Week 4 Flashcards
(76 cards)
1
Q
Describe the structure of antibodies
A
2 heavy chains with 1 variable region and 3-4 constant regions
2 light chains with 1 variable region and 1 constant region
all linked together via disulfide bonds
2
Q
What are complementary determining regions?
A
CDRs
3 non-contiguous, “hyper-variable” loops of protein in the variable domain that determines the specificity of the antibody
3
Q
Which CDR is the most variable?
A
CDR3
4
Q
What is the Fc region?
A
Fragment crystallizable
The “handle” of the antibody
5
Q
What is the Fab region?
A
Fragment antigen-binding
Portion that binds to antigen
6
Q
What is the difference between membrane bound and soluble antibody?
A
Soluble is not bound to B cell
7
Q
What is an antigen?
A
Any substance that may be specifically bound to an antibody or T cell receptor
8
Q
What is an epitope?
A
a segment of an antigen
9
Q
What makes a good epitope?
A
Good epitopes often have charged amino acids with bulky side chains, which makes it easier to bind
10
Q
What are linear epitopes?
A
average length is 7-9 amino acids
Bind to receptor in a linear manner
11
Q
What are conformational epitopes?
A
Portions of folded antigen are recognized
12
Q
What kind of antigens can T cells recognize?
A
Short peptide fragments based on their amino acid sequence
13
Q
What kind of antigens can antibodies recognize?
A
Capable of recognizing virtually any molecule, linear and conformational epitopes
14
Q
What are the 5 types of antibodies?
A
IgM, IgD, IgG, IgE, IgA
15
Q
What are some characteristics of IgM?
A
- Pentameric when soluble (held together by J chain)
- High avidity
- 1st Ab made by fetus
- 1st Ab secreted by activated naive B cells
- Can activate complement
- Can agglutinate bacteria and viruses
16
Q
What are some characteristics of IgD?
A
Found on naive B cells
17
Q
What are some characteristics of IgG?
A
- Most abundant Ab in serum
- opsonization
- neutralization of toxins/viruses
- activates complement (IgG3>IgG1>IgG2)
- Can agglutinate antigens
- activates Ab-Dependent Cell-mediated Cytotoxicity (ADCC)
- Can pass through the placenta and protect fetus
18
Q
What are some characteristics of IgE?
A
- Binds tightly to Fc receptors on basophils and mast cells, which acts like a “tracker”
- Activates mast cells, basophils, and eosinophils when bound to antigen
- important for parasitic infections
- plays a role in allergic reactions
19
Q
What are some characteristics of IgA?
A
- Dimeric when soluble (held together by J chain)
- Secreted onto mucosal surfaces (GI, GU, respiratory, mammory tissue) as a first line of defense
- Passed from mother to infant via breast milk
20
Q
What Ab classes activate complement?
A
IgM and IgG
21
Q
What Ab is passed to infant via breast milk
A
IgA
22
Q
What Ab can pass through the placenta to protect the fetus?
A
IgG
23
Q
What are the 4 major functions of Abs?
A
1) Act as a receptor on B cells
2) Neutralization of toxins and pathogens
3) Mediate responses to antigen by Fc receptors
4) activation of complement cascade
24
Q
Describe how binding of antibody to specific Fc receptors on effector cells can mediate opsonization, ADCC, and killing of parasites
A
Antibodies bound to antigen can result in a number of actions
1) opsonization, which promotes phagocytosis of the microbe and release of granules
2) ADCC, which promotes NK cells to destroy the microbe/abnormal cell via degranulation
3) parasite elimination, which promotes degranulation of eosinophils when it binds to IgE bound to antigen
25
Describe the structure of the T cell receptor
TCRs resemble the Fab portion of antibodies
they are heterodimers that contain 1 alpha and 1 beta chain, each containing 1 variable region and 1 constant region
26
How many CDRs do the alpha and beta chains contain?
Each chain (alpha and beta) contains 3 CDRs, which recognize peptides bound to MHCs
27
Can T cells recognize free floating antigens?
NO! They can only recognize antigen bound to MHCs
28
How do super antigens activate T cells?
Superantigens bind outside of the receptor and cross-link the MHC and TCR resulting in premature activation.
