10.3 Immunology Flashcards

1
Q

General overview of the Complement immune system

A

= fast , not powerful, non-specific

  • involves wide variety of proteins produced by liver?
  • recognize compounds such as those with mannose sugars in the walls (we don’t have these) and destroy with chemical burst or opsonize the invader
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2
Q

Opsonization

A

= tagging of something fro removal

  • identifies the object/invader for the macrophage to digest and destroy it intracellularly
  • if macrophage can’t digest it - releases cytokines and the neutrophils will be the first to respond (rolling adhesion and diapedesis) –> which will real ease extracellular granules and destroy extracellularly
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3
Q

What are the 3 activities of the complement protein

A

1) lectin activation pathway
2) Constant attack system
3) Classical pathway

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4
Q

Describe the lectin activation pathway of the complement system

A
  • recognition of invaders by presence of mannose sugars followed by opsonization and/or destruction (phagocytosis)
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5
Q

Describe the constant attack pathway of the complement system

A

= also called the alternative pathway

  • NK-cells non-disciminantly and continuously attack self and non-self cells
  • self-cells have ability to neutralize this attack
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6
Q

Describe the classical pathway of the complement system

A

= the most complex pathway

  • relies on detection of antibodies on surface of the invaders
  • antibodies are placed on surface of invade in response to invaders antigens by B-cells
  • B-cells recognize the antigen and produces antibodies which sticks to the invader (opsonizes) and activates the complement system
  • through this method the B-cells (adaptive immune system) is taking advantage of complement system macrophages and neutrophils
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7
Q

What are the characteristics of the adaptive immune system - give the two parts, overview of their function, and the comparative response time to the innate system

A
  • adaptive immune system takes more time to respond than innate system
  • Cells in distress produce cytokines that recruit the innate immune system for self-destruction of the “greater good” of the system
  • 1st part of adaptive system deals with antigens - like bacteria and functions in the extracellular space - is the domain of the B-lymphocyte
  • 2nd part of the system deal with viruses (intracellular antigens) - is mediated by the T-cells
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8
Q

Describe the B-cells and their specific functioning in response to recognizing an antigen

A
  • express a B-cell receptor - an antibody that is bound to transmembrane constant domain
  • the antibody expressed is chosen randomly so for a given antigen - many different B-cells might respond
  • FXN to monitor the body until contact an antigen that stimulates them to migrate to the lymph tissue/nodes and undergo mitosis to create many B-cells responsive to that antigen (due to varied receptors there will be many different B-cells undergoing mitosis)
  • they divide by polyclonal expansion
  • disadvantage is this process exhibits a time lag that can last hrs –> days
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9
Q

Describe the T-cells

A
  • respond to intracellular invaders (e.g. viruses)
  • strategy is based on recognition of surface receptors (MHC receptors) - will opsonize if the invader should be killed
  • MHC receptors can be MHC I or MHC II depending on the type of T-cell and exist in some form on every cell in the body
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10
Q

Describe MHC receptors

A
  • exist on every cell in body
  • are plieomorphic (changing from person to person allowing self and non-self recognition)
  • contains short variable section of protein on the outside
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11
Q

Describe the MHC I receptors FXNing

A
  • choose a chunk of protein from what ever is being actively translated on the ER intracellular at the time
  • expresses that protein on the external portion of the MHC I receptor
  • Killer T-cells recognize this protein and mark it for destruction
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12
Q

Describe the MHC II receptors and their FXNing

A
  • Exist on leukocytes and other antigen presenting cells (APCs) such as B-cells (CT), Macrophages (CT), dendritic cells (all epithelial tissues)
  • monitor for presence of foreign protein and when finds one will ingest it and present a part of it on MHCII molecule (must like in MHCI?)
  • Helper T-cells monitor MHC II containing cells and recognize and then direct the immune system to what it is and how to attack
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13
Q

