Chapter
10
Immune systems
I.
Overview
1.
The immune system is to
protect vertebrates from infection by microorganisms/pathogens (viruses,
bacteria, and fungi) and large parasites.
2.
There are 2 main types of
immune systems:
(1)
The innate immune system is a
type of immune system found in all animals, and is a collection of defenses that
respond without specificity to the type of invader, e.g., protective barriers,
toxic molecules (granulocytes and natural killer cells), and phagocytes
(neutrophils and macrophages).
(2)
The adaptive (also called
acquired or induced) immune system is a complicated type of immune system found
in vertebrates, and has receptors to deal with specific pathogens.
3.
Three characteristics of the
adaptive immune system:
(1)
High specificity (measles
vs measles virus, but not chicken pox)
(2)
Memory
(3)
Distinguishment (tolerance;
foreign vs self molecules), e.g., autoimmune diseases
II.
Innate Immunity
1.
The cells of the innate immune
system share 3 main elements:
(1)
Recognition of pathogens
(2)
Phagocytic cells
(3)
Excuting pathogens
2.
Recognition of pathogens
(1)
Pathogen-associated molecular
patterns (PAMPs) are molecules arising from pathogens that can be recognized as
foreign.
(2)
Pattern-recognition receptors
(PRRs) are proteins produced by the innate immune system that bind PAMPs.
(3)
When a PRR binds its PAMP, the
cell responds by triggering signal transduction pathways to initiate an immune
response.
3.
Phagocytic cells
(1)
Many leukocytes use
phagocytosis to clear pathogens.
(2)
The main types of phagocytes
are neutrophils and macrophages in the innate immune response. (Both phagocytes
also participate in the adaptive immune system.)
(3)
Neutrophils are the most
abundant of the leukocytes in mammals.
(4)
The progenitors of macrophages
are monocytes. Activated macrophages digest foreign cells and secrete chemical
signals, cytokines (also called lymphokines; interleukins; chemokines).
(5)
Opsonins are proteins that
bind to pathogens, enabling them to be better recognized by immune cells
(phagocytes). Opsonization is the addition of opsonins to pathogens.
(6)
The complement system is a
part of the immune system. The collection of many proteins after a series of
enzyme digestion found in the innate immune system, and also helps promote the
adaptive immune system.
4.
Executing pathogens
(1)
Granulocytes,
cytotoxic T cells (TC), and natural
killer (NK) cells secrete cytotoxic (antimicrobial) compounds and act as executioners.
(2)
Two types of granulocytes,
eosinophils (also called acidophils) and basophils,
derived from myeloblasts are rich in secretory vesicles.
(3)
Natural killer
(NK) cells
derived from lymphoblasts are a type of cytotoxic lymphocyte.
(4)
The executioners secrete
cytotoxic chemicals to kill the pathogen or induce an infected host cell to
undergo apoptosis (programmed cell death).
(5)
Inflammation is an early
response to pathogens and tissue damage. The inflammation response refers to
local changes sparked by tissue damage, including increased blood flow, changes
in vascular permeability to cells and fluids, recruitment of immune cells, and
elevated tissue temperature.
III.
Adaptive Immunity of
Vertebrates
1.
The adaptive immune system is
divided into 2 categories: humoral and cell-mediated immunity. Humoral immunity
refers to those processes mediated by components in solution (e.g., antibodies
or complement proteins), while cell-mediated immunity refers to those processes
directly involving cells.
2.
The immunoglobulin (Ig)
superfamily contains the members sharing a structural feature of the Ig domain,
e.g., antibodies, B-cell receptors (BCR), T-cell receptor (TCR), and major
histocompatibility complexes (MHC).
3.
Humoral immunity
(1)
Antigen (antibody
generator) is a macromolecule, usually protein, that can be bound
specifically by antibodies.
(2)
Antibodies contain variable
and constant regions.
1)
The structure of an antibody
shows a Y-shaped protein with 4 polypeptides: two identical Ig heavy chains and
two identical Ig light chains.
2)
These 4 polypeptides are
joined by cross-bridges.
