Complement, MHC, And Antigens Flashcards

1
Q

What are the three complement pathways?

A

Classical
Lectin
Alternative

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2
Q

What are the main outcomes of the complement system?

A

Recruitment of inflammatory cell
Opsonization of pathogens
Killing via pores in membrane

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3
Q

What are the three ways the classical pathway is activated?

A

Bind directly to surface of bacterial components
Binds C-reactive proteins that binds to phosphocholine residues on bacterial polysaccharides
Binds to antigen-antibody couples on pathogen surface

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4
Q

How is the lectin pathway initiated??

A

Binding of carbohydrate-binding protein (mannone-binding lectin or Ficolins) on surface of pathogen

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5
Q

How is the alternative pathway initiated?

A

Spontaneously derived plasma C3b to pathogen surfaces

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6
Q

Activation of C1 in the classical pathway is caused by?

A

C1 binding to Fc region of the antibody

C1- cleaves C4 to C4a and C4b

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7
Q

What are the steps of classical complement cascade?

A
  1. C1 cleaves C4 to C4a and C4b
  2. C1 cleaves C2 to C2a and C2b
  3. C4b and C2a bind and form C3 convertase
  4. C3 convertase cleaves C3 to C3a and C3b
  5. C3b binds to C3 convertase to make C5 convertase (C4b2a3b)
  6. C5 convertase cleaves C5 to C5a and C5b
  7. C5b recruits C6 and C7 to form C5b67 compelx
  8. C8 joins complex with hydrophobic tail that is inserted into membrane
  9. C9 recruited (9-10copies) to form pore in membrane (MAC)
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8
Q

How is C3 convertase formed in the lectin pathway?

A

Mannose binding lectin binds to surface of pathogen, becomes activated, and cleaves both C4 and C2.
C4b and C2a bind to form C3 convertase

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9
Q

Describe the alternative pathway of the complement system.

A
  1. C3b spontaneously hydrolyzes
  2. C3b binds to Factor B on microbe surface -> C3bB complex
  3. Factor D cleaves C3bB to C3bBb (C3 convertase)
  4. C3 convertase cleaves C3 to C3b and C3a
  5. C3b combines with C3 convertase (C3bBb) to form C5 convertase (C3bBb3b)
  6. C5 cleaved
  7. C5b recruits C6, C7, C8, and C9 to form MAC
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10
Q

If a C3b (spontaneously lysed) binds to a host cell, what is the outcome?

A

Sailic acid promotes binding of C3b to Factor H

Factor H and I degrades C3b

Prevent lysis of host cells

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11
Q

How does C1 inhibitors prevent the complement cascade?

A

Inactivates C1r, C1s, and MASPs (classical and lectin pathways)

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12
Q

How does decay-accelerating factor control the complement pathway?

A

Accelerates the decay of C3 convertase (alternative)

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13
Q

How does Protectin contro the complement pathway?

A

Binds to C5b678 and prevents C9 recruitment and MAC formation

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14
Q

What are the possible outcomes of the complement pathway?

A
Direct target lysis
Tissue inflammation 
Endothelial activation 
Chemotaxis 
Opsonization
Immune complex clearance
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15
Q

The genes responsible for survival or rejection of a graft are called ______________________

A

Tissue or histo-compatibility genes

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16
Q

Each MCH cluster of genes has at least _____ classs of gene loci

A

3

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17
Q

Class I MHC are expressed on ?

A

All nucleated cells

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18
Q

Class II MHC are expressed on?

A

Professional antigen presenting cells
B cell
Macrophage
Dendritic cells

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19
Q

MHC class III genes encode proteins which function as?

A

Complement proteins

Not antigen presenting molecules

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20
Q

MHC genes are ____________ expressed, therefore each individual will have ______ MHC I genes

A

Co-dominantly

Six

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21
Q

What is the main role of MHC I and II in adaptive immunity?

A

Antigen presenting

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22
Q

MHC I present antigens to __________ T lymphocytes

A

CD8+

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23
Q

MHC II presents antigens to ________ T lymphocytes

A

CD4+

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24
Q

What is the structure of MCHi

A

Heterodimer - a (a1, a2, and a3) and B2-microglobulin

Extracellular domain makes up antigen binding groove
Transmembrane domain
Cytoplasmic domain

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25
Q

The T cell co-receptor binds to the _____ region of MHC I

A

a3

26
Q

What is the structure of MHC II?

A

a (a1 and a2), B (B1 and B2)

Peptide binding groove made of a1 and B1

27
Q

What cytokines increase expression of MHC I

A

IFNa, IFNB, or IFNy

28
Q

What cytokines increases expression of MHC II?

A

IFNy

29
Q

How does the immune response differ between animals with heterozygous and homozygous MHC alleges

A

Heterozygous-able to bind a large variety of antigenic peptides
Homozygous - able to bind few antigenic peptides

If MHC is unable to bind an antigen -> no immune response

30
Q

What are the two subcategories of antigens?

A

Immunogens

Haptens

31
Q

Immunogens are?

