antibodies (Abs) / immunoglobulins (Igs)
Antibodies bind to and inactivate specific extracellular antigens
which cell type aids in both Cell-mediated immunity & antibody-mediated immunity
Both of these types of responses are aided by helper T cells
Cell-mediated immunity is effective against:
Intracellular pathogens: viruses, bacteria, fungi
Some cancer (tumour) cells
Foreign tissue transplants
Antibody-mediated immunity is effective against:
Extracellular pathogens
—> Viruses, bacteria, fungi that are in extracellular fluids
in other words, T cells…
attack infected cells
in other words, B cells…
attack invaders outside cells (via antibodies they release)
Antigens
any substance that causes the body to make an immune response against that substance
antigen =
antibody generator
antigen may be
Bacteria or virus
Chemicals or toxins
Pollen
Self-protein (autoimmune)
Abnormal cellular protein (E.g. cancer cells)
small portion of the antigen that interacts with immune receptors
The small portion of the antigen that interacts with immune receptors on T cells or antibodies is called an EPITOPE
epitope
upon + place
“the part of an antigen molecule to which an antibody attaches itself.”
“An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that binds to the epitope is called a paratope.”
Antigens have 2 important characteristics:
Antigenicity
Immunogenicity
Antigenicity
the ability of antigen to combine specifically with immune cells or antibody
Immunogenicity
The ability to provoke an immune response by stimulating the production of specific antibodies, the proliferation of specific T cells, or both
Hapten
a small molecule which, when combined with a larger carrier such as a protein, can elicit the production of antibodies which bind specifically to it (in the free or combined state).
Haptens
Have antigenicity but lack immunogenicity
Can stimulate an immune response only if it is attached to a larger carrier molecule
Example: poison ivy (reacts with skin proteins to generate immune response)
epitope aka
antigenic determinant site (?)
bacterium can contain millions of…
A bacterium can contain millions of antigenic determinant sites
Can become carpeted with antibodies
which routes do antigens follow when they get past innate immune system?
Antigens that get past our innate defenses generally follow one of three routes into lymphatic tissue:
a) Via blood stream to the spleen
b) Via skin through lymphatic vessels to lymph nodes
c) Via mucous membranes to MALT
Clonal Selection
The process by which lymphocytes proliferate (divide) and differentiate (form more highly specialized cells) in response to a specific antigen
result of clonal selection
Formation of a population of identical cells, called clones, that can recognize the same specific antigen as the original lymphocyte
where does clonal selection occur?
Occurs in secondary lymphatic organs
secondary lymphatic organs
lymph nodes, spleen, tonsils (MALT?), …
Lymphocytes that undergo clonal selection give rise to 2 major cell types:
a) Effector cells
b) Memory cells
a) effector cells
Carry out immune responses that ultimately result in the destruction or inactivation of the antigen
Die after immune response is completed
E.g.
active helper and cytotoxic T cells, plasma cells
b) memory cells
Do not actively participate in the initial immune response to the antigen
Do not die at the end of an immune response
Result in a quicker response to any subsequent exposures
E.g.
memory helper T cells, memory cytotoxic T cells, memory B Cells
where?
lymph nodes, MALT, spleen (?)
Major histocompatibility complex (MHC) proteins
aka Human Leukocyte Antigens (HLA)
Genetically determined membrane glycoproteins
MHC proteins display antigens that were processed inside the cell
Placement of the antigen-glycoprotein combination on the plasma membrane is called antigen presentation
what is the function of antigen presentation
Capable of activating T cells
“the functioning of both cytotoxic and helper T cells is dependent on APCs”
Two classes of MHC proteins
a) Class I MHC proteins (MHC I)
b) Class II MHC proteins (MHC II)
a) Class I MHC proteins (MHC I)
Present in all nucleated cells
Triggered by viral or bacterial infection of a body cell
MHC I display intracellular or endogenous antigens
b) Class II MHC proteins (MHC II)
Present only in antigen-presenting cells (APCs)
—> Examples: monocyte–macrophages, dendritic cells, B cells
Appear only when the cell is processing antigens
MHC II display extracellular or exogenous antigens
recall, what else is related to intracellular/extracellular antigens?
