Download The Cell Membrane

The Cell Membrane
AP Biology
2007-2008
Overview
 Cell membrane separates living cell from
nonliving surroundings

thin barrier = 8nm thick
 Controls traffic in & out of the cell


selectively permeable
allows some substances to cross more easily
than others
 hydrophobic vs hydrophilic
 Made of phospholipids, proteins & other
macromolecules
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Phosphate
Phospholipids
 Fatty acid tails

hydrophobic
 Phosphate group head

hydrophilic
Fatty acid
 Arranged as a bilayer
Aaaah,
one of those
structure–function
examples
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Phospholipid bilayer
polar
hydrophilic
heads
nonpolar
hydrophobic
tails
polar
hydrophilic
heads
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More than lipids…
 In 1972, S.J. Singer & G. Nicolson
proposed that membrane proteins are
inserted into the phospholipid bilayer
It’s like a fluid…
It’s like a mosaic…
It’s the
Fluid Mosaic Model!
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Membrane is a collage of proteins & other molecules
embedded in the fluid matrix of the lipid bilayer
Glycoprotein
Extracellular fluid
Glycolipid
Phospholipids
Cholesterol
Transmembrane
proteins
Peripheral
protein
Cytoplasm
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Filaments of
cytoskeleton
Membrane fat composition varies
 Fat composition affects flexibility

membrane must be fluid & flexible
 about as fluid as thick salad oil

% unsaturated fatty acids in phospholipids
 keep membrane less viscous
 cold-adapted organisms, like winter wheat
 increase % in autumn

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cholesterol in membrane
Membrane Proteins
 Proteins determine membrane’s specific functions

cell membrane & organelle membranes each have
unique collections of proteins
 Membrane proteins:

peripheral proteins
 loosely bound to surface of membrane
 cell surface identity marker (antigens)

integral proteins
 penetrate lipid bilayer, usually across whole membrane
 transmembrane protein
 transport proteins
 channels, permeases (pumps)
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Why are
proteins the perfect
molecule to build structures
in the cell membrane?
AP Biology
2007-2008
Classes of amino acids
What do these amino acids have in common?
nonpolar & hydrophobic
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Classes of amino acids
What do these amino acids have in common?
I like the
polar ones
the best!
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polar & hydrophilic
Proteins domains anchor molecule
 Within membrane

Polar areas
of protein
nonpolar amino acids
 hydrophobic
 anchors protein
into membrane
 On outer surfaces of
membrane

polar amino acids
 hydrophilic
 extend into
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extracellular fluid &
into cytosol
Nonpolar areas of protein
H+
Examples
Retinal
chromophore
NH2
water channel
in bacteria
Porin monomer
b-pleated sheets
Bacterial
outer
membrane
Nonpolar
(hydrophobic)
a-helices in the
cell membrane
COOH
H+
Cytoplasm
proton pump channel
in photosynthetic bacteria
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function through
conformational change =
shape change
Many Functions of Membrane Proteins
Outside
Plasma
membrane
Inside
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Transporter
Enzyme
activity
Cell surface
receptor
Cell surface
identity marker
Cell adhesion
Attachment to the
cytoskeleton
Membrane carbohydrates
 Play a key role in cell-cell recognition

ability of a cell to distinguish one cell
from another
 antigens
important in organ &
tissue development
 basis for rejection of
foreign cells by
immune system

