introduction to physiology: the cell and general physiology · fc receptor antigen antibody action....

Chapter 34:Resistance of the Body to Infections:

II. Immunity and Allergy

Immunity

Innate = ability to resist damaging organisms and toxins

skin, gastric acids, tissue neutrophils

and macrophages, complement

Acquired = specific

humoral ----> circulating antibodies

cellular ----> activated cells

Sequenc

e

Dormant lymphocytes

Invasion of body by foreign antigen

Phagocytosis by macrophages

Presentation of antigen to lymphocytes

Antigen

An antigen is a substance that can induce

an immune response when introduced into

an immunocompetent host and that can react

with the antibody produced from that response.

Bone Marrow

Pre-B

Cell

Pre-T

CellT-Cell

T8-supressor

T4-helper

B-Cell Plasma Cell

IgG IgA IgM IgD IgE

Interactions between T- and B-Cells

virgin cellsfirst exposure to antigen

second exposure to antigen

activated cellsmemory cells

Formation of Activated and Memory Cells

Primary and Secondary Response

Days

Imm

une

Res

ponse Antigen A

Antigen A

Antigen B

0.01

0.1

1

10

100

0 5 10 15 20 25 30 35 40 45 50 55 60

activation

antibody

secreting

plasma

cell

antigen

antig

en

tiny fraction

of total

lymphocytes

Formation of Antibodies

One antigenic determinant

Two antigenic determinants

Binding of Antibodies to Antigens

Antibodies

antigen

binding

site

hinge region

light chain

heavy chain

Fab fragment

Fc fragment

IgA, IgD, IgE, IgG, IgM

IgM Antibody

Antibodies

• IgG- 80% total, cross placenta, opsonization

• IgM- first produced, 10-15% total, activate complement

• IgD- not known, may help CD4 Th

• IgA- body fluid, tears, bronchiole secretions, saliva

• IgE

- allergic reactions, histamine release

Specific binding

sites

antibody

Fab

FcFc activation of

complement

No

binding

Microbe 2Microbe 1

binding

Fc binding to

phagocyte

Fc receptor

Antigen Antibody Action

Antibody-Activated Phagocytosis

Fc receptorbacterium

opsonization

Complement System

Series of ~ 20 proteins

Activated by microorganisms

Will coat the microorganisms

Adherence reactions

phagocytic cells have receptors for C3

Biological active fragments

produce reactive oxygen intermediates

Membrane lesions

Activate mast cells

complement

bacteria phagocyte bacteria

2. chemotaxis1. lysis 3. opsonization

Functions of Complement Activation

Complement-Mediated Acute Inflammatory Reaction

bacterium

C3b

C3bBb

C3C3b

C5a C3a

vascular permeability

mediators

MC

activation

chemotaxic

factors

antigen-

antibody

reaction

IgE and Histamine Release

IgE receptor

histamine

vesicles

binding of IgE

to Fc receptor

antigenantigen

release of histamine

T-cells

Act over a short range

Interact with another cell in body

Can kill or signal other cell

Only recognize antigen when presented

on surface of target cell

T-cells

Cytotoxic Cellskill infected cells

Helper Cells (two types)

activate macrophages and B-cells

Suppressor Cellsregulate activity

TH1 TH2

TC LGL

B

Antibody Production

Virally infected cell and

some tumor cells

Antigen

presentation

Antigen

presentation

activation activation cytotoxicity

macrophage

T-Cell Function

Mhc-molecules

MHC-Ipresent foreign peptides to cytotoxic cells

MHC-II

present foreign peptides to helper cells

CYTOTOXIC T-CELLS HELPER T-CELLS

Tc Th

Class I

MHC

Class II

MHC

foreign

protein

infected

target

cell

antigen-

presenting

cell

Mhc-molecules

Helper T-cells

Helper T-Cells recognize foreign antigen bound to

MHC-II proteins on surface of antigen-presenting cells

Helper T-Cells stimulate macrophages and B-cells

Two signals are required for activation of Helper T-Cells

Activation of Helper T-cells

Th

antigen-

presenting

cell

signal 1

signal 2

activation

signal 2 is chemical (interleukin-1) or membrane bound molecule

CD4

antigen

Activation of Helper T-cells

Th

antigen-

presenting

cell

signal 1

signal 2

Th

Il-2 receptor

Il-2

Th Th

proliferation

CD4

Cytotoxic T-cells

Cytotoxic T-Cells recognize viral protein fragments on

surface of infected cells.

Cytotoxic T-Cells induce infected cells to kill themselves

Bind to infected cells

Induce cell death

Punch holes in cell membrane

Cytotoxic T-cells

Class I

MHC

Tc

infected

target

cell

CD8

Perforin discharge

Natural Killer

• destroy virus-infected cells

• do not express antigen specific receptors

• cells with low levels of MHC I

• induce cells to undergo apoptosis

TC

TCRCD8

MHC

Class I

Inhibitory

receptor

NK

Target

No MHC

Class I

NK receptor