In some cases, superantigens bind to the outside portion of the variable region of the beta chain (v-beta). This means that all T cells with that specific V-beta chain allele can become activated, resulting in polyclonal activation
29
What clinical condition do superantigens cause?
Cytokine storms
30
What are the two bacteria that cause cytokine storms and their toxins?
Strep pyogenes = spe-A
| Staph aureus = TSST
31
What is a CD4 co-receptor?
Co-receptor that is expressed on CD4+ cells, which allows binding to MHC-2
32
What is a CD8 co-receptor?
Co-receptor that is expressed on CD8+ cells, which allows binding to MHC-1
33
Describe T cell activation
1) antigen/MHC and ICAM binds to TCR and LFA-1, respectively
2) If the antigen is recognized, multiple LFA-1 molecules on the T cell will bind with multiple ICAMs on the APC forming an immunoligic synapse. In addition, B7 on APC will bind to CD28 on T cell further activating T cell
3) Co-receptor's (CD4/CD8) cytosolic Lymphocyte-specific protein kinase (Lck) tail becomes activated
4) Lck phosphorylates the 4x CD3 and 2x zeta chain ITAMs
5) activated zeta chains bind to ZAP-70
6) ZAP-70 activates PLC
7) PLC cleaves PIP2 to IP3 and DAG
8) IP3 increases [Ca2+]
9) Calcineurin becomes activated
10) Calcineurin activates transcription factor NFAT
11) NFAT promotes IL-2 secretion
34
What does cyclosporin do?
It inhibits Calcineurin from activating NFAT, therefore preventing proliferation and differentiation of the T cell
35
What is an immunologic synapse?
Immunologic synapse occurs when a TCR finds its antigen/MHC. This results in increase binding of adhesion molecules around the TCR to stabilize interactions between the APC and T cell
APC = ICAM
T cell = LFA-1
36
Where do T cells and B cells mature?
T cells = Thymus
B cells = Bone
37
Describe the coding regions for B cells
```
3 loci
- Heavy chain
- V, D, and J regions
- Kappa light chain
- V and J regions
Lambda light chain
- V and J regions
```
38
Describe the coding regions for TCR
2 loci
- alpha chain
- V and J regions
- beta chain
- V, D, and J regions
39
Describe B cell activation
1) Antigen binds to BCR
2) BCR activates Ig-alpha and Ig-beta subunits
3) BTK phosphorylates
4) B cell becomes active
5) Type switching requires T cell's CD40L binding to B cell CD40
40
Describe B cell maturation
Include pre/pro
41
Which antibodies have 4 constant regions?
4 ME!
42
What are the 4 major roles of antibodies?
1) B cell receptor
2) neutralization
3) mediate responses to antigen by Fc Receptor
4) Activation of complement
43
How are T cells deactivated?
T cells express CTLA-4 which binds to CD28 on activated
44
Describe the maturational stages of developing lymphocytes
```
stem cell
pro-lymph
pre-lymph
immature
mature/naive
```
45
When does heavy chain recombination occur?
D-J = between stem cell and pro B
V-DJ = between Pro and pre
46
When does B cell positive selection occur?
pre-B
47
When does light chain recombination occur?
V-J = pre-B and immature
48
When does B cell negative selection occur?
immature B cell
49
What enzymes occur in somatic recombination?
RAG enzymes create the hairpin loops and cut the TRECs and TdT joins the ends
ONLY 12 and 23 can join
50
Describe T cell maturation
- Pro T cells enter the Thymus via the corticomeduallry junction and migrate to the subcapsular space
- Once in the subcapsular space, double negative T cell precursors proliferate.
- The T cells then undergo gene rearrangement and become double positive.
- +/+ cells undergo positive selection to become +/- with the help of cortical epithelial cells and macrophages
- +/- undergo negative selection
- after negative selection. +/- cells move to the medulla, where they undergo another round of negative selection via medullary epithelial cells with AIRE genes
- mature/naive t cells leave the thymus via corticomedullary junction following S1P chemotactic gradient
51
Describe allelic exclusion
express only one chromosome when developing a receptor
52
What is X-linked agammaglobulinemia?
mutation in BTK
no B cell maturation
low Igs
53
RAG mutations
SCID
54
AIRE
leads to autoimmune polyendocrine syndrome type -1
55
DiGeorge syndrome
```
Cleft palate
Abnormal facies
Thymic aplasia
Cardiac abnormalities
Hypothyroidism/hypocalcemia
```
56
What is CCL21? CCR7?
