Immune System
Immune System
The immune system is the body’s response to
disease and injury.
Functional system rather than organ system
Two types of Immune Response:
Non-specific response (innate immunity): Basically just
recognizes foreign vs native
Specific response (acquired immunity)
2
3
Innate: structural defenses; responds to non-specific
foreign substances
Present before any exposure to pathogens and is
effective from the time of birth
Adaptive: responds to specific foreign substances
Antigen-antibody relationship (acquired immunity)
Vaccinations depend on this
Involves lymphocytes (B, T and plasma cells)
4
Originates in bone marrow
Rich supply of hematopoietic stem cells
Asymmetric cell division (one daughter stays in bone marrow)
Lymphoid and Myeloid lineage cells begin and are released from here
Differentiation into lymphoid
stem cells in the bone marrow – General B cells mature in the bone marrow
Differentiation into lymphoid
stem cells in the thymus – General T cells mature in the thymus
5
6
Migration
Migration of mature general B and T cells to secondary lymphoid organs:
Lymph nodes
Spleen
Tonsils
External body surfaces (intestinal, respiratory, urinary, reproductive)
7
Skin Physical barrier to microbes
Keratin resistant to most bacterial enzymes & toxins
Secretions are acidic pH 3-5
Mucosa Physical barrier & produces a variety of protective chemicals
Gastric mucosa Very acidic & produces proteolytic enzymes
Saliva & lacrimal fluid contain lysozyme
Mucous Traps bacteria & moves them away from epithelial surface
8
Phagocytes
Macrophages: derived from monocyte
Free Macrophages: Roam through tissues
Fixed Macrophages: e.g. In liver & brain
Ingest cellular debris, foreign material, bacteria, fungi
Neutrophils: Ingest pathogens
Eosinophil: Weakly phagocytic of pathogens. Attack
parasites
Mast Cells: Phagocytic of various bacteria
9
Phagocytes attach to their prey via surface receptors and engulf them, forming a
vacuole that fuses with a lysosome
Pseudopodia surround
microbes.
1
Microbes are engulfed
into cell.
2
Vacuole containing
microbes forms.
3
Vacuole and lysosome
fuse.
4
Toxic compounds
and lysosomal enzymes
destroy microbes.
5
Microbial debris is
released by exocytosis.
6
Microbes
MACROPHAGE
Vacuole Lysosome
containing
enzymes
10
Natural Killer Cells:
Small population of large granular lymphocytes
Non specific for “non-self”
Not phagocytic: attack is by release of perforins that
perforate the target cell plasma membrane.
Shortly after perforation the target nucleus disintegrates.
Release chemicals that enhance the inflammatory response
Attack virus-infected body cells and cancer cells
11
Inflammation
Tissue response to injury
Triggered by injury – trauma, heat, chemical irritation, infection, etc.
Beneficial effects Prevents spread of injury
Disposes of cellular debris & pathogens
Promotes repair
Signs of inflammation Redness
Heat
Swelling
Pain
Loss of function 12
13
Antiviral proteins: Not virus specific.
Some cells produce & release interferon (IFNs) when invaded by virus
Released IFNs stimulate nearby cells to produce proteins (PKR) that interfere with viral replication by disrupting protein synthesis
14
Complement – a group of plasma proteins (30) that
are activated in the presence of foreign substances
Complement activation
Enhances both innate & adaptive defenses
Enhances & amplifies inflammation
Bacteria & some other cell types are lysed
Innate & adaptive mechanisms
work together in a cohesive
fashion
15
Specificity: directed at specific targets
Systemic: not restricted to initial site of infection / invasion
Memory: after initial exposure & activation, a more rapid & more vigorous response is made to subsequent exposures to pathogens (secondary response)
Components:
Humoral Immunity: (antibody mediated immunity) provided by
antibodies floating free in body fluids
Cell mediated immunity: Lymphocytes directly attack specific
invaders by lysis or indirect attack by initiating inflammation
and/or activating other lymphocytes & macrophages
16
Antigen-
binding
sites Antibody A
Antigen
Antibody B Antibody C
Epitopes
(antigenic
determinants)
An antigen is any foreign molecule
That is specifically recognized by lymphocytes and
elicits a response from them
A lymphocyte actually recognizes and binds
To just a small, accessible portion of the antigen called
an epitope
17
The body is populated by two main types of lymphocytes
Which circulate through the blood
B lymphocytes (B cells) and T lymphocytes (T cells)
The plasma membranes of both B cells and T cells
Have about 100,000 antigen receptor that all recognize the
same epitope
18
B cell receptors consists of two identical heavy chains and two
identical light chains linked by several disulfide bridges.
Bind to specific, intact antigens
Are often called membrane antibodies or membrane immunoglobulin
Antigen-
binding
site
Antigen-
binding site
Disulfide
bridge
Light
chain
Heavy chains
Cytoplasm of B cell
A B cell receptor consists of two identical heavy chains and
two identical light chains linked by several disulfide bridges.
(a)
Variable
regions
Constant
regions
Transmembrane
region
Plasma
membrane
B cell
C C
19
Antigen-
Binding site
b chain
Disulfide bridge
a chain
T cell
A T cell receptor consists of one α chain and one b
chain linked by a disulfide bridge.
(b)
Variable
regions
Constant
regions
Transmembrane
region
Plasma
membrane
Cytoplasm of T cell
Each T cell receptor consists of two different polypeptide chains (one α
chain and one b chain) linked by a disulfide bridge.
