histology more Flashcards
1
Q
delivery of oxygen
A
number of roads, how fast can trucks go, how full are the trucks?
cardiac output x hemo x %saturation
2
Q
Pancytopenia?
A
decreased circulating elements of all types of formed elements in blood. EG - no WBCs, few RBCS -
3
Q
Eosinophils?
A
Major Basic Protein MBP
4
Q
Antibodies - GAMED
Who secretes? PLASMA -
Where do plasma cells come from ? B cells (make plasma and memory cells)
A
IgG IgA IgM IgE IgD
5
Q
IgG most common
A
Monomer from plasma cells
70% in blood plasma
primary and secondary immune response - (most abundant action in 2nd)
on bacteria - if antigen - if igG binds can initiate
Complement system -> forms Membrane Attack Complex OR enhance Optimasation AND c3, c5 - enhance inflammation
if VIRUS - blocks binding points - NEUTRALIZATION
PRECIPITATE - can initiate opsonization, phagocytosis
6
Q
IgG and passive immunity
A
can pass to baby from mother
IgA - mother milk
7
Q
IgA? - Dimer if secreted - monomer if not - usually secreted in some type of fluid
A
plasma cells secrete -
Dimer - 2 breasts - mother’s milke
fluids w/in body
saliva, skin secretions (sweat), mucusal lining of GI, mother’s milk - passes to baby, urogenital
8
Q
IgM - mismatch blood
A
Plasma primary secretors -
2 forms: Pentemer (J protein link) and Monomeric
PRIMARY immune response - if see elevated IgM - see infection happening (a little in 2nd)
Activates COMPLEMENT proteins -> MAC or opsinozation
Mismatched blood transfusion - helps w agglutination - Type II hyper sensitivity
10 antigen binding sites - trust
9
Q
IgE - Allergic - Anaphalaxis - Worms
A
Monomer - from plasma
Respiratory tract mucusa
urogenital
lamina propria and lymphatic
Gi Tract - calls in Eisonphils (major basic protein and cat ionic peptide)
type 1 hyper sensitivities
mast cells - FCepsilon R 1 receptor - ALLERGEN,
signals to mast cells to produce histamines, prostoglandins, neutro?
leaky vessels, vasodilation, edema - restricts airways - NOT GOOD and contract smooth muscles - decreases airway size - effects breathing - ANAPhalxis - Type 1 hypersensitivity
10
Q
IgD
A
Monomeric - plasma
safeword
Monomer on B cell surface - B cell receptor - in adaptive immunity
11
Q
IgM - can it be a B cell receptor?
A
Yes, just like IgD
12
Q
What is the difference between a B-cell receptor and an antibody “immunoglobulin”?
A
Antibodies or immunoglobulins are found as a secreted product of effector B cell (plasma cell) which is not bound to any surface membrane and can perform various effector functions. … B cell receptor is found on the membrane of the B lymphoctyes.
13
Q
First antibody produced?
A
IgM - cytokines, etc calling them to work
14
Q
Second antibody?
A
IgG (most common)
15
Q
What is shift called?
Left shift?
A
Somatic hyper mutation
A “left shift” is a phrase used to note that there are a high number of young, immature white blood cells present. Most commonly, this means that there is an infection or inflammation present and the bone marrow is producing more WBCs and releasing them into the blood before they are fully mature.
16
Q
2nd exposure to x bacteria?
A
IgG blows up! IgM being produced at low level during this phase
17
Q
two types of immunity?
A
passive - active
passive - didn’t have to do anything to get it - or produce any antibodies -
Active
18
Q
Two types of passive immunity?
A
Natural, artificial
Natural - IgG (placenta), IgA (milk) from mom
Artificial - snake bite ie - dr. gives me antibodies - antivenom
Immunoglobulous (antibodies) But I didn’t have to make them.
19
Q
Active immunity?
A
Natural, Artificial
natural - I was exposed in past by the pathogen - strep throat
Artificial - vaccines, booster shots
your body has to work w/ it. Body produces antibodies against weak or dead pathogen
20
Q
Structure of antibody?
A
chains -
Constant heavy chain -
constant light chain
variable heavy/light chain
connected - disulfide bonds
compliment proteins love to bind
Variable regions differ from antibody to antibody - cloud formation,
they can recombine, recreate to accommodate various types triangle, etc
two binding cites - that’s why ten binding cites
21
Q
Actions of antibodies?
A
Neutralization Agglutination precipitation Opsonization Activation of NK cells
22
Q
Neutralization?
A
antibody covers biologically active portion of microbe or toxin
23
Q
Agglutination - cross link
A
Antibody cross-links cells - forming a clump
24
Q
Precipitation - cross link
A
Crosslinks,
Precipitation reactions are based on the interaction of antibodies and antigens. They are based on two soluble reactants that come together to make one insoluble product, the precipitate. These reactions depend on the formation of lattices (cross-links) when antigen and antibody exist in optimal proportions
25
Opsonization, C3b and C4b,
or enhanced attachment, refers to the antibody molecules IgG and IgE, the complement proteins C3b and C4b, and other opsonins attaching antigens to phagocytes. The Fab portions of the antibody IgG react with epitopes of the antigen.
26
Activation of NK cells
Cytokines play a crucial role in NK cell activation. ... NK cells are activated in response to interferons or macrophage-derived cytokines. They serve to contain viral infections while the adaptive immune response generates antigen-specific cytotoxic T cells that can clear the infection.
What is the main function of natural killer cells?
Natural killer cells (or NK cells) are cytotoxic lymphocytes that are critical to the innate immune system. NK cells can function as an interface to the adaptive immune response. NK cells rapidly respond to virally infected cells and tumor formation in the absence of antibodies and MHC.
27
FC portion of antibodies - TAIL
FUK - tail think of it that way -
The tail goes into the cell surface
The fragment crystallizable region (Fc region) is the tail region of an antibody that interacts with cell surface receptors called Fc receptors and some proteins of the complement system. This property allows antibodies to activate the immune system. ... The Fc regions of IgGs bear a highly conserved N-glycosylation site.
28
Do complement proteins and surface receptors on many leukocytes bind?
yes, producing active complement - more effecient phagocytosis (opsonization) and NK activation
29
What does aggultination do?
creates easier removal
30
Cytokines?
small, soluble secreted proteins - that enable cells to communicate
thereby initiating, perpetuating and downregulating immune response
31
What are chemokines?
cytokines causing chemotaxis
32
Do cytokines increate mitotic activity< If so, with what, where?
yes - certain leukocytes, locally and in bone marrow
33
Do cytokines stimulate or suppress lymyphocyte activity in adaptive immunity?
Both - INTERleukins - thought to be produced by and to target leukocytes
34
Do cytokines stimulate phagocytosis or directed cell killing by innate immune cells?
yes.
35
Cytokine redundancy?
many different cytokines can perform the same jobs
36
cytokin pleiotropy ?
single cytokine can perform many functions
37
cytokines - autocrine v. paracrine manner?
Cell TARGETS ITSELF
autocrine- act on itself -
paracrine? act on nearby cells
38
Cytokines and cascades?
Cytokines are often produced in cascades - its target cell produces more cytokines
39
synergistic vs antagoistic cytokine action?
IL 10 vs. 12 (suppress vs. promotes cell mediated immunity)
IL3 + 6
IL4 vs. IL10
40
Thymus - how protect developing T cells?
blood - thymus barrier - capillary wall, CT, basement lamina and cytoplasm
41
divisions of lymph node?
outer cortical,
most of nodules and germinal centers - B lymph here ~
inner (paracortical) - T lymph
, and medullary
42
Do lymph nodes have dendritic cells?
yes, - they are antigen presenting
Dendritic cells (DCs) are antigen-presenting cells derived from bone marrow precursors and form a widely distributed cellular system throughout the body. DCs exert immune-surveillance for exogenous and endogenous antigens and the later activation of naive T lymphocytes giving rise to various immunological responses.
43
Where do dendritic cells come from?
Dendritic cells are derived from hematopoietic bone marrow progenitor cells. These progenitor cells initially transform into immature dendritic cells. These cells are characterized by high endocytic activity and low T-cell activation potential.
44
What type of cell are dendritic cells?
Dendritic cells are a type of antigen-presenting cell (APC) that form an important role in the adaptive immune system. The main function of dendritic cells is to present antigens and the cells are therefore sometimes referred to as “professional” APCs.
45
Are dendritic cells in blood?
