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Lymphatic and Immune System (Autoimmune Diseases (Diabete mellitus type 1,…
Lymphatic and Immune System
Anatomy
Lymphatic Capillaries
Located in almost all tissues
interstitial fluid enters here
lymph fluid is made
enabled by anchoring collagen fibers
endothelial cells
empty into larger lymphatic vessles
similar to veins
three-tunic structure
valves
lymphatic trunks
merged lymphatics
right lymphatic duct
right side of body, head, limbs, thorax
goes into right subclavian vein
thoracic duct
left side of body
drains into left subclavian vein
begins beneath diaphragm
cisterna chyli
lower left side of body
asymmetrical drainage
Lymphocytes
T Cells
Large central nucleus, thin cytoplasm
Mature in thymus, dev from bone marrow
Secrete soluble factors
Comm w other cells of AIR
(chem messengers)
Destroy cells infected with intracellular pathogens
Plasma Cells
Activated B cells
Contain large amt of cytoplasm
Packed with rough ER
Protein synthesis
Secretes antibodies
B Cells
Identical to T cells morphologically
Mature in red bone marrow
Immune cells
Produce antibodies
Binds to antigen
Differentiate into secretory cells
Secrete soluble form of their surface antibodies
Natural Killer Cells
Innate immune response
Circulating blood cell
Contains cytotoxic granules
Among first line of defense
Against viruses, cancer types
Primary cells of adaptive immune responses
Body contains 10^12
Primary Lymphoid Organs
Bone Marrow
Where hematopoiesis occurs
Red bone marrow
Thymus Gland
Thymocyte matures here
Bilobed, connective tissue form capsule
Divided into lobules via trabeculae
Above the heart
Regions
Cortex
large # of thymocytes
Densely packed
Epithelial cells
Macrophages
Dendritic cells
phagocytic cells from monocytes
Medulla
Where thymocytes migrate b4 leaving thymus
Less dense than corrtex
Epithelial cells
thymocytes
dendritic cells
Secondary Lymphoid Organs
Naive lymphocytes enter here
After maturation/dev in primary organs
Mount immune responses here
Fully functional immunologically
Haven't encountered antigens yet
Lymph nodes
Remove debris and pathogens from lymph
Filters of the lymph
Bacteria transported here
Dendritic cells and macrophages
Kill many pathogens that pass thru
Site of A.I.R.
Mediated by T cells, B cells, accessory cells
Connective tissue
Separated by trabeculae
Structural support from ret fibers
Major routes
Afferent Lymphatic vessels
Efferent Lymphatic vessels
Vessels are similar to veins
three-tunic structure and presence of valves
one-way valves located close to each other
each valve causes a bulge in lymphatic vessel, giving beaded appearance
Spleen
"Filter of the blood"
Extensive vascularization
Macrophages/dendritic cells
Remove microbes/dying RBCs
Immune responses to blood-borne pathogens
Divided by trabeculae of connective tissue
Splenic nodules
Red pulp
RBCs
Reticular fibers
Fixed&free macrophages, lymphocytes
Filtration system
White pulp
Resembles lymphoid follicles
Germinal centers
Where adaptive T&B cell responses are mounted
Splenic artery
Splits into arterioles
Eventually into sinusoids
Blood collects in venous sinuses
Leaves through splenic vein
From capillaries
Lymphoid Nodules
Dense cluster of lymphocytes
No fibrous capsule
Located in resp and digestive tracts
Exposed to environmental pathogens
Tonsils
Inner surface of pharynx
Immunity to oral pathogens
Swelling indicates A.I.R. to infection
Mucosa-associated lymphoid tissue
MALT
Peyer's patches
Combat pathogens in S.I.