cell-mediated immunity is against INTRACELLULAR PATHOGENS (via T cells)
antibody-mediated immunity is against EXTRACELLULAR PATHOGENS (via B cells)
antigen-MHC complex
Antigenic proteins are broken down into peptide fragments and attached to either an MHC I or MHC II protein depending on the cell
Antigen–MHC complex is inserted into the plasma membrane of the cell (antigen presentation)
peptide fragment source vs response
If peptide fragment comes from:
—> a self protein, then lymphocytes ignore it
—> a foreign protein, then lymphocyte initiates immune response
Processing Extracellular or Exogenous Antigens
Extracellular or exogenous antigens exist outside of cells
Examples:
bacteria and bacterial toxins
viruses
parasites
inhaled pollen and dust
APCs vs exogenous antigens
Antigen-presenting cells (APCs)
–> Process and present exogenous antigens
–> Include: dendritic cells, macrophages and B cells
–> Located in areas where antigens are likely to penetrate innate defenses
–> After processing and presentation of antigen they migrate from tissues via lymphatic vessels to lymph nodes
how are extracellular antigens displayed
EXTRACELLULAR OR EXOGENOUS ANTIGENS ARE DISPLAYED ON MHCII PROTEINS
what happens after exogenous antigen is displayed by apc
APCs process antigens and present them to T cells. Antigen presentation stimulates immature T cells to become either mature “cytotoxic” CD8+ cells or mature “helper” CD4+ cells.
“Lymph tissue and bloodstream: Fully mature T-cells travel to tissue and organs in your lymph system, like your spleen, tonsils and lymph nodes. They may also circulate in your bloodstream.”
“…. The dendritic cell is then a fully mature professional APC. It moves from the tissue to lymph nodes, where it encounters and activates T cells.”
Processing Intracellular or Endogenous Antigens
Intracellular or endogenous antigens exist inside cells
Examples:
–> viruses
–> bacterial toxins
–> abnormal protein synthesis by a cancerous cell
INTRACELLULAR OR ENDOGENOUS ANTIGENS ARE DISPLAYED ON MHCI PROTEINS
Cytokines
Small protein hormones that stimulate or inhibit many normal cell functions, such as cell growth and differentiation.
Secreted by lymphocytes, APCs, fibroblasts, endothelial cells, monocytes, and more
Examples include;
Interleukins (ILNs), Tumor Necrosis Factor (TNFs), Granzymes, Perforin, Interferons (IFNs)
cytokine define
any of a number of substances, such as interferon, interleukin, and growth factors, which are secreted by certain cells of the immune system and have an effect on other cells.
interleukin define
any of a class of glycoproteins produced by leukocytes for regulating immune responses.
interferon define
a protein released by animal cells, usually in response to the entry of a virus, which has the property of inhibiting virus replication.
**ACTIVATING CELL-MEDIATED IMMUNITY
The surface of cytotoxic T cells have:
a) T cell receptors (TCRs)
b) CD8 co-receptor
Antigen binding by a TCR with CD4 or CD8 proteins is the first signal in activation of a T cell
a) T cell receptors (TCRs)
Antigen receptors on the surface of T cells that recognize and bind to specific foreign antigen fragments that are presented in antigen-MHC complexes.
b) CD8 co-receptor
help maintain the proper TCR-MHC coupling
Activation of CD8 T cells
(Activating Cell-mediated Immunity)
1) Antigen recognition
2) Costimulation
3) Activation and cell division
Activation of CD8 T cells
(Activating Cell-mediated Immunity)
Step 1)
“Antigen recognition”
Occurs when CD8 T cell encounters specific antigen bound to a class I MHC protein on the surface of another cell
—> Body cells infected by microbes (usually APCs)
—> Some tumor cells
—> Cells of a tissue transplant
(antigen within cell, non-self proteins)
Activation of CD8 T cells
(Activating Cell-mediated Immunity)
Step 2)
“Costimulation”
Physical or chemical stimulation of T cell in addition to the class I MHC molecule
More that 20 known costimulators
—> Some cytokines (e.g. interleukin-2)
—> Pairs of plasma membrane molecules
Like the safety on a gun: prevents T cells from mistakenly attacking normal cells
Recognition with no costimulation leads to a prolonged state of inactivity called ANERGY
anergy define
absence of the normal immune response to a particular antigen or allergen.