3)
The Fab fragment retains the
ability to bind antigen, whereas the Fc fragment cannot.
4)
Heavy and light chains contain
N-terminal variable (V) and C-terminal constant (C) regions.
(3)
B cells produce antibodies.
1)
Small, undifferentiated,
immature B cells express B-cell receptors (BCR; i.e., membrane-bound antibodies) on cell
surface and circulate through the blood and lymph.
3)
Once they (memory B cells)
encounter the antigen or are activated by helper T cells (TH), the
activated B cells become plasma cells to produce (membrane-unbound) secreted antibodies (without
transmembrane domains).
(4)
Antibody diversity arises
through gene recombination. Proposed by Susumu Tonegawa in 1976, antibody genes
are assembled from separate gene segments by site-specific genetic recombination
(gene rearrangement) during B cell development.
(5)
Mammals have 5 main classes of
immunoglobulins (IgG, IgA, IgM, IgE, and IgD), which differ in the structure of
their C regions.
4.
Cell-mediated immunity
(1)
The 2 most common lymphocytes
are B and T cells. Their names reflect their sites of synthesis: B in
bursa of fabricius in birds
or bone marrow in mammals; and T in thymus.
(2)
Both phagocytes (neutrophils
and macrophages) also participate in the adaptive immune system.
(3)
Antigen-presenting cells (APC)
display fragments of pathogens on the cell surface.
1)
Antigen-presenting cells (also
known as accessory cells or dendritic cells) ingest pathogens or foreign
material into smaller fragments, and display smaller fragments on the cell
surface as antigens by MHC.
2) Phagocytes act as APCs in the adaptive immune
system.
3)
The most important APCs in
mammals are B cells and macrophages, which when specialized for APC function are
often called dendritic cells.
4)
MHC class I proteins are
expressed in almost all cell types, where they can display antigens arising from
intracellular pathogens. MHC class I proteins contain α chain folded into α1, α2
and α3 extracellular globular domains and associated with
β2-microglobulin (α1 and α2 are extremely polymorphic,
while α3 and β2-microglobulin are Ig-like domains).
5)
MHC class II proteins are
expressed in phagocytes, where they participate in presenting antigens derived
from ingesting pathogens. MHC class II proteins contain α and β chains (α1 and
β1 are polymorphic, while α2 and β2 are Ig-like).
(4)
T cells recognize MHC.
1)
T cells use a surface T-cell
receptor (TCR) to bind the antigen-MHC complex displayed on APCs.
2)
T cell receptors (TCR)
contains antibody-like heterodimers (α and β chains).
3)
The TCR complex contains other
proteins associated with the TCR. These proteins are called copies of TCR,
including coreceptor (also called cluster of differentiation;
associate receptor; e.g., CD4 or CD8), CD3, and ζ (zeta) chains.
4)
The binding between TCR and
antigen-MHC complex causes T-cell activation and triggers the signal
transduction pathway after a series of protein-protein interactions.
5)
T cells express either CD4 or
CD8 coreceptors. CD8-bearing T cells are called cytotoxic T cells (TC),
and activation of the TCR initiates a signal transduction pathway that causes
the TC cell to kill the infected target cells.
6)
CD4-bearing T cells are called
helper T cells (TH), and activation of the TCR causes the TH
cell to synthesize and release cytokines to promote other cells into action. For
example, if the APC is a B cell, the activated TH cell causes the B
cell activation, transforming into plasma cells, and producing antibodies. If
the APC is a macrophage, the activated TH cell activates macrophage
to destroy the pathogen.
(5)
Allergic responses are
stimulated by mast cells.
1)
Allergen antigen enters
tissues and binds IgE on mast cells.
2)
This causes mast cells to
release histamine. Histamine causes blood vessels to dilate and leak fluid,
leading to nasal irritation, itchy skin, and tears.
3)
Diverse effects throughout the
body are caused by the binding of histamine to histamine receptors, triggering
signal transduction pathways.
4)
Antihistamines used in allergy
medicines (antagonists) work by blocking these histamine receptors.