Week 9 Lymphatic system and Immunity Flashcards
_________ make up 20 - 25% of the total leukocyte count – they are the primary cells of the immune response.
Lymphocytes.
Lymphocytes have the ability to meet, adapt, recognize, and target specific antigens. They belong to the __________ immunity pathway.
Adaptive.
B-Cells can differentiate into _________, that are capable of making antibodies.
Plasma cells
What do CD4 T-cells do?
These are also known as T-helper cells, they are part of the process of stimulating a B-cell to differentiate into a plasma cell to produce a specific antibody. They also release cytokines (“alarm system”) that will stimulate an activated T-cell to differentiate into a cytotoxic T-cell.
What do CD8 T-cells do?
These are also called cytotoxic T-cells, or killer T-cells. They can identify and kill a target cell.
Where is red bone marrow found?
It is found in long and flat bones of pelvis, vertebrae, cranium/mandible, sternum/ribs, upper limb girdle and prox. portions of the femur (epiphyses).
Red bone marrow is the primary residence of hematopoietic stem cells (HSCs) (blood making cells). Red marrow is also called ___________?
Myeloid tissue, or active marrow, or hematopoietic marrow.
Hematopoietic stem cells give rise to lymphoid progenitor cells and myeloid progenitor cells. What do each of these mature/differentiate into?
Lymphoid progenitor cells mature and differentiate into lymphocytes (T and B cells).
Myeloid progenitor cells differentiate into RBCs, platelets, and myeloblasts (progenitors of basophils, neutrophils, eosinophils and monocytes).
Most marrow is red during birth/early adolescence and is replaced with _______ marrow as we age.
Yellow, or inactive, marrow.
The hematological compartment of both red and yellow bone marrow is made up of cellular microenvironments, or niches.
What do the niches control?
Niches control the differentiation of hematopoietic progenitor cells.
(Special cells within niches support cellular communication, which then determines differentiation).
Yellow (inactive) marrow is found in which kinds of bones?
Long bones.
What is the structure of yellow bone marrow?
-consists of cells and blood vessels held within connective tissue framework
-majority of cells = adipocytes (main cell found in adipose) and mesenchymal stem cells (MSCs)
-large quantity of fat adipose makes it appear yellow
In yellow bone marrow, ____________________ give rise to osteoprogenitor cells, which differentiate into osteoblasts (and under certain circumstances, can differentiate into fibroblasts (connective tissue), adipocytes, chondrocytes (cartilage), and muscle cells)
Mesenchymal stem cells (stromal cells)
Most bone marrow is red during our early years, and is replaced with yellow marrow as we age.
Is this permanent or reversible?
Yellow marrow an be converted to red marrow in times of stress (eg. acute blood loss) to assist in hematopoiesis.
The innate and adaptive immune systems are highly interactive and complementary. They are connected (mainly) via _____cells.
Dendritic.
What is clonal diversity?
Clonal diversity: the process by which B and T cells establish their diversity of antigen receptors.
What is clonal selection?
Clonal selection: begins when an infection occurs. An antigen is processed and presented to lymphocytes which causes further B-cell and T-cell differentiation.
Differentiate between cellular immunity and humoral immunity.
Cellular Immunity – T-cells circulate in the blood and tissues and defend against intracellular pathogens and cancer cells
Humoral Immunity – antibodies circulate in the blood and defend against extracellular microbes and microbial toxins.
Explain the difference between autoimmunity and alloimmunity.
Autoimmunity (i.e. against self) – disturbance in the immunological tolerance of self-antigens. All healthy individuals can produce low quantities of antibodies against their own antigens without developing overt disease
Alloimmunity (i.e. against other humans) – the immune system of one individual produces an immunological reaction against tissues of another individual. Can be seen with transfusions, transplants, or a fetus during pregnancy.
What types of hypersensitivity reactions are usually seen in an allergic reaction?
Mostly Type I, can be type IV
(Type II and III are rare)
Type I: ie
-Peanuts
-Bee Stings
-Eggs
-Shellfish
-Seasonal Allergies
Type IV: ie
-Poison ivy
-Metals
-Latex
What types of hypersensitivity reactions are usually seen in an autoimmune reaction?
Mostly Type III, can be Type II or IV.
(Type I is rare |)
Type III: ie Systemic Lupus Erythematosus
Type II: ie Autoimmune Thrombocytopenia
Type IV: ie Hashimoto Thyroiditis
What types of hypersensitivity reactions are usually seen in an alloimmune reaction?