What are the two parts to the lymphatic circulation through lymph nodes

A

1) afferent lymphatics

2) Systemic circulation

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14
Q

Describe the afferent lymphatics role in circulation within lymph nodes

A
  • lymph and lymphocytes arriving from the periphery
  • lymph enters here and travels in subcapsular sinus - occasionally branching in peritrabecular sinus and then flows into the medullary sinus and out through the efferent lymphatics
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15
Q

Describe the systemic circulatory role in circulation within lymph nodes

A
  • small venues at sites near cortex and medulla are major sites of diapedesis out of systemic circulation into cortex/paracortex of lymph nodes
  • you would commonly see HEV (high endothelial venues - cuboidal shaped cells) in these areas
  • there is no way for the cells that have left circulation to re-enter it –> they met leave via the lymphatic efferent circulation
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16
Q

What is the hilar region

A
  • where the major vessels enter and exit the lymph nodes
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17
Q

What are the lymphoid follicles and what is the pericortex, differences between the functional significance of the two

A
  • The lymphoid follicles are located in the cortex and contain most of the B-lymphocytes
  • outside of the follicles and especially in the paracortex area is the location of most of the T-lymphocytes of lymph nodes
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18
Q

What are the 2 pathways through the spleen

A

1) Open circulation - involves both the CT compartment and sinus compartment
2) closed Circulation - blood cells never leave the endothelial lined space (in through splenic artery and out through splenic vein)

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19
Q

Describe the red pulp

A
  • CT compartment of the Red pulp is filled with erythrocytes and other leukocytes
  • Sinus compartment of the red pulp is where blood cells can exit back into circulation and out via splenic vein
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20
Q

what are the 3 FXNs of the spleen

A

1) removal of effete (aged/old) RBCs from circulation
2) Immune Surveillance
3) Storage of WBCs

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21
Q

Describe the removal of effete RBCs from circulation FXN of the spleen

A
  • RBCs that begin to loose deformability represent a potential danger to the vascular system or cells that express abhorrent surface molecules will be target for removal/destruction
  • there are 2 mechanisms for removal
    1) Macrophage removal
    2) Mechanical removal - FXNs because RBCs need to squeeze through the reticular fiber matrix from the splenic cord to be able to enter the splenic sinus
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22
Q

Describe the immuno-surveillance FXN of the spleen

A
  • lymphatics/lymph nodes are good if the invader is in the CT compartment, but the spleen looks for those invaders that hide in blood
  • the White pulp of the spleen harbors WBCs that have been removed from circulation in an area farther away from splenic sinus –> in the lymphoid nodules of blood called the splenic nodules
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23
Q

What is the marginal zone

A

= area where the cells that have exited the radial arteries in the CT compartment of the spleen choose to go to white pulp or red pulp areas

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24
Q

Describe the storage of WBCs FXN of the spleen

A
  • WBCs are stored in the white pulp and specifically in the splenic nodules
25
Q

What are trabeculae in the spleen

A
  • where the walls of the CT capsule surrounding spleen extend inward from the capsule surrounding the major vasculature entering and exiting the spleen (splenic trabecular artery and splenic trabecular vein)
26
Q

Describe the flow of the open circulation through the spleen

A

1) Splenic artery
2) Trabecular artery = surrounded by tabeculae
3) Central Artery = surrounded by white pulp - periarterial lymphatic sheath (PALs = white pulp minus splenic nodules) –> is the smallest vessel normally seen in LM
4) Radial Artery = artery that extends into marginal zone
5) Penicillar artery + 6) Sheather capillary = not recognized in LM just EM - are vessels in the marginal zone
7) Splenic Cords of Billroth (Splenic Cord) = where blood cells need to pass in the CT space in Red Pulp to enter the sinuses
8) Splenic sinus - contains reticular fibers surrounding them - where blood leaves the CT compartment
9) Trabecular Vein
10) Splenic Vein

