Humoral Immune Response Flashcards

1
Q

Components of mature naive B cell

A

BCR: IgM, IgD, Ig a & Igβ

Co-BCR: CD19, CD81 & CR2 (CD21)

HLA-Class II

CD40

CD20

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2
Q

Two Types of B-2 cells

A

Follicular B cells are re-circulating B cells: Majority

Marginal B cells reside in the spleen: blood-borne polysaccharide Ags

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3
Q

What signal allows for migration to the Primary Follicle

A

CXCR5

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4
Q

First Signal Activation

A

via mIgs

Must cross link 2 or more BCR

signaling occurs through Igα& Igβcytoplasmic tails

phosphorylation of Syk-B
activate PLCy
leads to inositol triphosphate and DAG
activate Ca2+ dependent enzymes and PKC

Also Activation of RAS and RAC lead to ERK and JNK

All three pathways promote Myc, NFAT, NFkB, and AP-1 which increase
protein synthesis

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5
Q

First signal helping activation signals

A

Ag bound with C3d binds CR2 and enhances signal 1000 fold. Occurs through: Igα& Igβ, CR2 & CD19 cytoplasmic tails (BCR co-receptor complex*)

also can be TLR signaling

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6
Q

Outcomes of First signal

A
  • Increased survival and proliferation
  • Interaction with helper T cells (increased B7 expression)
  • Responsiveness to cytokines
  • Migration from follicle to T cell area (expression of CCR7)
  • Secretion of IgM
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7
Q

what are the two types of Second Signals

A
  • T independent signal- would be the mitogen
  • T dependent antigen would be the T helper cell and the CD40/CD40L interaction

Both signals cause the B cell to Proliferate and expand

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8
Q

Once activated by T helper cells B cells will begin to?

A

Change their chemokine receptor expression (class switch) and affinity maturation

Successful re-arrangements are selected/supported by TFH and follicular dendritic cells

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9
Q

What two things do cytokines released by Th cells promote

A
  • induce H chain class switching

- Augument B cell differentiation and proliferation

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10
Q

Cytokine IL-4 causes activated Isotype switching in B cells to?

A

IgE

Immunity against Helminths and Mast cell degranulation

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11
Q

Cytokine TGF-beta, APRIL, BAFF causes activated Isotype switching in B cells to?

A

IgA

Mucosal Immunity

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12
Q

Cytokine IFN-y causes activated Isotype switching in B cells to?

A

IgG?

Opsonization of phagocytosis and complement activation

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13
Q

Switch Recombination occurs in what region of DNA and by what type of antigen

A

CD40: CD40L ligation and cytokines in T dependant AG binding (protein)

Occurs in a downstream C region, intervening DNA is deleted

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14
Q

Affinity Maturation

A

Introduction of Point Mutations in the Variable areas of Ig genes

AID converts C’s to U’s

UNG creates the abasic cites

Ape 1 Endonuclease generates nick ( double strand breaks in DNA)

Idea of Somatic Hypermutation,

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15
Q

Where do the majority of Mutations occur in Somatic Hypermutation

A

Heavy chain and Light chain V regions,

Mutations mainly occur in secondary and Teritary Antibodies

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16
Q

Characteristics of T follicular Helpers

A

CD4+ and low levels of CD25 expression

Have ICOS/ICOS-L essential for germinal center reaction

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17
Q

What do T follicular helper cells secrete?

A

IL-21 to facilitate differentiation to plasma blasts

also provide IFN-y and IL-4 cytokine for switching

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18
Q

What is the selection checkpoint?

A

Where T Follicular Helper cells and Follicular Dendritic Cells choose the B cell with the highest Affinity to the presented antigen for its necessary survival

Rest of cells Apoptosis

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19
Q

Plasma Cell components?

A

Terminally differentiated effector B cell

Decrease in CD19 and CD20 expression,

Increase in CD27 cell marker

only secrets its class dependent Antibody

Expansion of ER in Cytoplasm

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20
Q

What is the effector of the Humoral Immunity

A

Antibodies

21
Q

What is the type of B cells that are T-Independant

A

B-1 cells respond to T- independent responses (non-protein) Ag in mucosal tissues

Marginal zone B cells (B-2) in spleen recognize blood-borne polysaccharides.