Dendritic cells are present in those tissues that are in contact with the external environment, such as the skin (where there is a specialized dendritic cell type called the Langerhans cell) and the inner lining of the nose, lungs, stomach and intestines. They can also be found in an immature state in the blood.
46
Where do mast cells come from?
Mast cells derive from the bone marrow but unlike other white blood cells, mast cells are released into the blood as mast cell progenitors and do not fully mature until they are recruited into the tissue where they undergo their terminal differentiation.
47
Where are mast cells found in the human body?
Mast cells are located in connective tissue, including the skin, the linings of the stomach and intestine, and other sites. They play an important role in helping defend these tissues from disease.
48
Are mast cells found in blood?
Mast cells are not normally found in blood. They develop in tissues from precursor cells produced in the bone marrow.
49
What triggers mast cells?
What is an allergy?
Mast cells are allergy cells responsible for immediate allergic reactions. They cause allergic symptoms by releasing products called “mediators” stored inside them or made by them. ... Mast cells can also be activated by other substances, such as medications, infections, insect or reptile venoms.
What is an allergy? a damaging immune response by the body to a substance, especially pollen, fur, a particular food, or dust, to which it has become hypersensitive.
50
Antigen-Presenting Cell ?
A type of immune cell that enables a T lymphocyte (T cell) to recognize an antigen and mount an immune response against the antigen. Antigen-presenting cells (APCs) include macrophages, dendritic cells, and B lymphocytes (B cells).
51
What are the 3 antigen presenting cells?
The immune system contains three types of antigen-presenting cells, i.e., macrophages, dendritic cells, and B cells.
52
What is the function of antigen presenting cells APCs?
An antigen-presenting cell (APC) is an immune cell that detects, engulfs, and informs the adaptive immune response about an infection. When a pathogen is detected, these APCs will phagocytose the pathogen and digest it to form many different fragments of the antigen.
53
What are antigen presenting cells and why are they important?
Antigen-presenting cells are vital for effective adaptive immune response, as the functioning of both cytotoxic and helper T cells is dependent on APCs. Antigen presentation allows for specificity of adaptive immunity and can contribute to immune responses against both intracellular and extracellular pathogens.
54
Are natural killer cells antigen presenting cells? NO
In contrast to NKT cells, NK cells do not express T-cell antigen receptors (TCR) or pan T marker CD3 or surface immunoglobulins (Ig) B cell receptors, but they usually express the surface markers CD16 (FcγRIII) and CD57 in humans, NK1.
55
Where are Natural Killer cells made?
NK cells are known to differentiate and mature in the bone marrow, lymph nodes, spleen, tonsils, and thymus, where they then enter into the circulation.
56
white pulp of spleen?
White pulp is a histological designation for regions of the spleen (named because it appears whiter than the surrounding red pulp on gross section), that encompasses approximately 25% of splenic tissue. White pulp consists entirely of lymphoid tissue.
57
What is the difference between white pulp and red pulp?
The Cords of Billroth
The spleen contains two main types of tissue - white pulp and red pulp. White pulp is material which is part of the immune system (lymphatic tissue) mainly made up of white blood cells. Red pulp is made up of blood-filled cavities (venous sinuses) and splenic cords. The Cords of Billroth
58
What tissues make up the spleen?
The spleen is the largest lymphatic organ in the body. Surrounded by a connective tissue capsule, which extends inward to divide the organ into lobules, the spleen consists of two types of tissue called white pulp and red pulp. The white pulp is lymphatic tissue consisting mainly of lymphocytes around arteries.
59
What are the 3 -4 functions of the spleen?
Clearance of microorganisms and particulate antigens from the blood stream.
Synthesis of immunoglobulin G (IgG), properdin (an essential component of the alternate pathway of complement activation), and tuftsin (an immunostimulatory tetrapeptide)
Removal of abnormal red blood cells (RBCs)
60
What does white pulp do in the spleen?
Very important role in the normal immune response to infection. Antigen presenting cells may enter the white pulp, resulting in activation of the T-lymphocytes stored there.
61
What does red pulp of spleen do?
Removal of old, damaged and dead red blood cells along with antigens and microorganisms – the venous sinuses have gaps in the endothelial lining which allows normal cells to pass through, abnormal cells remain in the cords and are phagocytosed by macrophages.
62
What happens in the red pulp of the spleen?
Composed of connective tissue known also as the cords of Billroth and many splenic sinusoids that are engorged with blood, giving it a red color. Its primary function is to filter the blood of antigens, microorganisms, and defective or worn-out red blood cells.
63
Are T cells white blood cells?
T cell, also called T lymphocyte, type of leukocyte (white blood cell) that is an essential part of the immune system. T cells are one of two primary types of lymphocytes—B cells being the second type—that determine the specificity of immune response to antigens (foreign substances) in the body.
64
can the spleen make white or red Blood cells?
The spleen also stores red blood cells, platelets, and infection-fighting white blood cells. The spleen plays an important role in your immune system response. When it detects bacteria, viruses, or other germs in your blood, it produces white blood cells, called lymphocytes, to fight off these infections.
B cells mature in the bone marrow or in the lymph node. Bone Marrow: Mature B cells express antibodies on their surface, which are specific for a particular antigen.
65
function, number of lymph nodes
filter lymph
maintain/produce B cells
house T cells
400 - 450 - in series, at root of limbs, neck, retroperitoneum, mediastinum
66
structure of lymph node
capsule, parenchyma divided into cortex and medulla
capsule - collagenous, surrounded by adipose
convex but for indentation called HILUM
67
Hilum role in lymph?
efferent lymph vessels leave node, and blood vessels enter
68
how do afferent lymph vessels enter?
convex surface of capsule to open into subcapsular lymph sinus
69
retinaculum of lymph?
delicate meshwork - fibers and cells -
cells secrte fiber which form mesh
70
two zones of cortex of lymph?
outer - under capsule
loose lymphoid tissue under capsule "subcapsular sinus"
composed of loose network of reticular cells and fibers
Lymph w/ antigens, lymphocytes and APCs circulate in sinuses once enter via afferent system
also in space - T cells, reticular macrophages and APCS also present
71
Lymphoid follicle?
prolif B cells or lymphoblasts
mantle and germinal center containing
prolif B cells or lymphoblasts
resident follicular dendritic cells (FDCs)
migrating dendritic cells -macrophages
supporting reticular cells - producing TYPE III collagen
72
primary vs. secondary lymphoid follicle?
primary lacks mantle and germinal center
secondary has both- develops in response to antigen stimulation
Primary splenic follicles are located eccentrically in PALS and are primarily composed of B lymphocytes. When exposed to antigen, the splenic lymphoid follicles develop germinal centers
73
Where are B cells and T cells in follicles of spleen?
B are in follicles
T are in interfollicular areas
74
follicular dendritic cells? FDCs
branched cells, forming network w/in follicle
75
resident vs migrating dendritic cells?
Resident - B cell interaction
migrating - T cell interaction
resident FDCs come from mesenchyme - not bone marrow -
live at edge of germinal centers - interact w/ mature B cells (migrating dendritic work w/ T CELLS)
76
what do FDCs do?
trap antigens bound to Immunoglobulins or complement proteins on surface for recognition by B cells
77
interaction of Mature B cells with FDCs?
rescues B cell from apoptosis - displaying antigen that complements a high - affinity surface immunoglobulin
78
What B cells apoptosise? DIE?
Only if low affinity surface immunoglobulin
macrophages phagocytose apoptotic b cells
79
What is antibody affinity?
Antibody affinity refers to the strength with which the epitope binds to an individual paratope (antigen-binding site) on the antibody. High affinity antibodies bind quickly to the antigen, permit greater sensitivity in assays and maintain this bond more readily under difficult conditions.
80
Why does IgG have higher affinity than IgM?
Due to the affinity maturation and class switching processes, IgG and IgA antibodies typically have substantially higher affinities than IgM antibodies [18,19]. ... Unlike protein antigen, monovalent interactions between a single binding site of an antibody and a single glycan are generally weak.
81
cortex and paracortex?
intermediate or radial sinuses communicate with subcapusular sinuses through spaces similar to those in medulla - lines simple squamous
82
Inner cortex or paracortical region?
no precise boundaries - houses CD4 + helper T cells and high endothelial venules
83
What do CD4 + helper T cells do together?
interact w B cells to induce their proliferation and differentiation when exposed to specific antigen (adaptive immune response)
84
High endothelial venules? PEYER patches
HEVs - located in inner or deep cortex (paracortex) are sites of entry of most B and T cells - by homing mechanism
specialized cells - include Peyer patches in small intestine and cortex of thymus
85
High endothelial venules?
