Cells and Anatomy of the Immune System 29/09/2020
REVIEW: The B (bone marrow) and T
(thymus) lymphocytes of the white blood
cells form the backbone of the adaptive
immune system. B cells release
antibodies into the bloodstream to bind to
microbes and neutralize them. Each
antibody molecule is highly specific in
binding to a particular molecular
component of a microbe. Dendritic cells
capture pathogens, travel to lymph nodes, and present pieces of the pathogen to other cells of
the immune system. B cells are activated at the lymph node and start to make antibodies
specific to the pathogen. An antigen is a foreign molecule that elicits a specific immune
response against it. A macrophage, a cell of the innate immune system, engulfs and digests a
pathogen and then presents fragments on its surface as a signal. Such signals are picked up by
other cells of the adaptive immune system. T cells are a type of white blood cell. They have T
cell receptors (TCRs) on the cell surface. Like antibodies, TCRs are highly variable molecules.
The TCRs on a given type of T cell are all the same and bind the same antigen. Helper T
lymphocytes have TCRs and CD4 receptors that bind to antigen-presenting cells when their
TCRs recognize the antigen being presented. Once bound, helper T cells release cytokines to
stimulate a defense against that specific antigen. Infected cells actively making viral proteins
present pieces of those proteins on their surfaces. Cytotoxic T cells have TCRs and CD8
receptors on their surfaces. When their TCRs match the viral antigen, they proceed to kill the
infected cells. Next is lecture.
First defense: the cells of the innate immune response fight the pathogen at site of entry (local)
immediately remove pathogen within a few days without illness and incapacitation. Innate:
present ASAP, rapid response, no memory, cellular and humoral components.
Second defense: the cells of the adaptive immune response are initiated following the innate
immune response to pathogen. Releases cytokines which can create the snot and other ‘we are
sick’ things when we are unwell. When we are older, we have less responses (cells reproduce
less). Adaptive: learnt with experience, antigen-specific, slower response (days not hours),
memory, uses cellular and humoral components.
Both are poorly effective without the other <3.
Cells are active at different stages of the immune response. Start
as hematopoietic stem cell, which gives rise to the rest of the cells
(picture). NK cell is classed as innate, but is now classed as
innate lymphoid cell. Myeloid progenitor makes innate ones,
because dendrites have myelin sometimes. No memory for these
cells (macrophage is debatable, but say no). Monocyte-can
change what they become; can become a dendritic cell even; just
depends what pathogen they see!
Granulocytes are polymorphonuclear leukocyte (neutrophil),
eosinophil, basophil, mast cell. Commonality: granules-the little
dots. In lab we see what happens when activated. Granules get
,released and they kill bacteria-Mast cells in allergies; they are why you sneeze and itch.
Main function of innate is phagocytosis (ingest and destroy microbes and damaged tissues) and
antigen presentation (to the adaptive immune cells).
Neutrophils (polymorphonuclear leucocytes): most abundant circulating white blood cells.
10^11 are produced each day (short life span). They mediate the earliest phases of the
inflammatory response. We look at these in the practical. They are recruited to the site of
infection rapidly (first cell response). After migrating to the tissue, they last 1-2 days. Contain
granules with enzymes and anti microbicidal substances. Horseshoe shaped nucleus defines
them.
Monocytes: mononuclear phagocytes. Look like a smile! 10% are them. Very heterogenous,
lots of different subsets. Classical-majority, circulate in the blood and migrate to the
inflammatory tissues where they differentiate into monocyte derived macrophages.
Nonclassical-minority, patrol the surface of blood endothelial cells, contribute to tissue repair.
Difference: what they express on their cell surface as well as the cytokines released (non- helps
tissue repair). Blood monocytes have short lifespan.
Macrophages can derive from blood derived monocytes. They
are phagocytes. Tissue resident macrophages are present in
most tissues. They are long-lived cells, undergo division at
infected sites. We have these at birth, remember. They can be
classified as classical M1 (inflammatory) or non classical M2
(repair) macrophages as well as regulatory
macrophages-picture. Regulatory-we do not want them to
continue if we are not sick (or always feel ill). Tissue
macrophages are everywhere; bone marrow, skin, eyes, etc.
Key cell in terms of recognising infection. Picture-where we
find tissue macrophages (everywhere).
Pathogens can kill them and that though, then
we need antibiotics and that.
They are everywhere as they are the first cells
responding. Involved in ingestion and killing
microbes, removal of dead tissue and dying
cells. Macrophages orchestrate the overall
immune response (secretion of signalling
proteins, inflammatory cytokines). They also
present antigen to T cells and promote repair of
damaged tissues via cytokine release.
Remaining granulocytes: all short lived, no
self replicating. Produced by bone marrow.
Mast cells: phagocytes found in tissues, skin,
and mucosal epithelia. Large granules filled
with histamine in the cytoplasm released when
the cell is activated. Hayfever, you sneeze because of the mast cells. This is used against
parasites. They play a key role in inflammatory process (and allergic response). Parasite wants
to kill these cells.
,Eosinophils-phagocytes that are found in blood and tissues (migrate when required). Some
present in tissues, mucosal linings. Thought to play a role in defense against parasites.