22
Q

What do T-independent cells secrete

A

IgM

Considered short lived plasma cells

23
Q

Memory B cell components

A

Survive long time without AG

Express high levels of Bcl-2 (anti-apoptotic protein)

surface markers: CD27 and CD45R(O)

Secretory class Ig dependant

Capable of mounting rapid response to similar Ag: Secondary immune mresponse

24
Q

Antibody feedback

A

Control mechanism triggered by IgG and when there are too many antibodies for an ending immune response

ITIM - activates SHIP which blocks B cell receptor signaling

25
Q

what is the effector region of of an antibody and how is it triggered

A

Fc Region is the effector function but it is triggered by the binding of Ag to Fab(V) region

26
Q

Aspects of the Primary Response

A

usually 5-10 days
peak is smaller
usually more IgM vs IgG
Lower affinity

27
Q

Aspects of the Secondary Response

A

Usually 1-3 days
peak is larger
More IgG and even IgA or IgE
Higher average Affinity

28
Q

Antibody Effector functions

A

Neutralize microbes and toxins

Opsonization and phagocytosis of microbes

Antibody dependent cellular cytotoxicity

Complement activation

  • inflammation
  • lysis of microbes
  • Phagocytosis of microbes with complement fragments
29
Q

What binds to Fc and what is Fc’s two main functions

A

FcR

Deliver antibody to inaccesible anatomical sites

link bound antigen to molecules/cells that effect destruction

30
Q

FC receptor FcyRI (CD64)

A

High affinity for IgG

On
-Macrophages, neutrophils, eosinophils

Function: Phagocytosis

31
Q

FcyRIIA (CD32)

A

low affinity

Macrophages and Neutrophils and eosinophils

Phagocytosis, and cell activation

32
Q

FcyRIIB (CD32b)

A

Low affinity

B lymphocytes,DC, mast cells, and neutrophils

Feedback inhibition of B cells
attenuation of inflammation

33
Q

FcyRIIIA (CD16)

A

Low affinity

NK cells

Antibody dependant cellular cytotoxicity

34
Q

FceRI

A

High Affinity

mast cells and basophils and eosinophils

Activation/degranulation of mast cells and basophils

35
Q

Neutralization via Ntibodies

A

Any Ab class can do this

Blocks penetration of microbe through epithelial barrier

Blocks binding of microbe and infection of cells

Blocks binding of toxin to cellular receptor

36
Q

Waste Management

A

Clearance of immne complexes

CR1 on erythrocytes bind to C3b or C4b on IC floating through the blood

Take to spleen or liver to drop off IC

IC gets phagocytosed by local macrophage

37
Q

ADCC anti viral state

A

NK binds to CD16/ FcR receptor on IgG that locates a surface antigen on host cell

NK kills the cell

38
Q

IVIG

A

treats autoimmune/ inflammatory disesses

Ig engages the inhibitory FcR on B cells and DC

39
Q

Natural Antibodies

A

IgM and some IgG

Produced by B-1 and marginal zone B cells

reacts with alloantigens (ABO blood type)

40
Q

IgE mediated reactions

A

Binds FceR on Eosinophils and mast cells and cause them to degranulate to kill helminth

41
Q

Mother provides what types of immunity for fetus and babies

A

Physical barrier for fetus

IgG during pregnancy

IgA through secreted breast milk

42
Q

What receptor does IgG travel through in the placenta

A

FcRn due to the low pH causes the tight binding to prevent lysosome destruction

43
Q

Why are babies at risk for disease after birth

A

IgG and IgA are just starting to be synthesized

IgM has started only a little bit

44
Q

Passive Immunity

A

given antibodies

Prevent disease after known exposure

protect immunosuppressed patients

get rid of ongoing symptoms

Prevent the cause of the disease

ie snake bite
mother giving antibodies to child

45
Q

Active Immunization

A

Delayed but more permanent
Produces immunological memory

ie natural exposure
vaccines

46
Q

Criteria for an effective vaccine

A

safe
provide protection
cost effective
establish long term immunity

47
Q

Problems with vaccines

A

Clinically important epitopes may not be intact in vaccine•

Individual genetics may effect efficacy•

Some individuals may be genetically predisposed to adverse events •

Often work poorly in very young infants or the elderly•

Many do not induce CMI; Ab may not be sufficient•

Allergies to vaccine components

48
Q

Types of evasions of the Humoral immunity

A

Antigenic Variations

Inhibition of complement activation

Blocking by Hyaluronic Acid capsule