General Pathology (inflammation & tissue healing / immunopathology & hypersensitivity) Flashcards
1
Q
classification of inflammation via:
A
1) duration (acute/chronic)
2) Etiology
3) Location (local/systemic)
4) Morphology
2
Q
1) DURATION
A
Acute or Chronic?
3
Q
acute inflammation
A
short term process
immediate onset
swelling, redness, heat, altered/loss of function, pain
stops when “injurious” stimulus is:
a) removed
b) walled off (scarring/fibrosis)
c) broken down
4
Q
acute inflammation process
A
Increased Vessel wall permeability of nearby BV
= Increased emigration of LEUKOCYTES
5
Q
how do leukocytes emigrate?
A
via (along/up) CHEMOTACTIC gradient
6
Q
combination of which systems?
A
cascade of events involving vascular system, immune system, and injured/damaged cells
7
Q
conclusion of acute inflammation?
A
removal of stimuli = removal of inflammatory process
inflammatory response requires the presence of stimulus
Outcome?
either resolution
or
abscess formation
or
continued chronic inflammation
8
Q
abscess define
A
An enclosed collection of pus in tissues, organs, or confined spaces in the body. An abscess is a sign of infection and is usually swollen and inflamed.
9
Q
chronic inflammation
A
not necessarily classic symptoms/signs of inflammation (SHARP?)
delated onset
long duration
leads to tissue destruction/fibrosis
10
Q
2) ETIOLOGY
A
infections
chemical
physical
immune
multifactorial etiology
11
Q
infections as cause for chronic inflammation
A
bacteria, viruses, protozoa, fungi, helminthis (worms)
12
Q
chemical cause for inflammation
A
Chemical – organic or inorganic, industrial, medicinal,
13
Q
physical cause for inflammation
A
foreign bodies, heat, irradiation, trauma
14
Q
immune cause for inflammation
A
..
15
Q
3) LOCATION (classification of inflammation)
A
E.g. localized vs systemic
systemic can begin as localized
16
Q
4) MORPHOLOGY (4th way to classify inflammation)
A
a) Serous
b) Fibrinous
c) Purulent
d) Ulcerative
e) Pseudomembranous
f) Chronic
g) Granulomatous
17
Q
a) SEROUS INFLAMMATION
A
MILDEST TYPE
characterized by clear fluid
occurs in early stages of inflammation
typical in:
viral infections
arthritis
burns
generally “Self-limiting” (I.e. resolves without measure)
Resolves without consequences generally (E.g. Herpes)
18
Q
b) FIBRINOUS INFLAMMATION
A
EXUDATE present
exudate rich in Fibrin
indicates severe inflammation
present in:
bacterial infections
E.g.
Strep throat, bacterial pneumonia, bacterial pericarditis
Doesn’t resolve easily
LEADS TO SCARRING IN “PARENCHYMA” (functional portion of organ)
Fibrosis of parenchyma = loss of function of tissue
19
Q
parenchyma define
A
“In anatomy, parenchyma refers to the functional part of an organ in the body.”
“This is in contrast to the stroma or interstitium, which refers to the structural tissue of organs, such as the connective tissues.”
20
Q
stroma define
A
the supportive tissue of an epithelial organ, tumor, gonad, etc., consisting of connective tissues and blood vessels.
21
Q
interstitium define
A
Interstitium refers to the space or compartment between the cells in a tissue, particularly connective tissue. It is often filled with interstitial fluid and contains various structures such as collagen fibers, elastin fibers, and ground substance.
22
Q
where is fibrinous inflammation seen (e.g.)?
A
present in:
bacterial infections
E.g.
Strep throat, bacterial pneumonia, bacterial pericarditis
23
Q
c) PURULENT INFLAMMATION
A
PUS-forming bacteria
E.g.
Staphylococci
Streptococci
Pus accumulation @ mucosa, or skin, or @ internal organs
abscess = localized “collection” of pus
24
Q
staphylococcus define
A
“a bacterium of a genus that includes many pathogenic kinds that cause pus formation, especially in the skin and mucous membranes.”
25
streptococcus define
"a bacterium of a genus that includes the agents of souring of milk and dental decay, and hemolytic pathogens causing various infections such as scarlet fever and pneumonia."
26
d) ULCERATIVE INFLAMMATION
inflammation of body surfaces
or inflammation of mucosa
leads to ulceration or necrosis of epithelial lining
27
ulcer define
defect involving the epithelium;
can also extend into the connective tissue
"A break on the skin, in the lining of an organ, or on the surface of a tissue. An ulcer forms when the surface cells become inflamed, die, and are shed. Ulcers may be linked to cancer and other diseases."
E.g.