Mostly Type II or IV.
(Rarely Type I or III)
Type II: ie Hemolytic disease of the newborn
Type IV: ie Graft Rejection
Which of the 4 hypersensitivity types is cell mediated?
(The other 3 are antibody mediated.)
Type IV is cell mediated as it is a response initiated by T-helper cells. Leads to cytotoxicity.
What is the response time for a Type IV hypersensitivity reaction?
It is a delayed reaction, 48-72 hours.
What type of hypersensitivity reaction are you looking for when you do a TB skin test?
Type IV.
Which two types of effector cells are involved in a Type IV hypersensitivity reaction?
Lymphocytes and macrophages.
Where do B cells mature
Bone marrow
What do B cells differentiate into
Plasma cells (produce antibodies) and memory cells
Where do T cells mature
Thymus
What do T cells differentiate into
Th cells, Tc cells, T reg cells, memory cells
What do Th cells do
Assist in clonal selection, including B cell differentiation into plasma cell. Secrete cytokines to stimulate marcrophages
What do Tc cells do
cytotoxic; recognize antigens on cells on surface of virus infected or cancerous cell, then attach and kill (usually makes the target cell undergo apoptosis)
What do T reg cells do
regulatory, suppress innapropriate immune response. Maintains tolerance against self antigens.
What kind of T cell does HIV target
Th cells (thus making you vulnerable to infection cause interferes with differentiation and adaptive response)
What are memory cells
Differentiated B or T cells that last for decades or lifetime; quickly response to familiar antigens
Describe the structure of a lymph vessel
thin walls, structured similarly to vein with endothelial flaps (1 way valves). Capillaries closed at ends.
Describe pathway of lymphatic vessel
Lymphatic capillaries > lymphatic venules > lymphatic veins > ducts (R lymphatic duct drains from R arm, head, and thorax into R subclavian vein; L lymphatic duct is larger and receives lymph from rest of body and drains into L subclavian vein
where are lymphatic vessels located
runs in sheath with arteries and veins
Function of lymphatic vessels
collect interstitial fluid from tissues, transports as lymph through vessels of increasing size to lymph nodes, eventually draining into systemic circulation via subclavian vein
Describe the structure of the thymus
two lobes with cortex and medulla. Many types of cells (thymus epithelial cells and thymocytes are important ones; also has fibroblasts, dendritic cells, macrophages, monocytes, B cells)
Location of thymus
behind sternum between lungs in front of ascending aorta
Function of thymus epithelial cells
make cytokines that play a role in thymocyte development
Function of thymus
-in utero and childhood, thymus involved in production and maturation of T-lymphocytes (important in adaptive immunity)
-The thymus produces and secretes thymosin, a hormone necessary for T cell development and production
True or false: the thymus is an endocrine and lymphatic gland
True. Secretes a hormone making it an endocrine gland (thymosin). Development of clonal diversity of T cells making it lymphatic
True or false: the thymus grows larger as we age
False. After puberty, the thymus shrinks and is replaced by fat. It does not function throughout a full lifetime.
What are adenoids?
Pharyngeal tonsils
Describe the structure of the adenoids
-mucosa associated lymphoid tissue
-pyramid shaped
-composition= respiratory epithelium and lymphoid tissue
-surface has specialized antigen capture cells (ACC)
Location of adenoids
-in the nasopharynx
-apex directed towards nasal septum and base of the pyramid between the roof and the posterior wall of the nasopharynx
*part of Waldeyer ring
Function of adenoids
-defence against potential pathogens in pharynx
-involved in development of T cells and B cells
-ACC uptake pathogenic antigens, alert and activate B cells, results in proliferation in germinal centers, results in production of IgA immunoglobulins
What is innate immunity
Natural barriers (physical and biochemical) and inflammatory response. Non specific and immediate. Protects body from injury/ infection, and responds to prevent further injury/ infection, promote tissue healing, and initiate the adaptive reponse.
Describe some physical barriers
epithelium, cilia, mucous, earwax, mechanical processes (cough, sneeze, vomit, urinating), temperature (low skin temp), pH (skin and stomach), normal microbiome
Briefly describe inflammation
Systematic process that responds to cellular or tissue damage, whether the damaged tissue is septic or sterile. Rapid initiation of interactive system or humoral and cellular systems to limit tissue damage, destroy contaminating infectious microorganism, initiate the adaptive immune response, and begin healing.