HEVs - located in inner or deep cortex (paracortex) are sites of entry of most B and T cells - by homing mechanism
specialized cells - include Peyer patches in small intestine and cortex of thymux
High endothelial venules (HEV) are specialized post-capillary venous swellings characterized by plump endothelial cells as opposed to the usual thinner endothelial cells found in regular venules. HEVs enable lymphocytes circulating in the blood to directly enter a lymph node (by crossing through the HEV).
86
medulla of lymph?
surrounde by cortex except at hilum
two major components -
medullary SINUSOIDS- retic fibers, lymph, circulating cells and antigens - trabeculae
CORDS - w/ B cells, macrophages, plasma cells
Activated B cells migrate from cortex as plamsa cells and enter medullary sinus
Strategic location because plasma cells can secrte immunoglobulins directly into medullary sinus w/o leaving lymph node
87
Lymph vessels - afferent ?
carry from CT or other lymph nodes - pierce capsule and empty in large subcapsular sinus - just below capsule
from subcpasular sinus - lymph enters cortex through cortical sinuses and enters medullary sinuse
medullary sinuses converge toward hilus to drain in efferent lymph
88
how lymph nodes works - if understand this - spleen and MALT< GALT, Peyer's Patches, Tonsils work similarly
Afferent lymph
10% comes thru capsule
90% via arteries
Bringing antigen presenting cells
If enter thru capsule
goes by lobed cortexes where B cells sample antigen
if recognize antigen B cell asks T cell for permission in paracortex (looks behind and gets OK)
If T cell oks - B activates - forms Germinal Center - proliferates antibodies
In Medulla (Center) Memory cells stay behind to sample for more of this antigen
AND - have HEVs - High Endothelial Venules - these works with capillary system and other 90% of blood - to strain antigen presenting cells - letting them wander around to cortex in lymph - looking for B cells that want to recognize their antigen
All lymph leaves via Hilem - and goes to next lymph as the Afferent - processing yet again - looking for the right B cell that recognizes the Antigen (unless it already has ... then does it just proliferate?)
89
Hilem in lymph node, what structures?
3 things:
artery 90% antigen presenting cells enter here
vein
efferent lymph
90
Spleen - how work like a lymph node?
afferent can only enter via artery - not thru capsule
Four function in spleen
1. Red Pulp - cleans out old, too big RBCs because can't get thru fenestrations and other bad things
2. White pulp - is immune system like lymph w/ cortex (b cells), paracortex (t cells giving permission) and medulla - memory cells and ?? - recognizes antigens, generates antibodies
3. Makes IgG, properdin, tuftsin
4. extramedullay hematopoiesis (fetal blood creation mainly in fetus) MYELOID METAPLASIA
91
Extramedullary hematopoiesis ?
(EMH or sometimes EH) refers to hematopoiesis occurring outside of the medulla of the bone (bone marrow). It can be physiologic or pathologic. Physiologic EMH occurs during embryonic and fetal development mainly.
MYELOID METAPLASIA - spleen starts making RBC and WBC - in leukemia ie.
92
Innate immune system -
This is neutrophils, vasodilation, margination, Emmigration, chemotaxis, Phagocytoses, compliment system, Interfeurons, Toll Receptors
May meet adaptive immunity during opsonization
93
Is a macrophage an Antigen Presenting Cell? Is a neutrophil?
Yes and NO.
Yes re macrophage - can take antigen back to B cells and show it off - and ask for help. It can also just phagocytose.
A neutrophil can only phagocytose.
94
Opsonizataion - C3b ?
What is it - our cells recognize antigens easily via PAMPS - Patholgen Associated Molecular Patters - so our cells know to put C3b complement on the outside, so that C3b receptors on phagocyte can bind - and hold on tightly while ingest.
Can additional bind MORE if IgG, IgM, etc are on the outside too of the bacteria - this involves adaptive immunity FCs
FCs are fragment crystalization - FCs mean there is an IgG< M< A< E ETC on the cell
95
MHCI vs MCH2?
MHC1 is a safeword - all cells manufacture this to tell our immune system that they are OK>
IF there is no MHC1 on a cell - our immune system knows it is malfunctioning - due to virus or malignancy and KILLS IS via CH8
8 divided by MCH1 = CD8
96
MCH2 ? who can make these>
Only antigen presenting cells can make these - If these are on outside of cell - phagocytes know to KILL via CD4.
8 divided by MCH2 = CD4
97
B Cell - mature but naive?
How does it get to become not-naive? Gets activated with permission of T cell in spleen, lymph in paracortex after being recognized by B cell
98
What happens to an activated B Cell?
Becomes a PLASMA cell and Fights OR stays in spleen, lymph as memory cell -
If becomes plasma cell - can speciailize and build antibodies - immunoglobins
pre specialization - it is an IgM - pentemere 10 chances to catch a fish
99
Y shpae of IG cells - immunoglobins
lower part is isotope which will become the M, G, A, E or D
upper part of Y is variable, and will best try to bind with antigen
these can circulated through blood on their own OR be attached as a surface protein on a cell
100
Affinity vs. Avidity?
Affinity is whether TIP of Y is specific enough to fight successfully - higher affinity, better success rate
IgM lease specific - primary fighters - but 5 arms to try to catch something
Affinity is one, but avidity (hope to catch) is 10 (highest rate)
for IgG - Affinity is already 10 because it has been worked on already and tweaked - and it has two small arms - so total avidity is 20. Stronger!
101
IgM - primary fighter, G, A E? D?
G - monomer - most common
A - dimer - mucosal liquid related (mother's milk - dimer = 2 breasts to remember - WORMS
E - mast cells - allergy
D - impotent cell - will be killed
102
Neutralization? optimazation? complement?
Neutralization - see mostly in virus - COAT outside of virus with antibody - it can't succeed - or coat all of receptors
103
Optimatzation? c3b -
outside of antigen has FC IgG, IgA - so that makes a tighter hold with receptor cells
104
Complement? C1
C1, c3b -
C3a, 4a, 5a - chemotaxis
c5 - 9 forms pore in cell which allows LYSIS and death
105
when do cells synthesize interfuerons?
Virus - interfuerons interfere
106
HELP! when macrophage has transmigrated and is fighting bacteria - what does it secrete to ask for more help? cytokines?
Interleuken 1,
Tumor Necrotic Factor alpha,
Interleuken 8
ENDOthelial cell in response release Selectins E (response to IL1 and TNFalpha
Interleuken 8 release - endothelial expose Icam, Vcam - integrins on neutrophils activated, bind in- VCAM, ILAM, ? firm binding, more diapedis
107
Do Interleuken 1 and TNF give you a temperature during infection? released by Macrophage...
Yes.
PGE2 -(resets body temperature) initiates fever - comes from hypothalmus when IL1, and TNF report to hypothalmus
why?
1. High temperature harsher for bacteria to survive
2. Speeds up cellular metabolism - healing happens faster
3. zinc, iron sequestered that bacteria needs to flourish
108
IL1 - TNF in liver affects?
Acute Phase Reactive proteins in Liver created -
C Reactive Peptide
These high rates in blood - tells Dr. there is infection
109
IL1, TNF affect on bone marrow?
stim bone marrow to blast out more WBCs - more neutrophils, monocytes, eosinophiles (whatever kind of WBCs needed )
LEUKOCYTOSIS
110
phagosome?
WBC with bacteria engulfed within.
111
Phagolysosome?
when lysosome fuses with bacteria - in the phagosome.
hydrolytic enzymes of lysosome - breaks down bacteria.fungal/parasitic, etc - antigens persist
112
Neutrophil - can not present antigen so what do with antigen do?
spits them out - excotysis - into interstitial fluid - circulated into lymph nodes
113
types of Antigen presenting cells? 3
can produce MHC2
b cells
macrophages
dendritic cells
114
Can neutrophil always successfully break down bacterias, etc?
