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Immunology > Humoral immunity > Flashcards

Humoral immunity Flashcards

1
Q

What molcecules do B cells recognize

A

BCR recognizes native molcules

  • Peptides
  • proteins
  • nucleic acids
  • carbohydrates
  • Lipids
  • small chemicals
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2
Q

Phases of humoral immune responses

A

Antigen recognition
Clonal Expansion
Differentiation into antobody recreting Plasma cells

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3
Q

Antigen capture and delivery to B cells

A
  • mature B lymphocytes migrate from one secondary lymphoid organ to the next in the search for Antigen
  • naive B cells reside in the follicles of peripheral lmyphoid Organs and circulate through them in search of specific antigens
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4
Q

Primary and secondary humoral immune response

A

Primary:

  • naive B cells are stimulated by Antigen, become activated
  • differentaite into antobody secreting cells
  • some migrate to bone marrow
  • usually IgM>IgG

Secondary:

  • elicited when the same Antigen stimulates These Memory B cells
  • more rapid Proliferation
  • production of greater quantities
  • relative increase in IgG (sometimes (IgA, IgE)

Seconary immune Response is typical of T cell dependent antibody Responses to protein antigens

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5
Q

Activation of B cells by helper T

A
  • Antigen-activated helper T cells and B cells move toward one another in Response to chemokine Signals
  • make contact adjacent to the Edge of Primary follicles
  • B cells presents Antigen to T cell
  • B cell recieves activating Signal from T cells
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6
Q

Antigen presentation on B cells to helper T cell

A
  • protein Antigens Bound to membrane Ig are endocytosed and processed
  • Peptide Fragments are presented on MHC II
  • Heper T cells recognize MHC-Peptide complexes and stimulate B cell Response
  • Activated B cells also express co Stimulators that enhance helper T cell responses
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7
Q

Germinal Centers in secondary lymphoid organs

A
  • are involved in T cell dependenet antibody Response
  • within the lmyphoid follicle (B cell Zone)
  • contain follicular dendritic cells
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8
Q

Processes in germinal centers

A
  • extensive Ig isotype switching
  • hypermutation of Ig V genes
  • B cells migrate into the light Zone –> Encounter follicular dendritic cells displaying Antigens and TFH cells
  • B cells with the highest Affinity Ig receptors are selected to survive
  • differentiate into antibody secreting or Memory B cells
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9
Q

heavy chain isotype (class) switching

A

Isotype switching in Response to different types of microbes is regulated by cytokines

  • in activated IgM and IgD expressing B cells
  • Induced by CD40 and cytokines

Result: production of antibodies with heavy chains of different classes: γ, α, and ε

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10
Q

Mechanism of heavy chain isotype switching

A
  • in the Absence of helper T Signals, B cells produce IgM
  • when there are Signals from helper T cells –> B cells unfergo swithcing to other isotypes
  • Stimuli initiate germline transcription through the Iε-SεCε locus
  • proximal CH genes are deleted in a circle of DNA, leading to recombination of the VDj exon with the Cε gene
  • switch regions: Sμ or Sγ
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11
Q

Affinity maturation

A
  • T-dependent humoral immune Response
  • somatic Mutation of Ig genes and selection of high Affinity B cells
  • early in the immune Response: low Affinity antibodies
  • in germinal Center reaction: mutated B cells with high Affinity Antigen receptors start to produce high afiinity antibodies
  • binding of the B cells to Antigen displayed on follicular dendritic cells –> necessary to Rescue B cells from programmed cell death
  • B cells may also present Antigen to germinal venter TFH cells –> promotes B cell survival
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12
Q

Antibody Responses to T cell independet antigens

A
  • non-protein Antigens (Polysaccharides and Lipids) stimualte antibody production in the Absence of helper T cells
  • antibodies are generally low Affinity and consist mainly of IgM
  • Limited isotype swithcing to some IgG and IgA
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13
Q

Effector functions of antibodies (in General, all of them)