Briefly describe process of inflammation
Processes
1) Vasodilation (slower blood velocity, increased blood flow to injured site)
2) Increased vascular permeability (edema, erythema, warmth)
3) White blood cell adherence to endothelium (and migration into vessels/ tissue)
Benefits of inflammation.
Benefits
* Prevents infection and further damage; inflammatory exudate dilutes toxins produced by bacteria/ released from dying cells. Activation of plasma protein systems (completement and clotting) contain and destroy bacteria. Influx of phagocytes to destroy cell debris and microorganisms
* Limits and controls inflammatory response (keeps it contained/ localized)
* Interacts with components of adaptive immune system to elicit a more specific response
* Prepares area for healing
Phagocyte role in innate immunity
- Circulate through body looking for potential threats to engulf and destroy
- Security guards on patrol
Macrophage role in innate immunity
- Phagocytic cell that can leave the circulatory system to hunt for pathogens
- Release cytokines in order to signal and recruit other cells to an area where there are pathogens
Mast cell role in innate immunity
- Found in mucous membranes and connective tissue
- Important for wound healing
- When activated, they release cytokines and granules that contain chemical molecules to create an inflammatory cascade
Histamine – causes blood vessels to dilate, increasing blood flow, vessel permeability and cell trafficking to the area of infection
Cytokines – messenger service, alerts other immune cells (neutrophils and macrophages) to make their way to the area of infection or to be on alert for circulating threats - Key player in mounting allergic response
Neutrophil role in innate immunity
- Phagocytic cells with granules that are toxic to bacteria and fungi, and can stop them from proliferating or die on contact
- 1st cell to arrive at side of an infection because there are so many in circulation at any given time
Eosinophil role in innate immunity
- Granulocytes that target parasites and are involved in allergic response
- Secrete highly toxic proteins and free radicals to kill bacteria and parasites
- Found in thymus, lower GI tract, ovaries, uterus, spleen and lymph nodes
Basophil role in innate immnuity
- Granulocytes that attack multicellular parasites
- Release histamine – key player in mounting allergic response
Dendritic cell role in immunity
- Antigen-presenting cells located in tissues
- Can contact external environments through skin, inner mucosal lining of the nose, lungs, stomach and intestines
- Can identify threats and act as messengers for rest of the immune system by antigen presentation
- Bridge between innate immune system and adaptive immune system
What is the role of the complement system
typically acts as part of the innate immune system but can work with adaptive system if necessary. Activation produces factors that can destroy pathogens directly or can activate or increase the activity of many other components of the inflammatory and adaptive immune response. Factors produced in the activation of the complement cascade are very potent (esp against bacteria)
Describe 4 steps of complement cascade
Complement Cascade:
1) Opsonization – foreign particles are marked for phagocytosis (opsonins coat the bacteria, increase chance of phagocytosis and death by inflammatory cells (i.e., neutrophils)
* Antigen signals that there is a threat, opsonization tags infected cells and identifies circulating pathogens expressing the same antigens
2) Chemotaxis – attraction and movement of macrophages to a chemical signal (diffuse from a site of inflammation, attract phagocytes)
* Cytokines and chemocytokines attract macrophages and neutrophils to site of infection, ensuring that pathogens in area will be destroyed – improves likelihood that the treats will be destroyed, and infection treated
3) Cell lysis – breaking down or destruction of the membrane of a cell
* Proteins of the complement system puncture the membranes of foreign cells, destroying the integrity of the pathogen – weakens their ability to proliferate and helps to stop the spread
4) Agglutination – antibodies cluster and bind pathogens together (like a cowboy rounding up cattle)
* Pathogens are rounded up in same area so cells of immune system can mount an attack and weaken the infection
What is alloimmunity
Alloimmunity: immune system of one person produces an immunological reaction against the tissues/ antigens of another individual of the same species
* Immunological reactions against transfusions, transplanted tissue, fetus in pregnancy
Describe alloimmunity in transfusion reactions
Transfusion reactions
* RBCs express surface antigens and can be targets of alloimmune reactions.
* There are more than 80 different red cell antigens but the ABO and Rh systems are most important as they provoke the strongest humoral alloimmune response.
Describe alloimmunity in transplant reactions
Transplant Rejections:
* There is a large diversity of MHC (or human leukocyte antigens) molecules. This diversity is clinically relevant in transplant as one can have an immune response against the foreign HLA antigens on the donor tissue resulting in rejections.
