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immunology > Week 4 > Flashcards

Week 4 Flashcards

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

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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

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3
Q

Which CDR is the most variable?

A

CDR3

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4
Q

What is the Fc region?

A

Fragment crystallizable

The “handle” of the antibody

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5
Q

What is the Fab region?

A

Fragment antigen-binding

Portion that binds to antigen

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6
Q

What is the difference between membrane bound and soluble antibody?

A

Soluble is not bound to B cell

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7
Q

What is an antigen?

A

Any substance that may be specifically bound to an antibody or T cell receptor

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8
Q

What is an epitope?

A

a segment of an antigen

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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

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10
Q

What are linear epitopes?

A

average length is 7-9 amino acids

Bind to receptor in a linear manner

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11
Q

What are conformational epitopes?

A

Portions of folded antigen are recognized

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12
Q

What kind of antigens can T cells recognize?

A

Short peptide fragments based on their amino acid sequence

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13
Q

What kind of antigens can antibodies recognize?

A

Capable of recognizing virtually any molecule, linear and conformational epitopes

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14
Q

What are the 5 types of antibodies?

A

IgM, IgD, IgG, IgE, IgA

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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
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16
Q

What are some characteristics of IgD?

A

Found on naive B cells

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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
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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
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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
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20
Q

What Ab classes activate complement?

A

IgM and IgG

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21
Q

What Ab is passed to infant via breast milk

A

IgA

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22
Q

What Ab can pass through the placenta to protect the fetus?

A

IgG

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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

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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

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25
Q

Describe the structure of the T cell receptor

A

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

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26
Q

How many CDRs do the alpha and beta chains contain?

A

Each chain (alpha and beta) contains 3 CDRs, which recognize peptides bound to MHCs

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27
Q

Can T cells recognize free floating antigens?

A

NO! They can only recognize antigen bound to MHCs

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28
Q

How do super antigens activate T cells?

A

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

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29
Q

What clinical condition do superantigens cause?

A

Cytokine storms

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30
Q

What are the two bacteria that cause cytokine storms and their toxins?

A

Strep pyogenes = spe-A

Staph aureus = TSST

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31
Q

What is a CD4 co-receptor?

A

Co-receptor that is expressed on CD4+ cells, which allows binding to MHC-2

32
Q

What is a CD8 co-receptor?

A

Co-receptor that is expressed on CD8+ cells, which allows binding to MHC-1

33
Q

Describe T cell activation

A

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
Q

What does cyclosporin do?

A

It inhibits Calcineurin from activating NFAT, therefore preventing proliferation and differentiation of the T cell

35
Q

What is an immunologic synapse?

A

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
Q

Where do T cells and B cells mature?

A

T cells = Thymus

B cells = Bone

37
Q

Describe the coding regions for B cells

A 
3 loci
- Heavy chain
  - V, D, and J regions
- Kappa light chain
  - V and J regions
Lambda light chain
  - V and J regions
38
Q

Describe the coding regions for TCR

A

2 loci

  • alpha chain
    • V and J regions
  • beta chain
    • V, D, and J regions
39
Q

Describe B cell activation

A

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
Q

Describe B cell maturation

A

Include pre/pro

41
Q

Which antibodies have 4 constant regions?

A

4 ME!

42
Q

What are the 4 major roles of antibodies?

A

1) B cell receptor
2) neutralization
3) mediate responses to antigen by Fc Receptor
4) Activation of complement

43
Q

How are T cells deactivated?

A

T cells express CTLA-4 which binds to CD28 on activated

44
Q

Describe the maturational stages of developing lymphocytes

A 
stem cell
pro-lymph
pre-lymph
immature
mature/naive
45
Q

When does heavy chain recombination occur?

A

D-J = between stem cell and pro B

V-DJ = between Pro and pre

46
Q

When does B cell positive selection occur?

A

pre-B

47
Q

When does light chain recombination occur?

A

V-J = pre-B and immature

48
Q

When does B cell negative selection occur?

A

immature B cell

49
Q

What enzymes occur in somatic recombination?

A

RAG enzymes create the hairpin loops and cut the TRECs and TdT joins the ends

ONLY 12 and 23 can join

50
Q

Describe T cell maturation

A
  • 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
Q

Describe allelic exclusion

A

express only one chromosome when developing a receptor

52
Q

What is X-linked agammaglobulinemia?

A

mutation in BTK

no B cell maturation
low Igs

53
Q

RAG mutations

A

SCID

54
Q

AIRE

A

leads to autoimmune polyendocrine syndrome type -1

55
Q

DiGeorge syndrome

A 
Cleft palate
Abnormal facies
Thymic aplasia
Cardiac abnormalities
Hypothyroidism/hypocalcemia
56
Q

What is CCL21? CCR7?

A

CCL21 attracts T cells to secondary lymphoid organs and bind to CCR7 receptor

57
Q

Describe the signals for T cell activation

A 
Signal 1
-activation of TCR
signal 2
-co stimulatory molecules (B7 bind CD28)
Signal 3
-cytokines
58
Q

What turns off T cells (co-stimulatory molecule)?

A

CTLA-4 on T cell binds B7, preventing CD28 from binding

59
Q

What activates Th1 cells? What does it secrete/activate?

A

IL-12

It secretes INF-gamma, which activates M1 macrophages

60
Q

What activates Th2 cells? What does it secrete/activate?

A

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
Q

What activates Th17 cells? What does it secrete/activate?

A

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
Q

What activates Treg cells? What does it secrete/activate?

A

TGF-B, IL-2

It secretes TGF-B and IL-10, which stop immune response

63
Q

How does the immune system generate a productive antibody response to T cell dependent antigens?

A

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
Q

How does the immune system generate a productive antibody response to T cell independent antigens?

A

B cell binds to carbohydrate and produces antibodies, but no memory cells on its own

65
Q

Explain conjugate vaccines

A

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
Q

What are the activities of Cytotoxic T Lymphocytes?

A

Perforin
Ganzymes
FasL

Forms an immunologic synapse, protecting surrounding tissue

67
Q

What are the differences in receptors of naive T cells and effector cells

A

Naive

  • L-selectin
  • CCR7 (responds to CCL21)

Effector

  • V-CAM
  • Inflammatory cytokine receptors
68
Q

Describe the properties of memory T cells

A

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
Q

What are the clinical symptoms of patients who have B cell antibody deficiency disorders?

A
  • recurrent sinopulmonary infections

- recurrent or persistent GI infections with protozoa

70
Q

Explain how clinical laboratory tests can be used to diagnose B cell / antibody deficiency

A
  • Evaluate B cell and antibody quantity

- evaluate B cell anf antibody function

71
Q

Describe the major clinical features of patients who have T cell deficiencies

A

CD4+
- inability to generate effective antibody

CD8+
-severe viral and fungal infections

Treg
-autoimmunity

72
Q

What are some clinical features of TB

A

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
Q

What are some clinical features of leprasy

A
  • Leonine facies
  • raised lesions on extensor surfaces
  • peripheral neuropathy (schwann cells)
74
Q

What are some clinical features of Pneumocystis jiroveci?

A
  • typically seen in individuals who are immunocompromised (AIDS, SCID, hyper IgM)
75
Q

What are common clinical features of non-tuberculous mycobacterium?

A

Cervical lymphadenopathy without pain

76
Q

Describe the structure of HIV and the gene functions

A
  • bar-shaped caspid
  • envelope
  • gag -> P24 -> HIV marker
  • pol -> integrase, RT, protease
  • env -> mediate attachment (GP41 GP120)

immunology (7 decks)

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