Basophils are non-phagocytic. 1% of blood leukocytes. Not normally in tissues. Release
pharmacologically active substances from their granules. Mostly in the allergic response.
Dendritic cells. They are innate cells, found everywhere in
the body (in picture <-). Constantly explore-it’s their job.
They are key cells in antigen presentation to lymphocytes,
and known as a professional Antigen Presenting Cell
(APC). Phagocytic cells. Found in skin and mucosal
barriers (tissue resident and migratory). Can migrate
throughout the body in the bloodstream. Link the innate
with the adaptive immune response due to their role in
antigen presentation to lymphocytes. Key to making
antibodies and T cells/helper T cells. Different types in
mice (picture). There is classical, plasmacytoid,
inflammatory (those in tissue), and langerhans cells
(skin). Painful lump on neck or armpit-dendritic cell went
there and presenting the antigen to the T cells that are
now activated. APC-macrophages and dendritic cells
(moreso dendritic cells).
Natural Killer cells: Although derived from common
lymphoid progenitor cells. NK cells are part of the innate immune response. These are large
granular lymphocytes. Directed against tumour cells and virally infected cells. Not highly antigen
specific. They do not recognise Covid 19 from SARs or anything like that. Cytotoxic activity,
cytotoxic granules. Part of the innate lymphoid cells (ILCs)-more recent addition. Thought to be
involved around mucous area vs virus and protect from parasites (especially in the gut).
ADAPTIVE NOW. B and T lymphocytes: essential, specific roles. B has immunoglobulin; T has
TCR on surface.
B cells: B cells develop in the bone marrow. B cells express a receptor that is specific for
antigen on their cell surface (B Cell Receptor (BCR)). B cells recognise naïve intact antigen
particles. Can see the antigen as a whole, no need to split into particles like innate. On
encounter with antigen some B cells start to proliferate and become much larger (plasma cell).
Plasma cells secrete immunoglobulins specific for antigen (antibodies). If individuals made
antibodies for Covid, they have it. Other B cells differentiate to become memory B cells. Memory
is important so you make the same response and know what to do. Some after reinfected with
Covid are ill again; memory cells not working properly-sus; imposter? A lot of different varieties
of B cells. Not just plasma, memory B cells, but in bone marrow and spleen there are so many!
Spleen: plasma, mature B cell, T1, T2.
Regulatory B cells: repair and switch off immune responses. They inhibit autoimmune
responses, anti-tumor responses, and have other suppressive mechanisms.
T cells: thymus. Once mature they exit the thymus and enter the peripheral tissues. Epress a
receptor that is specific for antigen on their cell surface, T Cell Receptor (TCR). CD4+ T helper
cells: cytokine secreting T cells that ‘help’ B cells, Macrophages and cytotoxic T cells to become
activated. CD8+ Cytotoxic T cells: kill infected target cells by release of cytotoxic granules.
, Tahxic! Regulatory T cells: suppress the immune response. Without them, autoimmune disease
(arthritis). Several subsets of T cells within each of these categories. Lots of variety in T cells as
well (6 subsets just for CD4 T cells); regulatory has Natural Treg, Tr1, anergic, Ts.
CD8+ T Cells (CTLs-cytotoxic lymphocytes): Expression of death ligand. Cytolytic granules.
Release cytokines. Prevent excessive tissue injury. Three varieties: Effector memory CD8+,
Central memory CD8+, Suppressor CD8+ T cells.
Other lymphocytes: Natural Killer T cells (NKT) cells. gd T lymphocytes. MAITs (mucosal
associated invariant T cells). Populations of lymphocytes distinguished by history of antigen
exposure.
NAÏVE-mature B and T cells that have not seen foreign antigen (immunologically
inexperienced/resting); Live 1-3 months; Survival requires signals from receptors plus IL-7 and
BAFF. CD45RA-marker in clinic.
EFFECTOR – naïve B and T cells that have recognised antigen (dividing cells and clonal
expansion); Activate of immune cell; Short lived; Migrate to inflamed tissues. These are like if
you went to uni, you will be effective at your job.
MEMORY – generated during infections, long lasting, heterogenous population; (respond
quickly when exposed again). CD45RO-marker in the memory cells where we can compare
them to the naive cells.
Naive to effector cells: they are activated by dendritic cells, release soluble factors and switch
on some genes. They stay on the cells for life.
Cells and Tissues of the Immune System pg.32-63
Neutrophils also called polymorphonuclear leukocytes (PMNs) because their nucleus has 3-5
connected lobules. They have two types of membrane-bound granules in the cytoplasm; most of
them contain enzymes lysozyme, collagenase, and elastase. Production: stimulated by
granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating
factor (GM-CSF).
The mononuclear phagocyte system includes circulating cells called monocytes, which become
macrophages when they migrate into tissues, and tissue resident macrophages, which are
derived mostly from hematopoietic precursors during fetal life. Cells of the
monocyte-macrophage lineage arise from committed precursor cells in the bone marrow, driven
by a cytokine called monocyte (or macrophage) colony-stimulating factor (M-CSF). The
