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The Immune Response

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The non-specific component, innate immunity, is a set of disease resistance ... antigen enters a lymph node in afferent lymph it percolates through these areas ... – PowerPoint PPT presentation

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Title: The Immune Response


1
The Immune Response
  • Immunity, the state of protection from infectious
    disease, has both non-specific and specific
    components.
  • The non-specific component, innate immunity, is a
    set of disease resistance mechanisms encoded in
    the germline that are not specific to a
    particular pathogen.
  • In contrast, the specific component, adaptive
    immunity, displays specificity and memory.
  • Some form of innate immunity is present in all
    multicellular organisms whereas adaptive immunity
    evolved 400 million years ago and is only found
    in cartilaginous and bony fish, amphibians,
    reptiles, birds and mammals.

2
Contrasting Characteristics of Innate vs Acquired
Immunity
  • Innate Immunity
  • Characteristics
  • non-specific, present at birth, does not change
    in intensity with exposure
  • Components
  • Mechanical physiological barriers, secreted
    products and cells
  • Acquired Immunity
  • Characteristics
  • Specific responses, acquired from exposure,
    increases in intensity with exposure
  • Components
  • Secreted products and cells

3
Cells of the Immune System
  • All cellular elements of blood arise from
    pluripotent haematopoietic stem cells in bone
    marrow.
  • These cells divide to produce two more
    specialised stem cells, a myeloid progenitor and
    a lymphoid progenitor
  • These cells have lost the capacity for
    self-renewal but can differentiate into a variety
    of types in response to a range of growth factors

4
LYMPHOID LINEAGE
  • Constitute 20-40 of white blood cells and 99 of
    cells in lymph.
  • Approximately 1011 lymphocytes in the human body
    and are central components of the adaptive immune
    response.
  • Resting lymphocytes generally small, motile,
    nonphagocytic cells which cannot be distinguished
    morphologically.
  • Cytoplasm forms a narrow rim around nucleus and
    have densely packed chromatin, few mitochondria
    and poorly developed endoplasmic reticulum and
    Golgi apparatus.
  • When activated (by interaction with antigen)
    enlarge into lymphoblasts which have higher
    cytoplasmnucleus ratio and increased organellar
    complexity.
  • Lymphocytes can be subdivided into three
    populations

5
Lymphoid Organs
  • All of the cells of the immune system are
    initially derived from the bone marrow.
  • These cells, particularly the lymphocytes, mature
    in, and recirculate around, the lymphoid organs.
  • These can be divided into the primary or central
    lymphoid organs and the secondary or peripheral
    lymphoid organs.

6
Primary Lymphoid Organs
  • The primary lymphoid organs are the bone marrow
    and the thymus, a large organ overlying the
    heart.
  • B lymphocytes are produced in the bone marrow and
    mature there.
  • T lymphocytes leave the bone marrow and mature in
    the thymus.

7
Secondary Lymphoid Organs
  • A network of organised lymphoid tissues placed at
    strategic points around the body
  • Comprises lymph nodes and white pulp areas of the
    spleen
  • Can also be subdivided into anatomical
    compartments e.g. gut-associated lymphoid tissues
    (GALT) includes the tonsils, adenoids, appendix
    and Peyers patches.
  • Structures are connected by the lymphatic vessels
    which drain the extracellular fluid (lymph) from
    tissues.
  • System designed to constantly sample material
    (antigen) from all of the tissues of the body and
    transport it to secondary lymphoid tissues to
    meet constantly recirculating lymphocytes
  • System provides constant immune surveillance

8
Lymph Nodes
  • Morphologically lymph node vaguely comprises
    three concentric rings.
  • Outer thymus-independent cortex comprises B
    cells, macrophages and follicular dendritic cells
    organised into primary follicles.
  • Beneath this is thymus-dependent area or
    paracortex which contains mainly T cells and
    interdigitating dendritic cells (IDC).
  • At the centre is the medulla which is primarily
    populated by antibody secreting plasma cells.
  • After antigen enters a lymph node in afferent
    lymph it percolates through these areas to be
    trapped by the network of phagocytic cells and
    dendritic cells (FDC and IDC). Antigen trapped on
    IDC is presented to T cells which become
    activated and then move to follicles to help B
    cells become fully activated.

9
Spleen
  • Spleen not supplied by lymphatic vessels
  • Blood-borne antigens enter via the splenic
    artery.
  • Lymph nodes are main mechanism of surveillance
    for tissue, spleen filters blood to trap
    blood-borne antigen.
  • Spleen comprises two compartments.
  • Red pulp primarily concerned with removal of
    effete erythrocytes.
  • White pulp surrounds the branches of the splenic
    artery to form the peri-arteriolar lymphoid
    sheath (PALS), which contains mainly T cells.
    Associated with this is the marginal zone which
    is rich in B cell follicles.