V V
C C
20
MHC molecules are encoded by a family of genes called the major histocompatibility
complex
Infected cells produce MHC molecules which bind to antigen fragments and then are
transported to the cell surface in a process called antigen presentation
T cells bind to small fragments of antigens that are bound to normal cell-surface
proteins called MHC molecules
A nearby T cell can then detect the antigen fragment displayed on the cell’s surface
21
T cells: recognize and destroy tagged antigens and proliferate
Cytotoxic T cells bind to antigen on plasma membrane of target cells and directly destroy the cells
Helper T cells activate B cells, cytotoxic T cells, Natural Killer cells and macrophages
Remaining cells can respond to secondary exposure
22
APCs: Macrophages & B lymphocytes
Antigen Presenting Cells (APCs) ingest foreign material,
then present antigenic fragments on their cell surface
where they are recognized by T-cells T-cells: respond to antigen only if it is displayed on plasma membrane.
Interactions between APCs & lymphocytes and
lymphocyte-lymphocyte interactions are critical to
immune response
23
B cells: recognize antigens, proliferate and produce
specific antibodies.
Differentiate into plasma cells- to produce more
antibodies
Differentiate into memory cells- keep antibodies in
supply for activation from second encounter by same
antigen
24
B cells recognize
antigens,
Differentiate into plasma cells- produce more antibodies
Differentiate into memory cells- keep some for later
proliferate,
and produce specific antibodies.
25
26
Active humoral immunity: B-cells encounter & respond to antigen to
produce an antibody
Naturally acquired: natural exposure to antigen (i.e. infection)
Artificially acquired: vaccines; dead/attenuated or fragmented pathogen
injected to elicit an immune response
Bestow immunity without disease; primary response
Booster shots (secondary response); intensify response
Shortcomings – adverse reactions & the immunity is less durable (poor memory) &
has less cell mediated component
Passive humoral immunity: Introduced “non-native” antibody
Natural: maternal antibody crosses the placental barrier conferring temporary
immunity to the baby (degrades after a few months)
Artificial: antibodies harvested from an outside source given by injection
protect from immediate threat but no memory is formed (antitoxins,
antivenins, gamma globulin, etc.)
27
Types of Acquired Immunity
28
Certain antigens on red blood cells (RBCs)
Determine whether a person has type A, B, AB, or
O blood
Antibodies to non-self blood types
Already exist in the body
Transfusion with incompatible blood
Leads to destruction of the transfused cells
29
ABO Type Per Cent
O +ve 48%
-ve 4%
A +ve 24%
-ve 2%
B +ve 17%
-ve 1%
AB +ve 4%
-ve 0.3% 30
If an individual is transfused with an incompatible blood
group, destruction of the red blood cells (RBCs) will occur.
This may result in the death of the recipient.
31
Recipient-donor combinations
Can be fatal or safe
32
Blood Group Antigens
(on RBC surface)
Antibodies
(in plasma)
Transfuse with
group
A A Anti-B A or O
B B Anti-A B or O
AB A and B none AB, A, B or O
O None Anti-A & B O
33
Another RBC antigen of next importance is the Rh type.
A blood group system with many antigens, one of which is D.
Rh refers to the presence or absence of the D antigen on the RBC.
Creates difficulties when an Rh-negative mother carries successive
Rh-positive fetuses
Unlike the ABO blood group system, individuals who lack the D antigen do not naturally make antibodies.
Production of antibody to D requires exposure to the antigen.
The D antigen is very immunogenic, i.e., individuals exposed to it will very likely make an antibody to it.
For this reason all individuals are typed for D, if negative must receive Rh (D) negative blood. 34
Pathogenesis
Fetomaternal Hemorrhage
Maternal Antibodies formed against Paternally derived antigens
During subsequent pregnancy, placental passage of maternal IgG antibodies
Maternal antibody attaches to fetal red blood cells
Fetal red blood cell hemolysis
35
36
MHC molecules
Are responsible for stimulating the rejection of tissue
grafts and organ transplants
The chances of successful transplantation are
increased
If the donor and recipient MHC tissue types are well
matched
If the recipient is given immunosuppressive drugs
37
Allergies are exaggerated (hypersensitive) responses To certain antigens called allergens
An acute allergic response sometimes leads to anaphylactic shock A whole-body, life-threatening reaction that can occur within
seconds of exposure to an allergen
38
The immune system loses tolerance for self and turns against
certain molecules of the body
Rheumatoid arthritis
Is an autoimmune disease that leads to
damage and painful inflammation of the
cartilage and bone of joints
Other examples of autoimmune
diseases:
Systemic lupus erythematosus
Multiple sclerosis
Insulin-dependent diabetes
39
An inborn or primary immunodeficiency
Results from hereditary or congenital defects that
prevent proper functioning of innate, humoral,
and/or cell-mediated defenses.
An acquired or secondary immunodeficiency
Results from exposure to various chemical and
biological agents
Range from temporary states to chronic diseases
40
Acquired Immunodeficiency Syndrome
(AIDS)
People with AIDS
Are highly susceptible to opportunistic infections
and cancers that take advantage of an immune
system in collapse
Because AIDS arises from the loss of helper T
cells: Both humoral and cell-mediated immune
responses are impaired
41
Growing evidence shows
That physical and emotional stress can harm
immunity
42