27
Q

Innate Immune Response

A
  • based on non-specific recognition of foreign substances + their removal by various mechanisms
  • including activation inflammatory response through opsonization and subsequent activation of the complement system, destruction by NK cells, phagocytosis by macrophages
28
Q

Adaptive immune response

A
  • has two parts
    1) based on recognition of external antigens via binding to immunoglobulin proteins mainly of IgG, but also IgM , IgA, IgE, IgD
    2) based on recognition of cells that have been infected with foreign proteins
  • major cells types mediating the two responses = B-cells, plasma cells, t-cells, APCs
29
Q

What are APCs

A
  • antigen presenting cells
  • use MHCII
  • include: macrophages, dendritic cells, B-cells
30
Q

Primary Lymphoid organs

A

= those involved in generation and maturation of lymphocytes

  • bone marrow
  • thymus
31
Q

Secondary Lymphoid Organs

A

= those in which lymphocytes congregate to carry out their FXN

  • can be diffuse accumulations of tissue –> Skin associated lymphoid tissue (SALT) and various subtypes of mucosa-associated lymphoid tissue (MALT) –> can accumulate in predictable locations: Tonsils, ileum, appendix
  • lymphatic drainage = lymph nodes
  • spleen
32
Q

Spleen

A

= serves as lymphatic organ for circulation

  • serves as reservoir for cells –> monocytes
  • removes effete erythrocytes from circulation
33
Q

Where do B-lymphocytes proliferate

A
  • in secondary lymphatics they proliferate in lymphoid follicles (in spleen they are called splenic nodules)
  • contain a recognizable germinal center
  • in tonsils, a reticulated epithelium allows passage of lymphocytes through an epithelial layer
34
Q

Reticulated epithelium

A

= sinusoidal/ discontinuous epithelium?

  • the tonsil epithelium
  • allows passage of lymphocytes through an epithelial layer
35
Q

Thymus

A

= encapsulated organ divided into two lobes and multiple lobules

  • each lobule consists of thymus cortex and thymic medulla regions
  • stromal cells of thymus are derived from embryonic epithelium = epithelioreticular cells
  • resident t-lymphocytes in thymus = thymocytes
  • thymic medulla contains Hassall’s cospuscles
36
Q

Epithelioreticular Cells (ERCs)

A

= stromal cells of thymus

- derived from embryonic epithelium

37
Q

Thymocytes

A
  • parenchymal cells of thymus

- resident t-lymphocytes of the thymus

38
Q

Hassall’s corpuscles

A

= special organization of multiple ERCs

  • they are present in the medulla of thymic lobules
  • are characteristic identifier solely for the thymus
39
Q

What are the names of the major clinically-important lymph nodes outlined in the lecture notes and their locations?

A
  • Cervical (neck)
  • Axillary (armpit)
  • hilar (draining lung)
  • mediastinal
  • abdominal
  • superficial inguinal
  • deep inguinal (groin)
  • femoral (leg)
  • popliteal (knee)
40
Q

Describe the organization of lymph nodes including both the systemic and the lymphatic circulation

A
  • arranged into a cortex and medulla
  • medulla surrounds a hilar region - where the blood vessels (afferent) enter and (efferent) exit, and where the efferent lymphatics leave
  • lymph enters via afferent lymphatics –> branches in subcapsular sinuses and trabecular sinuses –> percolates through the cortex and medullary cords –> leaves via the medullary sinus to efferent lymphatics
41
Q

Describe the Spleen’s closed circulation

A

= large organ consisting of a capsule divided by trabeculae

  • In the Closed circulation blood flow enters through the splenic artery and goes as follows
    1) splenic artery
    2) tabular arteries
    3) central arteries
    4) radial arteries
    5) penicillar arteries
    6) sheather capillaries
    7) splenic sinuses
    8) trabecular veins
    9) splenic vein
42
Q

What is the marginal zone

A
  • region of the spleen where blood is allowed to leave the smallest vessels and enter the CT space
  • is between the red pulp and white pulp
43
Q