Peptic Ulcer
28
e) PSEUDOMEMBRANOUS INFLAMMATION
combination of:
a) Ulcerative infl
b) Fibrinous infl
c) Purulent infl
Exudate present:
consist of:
Fibrin, pus, (cellular debris), mucous
--> Exudate forms pseudomembrane on the surface of ulcers
E.g. pathology
DIPHTHERIA
pseudomembranes form on throat
--> when scraped away, expose bleeding ulcers
29
inflammation type that is combination of purulent, fibrinous, and ulcerative
pseudomembranous inflammation
30
f) CHRONIC INFLAMMATION
Exudate present
contains:
monocytes, lymphocytes, (macrophage, plasma cell)
31
important feature of mechanism of Chronic inflammation
stimulation of proliferation of FIBROBLASTS
inflammation persists via constant recruiting of new inflammatory cells
Recall:
Loss of parenchyma via Scarring/fibrosis
32
fibroblasts and scar formation (fibrosis)
"Fibroblasts are expected to contract wounds and secrete ECM during the process, but uncontrolled proliferation of fibroblasts and excessive deposition of ECM contributes to the scar formation and should be avoided."
33
Chronic inflammation and loss of function
E.g.
Scarring of fallopian tubes associated with pelvic inflammatory disease can lead to infertility
E.g.
Fibrosis associated with chronic lung disease can impair passage of oxygen into lungs
34
g) GRANULOMATOUS INFLAMMATION
special type of chronic inflammation
NOT PRECEDED BY ACUTE INFLAMMATION
35
mechanism of granulomatous inflammation
accumulation at the site of injury by
-->T-lymphocytes and Macrophages
Cytokines released by lymphocytes
Cytokines transform macrophages into Epithelioid cells
36
what happens to epithelioid cells?
fuse together
form multinucleated "Giant cells"
Nodules are then formed
37
What are Nodules composed of? What are nodules called?
Multinucleated giant cells,
epithelioid cells,
and lymphocytes aggregate into nodules
called GRANULOMAS
--> "grain" "swelling"
38
what do granulomas do?
destroy tissue
persist for long time
E.g.
Syphilis
Tuberculosis
39
What are clinical findings (clinical correlations) of inflammation?
a) Fever
Leukocytosis
Constitutional symptoms
40
a) Fever
elevation in body temperature >37 degrees celsius
generally normal body temperature b/w 36-37
41
What causes fever? What is the mechanism?
Pyrogenic Cytokines:
--> Interleukin 1 (IL-1)
--> tumor necrosis factor (TNF)
42
interleukin define
"any of a class of glycoproteins produced by leukocytes for regulating immune responses."
43
IL-1
"The Interleukin-1 family is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults."
44
insult
MEDICINE
"an event or occurrence that causes damage to a tissue or organ."
E.g.
"the movement of the bone causes a severe tissue insult"
45
pyrogen
"A pyrogen is, by definition, a substance that produces a rise in temperature in a human or animal."
"differentiated into exogenous and endogenous pyrogens"
46
exogenous pyrogen
"Exogenous pyrogens are substances that induce fever reactions after parenteral administration."
47
parenteral
"situated or occurring outside the intestine."
para-
distinct from, but analogous to.
48
exogenous pyrogens E.g.
"Exogenous pyrogens are molecules found outside of the body, such as endotoxins from gram-negative bacteria or pyrogenic prions."
"Exogenous pyrogens either provoke endogenous pyrogen production to create a fever within the body or activate toll-like receptors (TLRs) to create a fever."
49
endogenous pyrogens E.g.
"Interleukin-1 (IL-1), tumor necrosis factor, and prostaglandin E have all been shown to act as endogenous pyrogens. IL-1β, the most potent endogenous pyrogen, is balanced by the IL-1 receptor antagonist (IL-1Ra)."
50
what activates endogenous pyrogens
"Fever, a common symptom of many diseases, is elicited by exogenous pyrogens (such as bacterial LPS) or an inflammatory insult, which results in the production of cytokines such as IL-1β that act as endogenous pyrogens.
These cytokines then stimulate the neural pathways that increase body temperature."
51
can fever occur without endogenous pyrogens, only exogenous?
yes (??)
52
are endogenous pyrogens always activated by exogenous pyrogens?
no
53
can fever occur without either?
??
54
b) Leukocytosis (Clinical findings/correlations of inflammation)
increase in circulating WBCs
Esp during infection
55
cytosis
"It essentially means 'of the cell'."
"sometimes refers to predominance of certain type of cells."
56
TNF (Tumor necrosis factor) -- a cytokine
"an inflammatory cytokine produced by macrophages/monocytes during acute inflammation"
"is responsible for a diverse range of signalling events within cells, leading to necrosis or apoptosis."
SOME STUDIES SUGGEST TNF IS CRYOGENIC, OTHERS SUGGEST TNF IS PYROGENIC
--> controversy
57
TNF and IL-1 (CYTOKINES), the hypothalamus, and prostaglandins
"Interleukin-1 initiates fever by inducing an abrupt increase in the synthesis of prostaglandins, particularly prostaglandin E2, in the anterior hypothalamus."