CCL21 attracts T cells to secondary lymphoid organs and bind to CCR7 receptor
57
Describe the signals for T cell activation
```
Signal 1
-activation of TCR
signal 2
-co stimulatory molecules (B7 bind CD28)
Signal 3
-cytokines
```
58
What turns off T cells (co-stimulatory molecule)?
CTLA-4 on T cell binds B7, preventing CD28 from binding
59
What activates Th1 cells? What does it secrete/activate?
IL-12
It secretes INF-gamma, which activates M1 macrophages
60
What activates Th2 cells? What does it secrete/activate?
IL-4
It secretes IL-4, IL-5, which activates basophils, mast cells, and eosinophils
It secretes IL-13, which results in mucus secretion
61
What activates Th17 cells? What does it secrete/activate?
TGF-B, IL-6, IL-23
It secretes IL-17, which acts on stromal cells to secrete G-CSF and IL-8 to recruit neutrophils
It secretes IL-22, which acts on epithelial cells to secrete antimicrobial peptides
62
What activates Treg cells? What does it secrete/activate?
TGF-B, IL-2
It secretes TGF-B and IL-10, which stop immune response
63
How does the immune system generate a productive antibody response to T cell dependent antigens?
APC binds to PAMP and shows it to the T cell. The cell activates it and B cell creates antibodies as well as memory cells
64
How does the immune system generate a productive antibody response to T cell independent antigens?
B cell binds to carbohydrate and produces antibodies, but no memory cells on its own
65
Explain conjugate vaccines
Conjugates are recognizable PAMPs that are bound to carbohydrates. This allows APCs to bind and phagocytose the conjugate-carbohydrate. This allows for MHC presentation of the carbohydrate, allowing for memory cell creation and vaccination for the carbohydrate
66
What are the activities of Cytotoxic T Lymphocytes?
Perforin
Ganzymes
FasL
Forms an immunologic synapse, protecting surrounding tissue
67
What are the differences in receptors of naive T cells and effector cells
Naive
- L-selectin
- CCR7 (responds to CCL21)
Effector
- V-CAM
- Inflammatory cytokine receptors
68
Describe the properties of memory T cells
pre-programmed cells that survive in a quiescent state and mount more rapid and robust responses to antigens.
Higher amount of anti-apoptotic proteins
69
What are the clinical symptoms of patients who have B cell antibody deficiency disorders?
- recurrent sinopulmonary infections
| - recurrent or persistent GI infections with protozoa
70
Explain how clinical laboratory tests can be used to diagnose B cell / antibody deficiency
- Evaluate B cell and antibody quantity
| - evaluate B cell anf antibody function
71
Describe the major clinical features of patients who have T cell deficiencies
CD4+
- inability to generate effective antibody
CD8+
-severe viral and fungal infections
Treg
-autoimmunity
72
What are some clinical features of TB
Pott's disease
-spondylitis
Ghon complex
- middle or lower granulatomous lesions
- hilar lymphadenopathy
miliary TB
-multi organ infection
TB meningitis
TB tuberculoma
reactivation if TNF-alpha suppressed
- cough, hemoptysis, night sweats, cachexia
73
What are some clinical features of leprasy
- Leonine facies
- raised lesions on extensor surfaces
- peripheral neuropathy (schwann cells)
74
What are some clinical features of Pneumocystis jiroveci?
- typically seen in individuals who are immunocompromised (AIDS, SCID, hyper IgM)
75
What are common clinical features of non-tuberculous mycobacterium?
Cervical lymphadenopathy without pain
76
Describe the structure of HIV and the gene functions
- bar-shaped caspid
- envelope
- gag -> P24 -> HIV marker
- pol -> integrase, RT, protease
- env -> mediate attachment (GP41 GP120)