“without” + “work”
IL-2
Interleukin-2 (IL-2) is an interleukin, a type of cytokine signaling molecule in the immune system. It is a 15.5–16 kDa protein[5] that regulates the activities of white blood cells (leukocytes, often lymphocytes) that are responsible for immunity.
Activation of CD8 T cells
(Activating Cell-mediated Immunity)
Step 2)
“activation and cell division”
Three different types of
CD8 T cells produced
(all sensitive to the same antigen):
-> Cytotoxic T cells
-> Memory T (cytotoxic?) cells
-> Regulatory T cells (T reg cells)
Activated Cell-Mediated Immunity
Activation and Clonal Selection of Cytotoxic T cells
A) Active Cytotoxic T cells
—> Leave secondary lymphatic organs and tissues and migrate to seek out and destroy infected target cells, cancer cells, and transplanted cells
B) Memory cytotoxic T cells
—> Act quickly during a second encounter with the same antigen
cytotoxic T cell action after Cell-mediated immunity activated
Cytotoxic T cells are like ‘assassins’ – they leave the secondary lymphatic organ to hunt down their victims (which have a specific antigen in a MHC I molecule).
which cells are cytotoxic T cells similar to
Cytotoxic T cells kill much like NK cells
a) Granzymes
b) Perforin and/or granulysin
c) Release lymphotoxin
a) Granzymes
Protein-digesting enzymes that trigger apoptosis (microbes are then killed by phagocytes)
b) Perforin and/or granulysin
Pierces the cell (cytolysis)
c) Release lymphotoxin
Activates enzymes in the target cell
Activating Antibody-Mediated Immunity
Antigen-presenting cells can stimulate activation of CD4 T cells, producing helper T cells that promote B cell activation and antibody production
Activation of CD4 T cells
First must be exposed to antigens bound to class II MHC proteins
Costimulation completes activation
Next step involves series of divisions
—> Daughter cells differentiate into active helper T cells (TH cells) and memory TH cells
Active helper T cells secrete cytokines
—> Stimulate both cell-mediated and antibody-mediated immunity
B cell sensitization
Preparation for activation is called SENSITIZATION
—> Antigens are brought into cell through endocytosis and then placed on surface of cell bound to class II MHC proteins
inactive B cell –> sensitized B cell –> activated B cell (via helper T cell)
B cell activation
Full activation requires helper T cell
—> Helper T cell must have been activated by exposure to the same antigen
—> Helper T cell binds to MHC complex of sensitized B cell
= Secretes cytokines to promote B cell activation
B cell division, differentiation, and antibody production
Stimulation by cytokines causes series of cell divisions in B cells
Two types of daughter cells
A) Memory B cells
B) Plasma cells
A) Memory B cells
Inactive until second exposure to antigen
Respond then by differentiating into plasma cells
B) Plasma cells
Activated B cells, each capable of secreting up to 100 million antibody (immunoglobulins) molecules per hour
Unlike Cytotoxic T cells which leave lymphatic tissues to seek out and destroy a foreign antigen, B cells remain in lymphatic tissue
WHERE DO B CELLS REMAIN??