58
prostaglandin and fever
"Fever is thought to be initiated by pyrogenic cytokines inducing the production of prostaglandin E2 (PGE2) in the preoptic area (POA)"
"PGE2 may act as a paracrine mediator that stimulates the neural pathways that raise body temperature."
59
c) Constitutional symptoms (Clinical findings/correlations of inflammation)
non-specific; include fatigue, weakness, depression, malaise, lack of appetite, achiness, etc.
60
INFLAMMATORY DISORDERS
Immune disorders
Infections
Injuries
Arthritides
Cancer
61
HEALING AND REPAIR, vs inflammation
inflammation may result in tissue loss
62
consequence of tissue loss (via inflammation) depends on the type of cell
(in terms of regenerative/dividing capabilities)
3 types
1) continuously dividing, mitotic
--> "LABILE" cells
2) "quiescent cells"
Aka "Facultative mitotic" / "stable" cells
3) non-dividing cells -- "post-mitotic" cells -- "permanent" cells
63
"Labile cell"
cells that continuously multiply and divide throughout life
64
quiescent cell
Quiescence is a cellular state in which a cell remains out of the cell cycle but retains the capacity to divide.
65
"stable" cell
"In cellular biology, stable cells are cells that multiply only when needed. They spend most of the time in the quiescent G0 phase of the cell cycle"
66
facultative cell
BIOLOGY
"capable of but not restricted to a particular function or mode of life."
67
permanent / post-mitotic cells
Permanent cells are defined as cells that are unable to replicate in postnatal life.
E.g.
Nervous cells
skeletal muscles
cardiac cells
68
1) continuously dividing (labile / mitotic)
"Undifferentiated stem cells divide by mitosis"
differentiate and replace los cells
E.g.
skin cells
resolution -- minimal tissue damage -- tissue returns to normal
(Note visible scars / scar tissue can still occur depending on severity of injury to skin)
69
2) Quiescent cells (facultative mitotic / stable cells)
I.e. cells in G0 phase
Do not divide regularly
can be stimulated to divide to replace lost cells
E.g. Hepatocytes (liver cells)
Outcome?
regeneration --> damaged tissue is replaced
-->
However, replacement can still be limited depending on extent of damage
70
3) Non-dividing cells (permanent / post-mitotic cells)
E.g. neurons, skeletal/cardiac muscle cells
No division/mitosis
Outcome?
Parenchymal tissue gets replaced with Scar tissue (connective tissue)
I.e.
Leads to loss of function
71
HEALING
(by first intention / by second intention)
.
72
healing by first intention
wound is clean
free of foreign materials
free of necrotic tissue
edges are closed together
73
healing by second intention
large break in tissue
more inflammation
longer inflammation
more scar tissue
presence of foreign bodies / bacteria
more "Granulation tissue"
74
granulation tissue define
"Granulation tissue is new connective tissue and microscopic blood vessels that form on the surfaces of a wound during the healing process."
75
intention define
MEDICINE
"the healing process of a wound."
76
granulation tissue, fibroblasts, myofibroblasts
"In the granulation tissue, fibroblasts are activated and acquire α-SM actin expression and become myofibroblasts."
"These myofibroblastic cells synthesize and deposit the ECM components that eventually replace the provisional matrix"
"Myofibroblasts mediate wound contractions, but their persistent presence in tissues is central to driving fibrosis"
77
Cells participating in wound healing
a) Leukocytes (i.e.WBC)
b) CT cells
c) Epithelial cells
d) Macrophage
78
a) Leukocytes (i.e.WBC)
Leukocytes (i.e.WBC)
--> Esp polymorphonuclear neutrophils ---> "scavenging at the initial site of injury"
79
b) CT cells
produce scar tissue
E.g. Fibroblasts/myofibroblasts
80
c) Epithelial cells
undergo mitosis and extend across the wound
(except for permanent / non-mitotic cells)
81
d) Macrophages
stay @ site of healing
produce:
growth factors
cytokines
mediators
all act on connective tissue cells
82
CT cells participating in wound healing
a) myofibroblast
b) angioblast
c) fibroblasts
83
a) myofibroblast
hybrid b/w smooth muscle cell and fibroblast
can contract and secrete ECM
84
function of contraction in myofibroblasts
"The contraction is considered one of the important events in wound healing because it results in the closure of the wound"
85
b) Angioblasts
precursor to blood vessels
86
fibroblasts
produce most ECM
87
THE HEALING PROCESS -- events
1) blood clot forms, seals area
2) inflammation develops
3) phagocytes (including monocytes & macrophages) remove debris
4) Granulation tissue forms in gap (highly vascular -- brings new blood supply)
5) tissue is fragile
88
THE HEALING PROCESS -- events (continued)
6) mitosis of epithelial cells
7) fibroblasts enter area -- produce collagen (basic component of scar tissue)
8) macrophages/fibroblasts produce cytokines to attract more fibroblasts
89
THE HEALING PROCESS -- events (3)
9) Fibroblasts also stimulate epithelial cell division --> and increase ANGIOGENESIS
10) cross-linking of collagen fibres = tight, strong scar
11) capillaries in area decrease
12) Note that scar tissue is not normal functional tissue
90
what increases effeciency of healing?