Found in mucosa of G.I. tract, breast tissue, lungs, eyes
Bronchus-associated lymphoid tissue
BALT
Foumd in/in btw bronchi and arteries
Effective against inhaled pathogens
Similarities among all tissues
Lymphoid follicles
Site of formation of lymphocytes
Specific B and T cell-rich areas
Reticular fibers
Associated w fixed macrophages
Gerrminal centers
site of rapidly dividing/differentiating B lymphocytes
High endothelial venules
Specialized post-capillary vessels
Columnar epithelial cells
thicker than endothelial
Allow blood cells to directly enter tissues
Innate Immune Defenses
Relatively rapid but nonspecific
Not always effective
Barrier defenses
Skin
Epidermal surface
Keratinized cells of surface
Langherhans cells
Sweat gland, sebaceous glands
Low pH, washing action
Oral Cavity
Salivary Glands
Lysozyme
Stomach
G.I. tract
Low pH
Mucosal surfaces
Mucosal epthelium
Nonkeratinized epithelial cells
Normal flora (nonpathogenic bacteria)
Mucosal tissues
Prevent pathogens from growing on mucosal surfaces
Cells of I.I.R.
Phagocytes
Surround/engulf particle or cell
Phagocytosis
Clean area or kill pathogenic organisms
First line of immunological defense
Against those who breached barrier defense
Fast acting
Macrophage
Versatile
Use pseudopodia
Squeeze thru tissues/cap walls
Found all over body
Angranulocyte
Precursor is monocyte
Neutrophils
Granulocyte
Found in blood
Natural Killer Cells
Can induce apoptosis
Respond to fas ligand
Release perforins and granzymes
Recognition of pathogens
Pattern recognition receptors
Membrane bound
Recognizes features of pathogens release by damaged cells
Must be specifically encoded
Limited number of receptors
Soluble mediators (chemicals of I.I.R.)
Cytokines
Allows short distance comm btw cells
Chemokines
Attracts cells from longer distances
Early induced Proteins
Interferons
Induce cells to make antiviral proteins
C-Reactive protein
Mannose-binding protein
Opsonization
Tagging of pathogen for phagocytosis
By binding antibody or antimicrobial protein
Complement System
Series of proteins found in blood plasma
Not part of early induced immune response
Made in liver
Label cells for phagocytosis
Form damaging pores in cell membrane
Attract phagocytic cells to inflamed sites
Inflammatory Response
heat, redness, pain, swelling
Can be caused by tissue injury
Can be caused by infection
Brings phagocytic cells to area to clear debris
Set the stage for wound repair
Acute Inflammation
Short-term
Chronic Inflammation
Ongoing
Can be caused by
Foreign bodies
Persistent pathogens
Autoimmune diseases
Important parts
Tissue Injury
Injured cells stimulate release of Mast Cells
Also histamines
Cause vasodilation
Increased blood flow
Heat and redness
Greater access of blood to inflamed site
Increase capillary permeabillity
Plasma leaks out, forms interstitial fluid
Causes swelling
Adaptive Immune Defenses
B lymphocytes (humoral response)
Clonal selection
B cells w appropriate antigen specificy are chosen
selected and expanded
Plasma cells secrete antibodies w antigenic spec. identical to chosen B cells
Memory B cells & plasma cells generated simultaneously
Primary response
Delayed several days
B cell clones expanding and differentiating
Into plasma cells
Level of antibody produced is low
Sufficient for immune protection
Secondary response
No delay
Level of antibody is v high
Overwhelms pathogens quickly
no symptoms felt
become immunocompetent & self tolerant in bone marrow
some self-reactive B cells face anergy
others are killed
T lymphocytes (cellular response)
Control immune responses directly
also control B cell responses sometimes
Makes attack-based decisions
Recognize antigens based on two-chain protein receptor
Alpha-beta T cell receptors
Each chain has two domains
Variable region domain
furthest away from T cell membrane
amino acid sequence varies based on recognizable antigens
Constant region domain
less amino acid variation
Antigen-binding site
uses terminal ends of both receptor chains
uses amino acid sequences of both receptors
Determines antigenic specificity
Each T cell produces one type of receptor only
Specific
Development and Differentiation
T cell tolerance
Getting rid of T cell that attack own cells
Positive selection
selection of thymocytes
within thymus
interact with self
do not interact with non-self
MHC molecules