B cells remain in lymphatic tissue
Antibodies
Antibodies are small soluble proteins that bind to specific antigens and whose abundance increases upon later antigen exposure
antibody molecule structure
Consists of two parallel polypeptide chains
—> One pair of heavy chains
—> One pair of light chains
**
Each pair contains:
—> Constant segments
(On heavy chains, form the base of antibody molecule)
—> Variable segments
(Free tips are antigen binding sites)
(Differences in amino acid sequences produce variability needed for different antibodies)
Classes of antibodies, or immunoglobulins (Igs) – determined by…
Class determined by
differences in structure of
the heavy-chain constant
segments
There are five classes of antibodies:
IgG
IgE
IgD
IgM
IgA
IgG
Most numerous of the 5 types (75 percent of all antibodies in the bloodstream)
Found in blood, lymph and the intestines
Responsible for resistance against many viruses, bacteria, and bacterial toxins
Only one to cross placenta from mother to child*****************
Only one to cross placenta from mother to child
IgG
IgE
Least common of 5
Attaches to basophil and mast cell surfaces
Involved in allergic, parasitic, & hypersensitivity reactions
IgD
On B cell surface, where it binds antigens in extracellular fluid
Plays role in B cell SENSITIZATION
IgM
First class of antibody secreted after antigen encountered
Production declines as IgG production increases
Therefore, indicates recent infection
Anti-A and anti-B antibodies are examples
(BLOOD CELL ANTIGENS/Ab)
Anti-A and anti-B antibodies
IgM
biggest Immunoglobulin
IgM
“IgM is the largest antibody and the first one to be synthesized in response to an antigen or microbe, accounting for 5% of all immunoglobulins present in the blood”
IgA
Found primarily in glandular secretions, such as mucus, tears, saliva, breast milk, and semen
Attack before pathogens gain internal access
Antigen-antibody complex
Formed when a specific antibody molecule binds to its corresponding antigen molecule
Binds to specific portions of the exposed surface called ANITGENIC DETERMINANT SITES or EPITOPE on an antigen
(Bacteria may contain millions of antigenic determinant sites)
Antibody Mechanisms
(Methods of eliminating antigens)
1) Neutralization
2) Prevention of pathogen adhesion
3) Activation of complement
4) Stimulation of inflammation
5) Attraction of phagocytes
6) Opsonization
7) Precipitation and agglutination
1) Neutralization
Antibodies occupy binding sites on viruses and bacterial toxins, preventing them from affecting body cells
2) Prevention of pathogen adhesion
IgA antibodies in glandular secretions cover bacteria or viruses, preventing adhesion and infection of body cells
3) Activation of complement
After antigen binding, complement also can bind to the antibody, accelerating the complement cascade
4) Stimulation of inflammation
Stimulate basophil and mast cells to release chemicals
5) Attraction of phagocytes
Attached antibodies attract eosinophils, neutrophils, and macrophages
6) Opsonization
Coating of pathogen with antibodies allows phagocytes to bind more easily
7) Precipitation and agglutination
Antibodies can bind to antigenic determinant sites on adjacent antigens
The linking of multiple pathogens by antibodies creates an IMMUNE COMPLEX
—> Formation of insoluble complexes (too large to stay in solution) is called PRECIPITATION
—> Formation of an immune complex from surface antigens is called AGGLUTINATION
E.g.
clumping of RBCs in a transfusion reaction
AGGLUTINATION
(immune complex?)
—> Formation of an immune complex from surface antigens is called AGGLUTINATION
E.g.
clumping of RBCs in a transfusion reaction
PRECIPITATION
(immune complex?)
—> Formation of insoluble complexes (too large to stay in solution) is called PRECIPITATION
LEAST COMMON IMMUNOGLOBULIN
IgE
Immunological Memory
Due to the presence of long lasting antibodies and very long-lived lymphocytes (memory cells) which arise during clonal selection of activated B and T cells
Primary response
Antibody-mediated response to initial antigen exposure
Takes time to develop
—> Appropriate B cells must be activated then differentiate into antibody-secreting plasma cells
antibody TITER
Antibody titer (level of antibodies in the blood) peaks 1–2 weeks after initial exposure
Levels decline if no longer exposed to the antigen
Secondary response
Triggered when antigen is encountered again
More extensive and lasts longer than primary response
–> Antibody titers increase more rapidly and reach higher concentrations
Result of immediate response by memory B cells for specific antigen
Appears even if second exposure is years after the first
how long can memory cells potentially survive?
—> Memory cells may survive 20 years or more
immunization / vaccines
Provides the basis for immunization by vaccination against certain diseases.
