Immunoglobulins Flashcards
1
Q
what is innate immunity
A
defends against nospecific manner
Phagocytes, Neutrophils, Natural Killer Cells (NKC)
2
Q
5 types of innate immunity
A
mechanical chemical micorbial complement system toll like receptors
3
Q
mechanical barries
innate immunity
A
skin
hair
mucus
macrophages
4
Q
chemical barriers
A
hyrdolytic enzyme of saliva
stomach acid
proteolytic enzymes of bile
low ph in the vagina
5
Q
properties of innate immune system
A
characteristics
immune components
6
Q
characteristics of immune system
A
Antigen Nonspecific: attacks foreign bodies
› Rapid response (Mins to Hrs)
› No memory
7
Q
properties of immune system
A
IMMUNE COMPONENTS › Natural barriers › Phagocytes and NK cells › Soluble mediators › Pattern recognition molecule
8
Q
cells in the innate immune system
A
polumorphnuclear cells Macrophages dendritic cells natural killer cells innate lymphoid cells
9
Q
cell in the innate system
- has basophils, neutrophils, eosinophils.
produces - peroxide, superoxide radicals, nitric oxide
short lived in phagocytic
A
Polymorphnuclear cells
PMN’s
10
Q
cell in the innate system
- phagocytes derived from blood monocytes
- small sperical cell
- little er
- abundant cytoplasm
A
Macrophages
11
Q
Migration of different macrophages
Kupffer cells Alveolar Splenic Peritoneal macrophages Microglial
A
Kupffer cells - liver
- Alveolar macrophages - lungs
- Splenic macrophages - spleen (red pulp)
- Peritoneal macrophage - peritoneal fluid
- Microglial cells - CNS
12
Q
cell in the innate system
- efficient APC that enables them to trigger adaptotive immune response by T cells
- plasmatocytoid
A
Dendritic cells
13
Q
this is another type of dendritic cells
- derived from lymphoid precursor cell
- ability to produce large amounts of beta/alpha interferos in response to viral bacterial stimuli
A
Plasmatocytoid dendritic cells
14
Q
cell in the innate system
- can recognize abnormal cells usch as cancer cells
- plays role in early stages of viral infection or
tumorogenesis before the large number of activated
cytotoxic T lymphocytes are generated
- large granular lymphocyte leading to LYSIS
A
Natural killer cells
15
Q
the process of disintegrating cells
A
Lysis
16
Q
these are the receptors in NKC
A
KILLER CELL
INHIBITORY RECEPTOR which binds to MHC-1
expressed in normal cells
17
Q
what happens to virus infected cells
A
Virus infected cells and tumor cells have
significantly reduced MHC-1 molecules on their
surface and the killer cell inhibitory receptor
18
Q
when NKC fails to engage to MHC-1
A
will fail to engage to the MHC-1 therefore
becoming susceptible to NK cell mediated toxicity
19
Q
cell in the innate system
- heterogeneous family
- associated with airway and gut inflammation
- diverse in making cytokines
A
INNATE LYMPHOID CELLS
20
Q
this system
- plays a major role in defense against infections
- both innate and adaptive immune
- enhances pathways that remove pathogens
A
COMPLEMENT SYSTEM
21
Q
The Three Complement Pathway
A
-CLASSICAL PATHWAY
-LECTIN PATHWAY
- ALTERNATIVE
PATHWAY
22
Q
this complement system pathway
- when c1 binds to antigen antibody to comples
A
Classical pathway
23
Q
this complement system pathway
- when MBL binds to terminal polysaccharide residue on surface
- activated protein called Ficolin binds to acetylated microbial surface
A
Lectin Pathway
24
Q
this complement system pathway
- when C3B deposit on surface of the pathogen
A
Alternate pathway
25
contributes to immunity and protection againts foreign objects
Immunoglobulins
26
immunoglobulins have 5 heavy chains with each have unique properties
```
G
A
M
E
D
```
27
what are the 5 heavy chains used to catergorize antibodies as
Isotypes
28
when there are minor differences in the major strains
| occuring between individuals
Aliotypes
29
monomeric in cell surface but secreted by
| plasma cell as pentamers
IgM
30
monomeric in cell surface and is secreted a
| monomer or as a dimer
IgG
31
– not secreted
IgD
32
secreted as monomers
IgE and IgA
33
this immuno globulin
- earliest synthesized- Fetus
- 20WOG maternal
- short lived
- primary response of antigen
- does not deffuse well
- 5-10%
Immunoglobulin M
34
presence of this immunoglobulin shows intrauterine infection
Monomeric IgM is the major antibody receptor on the
surface of B lymphocytes for antigen recognition. remains largely confined to bloodstream (80%).