Oxygen Burst
they may die in the process - can sacrifice themselves via oxygen production - free radicals - which can enter neutrophil and destroy bacterias -
sometimes kills neutrophil, or neutrophil kills itself
Oxygen burst -
115
NETS other option - Neutrophils Extracellular Traps
release their DNA into extracellular fluid - bind it to bacteria and tag it for destruction- scary because if releasing chromatin - body could decide this is a foreign bad thing and start fighting it - but Ninja Nerd says don't worry to much right now
Cathepsen J or G or other will then destroy or tag for opsonization by other WBCs
116
Macrophage - how can it present on cell? MHCII - recombination -
Major Histo Compatibility Complex Type 2
shuffling of genes on Chromosome 6
Binds with antigens in cell and puts them on the surface of the macrophage surface -
MHC2 in on surface of cell presenting antigen
117
MHC1 - with Self Molecule
all nucleated cells - safeword - as long as able to produce, cell is OK -
118
MHC2 - three types of genes? MCH1
DP, DQ, DR -
ABC
important in transplants
119
bacteria now spat out of neutrophils, and macrophages presenting antigen on surface -
Where do they now go?
Into lymph
B cell sees antigens go by, taste them,
every B cell is different - looking to see if they can fit against the bacteria -
can shuffle their parts, recombination
if antigen binds on to B cell because by random chance its a perfect fit -
uses clathrin to pull bacteria into cell, binds w/ MHC2 - and present whole package on cell surface -
Now B cell is activated - wants to proliferate - but can't yet - waiting on Macrophage (and T cell OK?)
120
What is difference between precipitation and agglutination?
The antigen in precipitation reaction is in soluble form whereas in agglutination reaction the antigen is in sedimented form. The sensitivity of agglutination reaction is more than that of a precipitation reaction. ... The end product in precipitation reaction appears as a large, insoluble mass of visible precipitate.
Aglutination often occurs with mismatched blood
121
Complement system? how harms antigens? LYSIS
makes hole in them - via MAC
122
Neutralization?
coats virus (usually) and virus can't do its dirty work.
123
Other types of complement system? opsonization?
if stops at C3B - macrophage eats because macrophage has C3b receptors -
OR
Macrophage can eat bacteria directly ? why go through whole c3b process????
124
Ways to kill bacteria, fungus, parasites, etc?
```
phagocytosis
complement system
interfuerons
toll receptors
??
```
125
Where are compliment proteins made and where are they stored? Which one binds first?
made in liver, flow through system looking for problems.
C1 binds first
126
What do c3b and C5a enhance?
the inflammatory response through chemotaxis
Proteases released by Mast cells activate C3b C5a -
127
Classical pathway of complement proteins ?
antibody mediated
c1 binds to ANTIBODY (like IgG) binds to antigen - FC portion of antibody attractive to complement proteins -
MAC - breaks off at c3b (C5b - 9) form MAC -> LYSIS
opsonization C3b - macrophage can bind right here once break off occurs - because has a c3b receptor - and then phagocytes - and then w/ MCH2 presents antigen again
release of c3a/c5a 9 enhances inflammatory response
128
Alternative pathway
C3b binds straight to Antigen - C3b so special
C5b - C9 break off - MAC - LYSIS
Macrophage can bind on C3B same as above
129
Lectin Pathway- antigen is mannose - a sugar molecule
lectin binds to mannose antigen
c4 binds, c2, c3b, c5b - c -9
MAC
130
What WBCs have c3b complimentary protein specific to C3B?
C3b is a good opsonator - tasty!
macrophage, dendritic, neutrophils
131
Are complimentary proteins part of innate or adaptive immune system?
Innate -
132
Toll like receptors?
Interfuerons?
VIRUSES re interfuerons
IRF -
innate immune system, proteins on cell membrane or in vesicles cells that respond to bacterias
interfeurons - signal telling others there is a problem, and to start proliferating, etc
133
If virus infected - and going to be killed, is there someway the cell before dying can notify other cells to save themselves?
IRF (interfeuron Regulatory Factor)
Yes -
IRF activated, which activates secretion of alpha, beta, gamma interfeurons from DNA
alpha, beta can be secreted by many cells, gamma by platelets
mainly alpha, beta secreted by cell - warns other cell - that produces Protein Kinase R (and others) is like a scissor -
if virus tries to penetrate 2nd cell - Protein Kinase R won't let virus get into 2nd cell -
almost any cell can produce Interfueron alpha, beta
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Gamma Interfuerons?
macrophage is dying, but it can notify others -
alpha beta - warns other cell
gamma? can go to 2nd macrophage - and tells him to grow bigger, hungrier, and proliferate - increasing also MHC1 and 2.
135
Are NKiller cells part of innate or adaptive?
innate
136
alpha and beta, can they activate N Killer cells?
Yes. NKIller goes to first cell infected by virus -
3 things can happen
mica (similar to IgG)?
IgG attach ?
down-regulate MCH1 - NK sees there is no MCH1 on cell - and KILLS it APOPTOSIS
137
interferons used to treat as a drug?
herpes, MS, genital wars -
138
Toll receptors - ?
Toll-like receptors (TLR) are a family of transmembrane receptors that serve as signaling receptors in the innate immune system; their ligation by exogenous and possibly endogenous ligands triggers a pro-inflammatory signaling cascade in various cells linking innate immunity to inflammation
Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-pass membrane-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes.
TLRs recognize highly conserved structural motifs known as pathogen-associated microbial patterns (PAMPs), which are exclusively expressed by microbial pathogens, or danger-associated molecular patterns (DAMPs) that are endogenous molecules released from necrotic or dying cells.
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Different Toll receptors
work to fight various bad things - parasites, virus, etc
secreting all sorts of signaling molecules for help - to enhance inflammatory response
can signal genes
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What happens when T cell goes to Thymus? Matures - what is process?
Eventually trying to get to a CD4 helper cell or a CD8 destroyer
When arrives in Thymus OUTER CORTEX, is given everything
CD4 arm, CD8 arm, Tcell Receptor (TCR) and TCR3 BINDS TCR to both arms.
"Double Positive"
To enter INNER Cortex, is tested via Positive Selection -
has to choose to use one of its two new arms and bind to either MCH1 or MCH2 using its TCReceptor- if successfully binds - advances as either a cd4 or 8
To move to MEDULLA - one more test - Negative Selection
DENDRITIC cell Test - Test to see if will bind and attack to Self (only antigen w/in Thymus ...
If Binds to Self - Killed
If doesn't bind to self - advances into medulla as a mature T cell.
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Double positive? Positive Selection, Negative?
1. Given both CD4 and CD8 plus TCR, bind arms of 4 and 8 to TCR w/ TCR3 - Double Positive - for both CD4 and CD8
In Outer Cortex
2. to advance into Inner Cortex - undergoes Positive Selection
If Binds - advances (can only bind to one at a time - either MCH1 or MCH2
If Binds - lives
cd4 binds to MCH2
CD8 binds to MCH1
3. To advance to Medulla - Negative Selection - if binds to Dendritic Cell (self antigen presented - is KILLED.
If Binds - Dies.
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CD4 works with MCH 1 or MCH2???
8 is the magic number
MCH2! 4 x 2
CD8 works w/ MCH1 8 x 1
8 is the magic number
143
Do B cells kills things?
No, they are two things - memory cells and plasma cells -
144
Do memory cells kill things?
Effective Memory T Cell-Mediated Immunity. ... The prominent view proposes that reactivated memory CD8+ T cells rapidly express cytolytic effector functions (such as perforin, Granzyme and Fas) that allow for direct killing of pathogen-infected cells, representing the major mechanism of host protection
145
Do Plasma cells kill things?
No, they create immunoglobulins... that present to T cells for killing
146
What is the difference between B and T cells?
Both T cells and B cells are produced in the bone marrow. The T cells migrate to the thymus for maturation. ... The main difference between T cells and B cells is that T cells can only recognize viral antigens outside the infected cells whereas B cells can recognize the surface antigens of bacteria and viruses ??
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How do T cells kill viruses?
When the perfectly shaped virus antigen on an infected cell fits into the Killer T-cell receptor, the T-cell releases perforin and cytotoxins. Perforin first makes a pore, or hole, in the membrane of the infected cell. Cytotoxins go directly inside the cell through this pore, destroying it and any viruses inside.
148
Can T cells kill bacteria?
Neutrophils and macrophages can capture and digest extracellular bacteria (ones that live free in tissues and the bloodstream). ... T-cells can kill cells infected by intracellular bacteria (ones that take up residence within cells).
149
what is the role of immunoglobulins in immunity?
Immunoglobulins, also known as antibodies, are glycoprotein molecules produced by plasma cells (white blood cells). They act as a critical part of the immune response by specifically recognizing and binding to particular antigens, such as bacteria or viruses, and aiding in their destruction.
150
Where are natural killer cells formed?
NK cells are known to differentiate and mature in the bone marrow, lymph nodes, spleen, tonsils, and thymus, where they then enter into the circulation.