What is the white pulp

A
  • location in the spleen where the white blood cells congregate
  • also surround the central arteries as a peri-arterial lymphatic sheath (PALS)
44
Q

What are the splenic cords / Cords of Billroth

A
  • location for erythrocytes to course throughout he splenic cords and attempt to re-enter the splenic sinus
45
Q

What is red pulp

A
  • location in the spleen comprised of the cords and sinuses
  • where the red blood cells have entered the CT space from the vasculature and are attempting to squeeze through the reticular network of the cords and sinuses to re-enter the circulation
  • is major aspect of the open circulation of the spleen
46
Q

Splenic macrophages

A
  • recognize and remove RBCs that lack functioning key surface proteins + one that can no longer deforms themselves are mechanical prevented from entering the splenic sinuses by encircling reticular fibers
47
Q

Describe IgM antibodies

A

= first antibody produced by naive B-cells

  • all other antibodies are produced from clippings of its sequence
  • short lived - 24hrs
  • good are recruiting complement via classical pathway
48
Q

Describe IgG antibodies

A
  • long lived - 3 wks
  • long life alows to protect newborn - actively taken up by placenta
  • most abundant antibody in blood
  • recruits NK cells
49
Q

Describe IgA antibodies

A
  • most abundant in mucosal surfaces
  • major class in breast milk (produced by plasma cells in the interlobular CT of breast)
  • specialized to resist acid + enzyme
  • specialized to cross epithelial surfaces
50
Q

Describe IgE antibodies

A
  • recruits mast cells
  • mediator of allergy and anaphylactic shock
  • recognizes parasites
  • activates Fc receptors on Mast cells, basophils, eosinophils, monocytes, macrophages, platelets
51
Q

Describe IgD antibodies

A
  • expressed on B-cells

- binds mast cells and basophils

52
Q

Polyclonal expansion

A
  • activated B-cells do this and have this term because many uniquely different B-cells with different antibodies all respond to the same antigen
  • this process occurs at the germinal center of lymphoid follicles
53
Q

What are the two ways “experienced” B-cells end their lives

A

1) Become machines for the production of secreted antibodies (as opposed to the antibody receptor), a.k.a become a plasma cell
2) Retained as memory cells - for quicker immune defense upon subsequent recognition of its specific antigen - are recruited from the B-cells that attain the tightest, most specific binding to a particular antigen

54
Q

MHC-I

A
  • present on virtually all somatic cells (except placental syncytiotrophoblast)
  • display proteins that are being currently transcribed and processed at the ER
  • killer T-cells respond to this by its T-cell receptor (TCR) that recognizes the MHCI and the protein segment
  • the killer T-cells express the CD8 coreceptor molecule (has intracellular domain associated with the TCR = CD3)
55
Q

MHC-II

A
  • present on leukocytes
  • display any proteins that have been internalized - obtained from endosomes
  • helper T-cells respond to the MHCII
  • help T-cells have TCR with has an intracellular domain = CD3
  • Helper T-cells have the CD4 coreceptor molecule that help recognize the MHCII
56
Q

Macrophage APCs

A
  • present antigen in MHCII
  • must be activated by Cytokines or by Toll-like receptors (TLRs) - specialized for recognizing generic foreign proteins
  • macrophages are responsible for activating T-cells/keeping activated at the site of infection
57
Q

Dendritic Cell APCs

A
  • associated with epithelia that specialize in activating T-cells (i.e. Langerhans Cells of skin)
  • have TLRs
  • one activated though (unlike macrophages) - leave their associated epithelia –> travel to lymph bodies in order to recruit virgin T-cells
  • response pathway is effective from 1-7 days following initial sensing by T-cells
58
Q

B-Cell APCs

A
  • activated by helper T-cells
  • activated present high level of MHCII and CD80/CD86 proteins –> become APCs
  • subset of these cells become memory B-cells –> specialized for responding to low levels of previously encountered antigens