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Any Questions??
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Movement across the
Cell Membrane
AP Biology
2007-2008
IMMUNOGENETICS
 IMMUNITY
The immune system in all its form is mankind’s defense mechanism, and in
order to understand the inherited disorders of immunity, we must first
understand the fundamentals of the genetic basis of immunity.
Immune defense mechanism can be divided into two main types:
innate immunity – includes a number of non-specific systems which do not
require or involve prior contact with the infectious agent.
specific acquired or adaptive immunity – involves a tailor-made immune
response that occurs after exposure to an infectious agent.
Both types can involve either humoral immunity, which combats extracellular
infections, or cell-mediated immunity, which fights intracellular infections.
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INNATE IMMUNITY
 The first simple type of defense against infection is a mechanical barrier.
This barrier is represented by skin and by membranes lining the respiratory
and gastrointestinal tracts.
 If an organism succeeds in invading the body, phagocytosis and bactericidal
agents come into effect.
HUMORAL INNATE IMMUNITY
A number of factors are involved in innate immunity by helping to minimize
tissue injury by limiting the spread of infectious microorganisms. These are
often called the acute phase proteins and include C-reactive protein,
mannose binding protein and serum amyloid P component.
In addition, cells when infected by a virus synthesize and secrete interferon ,
which interferes with viral replication through reducing mRNA stability and
interfering with translation.
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INNATE IMMUNITY
 COMPLEMENT
Is a complex series of 20 or so interacting plasma proteins that can be
activated by the cell membranes of invading microorganisms, in what is
termed the alternative pathway. The various components of complement
interact in a specific cascade sequence, resulting in a localized acute
inflammatory response through the action of mediators released from
mast cells and tissue macrophages. These result in increased vascular
permeability and the attraction of phagocytes in the process known as
chemotaxis. In addition, the latter components of the complement cascade
generate a membrane attack complex that induces defects in the cell
membrane, resulting in the lysis of microorganisms.
Complement can also be activated through the classic pathway, by the
binding of antibody with antigen.
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Classic and alternative pathways of complement activation
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INNATE IMMUNITY
 CELL MEDIATED INNATE IMMUNITY
PHAGOCYTOSIS
Microorganism are engulfed and digested by two major types of cells., either
polymorphonuclear neutrophils or macrophages. Polymorphonuclear
neutrophils are found mainly in the bloodstream, while macrophages occur
primarily in tissue around the basement membrane of blood vessels in
connective tissue, lung, liver and in the lining of sinusoids of the spleen and
the meddullary sinuses of the lymph nodes. Surface antigen (Ag) on
microorganisms result in their being engulfed and fusing with the granules
of the phagocytes-which leads to their destruction.
EXTRACELLULAR KILLING
Virally infected cells can be killed by large granular lymphocytes, known as
natural killer cells. Attachment of the natural killer cells to the infected cells
results in the release of a number of agents, which in turn results in damage
to the membrane of infected cell, leading to cell death.
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SPECIFIC ACQUIRED IMMUNITY
Many infective microorganisms have, through mutation and selective pressures,
developed strategies to overcome or evade the mechanisms associated with
innate immunity. There is the need, therefore, to be able to generate specific
acquired or adaptive immunity. This can, like innate immunity, be separated
into both humoral and cell-mediated processes.
HUMORAL SPECIFIC ACQUIRED IMMUNITY
The main mediators of this immunity are immunoglobulins or antibodies.
Antibodies are able to recognize and bind to antigens of infecting
microorganisms. Exposure to a specific antigen results in the clonal
proliferation of a small lymphocyte derived from the bone marrow, hence “B”
lymphocytes, resulting in mature antibody-producing cells or plasma cells.
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HUMORAL SPECIFIC ACQUIRED IMMUNITY