* Because of the large number of alleles it is highly unlikely that a perfect match can be found between someone who needs a transplant and a protentional donor. The more similar two individuals are in their HLA tissue type, the more likely the transplant will be successful.
o Hyperacute- immediate and rare, usually occurs due to pre-existing antibody (type 2 reaction- tissue specific, antibody mediated- IgG or IGM)
o Acute- cell mediated (type 4 reaction) immune response that occurs within day to months after transplantation. A biopsy of the rejected organ usually shows an infiltration of lymphocytes and macrophages
o Chronic- may occur after a period of months or years. Slow progressive organ failure. Usually occurs from a weak cell mediated reaction against minor histocompatibility antigens.
Describe alloimmunity in pregnancy
Rh in pregnancy:
* Haemolytic disease of the new born was most commonly caused by IgG and anti-D alloantibody produced by Rh negative mothers against erythrocytes of their Rh-positive fetus.
* The mothers antibody crosses the placenta and destroys the red blood cells of the fetus. This has decreased because of the use of the prophylactic anti-D immunoglobin (rhogam) (prevents sensitization)
What is a type III hypersensitivty reaction
immune complex mediated, immediate reaction
What antibodies are used in type III HS reaction
IgG or IgM
Main cell effector of type III HS reaction
neutrophils
What is happening in the body in a type III HS reaction
-antigen antibody (immune) complex formed and deposited in vessel waslls or tissues
-ab binds soluble ag in circulation
-not organ/tissue specific
-harmful effects through complement activation
Example of type III HS reaction
SLE, serum sickness
Is complement used in type III HS reaction
Yes
Describe features of LN that indicate higher risk of malignancy
- Duration of lymphadenopathy > 4-6 weeks; node not returned to baseline after 8-12 weeks
- Generalized lymphadenopathy (2+ regions)
- Palpable supraclavicular, popliteal, iliac nodes are abnormal, as are epitrochlear nodes >5mm in diameter
- Supraclavicular adenopathy is assoc with high risk of intra-abdominal malignancy
- Axillary adenopathy not associated with traumatic lesion or infectious source is highly suspicious for malignancy
- Hard or “matted” nodes (malignancy or infection)
- Painless, hard irregular mass or firm rubbery lesion that is immobile or fixed may represent malignancy, but this is unreliable; no specific size is associated with malignancy
What kind of diagnostics are used for LN suspicious for malignancy
History/clinical examination
US preferred for <14 yrs (for neck masses)
CT >14 yrs (for neck masses)
Biopsy:
*Fine needle aspiration and core needle biopsy can aid when etiology is unknown or malignant risk factors present
What systemic symptoms make you suspicious that a LN is malignant
Bruising, splenomegaly, fever night sweats, unexplained weight loss (>10% body weight).
What kind of malignancy does supraclavicular adenopathy carry high risk of?
Abdominal malignancy
Malignant axillary LN can arise from what?
*Hodgkin’s or non-Hodgkin’s lymphoma (frequently in infra-clavicular nodes)
*Breast, ovarian, kidney and skin CA (melanoma) can metastasize to axillar nodes
A palpable, matted, non tender 3 cm inguinal hernia is found. What malignancy could this be indicative of?
Inguinal *>2cm can be indicative of penile/vulva squamous cell CA. & melanoma.
*50% penile/vulvar cases have inguinal lymphadenopathy.
What are three functions of the lymphatic system?
Return fluid to the heart
Helps large molecules enter the blood (hormones, lipids)
Immune surveillance
What is lymphatic fluid composed of?
Mostly water
Small amounts of dissolved proteins (mostly albumin)
Lymphocytes and antigen-presenting cells
Where does the lymph fluid come from?
About 3 litres of fluid filters/leaks out of venous capillaries into body tissues (that’s not reabsorbed into blood stream) each day –> this fluid becomes lymph & is carried by lymphatic vessels to chest to enter venous circulation
Describe the path that lymph travels
Lymph travels through lymphatic capillaries, into lymphatic vessels, into lymphatic trunks –> drain into one of 2 large ducts in thorax (right lymphatic duct and thoracic duct)
Right lymphatic duct drains lymph from right arm & right side of head and thorax
Thoracic duct (which is larger) receives lymph from rest of body
Right lymphatic duct and thoracic duct drain lymph into right and left subclavian veins, respectively
This lymph tissue is innervated by the glossopharyngeal nerve and has vascular supply from branches of the external carotid artery
The tonsils
What type of tissue are the tonsils made up of?