151
What are natural killer cells?
Natural killer cells (also known as NK cells, K cells, and killer cells) are a type of lymphocyte (a white blood cell) and a component of innate immune system. ... They serve to contain viral infections while the adaptive immune response is generating antigen-specific cytotoxic T cells that can clear the infection.
152
How do NK cells Kill?
How do you kill NK cells?
Cancer cells and infected cells often lose their MHC I, leaving them vulnerable to NK cell killing. Once the decision is made to kill, the NK cell releases cytotoxic granules containing perforin and granzymes, which leads to lysis of the target cell.
153
How do viruses avoid NK cells?
Viruses possess more effective and distinct strategies to escape from NK cell immunity, including stimulating the inhibitory receptors and disrupting the activating receptors. Several viruses are able to inhibit NK cell activation through inhibitory receptors.Apr 12, 2016
154
Can NK cells kill bacteria?
NK cells are cytotoxic; small granules in their cytoplasm contain proteins such as perforin and proteases known as granzymes. ... α-defensins, antimicrobial molecules, are also secreted by NK cells, and directly kill bacteria by disrupting their cell walls in a manner analogous to that of neutrophils.
155
T cell - what type of T cell interacts with APC cell returning to 2dary lymphoid organ with antigen?
Naive CD4 helper cell -
listens to APC and decides what to do
APC knows more about antigen -
156
How do T cells kill?
Perforin first makes a pore, or hole, in the membrane of the infected cell. Cytotoxins go directly inside the cell through this pore, destroying it and any viruses inside. This is why Killer T-cells are also called Cytotoxic T-cells. The pieces of destroyed cells and viruses are then cleaned up by macrophages.
Perforins - make holes
granzymes, FAS lig.
Cause apoptosis
157
How are T cells activated, what do they do?
When they are presenting with an antigen from APC returning from the outback to a secondary lymphoid organ...
T cells hook up with MCH2 and antigen via TCR connection, and B7 (from APC) w/ CD28 (T cell) - tighter bind...
APC tells T helper cell about antigen - via cytokines - tHelper cell does one of three things
Thzero (Th0) becomes one of three things - Th1, Th2, Th17
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How does cd4 helper cell decide to become th1, th2, th17?
depends on cytokines released from APC -
if an intracellular virus - APC releases IL12
If parasite, worm, APC releasese IL4
If extracellular bacteria - TGf beat and IL6
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If IL 12 (virus) warming from APC?
becomes Th1 - -> IL2 from t cell -> calls forth CD8 to KILL (via performins , granzymes (apoptosis), Fas ligand - apoptosis cascade
AND
```
Th1 -> interferon gamma
ups macrophage production
IgG class switching!
```
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If parasite/worm (too big to phagocytose) APC releases IL4 - T cell becomes ...
Th2 ->
IL4 IgE class switching -
IL5 - Mast cell production goes up (IL5 goes with Mast cells in general)
IL13 - mucus secretion - flushing out worms
161
if Extracellular bacteria - TGF beta and IL6 released by APC...
Th17 -> releases IL17 - which ups neutrophil production.
162
Memory t cells 5%
Memory T cells are instead produced by naive T cells that are activated, but never entered with full-strength into the effector stage. The progeny of memory T cells are not fully activated because they are not as specific to the antigen as the expanding effector T cells.
163
Simplifying T cell activation?
TH1 - if a virus - helper calls in CD8 to kill and CLASS switching to IgG
TH2 - If a parasite - helper cell calls in class switching IgE (IL4), ups mast cell production (IL5), ups mucous production (IL13)
TH17 - if extracellular bacteria - ups neutrophils via IL17
164
What do you mean by class switching?
Immunoglobulin class switching is a biological mechanism that changes a B cell's production of antibody from one class to another, for example, from an isotype called IgM to an isotype called IgG. ... Instead, the antibody retains affinity for the same antigens, but can interact with different effector molecules.
165
What does IgG protect against?
Immunoglobulin G (IgG): This is the most common antibody. It's in blood and other body fluids, and protects against bacterial and viral infections. IgG can take time to form after an infection or immunization.
166
Why is IgG better than IgM?
IgM is specialized to activate complement efficiently upon binding antigen. IgG antibodies are usually of higher affinity and are found in blood and in extracellular fluid, where they can neutralize toxins, viruses, and bacteria, opsonize them for phagocytosis, and activate the complement system.
167
Do MHC2 cells decide if going to present every foreign antigent?
Yes - they make a decision within their cell. If DM not present - they do not present the antigen - and MCH2 is recycled
If DM appears - they present it on their surface
168
Do T cells generate B cells to make antibodies?
Yes! If T cell identifies a foreign antigen as bad, they signal B cells to make antibodies - (immunoglobins)
Generally this done for bacteria and fungi, because virus and cancers can not be phagocytosed easily -
if can't phagocytose (too big), can't present them to T cells via MHC2.
169
Do MCH1 and MCh2 differ in their structure -
Yes, MCH1 has a beta2 microglobulin
170
What is clip in immunology?
CLIP or Class II-associated invariant chain peptide is the part of the invariant chain (Ii) that binds to the peptide binding groove of MHC class II and remains there until the MHC receptor is fully assembled. CLIP is one of the most prevalent self peptides found in the thymic cortex of most antigen-presenting cells.
171
What do CLIPs do for APSc?
protect MCH2 and prevent antigen binding if not worthy.
172
What does DM do in MCH2/APC creation?
DM decides if antigen should be presented to the world. If DM APPEARS - then clip is displaced, antigen binds to MCH2, and presented.
173
HOw do plasma cells know it is time to create a certain immunoglobulin?
They are signaled by T cells - T helper cells determine that an APC has presented a dangerous antigen - and signals via cytokines (?) to B cells to produce immunoglobulins.
174
If APCs don't have functioning CLIP or DM, what happens?
They can't do their work, they can't present antigens - need CLIP and DM to make that happen
175
? Why is it more likely that bacteria and fungi are phagocytosed? More likely than virus and cancer?
??
176
Do t cells OK activating against all antigens presented ?
No, they have to decide it is worthy.
177
3 types of cells produced by Lymphoid line?
NK cells (not see much in immunology - they eat virus/cancer cells - self cells that have gone awry)
B cells
T cells
178
B cells - what happens to them when created?
B cells made in bone marrow - produce Immunoglobins when T cells tell them to.
Live in cortex of lymph - first recognizers when APCs come thru and present -
ask T cells for permission to make Immunoglobins
179
T cells?
go to thymus to mature
double positive -
positive test - have to bind to proceed
negative test - can't bind to proceed
180
What cells connect innate to adaptive immune system?
helper T cells. cd4s recognize antigens presented by APCs, and tell B cells to turn on. Activating adaptive immunity.
cd4 cytokines induce B cells to proliferation and maturation
181
cd8 cells - cytotoxic
cytokines produce death - they go after virus and cancers, can also perforate non-self cells
182
What are plasma cells?
B cells that are proliferating with appropriate antigen. Colonal expansion needs to be OKd by t cells.
Antigens are not attached to cell membrane but excreted -
183
Where do memory cells carry their immunoglobulines?
On their surfaces
184
Where do antibodies floating thru blood stream come from?
Plasma cells - antibodies mark pathogens which facilitate phagocytosis and complement activation
185
where do dendritic, monocytes, and neutrophils all come from?
same myeoloid precursor
186
Are basophils or mast cells phagocytes?
No.
187
Huge kidney bean nucleus cells?
Monocyte/macrocytes - not granular - they have vesicles.
heavy artillery
188
Huge kidney bean nucleus cells?
Monocyte/macrocytes - not granular - they have vesicles.
heavy artillery
Stain BLACK as do neutrophils
189
Eisinophils red - bilobed - fight fungi and parasites
granules are base
190
Basophil - blue granules,
bilobed - stain basic because granules are acidic
191
basophils and mast cells -
same line - vasoactive - not phagocytes - get rid of things too big
192
Vasoactive?
nose swells up and produces allergy response to cats, etc -
trying to flush out because too big to phagocytose
gets rid of big things - like tapeworm, if crap everywhere - hopefully flushing out.
193
lymphoid organs?
primary - where mature - bone marrow, thymus
secondary - where activate, lymph nodes, spleen, "others" MALT< GALT< peyer's patches, tonsils
194
What is in cortex of lymph nodes?
B cells - in follicles
195
primary vs. secondary follices?
secondary have activated B cells - clonal expansion - germinal center
196
What is in paracortex?