Immunoglobulins
The immunoglobulins (Ig), or antibodies, are one of the major classes of serum protein.
Their function, both in the recognition of antigenic variability and in effector activities,
was initially revealed by protein, and more recently by DNA, studies of their structure.
Ig structure – papain (a proteolytic enzyme), splits the Ig molecule into three fragments. Two
fragments are similar, each containing an antibody site capable of combining with a
specific antigen and therefore referred to as the antigen binding fragment or Fab. The
third fragment can be crystallized and was therefore called Fc.
The Ig molecule is made up of four polypeptide chains: two ‘light’ (L)-220 amino acid,
and two ‘heavy’ (H)-440 amino acid length. They are held together in Y-shape by
disulfide bonds and non-covalent interactions.
There are five different types of H chain, designated respectively as α,γ,µ,δ, and ε, one
each respectively for the five major antibody classes, or what are known as isotypes,
IgA, IgG, IgM, IgD and IgE. The L chains are one of two types, either kappa(κ) or lambda
(λ), occurring in all five classes of antibody, but with only one type of L chain occurring
in each individual antibody.
In addition there are four IgG subclasses(IgG1-IgG4), and two IgA subclasses
(IgA1,IgA2).
AP Biology
Model of antibody molecule structure.
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© 2005 Elsevier
Estimated number of the various DNA segments coding
for the κ, λ and various heavy chains.
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Downloaded from: StudentConsult (on 6 October 2006 07:59 AM)
© 2005 Elsevier
Classes of human immunoglobulin
-----------------------------------------------------------------------------------Class Mol. Wt. Serum
Antibody activity
concentration
(mg/ml)
-----------------------------------------------------------------------------------IgG 150 000 8 – 16
Binds to microorganisms, neutralizes
bacterial toxins
IgM 900 000 0.5- 2
Produced in early immune response
IgA 160 000 1.4- 4
Guards mucosal surfaces
IgD 185 000 0– 0.4
On lymphocyte cell surface, involved in
control of activation and suppression
IgE 200 000 trace
In parasitic and allergic reactions
------------------------------------------------------------------------------------
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THE MAJOR HISTOCOMPATIBILITY COMPLEX
The major histocompatibility complex (MHC) plays a central role in the immune
system. Association of an antigen with the MHC molecule on the surface of
the cells is required for recognition of the antigen by the T-cell receptor that,
in conjunction with the closely associated protein β2-microglobulin, results
in the recruitment of cytotoxic and helper T cells in the immune response.
MHC molecules occur in three classes: class I molecules occurring on virtually
all cells and which are responsible for recruiting cytotoxic T cells; class II
molecules that occur on B cells and macrophages and are involved in
signaling T helper cells to recruit further B cells and macrophages; the nonclassical class III molecules that include a number of other proteins with a
variety of other immunological functions.
Structural analysis of the class I and II MHC molecules reveals them to
heterodimeres with homology to immunoglobulin.
The genes coding for the class I (A,B,C,E,F and G), class II (DR, DQ and DP)
and class III MHC molecules, or what is also known as the human leucocyte
antigen (HLA) system, are located on chromosome 6.
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Transplantation genetics



Replacement of diseased organs by transplantation has become routine in clinical
medicine. Except for corneal and boner grafts, the success of such transplants
depends on the degree of antigenic similarity between the donor and recipient.
Rejection of the transplanted organ or tissue does not occur between identical twins,
or between non-identical twins where there has been mixing of the placental
circulations before birth. In all other instances, the antigenic similarity of donor and
recipient has to be assessed by testing them with suitable antisera or monoclonal
antibodies for antigens on donor and recipient tissue. As a general rule, a recipient
will reject a graft from any person who has antigens the recipient lacks.
The HLA system is highly polymorphic, two unrelated individuals are therefore very
unlikely to have identical HLA phenotypes. The close linkage of the HLA loci means
that they tend to be inherited en block, the term haplotype being used to indicate the
particular HLA alleles that an individual carries on each of his two number 6
chromosome.
Although crossing over does occur within the HLA region, certain alleles tend to
occur together more frequently than would be expected by chance., i.e. they tend to
exhibit linkage disequilibrium. An example is the association of the HLA antigens A1
and B8 in populations of Western European origin.
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HLA polymorphism and disease associations
 A finding which helps to throw light on the pathogenesis of certain


diseases is the demonstration of their association with certain HLA
types. The best documented is that between ankylosing spondylitis
and HLA B27. In the case of narcolepsy, a condition of unknown
etiology characterized by a periodic uncontrollable tendency to fall
asleep, almost all affected individuals are HLA DR2.
The possession of a particular HLA antigen does not mean that an
individual will necessarily develop the associated disease, merely
that he or she has a greater relative risk of being affected than the
general population. In family, the risks to first-degree relatives of
those affected is low, usually no more than 5%.
In general, the mechanisms involved in most HLA disease
associations are not well understood.
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H-Y antigen
 In number of different animal species it was noted that tissue grafts from


males were rejected by females of the same inbred strains. These
incompatibilities were found to be due to a histocompatibility antigen, known
as H-Y antigen.
The H-Y antigen seems, however, to play little part in transplantation in
humans. Although the H-Y antigen seems to be important for testicular
differentiation and function, its expression does not necessarily correlate
with the presence or absence of testicular tissue.
A separate sex-determining region of the Y chromosome (SRY) has been
isolated which is now known to be the testis-determining gene.
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The Basics Of Blood
W.B.C. & Platelet
R.B.C.
Plasma
ANTIGEN
ANTIBODY
>400 Agglutinogens on the cell
membrane
Natural & Immune
Agglutinins/
Isoantibodies
Antigen-Antobody reaction on the
cell surface  Hemolysis
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