Young age
Good nutrition
Adequate hemogloblin
Effective circulation
Clean wound
No foreign bodies
No complications
Small wound
Site of wound
91
what deceases effeciency of healing?
Advanced age
Poor nutrition
Anemia
Poor circulation
Presence of other disorders (diabetes)
Irritation or excessive mobility
Infection, foreign materials
Large sized wound
92
COMPLICATIONS OF WOUND HEALING
1) Loss of function
2) Deficient scar formation
3) Excessive scar formation
4) Infection
93
1) Loss of function
scar tissue replaces parenchymal tissue
94
2) deficient scar formation
?
age/genetic/medications/nutrition/infection?
95
3) Excessive scar formation
Keloids – overgrowth of scar tissue with excessive collagen
Contracture – fixation and deformity of the joint
Adhesions – bands of scar tissue that join two normally separated surfaces
e.g.
intestine
96
keloids cause
"Keloid growth might be triggered by any sort of skin injury — an insect bite, acne, an injection, body piercing, burns, hair removal, and even minor scratches and bumps."
"Sometimes keloids form for no obvious reason."
"Keloids aren't contagious or cancerous."
97
keloid scarring -- genetic susceptibility
"Keloid disease is considered a genetic disease due to a strong genetic susceptibility to keloid formation as it occurs predominantly in people of African and Asian descent, runs in families, and has been found in twins."
98
keloid vs hypertrophic scar
"Keloids are raised scar-like skin growths. Unlike hypertrophic scars, the connective tissues in keloids continue to grow beyond the wound site."
"Hypertrophic scars are contained within the site of injury and may regress over time, while keloids spread beyond the borders of the initial injury and do not regress."
"hypertrophic scars tend to have collagen in a wavy, regular pattern, whereas keloids have no distinct pattern of collagen."
99
contracture define (excess scar formation)
"a condition of shortening and hardening of muscles, tendons, or other tissue, often leading to deformity and rigidity of joints."
100
contracture cause
"Contracture can be caused by any of the following: Brain and nervous system disorders, such as cerebral palsy or stroke. Inherited disorders (such as muscular dystrophy) Nerve damage."
"Reduced use (for example, from lack of mobility or injuries)
Severe muscle and bone injuries.
Scarring after traumatic injury or burns."
101
adhesions (excess scar formation)
MEDICINE
"an abnormal union of membranous surfaces due to inflammation or injury."
"bands of scar tissue that join two normally separated surfaces"
102
adhesions causes
"can occur after surgery, infection, injury (trauma) or radiation"
103
4) infection (complications of wound healing)
"May develop in an inflamed tissue because microorganisms can more easily penetrate when the barrier is damaged and the blood supply is impaired"
104
***** LECTURE 4
Immunopathology
what is immunity?
cells of immune system
antibodies
antigen-antibody reaction
hypersensitivity
transplantation
105
immunity define
protection from disease
esp infectious disease
106
two kinds of immunity
1) natural immunity: born w/ it
2) acquired immunity: develops w/ exposure
107
natural immunity
non-specific
primitive
inherited
not dependent on previous exposure to foreign substances
can be:
a) mechanical
b) WBC
c) protein
108
natural immunity e.g.
mechanical factors
E.g.
skin
ciliated cells in mucosa of nose/bronchi
109
WBC E.g. of natural immunity
macrophages
PMNs (polymorphonuclear neutrophils)
Natural killer cells
110
natural immunity E.g. protein
protective proteins foundin tissue/plasma:
--> complement system (plasma proteins)
--> Properdin = plasma protein that activates "ALTERNATIVE" Complement pathway
--> Lysozyme = protein found in tears, in nasal/intestinal secretions --> Bactericidal
"lysis" + "enzyme" = lysozyme
111
note first/second/third line of defense
first line = mechanical/chemical barriers
second line = inflammation, phagocytosis
third line of defense = specific immune response (acquired)
112
Acquired immunity
reactions acquired
specific response to ANTIGENS
113
antigen
"a toxin or other foreign substance which induces an immune response in the body, especially the production of antibodies."
any chemical substance that can elicit a specific immune response
114
what is acquired immunity based on?
ability of immune system to:
a) DISTINGUISH self from nonself
b) GENERATE immunological memory
c) MOUNT reaction of various cells
115
acquired immunity and "immunocompetance"
IMMUNOCOMPETANCE:
body's ability to mount an appropriate immune response
116
some cells of the immune system that we cover here:
1) Lymphcytes
2) Plasma cells
117
1) lymphocytes
T lymphocytes (T cells)
= T helper cells (CD4+ cells)
= T suppressor (CD8+ cells)
(aka T cytotoxic cells)
B lymphocytes (B cells)
118
about Lymphocytes
agranular immune cells
ROUND nucleus
very little cytoplasm
Derived from BONE MARROW STEM CELLS (I.e. "Lymphoid Progenitor" cells)
119
where do lymphocytes come from?
from Lymphoid progenitor cells which develop @ bone marrow
120
what can lymphoid progenitor cells turn into?