—> Originally discovered by Edward Jenner in early 1796 working with cowpox
—> Redeveloped in 1950 by Jonas Salk working with polio
Types of vaccines
Inactivated vaccines
—> Killed whole pathogen
Live-attenuated vaccines
—> Weakened whole pathogen that can no longer replicate and cause disease
Subunit, recombinant, polysaccharide, and conjugate vaccines
—> Specific portion of pathogen
mRNA
—> Genetic material coded for specific pathogen antigen
Integrated Immune Response
Responses to bacterial and viral infection
Overcoming a bacterial infection
—> Most effective defenses involve phagocytosis and antigen presentation by APCs
Overcoming a viral infection
—> Cytotoxic T cells and NK cells can be activated by direct contact with virus-infected cells
—> Process also involves antigen presentation and subsequent responses
pathologies
Type I (anaphylactic)
—> Most common, occurs due to immediate hypersensitivity due to re-exposure to an allergen (mainly IgE)
Type II (cytotoxic)
—> Antibodies (IgG or IgM) directed against antigens on a person’s blood or tissue cells (basis of some autoimmune diseases)
Type III (immune-complex)
—> Ag/Ab complexes that escape phagocytosis leading to inflammation (IgA or IgM) (eg. RA)
Type IV (cell mediated)
—> aka delayed hypersensitivity
—> 12-72 hrs post exposure to an allergen, activated T-cells move to the site of initial antigen entry and stimulate an inflammatory response (eg. contact dermatitis)
Acquired Immunodeficiency Syndrome (AIDS)
Caused by human immunodeficiency virus (HIV)
Virus binds to CD4 proteins and infects helper T cells:
Infected cells synthesize and release new viral proteins
Helper T cells are destroyed by virus or immune defenses
Impairs both cell-mediated and antibody-mediated responses
Suppressor T cells not affected
HIV –> AIDS — what happens
Body more vulnerable to microbial invaders, opportunistic infections, and cancer
Spread by contact with body fluids
Infects 33 million people worldwide, with 2 million deaths each year
Infectious Mononucleosis
Mono or kissing disease
Contagious disease caused by Epstein-Barr Virus (EBV)
No cure, runs its course in a few weeks
Symptoms:
Fatigue
Headache
Dizziness
Sore throat
Enlarged, tender lymph nodes
Fever
Systemic Lupus Erythematosus (SLE)
Chronic, autoimmune, inflammatory disease that affects multiple body systems
Cause unknown
Affects many tissues around the body leading to wide ranging symptoms
Characterized by periods of active disease and remission (relapsing-remitting)
Develops between ages of 15-44 (mainly females)
Most common symptom is a ‘butterfly rash’
Arthritis is also very common
Rheumatoid Arthritis
Autoimmune and inflammatory disease creating severe joint pain
Body produces antibodies that recognize joints as foreign and attacks them causing severe pain, inflammation and joint deterioration
Risk factors include family history, being female and a smoker
(RA) Severe joint inflammation can lead to joint deformities such as:
Boutonniere deformity:The middle finger joint bends toward the palm while the outer finger joint may bend opposite the palm.
Swan-neck deformity:The base of the finger and the outermost joint bend, while the middle joint straightens.
Hitchhiker’s thumb:The thumb flexes at the metacarpophalangeal joint and hyperextends at the interphalangeal joint below your thumb nail. It is also called Z-shaped deformity of the thumb.
Claw toe deformity:The toes are either bent upward from the joints at the ball of the foot, downward at the middle joints, or downward at the top toe joints and curl under the foo
Myasthenia Gravis
Body produces antibodies that recognize the NMJ (neuromuscular junction) as foreign
Produces Abs that block Ach receptors on the motor end plate side and thus decrease the number of functional receptors
Causes progressive muscle weakness and atrophy
Lymphomas
Idiopathic cancers of the lymphatic organs.
Hodgkin’s Lymphoma (Hodgkin’s Disease)
—> Ages 15-35 and those over 60, males > females.
—> Painless, nontender enlargement of one or more lymph nodes in the neck, chest and axilla
—> better prognosis with early detection
**
Non-Hodgkin’s Lymphoma
—> All age groups; more common and more fatal
—> Starts the same way as HD but include an enlarged spleen, anemia and general malaise