Immuniglobulin M
35
helps detect congenital infections such as
| toxoplasmosis, syphilis, rubella, cytomegalovirus infection and HIV infection.
Immuno M
36
highest avidity of all immunoglobulins for antigens with multiple epitopes
- better agglutinin than other antibody isotypes.
Immuniglobulin M
37
more efficient than IgG
takes less than 100 to 1000 times than
less is required to neutralize viral interactivity
Immuniglobulin M
38
what happens when there is deficiency of LgM
Septicemias
39
what is the function of LGM
primary response to antigen
40
what does lgm promote
phagocytosis
| potent activators of complement
41
properties of lgm and location
3rd Most common serum (5-10%)
› Half-life in serum: 5 days
› Cannot cross placenta
Blood- Lymph- B cell surface
42
- Major immunoglobulin 85%
- 2 heavy chains and 2 light chains
- divalent
- 15% of healthy proteins in humans
- all 4 chains differ in loc and chains
- 75% antibodies of the body
LgG
43
in terms of complement activation power
IgG1 and IgG3 fix C1q = most effectively
IgG2 = weakly
IgG4 = does NOT bind complement...
44
what is the life of Lgg
IgG3: 7 to 8 days
IgG1, IgG2, and IgG4: approximately 21 to
24 days
45
key player in humoral immnue response
- reacts to MacroP, Neutrophils, NKCs
- y heavy chain
Lgg
46
location of Lgg
Location: blood, lymph fluid, cerebrospinal fluid
| and peritoneal fluids.
47
diseases when an increase in lgg occurs
-Hyperimmunization
-Chronic Granulomatous
Infection
-Malnutrition
-Liver Disease
48
diseases when an decreases in lgg occurs
- Lymphoid Aplasia
- CLL
- Selective IgG and IgA
Deficiency
- Agammaglobulinemia
49
what are the lgg subclasses and %
Lgg1 60-70%
Lgg2 - 20-30%
Lgg3 - 5-8%
Lgg 4 1-4%
50
- most abundant type of lgg class
- responsible for thymus mediated immune response
- can cross placenta
Lgg1
51
this lgg class activates classical pathway of the complement cascade via C1 complex
Lgg1
52
this type of lgg class
- shorter hinges
- poor activators
- only 1 alloted
- less susceptible to cleavage by proteoglycans
Lgg2
53
function of this lgg class is to almost exclusive anti-polysaccharide response
- in host defense against encapsulated bacteria
- activates both classical and alternative cs
- induces opsonization
lgg2
54
an immune process which uses opsonins to tag foreign pathogens for elimination by phagocytes.