(other than NK cells)
a) T cell (progenitor)
b) B cell (progenitor)
121
what do T/B progenitor cells do?
B lymphocytes via B progenitor
--> AT BONE MARROW
T lymphocytes via T progenitor
--> AT THYMUS
122
what are the THYMUS and BONE MARROW called?
PRIMARY LYMPHOID ORGANS
123
list of lymphocytes?
B cells, T cells, and NK cells
124
which lymphocytes are for natural immunity, which for acquired immunity?
B/T cell for acquired
NK cells for natural
125
where do B/T cells go from PRIMARY LYMPHOID ORGANS (where they are made)
they go from where they are made to
---> SECONDARY LYMHOID ORGANS
126
E.g. of secondary lymphoid organs
SPLEEN
LYMPH NODES
also include:
GI TRACT
BRONCHIAL MUCOSA ("mucosa associated lymphoid tissue" = MALT)
127
T vs B lymphocytes structure/function distinction
distinct functions
similar morphology
128
what percentage is T cell vs B cell?
about 2/3 T cells circulating
also found in -->
spleen & lymph nodes
(T helper = CD4+
& T cytotoxic = CD8+)
129
T lymphocytes and "surface T-cell receptor" (TCR)
Common to all T cells
TCR (receptor)
--> Linked to a protein called CD3
130
what do T cells use TCR-CD3 complex for?
recognition of ANTIGENS
essential for activity of T cells
131
what are NK cells?
T cells that do not have TCR-CD3 complex
I.e. function the same as T cells, but without Specificity of acquired immunity
--> therefore part of natural immunity
132
NK cells function
inhibit/destroy VIRUS-infected cells
Kill tumour cells / foreign cells
133
T helper (CD4+ cells)
immune response to ANTIGENS
help B cells PRODUCE ANTIBODIES
"Express" CD4 protein on surface
secrete CYTOKINES (including Interleukins)
134
T helper cell classification
TH1 and TH2
depending on which cytokines they produce
135
TH1 cells
make:
a) Interleukin-2 (IL-2)
b) IFN-gamma (interferon gamma)
--> stimulate macrophage
--> granuloma formation
136
TH2 cells
make:
a) interleukin-4
b) IL-5
c) IL-13
ILs important for
--> secretion of IgE
--> other Ig's
--> Eosinophil activation
137
T suppressor/cytotoxic T cells (CD8+ cells)
Prevent unwanted ANTIBODY production
have CD8 protein on surface
mediate killing of virus-infected cells / tumour cells
138
significance of CD4 and CD8 proteins
used as MARKERS for T lymphocytes
significant for COUNTING T cells in blood
CD4+ to CD8+ ratio = 2:1
So 2/3 = CD4+ (helper)
& 2/3 = T cell (vs Bcell)
139
B LYMPHOCYTES
differentiate into ANTIBODY-producing PLASMA cells
--> when stimulated by antigens "
140
what are antibodies?
protein produced by plasma cells
in response to stimulation by antigen
antibodies are produced to fight against antigens
141
what are plasma cells
fully differentiated descendent --> FROM B cells
OVAL SHAPED
round nucleus, not central
abundant ribosomes & RER @ cytoplasm
142
where are antibodies made in plasma cells?
RER
143
antibodies?
Proteins
of IMMUNOGLOBULIN class
each antibody = 110 amino acids
144
categories of antibodies
IgA, IgD, IgE, IgG, IgM
145
IgG
Smallest immunoglobulin
MOST ABUNDANT
acts as OPSONIN
--> binds to foreign substances --> facilitates phagocytosis
I.e.
OPSONIZATION
can cross placenta
produced in small amounts on initial immunization
--> BOOSTED production @ re-exposure
146
IgG placenta
only Ab that can cross placenta
provides protection to baby
147
IgA
found in mucosal secretions:
tears, nasal secretions
found in (breast?) milk, intestinal contents
"Mucosal Homeostasis"
148
IgM
via 5 basic units
neutralize Microorganisms
LARGEST IMMUNOGLOBULIN
FIRST immunoglobulin to appear after immunization
natural antibody against blood group ABO antigens
ACTIVATES COMPLEMENT SYSTEM (Classical pathway)
149
which Ig activates complement system? Via which pathway?
IgM
via classical pathway
Also IgG (??)
150
main Ig class for antibodies against antigens of blood types?
IgM
151
IgE
also via plasma cells
attached to MAST CELLS
involved in ALLERGIC REACTION
E.g.
hay fever, asthma
"Present in trace amounts in serum" (???)