Lymphoid tissue, covered by respiratory epithelium. Each tonsil is contained within its own fascia
Where are the tonsils located?
positioned laterally in the pharyngeal wall between the palatoglossal arch and palatopharyngeal arch (the anterior and posterior tonsillar pillars), which merge superiorly to become the soft palate
The Waldeyer’s ring is made up of which four lymphoid tissues?
palatine tonsils (“tonsils”), pharyngeal tonsils (“adenoids”), tubal tonsils, and lingual tonsils
What is the function of the tonsils?
Protect against infection in the area of the openings between the nasal and oral cavities
What does MALT stand for? What is another name for this system?
Mucosal associated lymphoid tissue. Also referred to as the Secretory Immune System
Which tissues are included in the MALT category?
lacrimal glands, salivary glands, bronchial associated lymphoid tissue in lungs, mammary-associated lymphoid tissue in breasts, gut-associated lymphoid tissue including lymph nodes and Peyer patches, genital associated lymphoid tissue
Plasma cells secrete antibodies in bodily secretions to prevent pathogens from infecting and penetrating body surfaces. What are some examples of these secretions?
tears, saliva, sweat, mucous, and breast milk
Which immunoglobulin dominates for MALT?
IgA
Define Autoimmunity
hypersensitivity reaction where the immune system reacts with self-antigens resulting in damage to tissues
The normal immune system does not strongly recognize an individual’s own antigens. What is called?
Tolerance. When tolerance breaks down, autoimmune diseases occur.
What are some examples of triggers that can lead to autoimmune disease in susceptible individuals?
infectious (ex. in rheumatic fever, body produces antibodies against group A strep which cross react with own heart antigens), environmental, or random
Autoimmune diseases can be classified as type II, III or IV. Provide a disease example for each type
Type II (tissue-specific) - Grave’s disease, autoimmune thrombocytopenic purpura
Type III (immune complex mediated) - Lupus
Type IV (cell-mediated) - Rheumatoid Arthritis, autoimmune thyroiditis (Hashimotos)
Which hypersensitivity reactions can be best described as tissue specific anti-body mediated reactions?
Type II Hypersensitivity Reactions
What is the rate of the development of type II hypersensitivity reactions?
Immediate
Which antibody classes are involved in type II hypersensitivity reactions?
IgG and IgM
What are the effector cells in type II reactions?
Macrophages in tissues
What are examples of type II hypersensitivity reactions?
Grave’s disease, Myasthenia Gravis, ABO mismatch transfusion reaction, hyperacute transplant reaction
What are patient features that increase the risk for malignancy related to lymph nodes?
Age older than 40yrs
Male
White race
Other features of increased risk:
Node not returned to baseline after 8-12wks
Supraclavicular region
Systemic signs: fever, night sweats, unexplained weight loss, hepatosplenomegaly
Duration of lymphadenopathy greater than 4-6wks
Generalized lymphadenopathy (2 or more regions involved)
What is the mnemonic MIAMI representing and what does it stand for?
MIAMI is a mnemonic for differential diagnoses of lymphadenopathy. It stands for: Malignancies, Infections, Autoimmune disorders, Miscellaneous/unusual conditions (Castleman disease, histiocytosis, Kawasaki disease, sarcoidosis, etc.) and Iatrogenic causes
Small (mm to cm) bean-shaped secondary lymphoid organs clustered along lymphatic vessels throughout the body =
Lymph nodes
Where are the superficial lymph nodes clustered? Where in the body are the lymph nodes at highest concentration?
Superficial regions of clustered lymph nodes include those in the inguinal, axillary, and cervical areas
Highest concentration of lymph nodes is in the mesenteries
What do we call lymph nodes in the intestinal wall?
Peyer’s Patches
What do we call the vessels that lymph follows into and out of the nodes?
Lymph enters the nodes through the afferent lymphatic vessels, filters through sinuses of the node, and leave by way of efferent lymphatic vessels
Does lymph flow quickly or slowly through the nodes? Why?
Flows slowly through node to allow phagocytosis of foreign substances & delivery of lymphocytes
Each lymph node is enclosed in a fibrous capsule, with _________ (branches) that extend inward to partition the node into several compartments
trabeculae
Connective tissue divides the compartments into a meshwork throughout the node
What are dendritic cells?
l antigen-presenting cell (APC) capable of activating naïve T cells and stimulating the growth and differentiation of B cells. Dendritic cells are found, for example, in the lymph nodes and spleen.