A

Substances capable of stimulating an immune response

32
Q

Haptens are?

A

Substances that by themselves do not stimulate an immune response, but can do so when complexed with larger molecules (eg host protein)

33
Q

What are the two cardinal features of an antigen?

A

Immunogenicity

Antigenicity

34
Q

____________ is the ability of an antigen to induce an immune response

A

Immunogenicity

35
Q

__________ is the ability of an antigen to bind with products of the immune system

A

Antigenicity

36
Q

What is an epitope?

A

Aka antigenic determinant

Part of an antigen that is actually responsible for inducing the immune response and binding to the immune system products

37
Q

What 8 factors can affect the immunogenicity of antigens?

A
  1. Foreignness
  2. Size
  3. Chemical composition
  4. Physical properties
  5. Degradability
  6. Genetic Factors
  7. Age
  8. Chemical nature of antigens
38
Q

How does forigenness affect immunogenicity of antigens?

A

Self vs non-self

Only non-self substances are immunogenic

39
Q

How does size affect immunogenicity of an antigen?

A

Larger the antigen, the more immunogenic

40
Q

How do the physical properties of an antigen affect its immunogenicity?

A

Particulate antigens- more immunogenic than soluble antigens

Denatured antigens are more immunogenic than native forms

41
Q

How does degradability of an antigen affect its immunogenicity

A

Antigens that are phagocytose and easily degraded are more immunogenic

42
Q

How can age and genetics affect immunogenicity ?

A

Species variation and severity to particular antigens
Different genes encoding antigen receptors on T or B cells

Very young and old individuals are less capable to mount immune response.

43
Q

How does the chemical nature of an antigen affect immunogenicity?

A

Protein- highly immunogenic
Polysaccharide - good immunogens
Nucleic acid- weak antigens, highly immunogenic when conjugated with protein
Lipids- generally not immunogenic (Haptens)

44
Q

What is an adjuvant?

A

Substance that enhances the body’s immune response to an antigen

45
Q

What are T-independent antigens?

A

Directly stimulate B lymphocytes to produce antibodies (no Helper Tcells needed)

Eg lipopolysacchride - polymeric structure with repeating epitope

46
Q

What are T-dependent antigens?

A

Indirectly stimulate B lymphocytes
Require helper T cells

Eg. Proteins - various epitope

47
Q

What is a superantigen?

A

Antigens that can activate a large number of lymphocytes at a time (Usually form bacteria or virus)

Bind to variable domain of the TCR and a chain of MHC -> induce strong signal to activate many Tcells

48
Q

What are autoantigens?

A

Natural part of body

Play a role in autoimmunity

49
Q

Do dendritic cells present to CD4+ or CD8+ Tlymphocytes?

A

Trick question- both

50
Q

Macrophages and B lymphocytes present antigens to ________ T lymphocytes

A

CD4+

51
Q

What are two important functions of antigen presenting cells?

A
  1. Convert protein antigens to peptides and they display peptide-MHC complexes to be recognized by Tcells
  2. Provide stimulus to Tcells called co-stimulation
52
Q

What is the processing of endocytosed antigens for presentation by MHC?

A
  1. Uptake into vesicular compartments (receptor mediated)
  2. Process proteins in endosomal and lysosomal vesicles (proteolytic enzymes-cathepsins)
  3. MHC II synthesized in ER and transported to endosome
  4. Associated of MHC II and peptide
  5. Expression of MHC II with peptide at surface
53
Q

How are cytosolic antigens processed?

A
  1. Cytosol location of foreign proteins
  2. Proteolytic degradation of cytosolic proteins in proteosome (ubiquinated proteins)
  3. Transport of peptides from the cytosol to the ER by “transporter associated with antigen presentation” (TAP)
  4. Assembly to peptide to MHC I in the ER
  5. Pass through golgi and expressed on the surface
54
Q

Exogenously acquired proteins will generate peptides that activate _________ T cells

A

CD4+

55
Q

Endogenously acquired proteins will generate peptides that activate ________ Tcells.

A

CD8+

56
Q

What are the two classes to T Cell Receptors (TCR)

A

TCR aB

TCR y&

57
Q

What TCR recognizes antigen in an MHC dependent manner?

A

aB TCR

58
Q

What TCR recognizes an MHC in an independent jammer?

A

y& TCR

59
Q

What is the purpose of the CD3 complex?

A

The CD3 compels is necessary for cell surface expression of TCR

Transduces activation signals to the cell nucleus following antigen interaction with the TCR.

60
Q

T lymphocytes recognize specific _______________, and only respond when they are attached to the surface of an APC with appropriate MHC

A

Peptide sequences (anchor residue)

61
Q

What antigens can be recognized by B cells?

A
Soluble antigen
Antigen exposed on cel surface
Peptide
Protein 
Nucleic acid
Polysaccharide 
Lipid
62
Q

Lipid antigens are presented by _______________________ which are found on APC’s and some epithelial cells

A

Class I like non-polymorphic molecules (CD1)

Present lipid to Tcells that are non MHC restricted (NKTcells)