152
IgD
found exclusively on B cells
membrane bound (Not circulating freely)
Not released into "serum" or body fluids (freely)
activates B cells in response to ANTIGEN
153
IgD vs antigen
antigen attached to IgD (on B cell membrane)
instead of freely circulating antibody attaching to antigen
154
ANTIBODY PRODUCTION
via contact b/w:
a) antigen
b) immune cell
any foreign substance may function as antigen
155
where does antigen bind first?
B cell @ "Antigen Receptor Complex" (ARC)
B cell consumes antigen
--> Functions as "Antigen Presenting Cell" (APC)
--> Presents antigen to T cells
156
why do APCs (B cells) present antigens to T cells?
"Antibody production requires the support of T helper cells"
Helper T cells:
"help activate B cells to secrete antibodies and macrophages to destroy ingested microbes"
"also help activate cytotoxic T cells to kill infected target cells."
157
how do T cells help B cells produce antibodies?
"antigens are presented to T cells in the context of the major histocompatibility complex (MHC)"
MHC on surface of APCs
T helper cells produce Cytokines:
--> transform the B cell into a plasma cell
--> plasma cell produces Ab
158
"Antigens are Multivalent"
multivalent = multiple binding sites (epitope)
159
epitope
"the part of an antigen molecule to which an antibody attaches itself."
160
Ag-Ab complexes
Ag and Ab bind --> form complexes
complexes enlarge
--> phagocytosed in Spleen/Liver by "fixed" Macrophages
--> smaller complexes can bind on RBCs / endothelial cells
161
what happens if Ag-Ab complexes attach to RBCs?
clumping --> "Agglutination"
= clumping of RBCs & separation from serum
162
Ag-Ab complexes and complement system
if complement system is activated, RBC lysis can occur (Hemolysis)
--> Classic complement system pathway
163
complement pathway -- recall:
"enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen's cell membrane."
164
HYPERSENSITIVITY REACTIONS
aka allergic disorders
"abnormal immune response to exogenous antigen"
"or reaction to endogenous auto-antigens (auto-immune disorders)"
165
hypersensitivity reactions
aka allergic disorders
including autoimmune disorders
166
hypersensitivity reaction is
abnormal immune response to exogenous antigen
or reaction to endogenous auto-antigens (autoimmune disorders)
167
auto-antigen define
"An autoantigen is usually a ... normal protein ... that is recognized by the immune system of patients suffering from a specific autoimmune disease."
"an antigen that is a normal bodily constituent and against which the immune system produces autoantibodies"
168
four types of hypersensitivity reactions
type 1 = anaphylactic type
type 2 = cytotoxic Ab-mediated reaction
type 3 = immune complex-mediated reaction
type 4 = cell-mediated, delayed-type reaction
169
type 1 hypersensitivity (anaphylactic type)
mediated by IgE + MAST cells (OR basophils)
NOTE THAT IgE is on MAST CELL membrane (vs freely floating)
170
IgE produced by
plasma cells sensitized to foreign stimuli (E.g. Pollen)
171
re-exposure (type 1)
Ag-Ab complex forms on Mast Cells
triggers release of HISTAMINE
(vasoactive granules)
Histamine release =
instantaneous - increased vascular permeability, edema, eosinophilia
172
vasoactive define
"something that causes the blood vessels to constrict or dilate"
173
Type 1 hypersensitivity E.g.
Hay Fever (allergic rhinitis)
seasonal allergy (pollens)
--> pollen, animal "dander" (skin/hair)
174
Hay fever symptoms
itching, sneezing, conjunctivitis (irritation/inflammation of conjunctiva of eyes)
175
Hay fever treatment?
antihistamines
corticosteroids
176
Type 1 hypersensitivity E.g. 2
Atopic dermatitis (eczema)
typical disease of childhood
chronic skin irritation
genetic predisposition exists
177
atopic meaning
"a" without
"topic" place
= unusual
"Atopy refers to the genetic tendency to develop allergic diseases such as allergic rhinitis, asthma and atopic dermatitis (eczema)"
"Atopy typically associated with heightened immune responses to common allergens, esp inhaled allergens / food allergens."
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atopic dermatitis (eczema) is associated with...
associated with hyperproduction of IgE vs. allergens
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atopic dermatitis generally
improves with age
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type 1 hypersensitivity (E.g. 3)
bronchial asthma
one of several types of asthma
not always immunologically mediated
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bronchial asthma -- common symptom/sign
coughing / wheezing
associated with constriction of bronchi
overproduction of mucous by bronchial glands
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type 1 hypersensitivity (E.g. 4 -- most severe)
anaphylactic shock
life-threatening, severe
systemic response to allergen
esp allergen that body was previously sensitized to
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what happens during anaphylactic shock?
massive release of histamine
+ other vasoactive substances
Can also lead to "Circulatory collapse"
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circulatory collapse define
condition where there is a complete or almost complete interruption of blood circulation
E.g.