Dendritic cells in lymph nodes continually sample lymph & present any invaders to B cells –> if what it presents in foreign, B cells differentiate into plasma cells & start producing antibodies
What are the three layers of the lymph node and what type of cells do you find predominantly in each of the two outer layers?
The lymph node consists of an outer cortex, inner cortex (paracortex) and an inner medulla
Outer cortex: contains lymphatic nodules of B cells
Inner cortex: does not contain nodules, mostly contains T cells
Inner medulla: contains medullary sinuses that drain into the efferent lymphatic vessel
Describe the flow of lymph into and out of the lymph node (5 structures)
Lymph enters through multiple small afferent lymphatic vessels into the subcapsular sinus (beneath capsule), drains into the cortical sinuses -> medullary sinuses -> efferent lymphatic vessel
Through what structures does BLOOD enter and exit the lymph node?
Blood flows into the lymph nodes through the lymphatic artery, which ends in groups of postcapillary venules distributed throughout the outer cortex
The blood is drained through the lymphatic vein
Lymph nodes are the primary site for the first encounter between ______ and _______
Antigen and lymphocytes
What type of immune cells reside in the lymph nodes?
What immune cell transiently comes to the node to present antigens?
B and T lymphocytes and macrophages reside in the lymph nodes where they filter lymph of debris, foreign substances, and microorganisms; and provide antigen-processing functions
Dendritic cells encounter and process antigens and microorganisms in other tissues and enter the lymph node through the afferent lymph vessels
How do the lymphocytes enter the node via the blood?
Lymphocytes enter the lymph node from the blood through the postcapillary venules by means of diapedesis across the endothelial lining
What are germinal centers in the lymph nodes?
The presence of antigen, either removed from the lymph by macrophages or presented on the surface of dendritic cells, results in the production of secondary lymphoid nodules (containing germinal centers)
In the germinal centers, lymphocytes, particularly B cells, respond to antigenic stimulation by undergoing proliferation and further differentiation into memory cells and plasma cells (secrete antigen)
What causes a swollen lymph node during infection?
The B-lymphocyte proliferation in response to lots of antigen (e.g., during infection) may result in lymph node enlargement and tenderness (reactive lymph node).
What is the largest lymphoid organ?
Spleen
Where is the spleen located?
Posterior to stomach, just inferior to diaphragm and behind ribs (at the level 9-10)
How big is th spleen? Describe its basic internal structure
concave, encapsulated, and about the size of a fist
strands of connective tissue (trabeculae) extend throughout spleen from splenic capsule à divide the spleen into compartments that hold masses of lymphoid tissue called splenic pulp
What are the two types of pulp in the spleen?
Red and white
Red pulp. What happens here?
What do the venous sinuses here do?
highly vascular
Where old blood cells are destroyed, components recycled
contain macrophages for blood filtration –> Because of the slow circulation in the sinuses, the macrophages easily phagocytose old, damaged, or dead blood cells of all kinds (but chiefly erythrocytes), microorganisms, macromolecules, and particles of debris
contain venous sinuses for blood storage and filtration (can store up to 300ml and expel up to 200ml of blood to restore volume as needed)
What’s going on in the white pulp of the spleen? WHat type of immune cells live here?
What are LYMPHOID FOLLICLES? What makes them the chief sites of immune function in th espleen?
Masses of lymphoid tissue, containing macrophages and lymphocytes
Like giant lymph node that recieves blood
Cellular clumps (lymphoid follicles) are formed in the white pulp around the splenic arterioles. The lymphoid follicles consist primarily of B cells and are the chief sites of immune function within the spleen. Here bloodborne antigens encounter lymphocytes, initiating the immune response and the conversion of lymphoid follicles into germinal centres
Blood flow through the spleen
Receives blood from splenic artery –> differentiate into arterioles –> first meets white pulp: [T cells sit proximal to arterioles, whereas clumps (lymphoid follicles) of B cells surround the splenic arterioles]
As blood continues through microcirculation, enter venous sinuses “storage areas” in the red pulp of spleen, then back to portal circulation
What are the functions of the spleen?
1) Fetal hematopoeisis
2) Filters and cleanses blood (recycles old RBCs & phagocytes eat up debris, microorganisms)
3) immune response (bloodborne antigens meet lymphocytes in white pulp)
4) Reservoir for blood
What is the only lymphoid organ that primarily filters blood instead of lymph?
spleen!