A
  • neutralize microbes and other Antigens
  • opsonize microbes for phagocytosis
  • sensitize them for antibody-dependent cellular cytotoxicity
  • induce antibody-mediated helminth killing
  • activate complement system
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14
Q

Fc receptors

A
  • -> activation of efefctor mechanisms

- recognize antibodies of different isotypes for optimal defense

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15
Q

Neutralization of microbes and toxins

A
  • antibodies against micorbes and microbial Toxins block the binding of These microbes and Toxins to cellular receptors
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16
Q

Antibody-mediated opsonization and phagycytosis

A
  • IgG antibodies coat microbes and promote their phagocytosis by binding to C phagocytes
17
Q

Antibody-dependent cell-mediated cytotoxicity

A
  • antibodies of certain IgG subclasses bind to infected cells
  • Fc regions of the Bounds antibodes are recognized by Fc-γ receptors on Nk cells
  • NK cells are activated and kill the antibody.coated cells
18
Q

Antibody-mediated clearance of helminths

A
  • antibodies, mast cells, eosinophils function together in killing some helminths
  • helminths are resistant to the microbicidal products of neutrophils and macrophages
  • can be killed by cationic protein –> Major Basic protein –> present in granules of eosinophils
  • IgE, IgG, IgA coat helminths and bind to Fc receptors of eosinophils and cause their degranulation
19
Q

Antibody-mediated activation of complement

A
  • activation of complement involves: sequential proteolysis of proteins to generate Enzyme complexes with proteolytic activity
  • zymogens: proteins that acquire proteolytic activity by the Action of other proteases
  • products of complement activation become attached to microbial cell surfaces or to antibodies Bound to microbes
  • complement proteins become activated after they are attached to microbes or ti antibodies
20
Q

Classical pathway of complement activation

A
  • initiated by cibding of the complement protein C1 to IgG or IgM that have Bound Antigen
  • igG3 and IgG1 are more efficient activators of complement Systems
21
Q

Late steps of complement activation and MAC formation

A

MAC = membrane attack complex

  • cell associated C5 convertase cleaves C5 and generates C5b
  • C5b, 6, 7 complex is directly inserted into the Lipid bilayer of the Plasma membranes –> then Insertion of C8
  • C9 molcules then polymerize around the complex to form the MAC
  • Mac creates pores in the mmebrane and induced cell Lysis
  • C5a released on proteolysis of C5 stimulates inflammation
22
Q

Complement-mediated inflammatory responses

A
  • proteolytic Fragments C5a, C4a, C3a –> induce acute inflamation activating mast cells and neutrophils
  • Peptides bind to mast cells and induce degranultation
  • Peptides are also called anaphylatoxins –> reactions they trigger are characterisitc of anaphylaxis
23
Q

Regulation of complement activation

A

regulated by various Plasma and cell membrane proteins that inhibit different steps in the cascades

24
Q

Pathologic effect of the complement system

A
  • can cause significant tissue Damage
  • may be due to complement-mediafed acute inflammatory Responses
  • intravascular thrombosis and can lead to ischemic injury to tissues
25
Q

Protective immunity in neonates

A
  • passive immuity is provided by maternal antibodies transported across the placenta by specialized neonatal Fc receptor (FcRn)
  • passive immunization by milk antibodies in newborns
26
Q

Humoral immunity in mucosa

A
  • prodcution of seceretory IgA by Plasma cells in the lamina propria
  • binds to the poly-Ig receptor at the base of an epithelial cell
  • Transport of the antibody into the lumen
  • Bound IgA is releasd by proteolytic cleavage
  • IgA bind to microbes and Toxins to neutralize them

–> process is called transcytosis

27
Q

Summary on effector functions of antibodies

A

IgG:

  • opsonization of Antigens
  • activation of calssical pathway
  • antibody.dependent cell-mediated cytotoxicity
  • neonatal immunity
  • Feedback Inhibition

IgM:
- activation of classical pathway

IgA:

  • mucosal immunity
  • activation of the lectin pathway

IgE:
- mast cell degranulation

IgD:
- Antigen receptor of naive B lymphocytes

Immunology (7 decks)

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