via heart
via pulmonary embolism
Or in this case:
SUDDEN GENERAL VASODILATION
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recall mechanism of macrophage, Bcell --> plasma cell; Ab --> mast cell
first exposure via macrophage (act as APC)
present to B cell. B cell differentiates to plasma cell
plasma cell produce ANTIBODIES
send antibodies to Mast Cells
upon second/later exposure, MAST cell release Histamine
--> causes vasodilation and VASCULAR PERMEABILITY
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Type 2 hypersensitivity (CYTOTOXIC ANTIBODY mediated Reaction)
Mediated by IgG or IgM
cytotoxic Antibodies react with Antigens in cells
ACTIVATES COMPLEMENT SYSTEM = cell LYSIS (Via classic pathway)
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Complement System via which pathway for type 2 hypersensitivity
Classic pathway --> leads to cell lysis
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type 2 hypersensitivity (cytotoxic Ab mediated reaction)
Antigen can be...
extrinsic or intrinsic
189
intrinsic antigen
proteins/DNA/RNA
190
extrinsic antigen
drugs, chemicals, bacteria, infected cell secretions/excretions
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re-exposure during type 2 hypersensitivity (cytotoxic Ab-mediated reaction)
re-exposure = Hypersensitive reaction/disease (when genetically predisposed)
I.e.
Autoimmune disease
192
type 2 hypersensitivity E.g.
Goodpasture's syndrome
autoimmunity to collagen type 4
Renal/pulmonary damage
193
Goodpasture's syndrome
"Goodpasture syndrome is a rare disorder in which your body mistakenly makes antibodies that attack the lungs and kidneys."
note:
hemoptysis (hemo + ptysis)
hematuria (hemat + uria)
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type 2 hypersensitivity E.g. 2
Hemolytic anemia
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hemolytic define
relating to or involving the rupture or destruction of red blood cells.
196
anemia
Anemia is a problem of not having enough healthy red blood
197
hemolytic anemia
In hemolytic anemia, red blood cells in the blood are destroyed earlier than normal
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acute hemolytic reaction define
"An acute hemolytic transfusion reaction (AHTR), is a life-threatening reaction to receiving a blood transfusion."
"transfusion of mismatched blood"
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systemic lupus erythematosus (SLE)
RBC are targeted among many other parts of body
E.g.
skin
joints
kidneys
heart/lungs
brain/nervous
blood vessels
other organs (liver, spleen, GI tract)
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type 2 hypersensitivity (cytotoxic Ab mediated reaction) E.g. 2
Graves disease
form of hyperthyroidism
common in women
antibodies to thyroid stimulating hormone RECEPTOR (TSH receptor)
results in overproduction of thyroid hormones
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hyperthyroidism and antibodies
"Antibodies that make the cells produce thyroid hormone can lead to hyperthyroidism (overactive thyroid)"
202
hyperthyroidism
weight loss despite an increased appetite.
rapid or irregular heartbeat.
nervousness, irritability, trouble sleeping, fatigue.
shaky hands, muscle weakness.
sweating or trouble tolerating heat.
frequent bowel movements.
an enlargement in the neck, called a goiter.
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Graves disease and hyperthyroidism
"Graves' disease accounting for up to 80% of cases [of hyperthyroidism] and being more common in Blacks compared with Whites."
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type 2 hypersensitivity (cytotoxic Ab mediated reaction) E.g. 3
Myasthenia Gravis
Antibodies block acetylcholine receptors @ NMJ
prevents binding of ACh (progressive weakness, even paralysis)
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type 3 hypersensitivity (Immune-complex mediated reaction)
mediated by immune complexes b/w Ag and specific Ab
systemic reaction:
Ag-Ab complexes in circulation
or
localized reaction:
complexes in tissues
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type 3 hypersensitivity (immune complex mediated reaction) ...
immune complexes are filtered through basement membranes of:
glomeruli (capillaries @kidney)
anterior eye chamber
brain choroid plexus
pericardium
lungs
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what happens to trapped immune complexes (AgAb complexes)?
Trapped agAb complexes activate Comlpement system
Via Classical pathway
Attract PMNs (polymorphonuclear neutrophils)
result in acute inflammation
--> fibrinoid necrosis
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fibrinoid necrosis
death of cells in small blood vessels
fibrinoid:
"acidophilic refractile material that somewhat resembles fibrin and is formed in the walls of blood vessels and in connective tissue"
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type 3 hypersensitivity E.g.
SLE
post-streptococcal glomerulonephritis
glomeruli (capillaries @ kidney = cleaning units of kidney)
nephritis = inflammation of kidney (nephros)
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post-streptococcal glomerulonephritis
acute renal disease
after upper respiratory tract infection (for those genetically predisposed)
211
post-streptococcal glomerulonephritis -- what happens?
antibodies to Streptococcal antigen
stuck on glomerular basment membrane
leads to COMPLEMENT-mediated inflammation
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note about post-streptococcal glomerulonephritis
"It’s also possible the antigens from the bacteria are first trapped in the glomeruli, and then antibodies bind in the glomerulus itself."