opsonization
55
```
this type of lgg
- extended hinges
- greater flexibility
- susceptible to proteolyytic enzymes like pepsin, plasmin and papain
- polymorphic w/ 13 alloitropes
- heaviest
- 62 AA and 11 disulfide sodium
-
```
Lgg3
56
- compromises of 5-8%
- has a major role in immune responses against protein or polypeptide antigens
- effective in induction of effector fucntions
- a potent proinflammatory antibody
- limit excessive inflammation
- highest C1 and Fc G receptors binding
lgg3
57
this kind of Lgg class
- heterobivalent
- fab arm exhange
- mimic lgg rheutamoid activity
- regulated by t helper cells
- allergy diagnosis
- lessens system inflammatory
lgg4
58
this lgg class
- does not bind
- bind to fcy receptor
- Prominent in the response to therapeutic proteins such as
clotting factor VIII and therapeutic antibodies such as
infliximab (Remicade)
lgg4
59
this immunoglbulin
- 2nd most abundant isotope
- 10-15%
- in tears, mucus, colstrum
- respi/unri, prostate secretion
LgA
60
2 types of LgA
Serum IgA
| Secretory IgA
61
this lgA
- does not fix complement
- lack of complete activation
serum lgA
62
this lgA
- most abundant immuno in mucus secretion
- confines bacteria to mucosal surface
Secretory lgA
63
```
this type of LGA
- -Most important Ig in
human breast milk
-Produced by maternal
plasma cells in the
mammary gland
```
Secretory Lga
64
this tyype of Lga
- peaks in colstrum
- remain high till 7 to 8 mos
- lga high in breast milk
secretory lga
65
diseases associated with lga
Linear Bullous IgA/Bullous Disease - autoimmune
- lga nephropathy - glmerular nephritis
66
Increase in IgA diseases
```
-Systemic Lupus
Erythmatosus
- Rheumatoid Arthritis
-Cirrhosis of Liver
-IgA Myeloma
```
67
decrease in IgA diseases
```
-Hereditary Ataxia
Telangiectasia
- Malabsorption Syndrome
- Chronic Lymphocytic
leukemia
```
68
this type of immuno
- most heat liable
- least abundant
- low concentration of serum
- 2.5 days half life
- important defense against parasitic disease by protzoa and helmiths
IMMUNOGLOBULIN E
69
```
this type of immuno
- have 2 types of receptors
- › FcεRI: high affinity IgE receptor
› FcεRII (also known as CD23): low affinity
IgE receptor
- does not activate complement
```
IMMUNOGLOBULIN E
70
this type of immuno
- Allergic Manifestations
› self-reactive IgE immune complexes
› IgE’s active basophils
IMMUNOGLOBULIN E
71
```
function of this immuno
- type 1 sensitivity
- protective role by triggering an acute
inflammatory reaction - recruits neutrophils and
eosinophils
- immunity from parasites
- activates eosinophil
```
IMMUNOGLOBULIN E
72
dieases when increase in lge
```
Anaphylactic shock
Asthma
Allergic rhinitis
Hypogammaglobulinemia
Atopic skin diseases
Congenital
agammaglobulinemia
```
73
diseases when decrease in lge
```
Atopic skin diseases
Congenital
agammaglobulinemia
Allergic rhinitis
Hypogammaglobulinemia
```
74
- high levels of lge in the blood
- stat3 mutation
- recurrent infections
- raches, scaling, pus, inflammatory skin disorder
- open sores
Lupus systemic lupus Erythematosuss (SLE)
75
this immunoglobulin
- unclear function
- not known to participate
- low in serum
- extra AA at C terminal
- does not bind to complement
loc: surface of b cells
LgD
76
diseases in ldg when increases
-Atopic Skin
Diseases
-Allergic Rhinitis
-Asthma
77
diseases in ldg when decreases
-Hypo gamma globullinemia
- Congenital
A gamma globulinemia
78
some function of microbes
- neutralize toxic material
- activate complement system
- immediate hypersensitivity
79
molecular structure of immunoglobulin
2 heavy H chains
in heavy Chain - Variable region → 1 Ig domain
b. Constant region → ~3 or 4 Ig domains
2 light chains
- disulfide bond
- variable region - binding
Constant region - antibody class
80
forms of antibodies
- Membrane bound
| - Secreted antibodies
81
form of antibody that is
- surface of b lymphocytes
- receptor for antigens
- hummoral response
Membrane bound antibody
82
form of antibody that is
- reside in circulation and mucus
- bind antigen
- neutralize toxins
- prevent entry and spread of pathogens
Secretory antibody
83
this region
- shallow crevice in center of hydrophobic core
- antigen binding site
Variable region
84
Fragment Antigen binding
Fab
85
complementary determining region
- form a complementary to 3 dimentsional strcuture
- CDR3 of both VL is most variable to CDrs
- form extended loops that are exposes on the surface
86
- area that gives molecule flexibility
- allow multiple biding sites
- cleaved papain
- cleaved pepsin
Hinge region
87
3 results fragments from the hinger region
2 Fab
| 1 FC - Fragment crystallizable)
88
G A M E D
| arrange from most prominent to least
Remember! [G → A→ M → E→D] (most prominent, to
| least prominent)
89
Subclasses / subtypes: in the Constant region
IgA – IgA1, IgA2
| IgG – IgG1, IgG2, IgG3, IgG4
90
What transpires in the Constant region?