Describe the structure of the appendix
- long narrow tube that is closed at one end & connects to cecum at the other
- 1.3cm wide by 8-10cm long
- cavity much narrower where joins to cecum
- Muscular walls to dump stuff into cecum
What is the cecum?
a pouchlike beginning of the large intestine into which the small intestine empties its contents.
We don’t really know what the appendix does, but what do we think it does?
-Housing and cultivating beneficial gut flora that can repopulate the digestive system following an illness that wipes out normal populations of these flora
- Providing a site for production of endocrine cells in the fetus that produce molecules important in regulating homeostasis
- Serving a possible role in immune function during the first three decades of life by exposing leukocytes (white blood cells) to antigens in the gastrointestinal tract, thereby stimulating antibody production that may help modulate immune reactions in the gut.
How does appendicitis come about?
- If anything blocks the opening of the appendix or prevents it from expelling its contents into the cecum, appendicitis may occur.
- The most common obstruction in the opening is a fecalith, a hardened piece of fecal matter (gross!)
Type I hypersensitivity rxn - what kind of antibodies does it involve?
IgE
What are examples of type I hypersensitivity?
Allergic reactions, asthma, eczema (atopic dermatitis), allergic rhinitis
Speed of a type I hypersensitivity is typically?
Rapid
Descrive the overall process of how type I hypersensitivity reactions occur?
There is a first exposure sensitization that precedes subsequent exposures
During the first exposure, macrophages and dendritic cells present the antigen to T helper cells
IgE antibodies are made, which attach themselves to the surface of mast cells ready to respond if there is a subsequent exposure
For subsequent exposures: External antigen (allergen) binds to IgE antibodies on mast cells or basophils.
This results in a large release of histamine (degranulation), which is a pro-inflammatory mediator
What causes the symptoms in type I hypersensitivity?
Huge histamine release (pro-inflammatory) causes:
- Blood vessel dilation and increased permeability of blood vessel walls –> edema and urticaria (hives)
- Bind H1 receptors causing broncho constriction –> difficult to breathe
Additionally, eosinophils are activated and proteases break down protein into peptides
Mild symptoms of a type I hypersensitivity rxn?
Hives, eczema, allergic rhinitis, asthma, redness, swelling, vesicles or blisters, pruritis
Note: depending on the location of these symptoms, they can be severe (ie. Hives in the pharynx may obstruct airflow)
Severe symptoms of type I hypersensitivity rxn
Symptoms of systemic anaphylaxis include pruritus, erythema, vomiting, abdominal cramps, diarrhea, and breathing difficulties, and the most severe reactions may include contraction of bronchial smooth muscle, edema of the throat, and decreased blood pressure that can lead to shock and death
Anaphylactic shock: increased vascular permeability and bronchoconstriction mean that the body cannot supply vital organs with sufficient oxygen rich blood
What types of drugs do we give for type I hypersensitivity?
Antihistamines: decrease vascular permeability and reduce bronchoconstriction
Corticosteriods: decrease inflammatory response
Epinephrine: constricts blood vessels to prevent anaphylactic shock
What is Asplenia? What causes it?
refers to complete loss of function of the spleen and may be anatomic or functional. May be due to surgical splenectomy (for trauma) or therapeutically (eg for hemolytic anemias or immunethrombocytopenias). Occurs frequently with sickle cell anemia.
What are the 4 main effects of asplenia?
1) Leukocytosis (spleen plays role in controlling leukocyte production in bone marrow)
2) Circulating levels of iron may also decrease <– reflects the spleen’s role in the iron cycle
3) Severely diminished immune response to encapsulated bacteria
4) Increase in defective old blood cells
What are the “encapsulated bacteria” and why is fighting them difficult without a working spleen?
Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), Haemophilus influenzae
Recall that the white pulp of the spleen houses approximately half of the body’s immunoglobulin-producing B lymphocytes, which are critical for producing antibodies that target antigens on the surface of the encapsulated bacteria
**Without spleen, patients at risk of severe and overwhelming sepsis
Why do we need to be quick to respond to a fever in an asplenic patient?
Fever in a patient with impaired splenic function should be interpreted as an early sign of sepsis. Without prompt and appropriate treatment, infections in asplenic patients can become fulminant and fatal within hours of symptom onset.