Negative selection
Selection of thymocytes
within thymus
react with self-antigen
Mechanisms
Activated by recog processed foreign antigen
in association w a self-MHC molecule
begins dividing rapidly
mitosis
clonal expansion
Clonal selection
antigen binding only to antigen specific T cells
Polyclonal response
stimulation of multiple T cell clones
leads to large # of specific lymphocyte
body can better fight infection
Types
Th1
Cytokines or mediators
Interferon-y and TGF-B
Macrophage
Helper inducer
extracellular pathogen
Surface marker CD4
Class 2 MHC
Th2
Cytokines or mediators
IL-4, IL-6, IL-10, others
B cell
Helper inducer
Extracellular pathogen
Surface marker CD4
Class 2 MHC
Tc
Target infected cells
cytotoxicity
intracellular pathogen
surface marker CD8
Class 1 MHC
Cytokines or mediators
Perforins, granzymes, fas ligans
Treg
Cytokines or mediators
TGF-B and IL-10
Th cell
Suppressor
No pathogen
Surface marker CD4, CD25
Primary adaptive response
first exposure to pathogen
first infection called primary disease
symptoms are usually severe
Secondary adaptive response
Re-exposure to pathogen
Eliminates pathogen b4 tissue damage, symptoms
immunological memory
cellular
memory T cells
long-lived, act rapidly
generates large # of effector T cells
Self-recognition
distinguish self-antigens and foreign antigens
prevents immune-response damage against body
breakdown leads to autoimmune disease
Active versus passive
Active
Natural
Adaptive immune response
Artificial
Vaccine respone
Passive
Natural
Trans-placental antibodies/breastfeeding
Artificial
Immune globulin injections
Antigens and Antibodies
Antibody
Group of proteins
Binds specifically to antigens
AKA immunoglobin
Classes
IgM
Five 4-chain structure
largest
10 antigen binding sites
usually first made during primary response
binds complement proteins
activates complement cascade
promotes chemotaxis, opsonization, cell lysis
IgG
late primary response
class switching occurs here
main antibody of secondary resp in blood
clears pathogens from blood
can activate complement proteins
Can cross placenta to protect fetus
IgA
Two forms
four-chain monomere
In blood
Eight chain structure (dimer)
in exocrine gland secretions
mucus, saliva, tears
only antibody to leave body
important to newborns
present in breast milk
IgE
Allergies and anaphylaxis
lowest concentration of the blood
makes mast cell degranulation v specific
can cause severe allergic reactions
Structure types
Polypeptide chain
Heavy chain
2 heavy chains form Fc region
important for Fc receptors
increases specificity
Light chain
2 heavy, 2 light each (identical)
Secrete, circulate, bind to pathogens
Label for ID later
Antigen
Chem structure on surface of pathogen
Binds to T or B antigen receptors
Large and complex
Antigenic determinant
Receptors can bind here
Limited by size of receptor
Usually consist of <6 A.A. residues in protein antigen
or 1-2 sugar moieties in carb antigen
less diverse on carbs, found in bacterial walls, or on RBCs
Protein antigens are complex
bc of variety of 3D shapes of proteins
important for resp. to viruses/worms
interaction of antigen shape and AA shape accounts for specificity
Processing
Enzymatically cleaves antigen into smaller pieces
Fragments brought to cell surface
Associated w special type of protein (MHC)
Major Histocompatibility Complex
Cluster of genes
Encode molecules
Types
Class 1
1 more item...
Class 2
3 more items...
Association known as Antigen Presentation
Results in recog of antigen by T cell!
Occurs inside the cell
Complex is brought to surface
Brought to peptide-binding cleft on MHC molecule
Furthest away from cell membrane
Fragment of antigen sits in binding site
Autoimmune Diseases
Celiac disease
Tissue transglutaminase
Damage to small intestine
Diabete mellitus type 1
beta cells of pancreas
Low insulin production
inability to regulate serum glucose
Graves' disease
Thyroid-stimulating hormone receptor
Antibody blocks receptors
Hyperthyroidism
Hashimoto's thyroidities
Thyroid-stimulating hormone receptor
antibody mimics hormone an stimulates receptor
Hypothyroidism
Lupus erythematosus
Nuclear DNA and proteins
Damage to many body systems
Myasthenia gravis
Acetylcholine receptor in neuromuscular junctions
Debilitating muscle weakness
Rheumatoid Arthritis
Joint capsule antigens
Chronic inflammation of joints