```
Agglutination
● Complement Fixation
● Antigen attachment (for opsonization)
● Ab-dependent cell cytotoxicity (ADCC)
● Viral neutralization
```
91
What transpires in the Constant region?
```
Agglutination
● Complement Fixation
● Antigen attachment (for opsonization)
● Ab-dependent cell cytotoxicity (ADCC)
● Viral neutralization
```
92
what is the longest
Lge
93
heavy chains C region
CH
94
how many tandems does CH contain in humans
4 tandems lg domain
Designated CH and numbered sequentially from
amino terminus to carboxyl terminus (eg. CH1,
CH2 and so on)
95
composition of light chains
2 Identical Light Chains (L Chain)
- L chain - half of H chain
› 2 identical heavy chains (H chain) in most IgS
- H chain – 440 amino acids (50 kDa)
Covalent linkage by disulfide bonds between
96
have the shortest H chains
Lgs
97
= variable region
Half of light chain toward carboxyl terminal (COO-) =
| constant region; amino terminal half
98
all light chains are either
```
either kappa (κ) or lambda (λ) type
(NEVER A MIXTURE) based on their C regions
```
99
what chains are frequent in the humans
Kappa K chains
100
what determines lg class and effecter
tyype of h chains
101
types of H chains
```
IgG γ – gamma
IgA α – alpha
IgM μ – mu
IgE ε – epsilon
IgD δ – delta
```
102
no 2 variable regions are identical
L chains – 3
| › H chains – 4
103
I. TWO PRIMARY FUNCTION OF IGs
1. Antigen recognition
- Recognize and bind an enormous variety of antigenic
determinants
2. Effector functions
-Mediate the biologic effects of immunoglobulin
104
is a foreign substance that includes
antibody and/or CMI after binding to its specific
antigenic receptor on T and B cell clones.
ANTIGEN
105
Specificity for binding an epitope of an
| antigen (epitope – T cell receptor response)
Fab portion
106
› Directs the biological activity
Fc Portion
107
lock and key concept
```
Ag = Key
Ab = Lock
```
108
constructed from the
hypervariable regions of the heavy and light
chains
Combining site
109
what happens in the fab portion combing site
(Ag) and antibodies (Ab) interacting shows
that the antigenic determinant nestles in a
cleft
110
these binds hold the AG
ex. hydrogen bond
vander waals
non covalent bonds
111
Ag-Ab reactions occur via non-covalent bonds
REVERSIBLE BONDING
112
functions of the effector
- neutralize toxic microbes
- complement system activation
- opsonization
- hypersensitivity
- H chain determines class
c region in FC defines effector funtion of specific lg
113
what can synthesize antibody molecules
Only B lymphocytes
| thru fluids in the body
114
Strength of reaction between single antigenic determinant
and a single combining site on antibody
Strength of reaction of 1 antigen to antibody
AFFINITY
115
overall strength of binding of an antigen with
| many antigenic determinants and multivalent antibodies
AVIDITY
116
more than one antigenic determinant
ability of ab to react to more than one ag
cross reactivity
117
FEATURES RELATED TO ANTIGEN-
| ANTIBODY INTERACTION
Specificity
● Cross Reaction
● Diversity
● Affinity Maturation
118
You only have 1 antigen-antibody
| reaction
Specificity:
119
Antibody fits with antigen because
of shared epitope. Antibody still slightly fits because of
similar epitope.
Cross reaction:
120
the part of the antigen that binds to a specific antigen receptor on the surface of a B cell.
epitope
121
factors affectting the measurement of antigen antibodyy
Affinity & avidity
| Antigen-antibody ratio
122
Physical form of the antigen if antigen is:
particulate
| soluble
123
precipitation of the antigen after the production of
| large insoluble Ag/Ab complexes
soluble
124
agglutination of antigen by antibody
particulate
125
Ability to respond to antigens that are “foreign” or non-self,
and to not respond to antigens that are self
hummoral infinity
126
ability to recall previous contact with a particular
| antigen so that a subsequent interaction leads to a quicker,
memory
127
vaccine types
Toxoid vaccines
Killed vaccines (e.g.