T cells - let's B cell knows if it should activate - which means form a germ cell
197
What's in medula?
memory cells and HEVs
198
How does 90% of apcs enter lymph?
through arterial supply - and are pushed thru HEVs into tubular system, where B cells can try to recognize antigens
199
What does spllen have that is similar to HEV of lymph?
fenestrated capillaries
200
hypersensitive immunity -
Hypersensitivity reactions are an overreaction of the immune system to an antigen which would not normally trigger an immune response. The antigen may be something which would in most people be ignored – peanuts, for example, or it may originate from the body.
201
What are the four types of hypersensitivity reactions?
Type I: Immediate Hypersensitivity (Anaphylactic Reaction) These allergic reactions are systemic or localized, as in allergic dermatitis (e.g., hives, wheal and erythema reactions). ...
Type II: Cytotoxic Reaction (Antibody-dependent) ...
Type III: Immune Complex Reaction. ...
Type IV: Cell-Mediated (Delayed Hypersensitivity)
202
Type 1 reaction example?
Type I reactions (ie, immediate hypersensitivity reactions) involve immunoglobulin E (IgE)–mediated release of histamine and other mediators from mast cells and basophils. Examples include anaphylaxis and allergic rhinoconjunctivitis. ... An example is contact dermatitis from poison ivy or nickel allergy.
203
What is a Type 2 hypersensitivity reaction?
| Type II Hypersensitivity.
Type II hypersensitivity is an antibody-dependent process in which specific antibodies bind to antigens, resulting in tissue damage or destruction (see Fig. ... If the antigen is present on cell surfaces, antibody binding can result in cell lysis through the in situ fixation of complement.
204
What is Type 3 hypersensitivity reaction?
Type III hypersensitivity is designated as immune complex hypersensitivity. This reaction occurs through the formation of antigen-antibody complexes that activate complement and result in tissue damage (Fig. ... On activation, neutrophils release their enzymes, and these result in tissue damage.
205
Type IV or Delayed-Type Hypersensitivity.
occurs at least 48 hours after exposure to an antigen. It involves activated T cells, which release cytokines and chemokines, and macrophages and cytotoxic CD8+ T cells that are attracted by these moieties.
206
What is difference between allergy and hypersensitivity?
Various autoimmune disorders as well as allergies fall under the umbrella of hypersensitivity reactions, the difference being that allergies are immune reactions to exogenous substances (antigens or allergens), whereas autoimmune diseases arise from an abnormal immune response to endogenous substances (autoantigens).
207
Is rheumatoid arthritis a type 4 hypersensitivity?
Type IV Hypersensitivity Reactions
Antigen is taken up, processed, and presented by macrophages or dendritic cells. ... TH17 cells have been implicated in contact dermatitis, atopic dermatitis, asthma, and rheumatoid arthritis.
208
Type 1 hypersensitivity - what happens?
The binding of IgE to FcεR triggers the release from Mast cells and Basophils of chemical mediators that include Histamine, Heparin, Eosinophil Chemotactic Factor, Leukotriene B4, Neutrophil Chemotactic Factor, Prostaglandin D4, Platelet-Activating Factor (PAF), and Leukotrienes C4 and D4
Influx of Eosinophils Amplifies and Perpetuates the Reaction
Effects May be Systemic (Anaphylaxis, as for example due to bee stings or drugs) or Localized (Food Allergies, Atopy (“hyperallergic”), and Asthma)
“Immediate” means seconds to minutes
“Immediate Allergic Reactions”, Atopic, may lead to Anaphylaxis, Shock, Edema, Dyspnea and Death
EXPOSURE to Allergen: TH2 CD4+ T cell activation leads to B cell production of IgE which bind to Fc Receptors (FcεRI) on Mast cells
IMMEDIATE phase: MAST cell Degranulates releasing Histamine, Vasodilatation, Vascular leakage, smooth muscle contraction, (broncho)-Spasm
LATE phase (hours, days): Eosinophils, PMNs, T-Cells,
209
urticaria? - Hives
Hives, also known as urticaria, are reddened, itchy welts that may be triggered by exposure to certain foods, medications or other substances. Hives (urticaria) are red, itchy welts that result from a skin reaction.
210
Anaphylactic Shock signs and Symptoms?
Skin reactions, including
Hives along with Itching,
and Flushed or Pale Skin
A Feeling of Warmth
A Weak and Rapid Pulse
The Sensation of a Lump in the Throat
Constriction of the Airways and a Swollen Tongue or Throat, causing Wheezing and Difficulty Breathing
Nausea, Vomiting or Diarrhea
Dizziness or Fainting
Symptoms usually occur within Minutes of Exposure
to an Allergen or Can Occur a Half-hour or Longer after Exposure
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Type II?
ie - pernicious anemia -
large, immature, nucleated cells (megaloblasts, which are forerunners of red blood cells) circulate in the blood, and do not function as blood cells; it is a disease caused by impaired uptake of vitamin B-12 due to the lack of intrinsic factor (IF) in the gastric mucosa.
AntibodiesType II hypersensitivity reactions (antibody-mediated) are characterized by production of an IgG or IgM antibody directed against a specific target cell or tissue
In complement-dependent cytotoxicity, fixation of complement results in osmotic lysis or opsonization of antibody-coated cells, e.g. autoimmune hemolytic anemia, transfusion reactions, and erythroblastosis fetalis
In antibody-dependent cell-mediated cytoxicity (ADCC), cytotoxic killing of an antibody-coated cell occurs, an example is Pernicious Anemia
Antireceptor antibodies can activate or interfere with receptors, e.g. Graves disease and Myasthenia Gravis
Antibodies bind to fixed tissue or cell surface antigens
OPSONIZATION of cells by antibodies
PHAGOCYTOSIS of opsonized cells
COMPLEMENT FIXATION (cascade of C1q, C1r, C1s, C2,…..)
Antibodies bind Fc Receptors of Leukocytes
Anti-GBM Glomerular Basement Membranes in Goodpasture’s
Anti- Desmogleins in Pemphigus Vulgaris
LYSIS: destruction of cells by membrane lysis
ANTIRECEPTOR Antibodies disturb receptor function
Anti-TSH Receptor Stimulates Thyroid in Graves Disease
Anti-Ach Receptor Inhibits Junction in Myasthenia Gravis
212
Goodpasture syndrome (GPS)?
, also known as anti-glomerular basement membrane disease, is a rare autoimmune disease in which antibodies attack the basement membrane in lungs and kidneys, leading to bleeding from the lungs and kidney failure.
213
Graves' disease
is an autoimmune disorder that causes hyperthyroidism, or overactive thyroid. With this disease, your immune system attacks the thyroid and causes it to make more thyroid hormone than your body needs.
214
Pemphigus Vulgaris
Pemphigus vulgaris is a rare, severe autoimmune disease in which blisters of varying sizes break out on the skin and on the lining of the mouth and other mucous membranes. Pemphigus vulgaris occurs when the immune system mistakenly attacks proteins in the upper layers of the skin.
215
Type II Antibody Mediated Hypersensitivity Diseases
Autoimmune Hemolytic Anemia (AHA)
Idiopathic Thrombocytopenic Purpura (ITP)
Goodpasture Syndrome (Nephritis & Lung Hemorrhage)
Rheumatic Fever
Myasthenia Gravis
Graves Disease
Pernicious Anemia (PA)
216
Type 3
```
Antibodies Bind to Antigens: Formation of in situ or circulating Antigen/Antibody “Complexes” that Deposit in
Kidney (Glomerular Basement Membrane)
Blood Vessels
Skin
Joints (Synovium)
Complement Activation
Acute Inflammation and Tissue Injury
```
Vasculitis if it occurs in blood vessels; Glomerulonephritis if it occurs in renal glomeruli;
Arthritis if it occurs in the joints
Systemic Lupus Erythemtosus (SLE),
Polyarteritis Nodosa (PAN),
Poststreptococcal Glomerulonephritis,
Arthus Reaction: Clumping of Serum of Sensitized Person after Repeated Booster Injections of Vaccines into the Individual who Already Possess High Titers to Vaccine Molecules, peak 4-10 hours
Serum Sickness: Patient Forms Antibodies to Xenogeneic Ig that is Administered During Passive Immune Therapy Regimens, peak in days
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Type IV
Immune-mediated inflammatory disease examples:
Contact Dermatitis, Multiple Sclerosis, Diabetes Mellitus I, Tuberculosis, Rheumatoid Arthritis, Hashimotos Thyroiditis
T cell–mediated (type IV) hypersensitivity disorders are caused mainly by immune responses in which T lymphocytes of the TH1 and TH17 subsets produce cytokines that induce inflammation and activate neutrophils and macrophages, which are responsible for tissue injury
CD8+ CTLs also may contribute to injury by directly killing host cells
```
Mediated by Sensitized
T Lymphocytes
CD4+ TH1 and TH17 cells
CD8+ Cytotoxic T cells (CTL)
Examples:
Contact Dermatitis: Direct Contact with Antigen
```
218
Granulomas forming?