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type 3 hypersensitivity other E.g.
Polyarteritis nodosa
poly = many
arteritis = arteries
itis = inflammation
nodosa = w/ knots/knobs
(nodules)
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polarteritis nodosa
immune complexes localized
via various forms of Vasculitis
damaged vessels thrombose/occlude
(thrombosis --coagulation/clotting)
arterial occlusion = INFARCTS
--> ischemic symptoms
215
infarct
a small localized area of dead tissue resulting from failure of blood supply.
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ischemic symptoms
Angina (chest pain).
Shortness of breath.
Lightheadedness or dizziness.
Difficulty speaking.
Loss of coordination.
Pain in your leg or arm.
Pale or cold leg or arm.
Paresthesia (tingling or numbness) in your leg or arm.
217
polyarteritis nodosa
"small and medium-sized arteries become swollen and damaged."
"produces painful, erythematous nodules."
note erythematous / erythematosus
218
erythematous define
"exhibiting abnormal redness of the skin or mucous membranes due to the accumulation of blood in dilated capillaries (as in inflammation)"
erythema:
"abnormal redness of the skin or mucous membranes due to capillary congestion (as in inflammation)"
219
erythematosus (SLE)
erythema + "osus" (?)
osus:
"full of, overly, prone to"
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type 4 hypersensitivity (Cell-mediated / delayed-type reaction)
involves T-Cells (T-lymphocytes)
involves macrophages
cells aggregate --> Form Granulomas @ injury site
221
granuloma define
"tiny cluster of white blood cells and other tissue"
"form as a reaction to infections, inflammation, irritants or foreign objects"
222
granulomas, T cells and marophages
"Chronic (aberrant) macrophage–T cell interaction leads to the formation of ... granulomas"
"typically formed during infection, especially when the host has difficulties to eliminate the infectious organism"
223
cell activity during Type 4 hypersensitivity reactions
(cell-mediated, delayed-type reactions)
involve macrophages & Langerhan's cells (epidermal immune cells)
--> These cells function as APCs (Langerhan's cells are DENDRITIC cells)
--> as APCs they process Ag-complexes --> present to T-Lymphocytes
--> T helper cells are exposed to Ag complex
--> leads to immune memory formation --> for subsequent re-exposure
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Type 4 hypersensitivity E.g.
Ag complex of:
M tuberculosis (Mycobacterium Tuberculosis)
Mycobacterium Leprae
various fungi
most commonly:
CONTACT DERMATITIS
E.g.
to gold, rubber gloves,
poison ivy, etc.
225
type 4 hypersensitivity and granulomas
accounts for granulomas developing in response to tumours
also note idiopathic granulomatous diseases:
sarcoidosis
226
sarcoidosis
sarco = flesh
oid = resembling
sis = condition
"Sarcoidosis is a condition that develops when groups of cells in your immune system form red and swollen (inflamed) lumps, called granulomas, in various organs in the body."
227
tuberculosis granuloma
Tuberculosis is the formation of an organized structure called granuloma
228
leprosy granulomas
"The structure of granulomas is distinct across the spectrum of leprosy."
229
contact dermatitis defin
"Contact dermatitis is an itchy rash caused by direct contact with a substance or an allergic reaction to it."
"rash isn't contagious, but can be very uncomfortable"
230
transplant
"Solid tissue transplant / graft will only “take” if donor and recipient are immunologically similar enough to avoid rejection"
"Immunosuppressive drugs used to facilitate acceptance of transplants"
used for life
231
transplant/graft types
"Autografts
Self donor - skin, hair, blood vessels"
"Isografts
Identical twins"
"Homografts / Allografts
Same species not genetically identical"
"Xenografts
Transplants between different species"
232
blood transfusion
type of transplant
"RBC in greater number than WBCs, success depends on matching RBCs"
"blood surface antigens lead to formation of four groups with specific antibodies"
233
blood type groups
Group A: (antigen A) anti-B antibodies
Group B: (antigen B) anti-A antibodies
Group O: (neither antigen) anti-B and anti-A (universal donor)
Group AB: (both antigens) neither antibody (universal acceptor)
234
blood transfusion reaction
if blood group of A donor is infused into B group, the recipient’s blood antibodies will hemolyze donor’s RBCs
"chills, shivering, fever and eventually shock"
235
Rh Factor incompatability
name from experiment done on Rhesus monkeys
Rh+ individuals have certain ANTIGENS on RBCs
if mother is Rh- and 1st child is Rh+, mother may create Rh antibodies during delivery
if 2nd child is Rh+, antibodies will destroy fetal RBCs
Therefore, doctor/nurse immunizes mother against Rh immediately after first delivery
236
which 3 cells can function as APCs
dendritic cells
monocytes/macrophages
B lymphocytes
237