Live attenuated
128
Live attenuated vaccine ex
mmr and varicella vaccine
129
Killed vaccines ex
inactivated polio vaccine [IPV])
130
Toxoid vaccines ex
diphtheria & tetanus
131
first arrangement of lg genes
Dh to h chain gene
- CD10 and CD19
Pro B cell
132
2nd arrangement
| Vdj recombinase joins heavy
pre cell b
133
Light chains are paired with μ chains to form monomeric IgM
which is expressed in the cell surface to form B cell receptor
CD20 – marks late stage development of B cell
› CD10: from pro-B to pre-B cell only
Immature B Cell
134
1st stage in B cell differentiation pathway to express receptor
(B lymphocyte factor which belongs to the tumor necrosis
no encountered antigen
Transitional B Cell
135
Monomeric IgM and IgD on the surface of B cell
naive cells
Mature B Cell
136
B cells not yet exposed to antigen
› Exposure to antigen in secondary lymphoid tissue
results in activation, leads to formation of either
plasma cell or memory cell
naive B cells
137
can synthesize and secrete lg molecule
Do not express surface Ig
Plasma Cell
138
key part of the innate immune system that enhances the
antibody-mediated adaptive immune system and its response
to microbial pathogens
complement system
139
major function
cell lysis
opsonization
C3b
140
most important opsonizing activity
CB3
| complement 3
141
proteins are inactive complement system
| what activates proteins
biochemical cascade pathways that
| sequentially generates biologically active molecules
142
Activation pathways:
Classical, Alternative, Lectin/
| Mannose-binding lectin (MBL)
143
Deficiencies of complement components, regulators, or
receptors may result in increased susceptibility to infection
or the development of inflammatory conditions
```
important complement functions
› Enhancement of B-cell responses
› Removal of immune complexes
› Removal of necrotic cells and subcellular membranes
› Responses to viruses
```
144
```
activated by antigen antibody complex
- initiated by lgg or lgm
- fc part of bind site
lgg phagocytic
- opsonization
```
classical pathway
145
1. C1q binds to Fc region of antibody bound to antigen C1
becomes activated. (C1 exists in blood and contains C1q, r, s)
2. 2. C1s esterase cleaves C4 molecules C4a (smaller) and
C4b (larger)
› C4a remains in fluid
› C4b binds to pathogen
3. C4b binds C2 then it cleaves it into C2a and C2b
4. C2a binds with C4b to form C4b2a complex which is a
protease known as (C3 convertase)
5. C3 convertase cleaves C3 into C3a and C3b
› C3a is a chemoattractant, it recruits leukocytes to
infection
sites to stimulate inflammatory response
› C3b binds with C3 convertase
6. C3a binds with C2a and c4b fragments to form a complex
known as (C5 convertase)
7. C5 convertase cleaves C5 into C5a and C5b
› C5a is a chemoattractant just like C3a
8. C5b combines with C 6, 7, 8, 9 to form membrane attack
complex (MAC)
MAC kills bacterial invaders by binding to and opening a pore
in their plasma membrane. Following lysis, the bacterial
remains are destroyed by phagocytic macrophages.
146
- triggered by any foreign substance in the absence of specific antibody
- key role in innate immune system
early response
alternate pathway
147
1. Deposition of C3b on the cell surface
› C3b is generated in small amounts by the spontaneous
cleavage of the reactive thiol group in C3
› “Preformed” C3b can bind to proteins and carbohydrates
expressed on cell surfaces, either of a pathogen or of a
host cell
› Alternative pathway is always “on” → can damage host
cells
› Host cell - regulates the progression of alternative
Pathway
2. Serum protein factor B binds with C3b → form C3bB
complex
3. Factor D cleaves factor B → generating fragments Ba and
Bb
› Ba - released into the fluid phase
› Bb - remains attached to C3b
› Formation of C3bBb - C3 convertase in the alternative
pathway
4. Shares the same steps (5-8) as the classical pathway