In Delayed Type Hypersensitivity (DTH) CD4+ Th1 Lymphocytes Mediate
Granuloma Formation;
examples include the PPD skin test and tuberculosis
219
type IV reactions
In Cytotoxic T-cell-mediated Hypersensitivity, CD8+ T Lymphocytes destroy antigen-containing cells; examples include viral infections, immune reaction to tumors,
Contact Dermatitis, and Graft Rejection
220
dusty -
IgE - Mast cell
Crosslinking
sensitized first time
second - immediate response
long term - prosteoglandins, leukotrines
What's supposed to happen - apc comes back w/ paracite/womr - Th0 turns into Th2 - releases IL 4 (IgE) and IL5 - (Mast cells)
221
Degranulization of histamine from Mast cell?
vasodilation - profound - annaphalaxia
Eoisinophil - think fungus, cancer, allergies
222
Antibody - made against a target organ - goes to organ - two types -
difference is
FC dependent - cytotoxic vs. non-cytotoxic from (FC independent)
cytotoxic - opsonization, neutralization, complement cascade - dealing w/ FC
cells of organ are tagged by organism MAC attack or phagocytosis
Good pastures,
transfusion reactions like RH+
TTP (antibodies against platelets - platelets destroyed)
Autoimmune hemolytic (against WBCs)
Non-cytotoxic - blocking or stimulating receptors (like at neuromuscular junction) Eaten Lambert, Myathinis Gravis, graves (stimulating - THS receptors - causes thyroid to grow - overproduce t4)
Antibody blocks or activates receptor - just have to learn which is which
223
third type - immune deposition - antibody not the problem, circulating antigen w/ antibody complex - its the problem 0
Don't go to organ - see systemic problem
to clear the antigen -
it clears good tissue -
the complex of antigen and antibody - too big to fit through capillary structure of endothelials
destroys the tissue where it can't get through
Vascultiis, Arthritis, Nephritis
Lupus, ABO incompatibility -
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fourth - t cell mediated "delayed hypersensitivity" disorder are
```
tubercolin test PPD,
Crohn's disease
Celiac sprue
rheumatoid arthritis
mulitple sclerosis,
Guillain Barre
Contact dermatitis
```
225
type 1 - IgE -Mast Cells (histamine), vasodilation, cross linking, Ig#
Type 2?
antibodies to the organs - see the problem in the organ not functioning -
Destruction - TTP, etc
inhibition - eaten lambert, myathenia gravis
activiation - Graves
226
3 - immune deposition
antigen/antibody complexes - where they get stuck
227
Job of lymph nodes?
filter lymph, main/produce B cells, House T cells
228
400 - 500 lymph nodes, lie in series - parenchyma?
lymph node has capsulae and parenchyma is divided into cortex and medula
229
Where are trabeculae found in lymph?
from inner surface of node
230
how do afferent lymph enter?
through capsule surace into subcapsular lymph sinus
231
What do reticular cells do in lymph?
large branches cells that secrete reticular fib - forming mesh - type 3 collagen
232
What are Trabeculae of lymph node?
The nodes are covered by a capsule of dense connective tissue, and have capsular extensions, of connective tissue, called the trabeculae, which provide support for blood vessels entering into the nodes.
233
lymph node cortec - two zones?
outer, inner
outer - sucapsula sinuses - loose retic cells and fiber
lymph have antigens lymphocytes, and APCs- circulating around sinues channels - t lymph, macropahages, etc are here
234
lymph node structure?
outer cortex with germinal centers and paracortex -
medulla inside - with sinus and cords
235
lymph follicle?
mantle + germinal center (develop in response to antigen stim)
containing
proliferating B cells or lymphoblasts
resident Follicular dendrtic cells
migrating dendrtic, macrophages,
supporting retic cells (type 3 coll)
236
primary vs secondary follicle?
primary lacks mantle and germinal center
237
Where are B cells in lymph?
in follicles - T cells are interfollicular
238
Resident dentritic cells? Who do they interact w/ and where are they found?
on edge of germinal centers - interact w/ B cells -
FCS present antigens bound to Immunoglobulins or complement proteins for recog by B cells
239
how do FCS (follicular dendritic cells - residents) rescue B cells from apoptosis?
if B cell displays an antigen that complements a high affinity surface immunoglobulin - FDC interaction rescues it from apoptosis.
??
Only B cells with low affinity apoptose - macrophages apoptose them
240
Intermediate or radial sinusues run between?
between lymphoid nodules - lined simple squamous
241
does inner cortex (or paracortical region) have nodules?
not many, if any -
houses CD4 T cells and high endothelial venules -
242
What is adaptive immune response?
when CD4 t cells interact w/ B cells to induce proliferatin and differentiation when exposed to specific antigen
243
What happens at High endothelial venules?
entry of most B and T cells by homing mechanism -
HEVs are specialized, also peyer's patches in small intestinse and in cortex of thymus
244
What is in medulla in lymph nodes?
surrounded by cortex,
two things
sinusoids -
cords (w/ b cells, macrophages, plasma cells)
Activated B cells migrate from cortex as plasma cells and enter medullary sinurse
strategic location because plasma cells can secrete immunoglobulins dictly into med sinurses w/o leaving lymph
245
What are in medullary cords?
B cells, plasma cells, macrophages - where work gets done!
246
medullary sinus?
circulating area
247
sinus flow in lymph?
enter through capsule, into sucapsular sinus to cortical sinus, medullary sinus, efferent vessles
248
How do lymphocytes get from blood to lymph?
thru arterioles, caps, HEVS, then circulate, leave thru efferent
249
how do lymph filtrate and phagocytoses?
reticular meshwork and paranchyma are a mechanical filter
flow is slow, macrophages capture
if lymph fails to destroy infection - nodes themselves pass on infection
250
parenchyma?
the functional tissue of an organ as distinguished from the connective and supporting tissue.
"the liver parenchyma"
251
Are B cells in cortex or nodules?
nodules - T cells out of nodules in "diffuse" cortex
252
percentage of plasma cells in lymph node?
1 - 3%, but increase if infection
253
"acute Lymphadenitis"?
when infection - lymph becomes swollen due to edema and proliferation
254
where are 55% of lymphnodes found in body?
head/neck -
25% generaled
14% inguinal
5% axillary
255
Spleen function?
traps old RBC, etc and eliminates
Sorts t and b cells into compartments where they work together to create immune response
stores 1/3 platelets in ready reserve
may store RBC, WBC
256
Can spleen work so fast it kills you?
yes, it may eliminate RBCs so quickly it must be removed to prevent complete depletion - of RBC or WBCs
257
structure of Spleen? 80% red pulp
capsule - splentic artery, vein, lymph
pulp - red, white
The spleen is made of red pulp and white pulp, separated by the marginal zone; 76-79% of a normal spleen is red pulp. Unlike white pulp, which mainly contains lymphocytes such as T cells, red pulp is made up of several different types of blood cells, including platelets, granulocytes, red blood cells, and plasma.
258
Stroma of spleen?
Stroma of spleen
Featured snippet from the web
Stromal cells in spleen organize tissue into red pulp, white pulp and margina
259
Where are the filtration beds in spleen?
both red and white have them - white pulp filters T and B lymphocytes from blood received from marginal zone
Red pulps receives blood from martinal zone and filters out macrophages, RBCs, platelets, granulocytes
260
What are trabecular arteries?
splenic arteries entering spleen via tabecula?
as leaves trabecula, sheath covers it PALS and goes into white pulp
261
Central artery of spleen?
aka follicular arteriole - because of nodular or follicle arrangement of white pulp
leaves white pulp to become pilicillar arters
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penicillar artery?
end as macrophage - sheathed capillaries
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How do terminal capillaries terminate in spleen?
drain directly into splenic sinusoids (closed circulation) or terminate as open eded vessels within red pulp - open circulation
splenic sinusoids are drained by pulp veins to trabecular veins to splenic veins
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blood flow of spleen?
Branches of the splenic artery enter the white pulp from trabeculae. Within the white pulp, these arteries are called the central arteries. ... The central arteries continues into the red pulp and branch into the thin straight penicillar arterioles.
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PALS spleen
Periarteriolar lymphoid sheaths (or periarterial lymphatic sheaths, or PALS) are a portion of the white pulp of the spleen. They are populated largely by T cells and surround central arteries within the spleen; the PALS T-cells are presented with blood borne antigens via myeloid dendritic cells.
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Where do T and B cells go that are in the spleen?
if not immunologically activated within a few hours - move out and continue to circulate
T cells are in the periarterial shealth (PALS0 and B cells in nodules
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Cords of Billroth?
separate splenic sinusoids - contain plasma cells, macrophages,
The 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.
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white pulp structure of spleen? 25%
blood enter - travels central artery - surrounded by PAS (T cells and macrophages), then marginal zone (macrophages) which has follicles within in (naive B cells)
end arteries - have no walls - allow blood to flow into surrounding system, venouse system around ends of arteries - here the Cords of bilroth are -
TONS of macrophages
red pulp - filters abnormal / old rBCS
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as blood comes out of arteries
tries to get back through into venouse system, if too big, can't get thru - and macropahages waiting there comsume them - or grab them because they are antigens and present them to T cells - which
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where are platelets stored in spleen?
cords of billroth
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where ar multipotent hematopoeitic stem cells and thythroid stem cells (CFu-E) stored in spleen
cords of billroth - so RBCs can be created here.
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penicillar arteries are found where?
taking blood into red plup, venous system in spleen
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closed and open circulation in red pulp?
closed - arterial vessels connect directly to splenic sinusoids
open - blood vessels open directly into red pulp spac e- and then entering through interendothelial cell slits of splenic sinusoids
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What cells in the liver complement the roll of white pulp in spleen by removing bacteria circulating in blood?
Kupffer cells of liver
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Peyer's Patches? are they part of lymph system?
Where are they found? ILEUM
Yes, how?
Peyer's patches are small masses of lymphatic tissue found throughout the ileum region of the small intestine. Also known as aggregated lymphoid nodules, they form an important part of the immune system by monitoring intestinal bacteria populations and preventing the growth of pathogenic bacteria in the intestines.
These are lymphoid follicles similar in many ways to lymph nodes, located in the mucosa and extending into the submucosa of the small intestine, especially the ileum. In adults, B lymphocytes predominate in Peyer's patches. Smaller lymphoid nodules can be found throughout the intestinal tract.
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appendix - is that part of the lymph system
yes
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Structure of lymphoid tissue?
retic fibers (type 3 collage) and free cells
retic cells secrete - and is indistinguishable from fibroblasts - exception is in thymus EPITHELIAL RETICULAR
Free cells - lymphocytes, macrophages, and plasma spaces occupy space between ret cells and fibers - each lymphoid organ has own organization
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EPITHELIAL RETICULAR cells ? where found?
of thymus - that secrete HORMONES
epithelial cell (TEC), are a structure in both the cortex and medulla of the thymus. ... These cells contain secretory granules which are thought to contain the thymic hormones
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What do reticular cells produce?
reticular fiber and trabeculae - creates a framework
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lymph nodule vs node?
nodules are unencapsulated - make up different lymph tissue
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capsulated vs. unencenapsulated?
Uncapsulated -
free cells
diffused lymph
lymph nodules
Partial
tonsils
Encapsulated
thymus
lymph node
spleen
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capsulated vs. unencenapsulated?
Uncapsulated -
free cells
diffused lymph LAMINA PROPRIA of mucous membrane - (MALT< GALT, apcs, different lymphocytes, etc)
lymph NODULES (aggregations of lymphocytes) - primary, secondary, peyer's patches
Partial
tonsils
Encapsulated
thymus
lymph node
spleen
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primary vs secondary NODULES that are unencapsulated
secondary - develop in response to antigenic stimulation
zone of rapid proliferation
size indicates size of problem (immunological response)
Mantle zone dark and lighter germinal center
Peyer's pathces in ileum are these
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MALT - where located
mucosa - MALT, Galt, Balt, etc - this is diffused lymphatic tissue - mostly B cells - some T and DC4, APCs, IGA secreting plasma cells
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Palantine Tonsils are covered w/ what time of cells?
stratified squamous non - keritanized
these tonsils can have crytps, lined by surface epithelium
lots of lymph nodules
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another word for a lymph nodule?
follicle
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hypertrophy of pharyngeal tonsils obstruct salsa opening?
adenoids
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thymus structure?
bilobed - lymphoepithelial organ
reticular fibers different here than in other lymph ??
weighs the most at puberty - then involutes - becomes fatty and fibrous
it is well developed before birth
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when rapid T cell proliferatin is needed, what can thymus do?
become restimulated !
however by age 50, the medulla is usually gone,
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structure - of thymus?
capsule - lymph nodules
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Thymus function?
responsible for rejected transplanted organs -
delayed hypersensitivity
cell mediated immunity
monitors T cell production - killing off 98% that don't pass tests -
Secretes thymosin - that stiumulate activity of T cells
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When t cells "pass" and leave thymus, what happens to them>
they complete their maturation in spleen or lymph nodes - then circulate as part of lymph pool
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capsule structure
capsule surrounded by CT
trabecular septa t0 divide gland into lobules
blood vessels -
efferent lymph vessels and nerves
Each lobule - divided into two zone - cortex, medulla
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where are T cells?
thymocytes within "epithelioreticular cells - macrophages here too
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What does thymus secrete?
growth factor to stim proliferation and differentiation of T cell
thymosin, thymopoietn, thyroxin and thymulin
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what does thyroxin do?
encourages thymulin production by epithelialreticular cells
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affect of adrenocorticosteriod on thymus?
depress T cell formation
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epithelioreticular cells role?
framework for developing 5 cells -
intercellular junctions and intermeidate filaments -
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Six types of epthelioreticular cells - 3 types in cortex, 3 in medulla
type 1 - separate thymus parenchyma from CT by occluding junctions
type 2 - nurse cells - expressing both MHC1 and 2 for developing cells, compartmentalizing babies
type 3 - barrier between cortex and medulla, also can express mhc 1 and 2
MACROPHAGES take out T cells that don't make it through the program
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medulla of thymus - one lobule continuous with other lobule
Type iv - like 3
type v - make compartments with desmosome like type 2
type 6, hassalls - compated, flattened nuclei - keratohylaine granules, intermediate filaments, lipid droplets, desmossome -
Produce thymic hormones
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where do T cells go if pass?
postcapillary venules incorticomedually junction OR efferent lymph -
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single positive stage of t cells?
when they have passed the test, getting ready to leave thymus, give up the 4 or 8 and go on with their lives
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cortex - most of the action is here
developement is rich here - double negative thymocytes proliferate in the cortex
GENE rearrangement leades to expression of pre TCR and cd 4 and cd3 -
deep in cortex become DOUBLE positive - if unable to recognize MHC 1/2 molecules are killed
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T cells recognize both self MHC and self antigens - with AIRE gene are eliminated where?
negative selection in medulla
dendritic
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Interleuken 4, 7, CSF and interferon gamma ?
cell eduction along with AIRE
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Virginal T cells - in the spleen - what happens if they don't find an antigen to fight?
they are killed - theyy were produced in an antigen free environment -
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Where is blood thymic barrier?
The functional blood-thymus barrier consists of epithelial reticular cells, their basal laminae, and endothelial cells joined by tight junctions. This barrier keeps antigens in blood vessels from entering the thymus, preventing reaction with developing T-cells.
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Why is the blood thymus barrier important?
The main purpose of the blood thymus barrier is to prevent cortical T lymphocytes from interacting with foreign macromolecules. Without the presence of this barrier, foreign antigens could cross the cortical capillaries and pose as self-antigens within the cortex.
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Do epithelioreticular type 1 cells play a role in the Blood thymus barrier
present only in CORTEX
Yes - with tight junctions and
Basel lamina of the underlying epithelial also
Pericytes and macrophages patrol the perimeter - protecting the babies
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neonatal thymectomy
if baby's thymus removed very hard to live - no cd4 helper cells to fight immunity
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to fix myathenisu gravis - ?
sometime remove thymus
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phangeal pouches 3 and 4 in fetus develop what? Di George Syndrome congenital
thymus and parathyroid glands - no T cells
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Aids and the thymus?
Aids selectively kills cd4 helper cells