10
B cells
  • Derived their letter of designation as a result
    of early studies demonstrating their maturation
    in the bursa of Fabricius in birds
  • Name apt as bone marrow is major site of
    production and maturation of B cells.
  • Mature B cells definitively distinguished from
    other lymphocytes by synthesis and display of
    membrane-bound immunoglobulin.
  • After recognition of antigen B cells
    differentiate into plasma cells which produce
    antibody.

11
B cells
  • See foreign protein (antigen) via their surface
    immunoglobulin
  • See parts of native antigen and tertiary (3D)
    structure of this
  • Produce antibody which is secreted form of their
    surface immunoglobulin
  • Often helped by T cells
  • Display memory

12
B cells
  • Deficiencies in B cell responses can result in
    susceptibility to infection e.g. X-linked
    hypergammaglobulinaemia
  • Inappropriate/misdirected/excessive B cell
    responses may result in autoimmunity e.g. Graves
    disease

13
T cells
  • Derive name from site of maturation in Thymus.
  • Each T cell expresses a single specificity of T
    cell receptor complex on surface.
  • Each T cell receptor sees a particular portion
    of antigen (peptide) in context of self Major
    Histocompatibility Complex (MHC) on antigen
    presenting cells (APC)
  • T cells from a particular individual only see
    particular peptides presented in the context of
    MHC molecules expressed by that individual - MHC
    restriction
  • T cell has specificity for combination of peptide
    MHC

14
T cells
  • CD8 T cells see peptide in context of MHC I
  • CD4 T cells see peptide in context of MHC II
  • Deficiencies in T cell responses can result in
    susceptibility to infection
  • Inappropriate/misdirected/excessive T cell
    responses may result in autoimmunity
  • Display memory

15
MHC - Major Histocompatibility Complex
  • Human Leukocyte Antigen (HLA) genes in humans
  • H-2 genes in mice
  • Class I, presentation to CD8 T cells, encoded by
  • HLA-A, -B, -C in humans
  • H2 -K, -D, -L in mice
  • Class II, presentation to CD4 T cells, encoded
    by
  • HLA-DR, -DP, DQ in humans
  • H-2A, -E in mice

16
MHC - Major Histocompatibility Complex
  • MHC is polygenic
  • There are several different class I and class II
    genes
  • MHC is polymorphic
  • There are multiple variants (alleles) of each
    gene within the population
  • The combination of polygeny and polymorphism mean
    that there is a wide diversity of MHC genes at
    both the individual and population level.

17
Antigen Presenting Cells - APC
  • Specialised phagocytic cells which acquire
    proteins and process them for presentation to T
    cells in the context of MHC
  • e.g. dendritic cells, macrophages, B cells

18
CD8 T cells
  • CD8 T cells see peptide presented on APC in
    context of MHC I.
  • CD8 T cells are generally T cytotoxic (Tc) T
    cells.
  • CD8 T cells are generally important for killing
    cells containing intracellular pathogens
    (particularly viruses) and controlling tumours.
  • Deficiencies in CD8 T cell responses can result
    in susceptibility to infection
  • Inappropriate/misdirected/excessive CD8 T cell
    responses may result in autoimmunity

19
CD4 T cells
  • CD4 T cells generally function as T helper (TH)
    cells.
  • Help or control other cells by expression of
    surface molecules (cognate interaction) or
    secretion of soluble mediators (cytokines).
  • CD4 T cells can be further subdivided into two
    subsets.
  • TH1 cells help cell mediated immune responses.
  • TH2 cells help B cell responses.

20
TH1 cells
  • TH1 cells help cell mediated immune (CMI)
    responses, often by production of cytokines such
    as IFNg.
  • Important for activating phagocytic cells to kill
    intracellular pathogens they have consumed e.g.
    protozoa such as Leishmania, mycobacteria etc
  • Deficiencies in TH1 cell responses can result in
    susceptibility to infection e.g. mycobacteria
  • Inappropriate/misdirected/excessive TH1 responses
    may result in autoimmune/inflammatory disease
    e.g. rheumatoid arthritis, IBD etc

21
TH2 cells
  • TH2 cells help cell humoral immune responses,
    often by production of cytokines such as
    Interleukin 4 (IL-4).
  • Important for protection against extracellular
    pathogens e.g. metazoa such as helminths etc
  • Deficiencies in TH2 cell responses can result in
    susceptibility to infection e.g. helminths
  • Inappropriate/misdirected/excessive TH2 responses
    may result in autoimmune/inflammatory disease
    e.g. asthma

22
Memory and self/non-self
  • Cells of the adaptive immune response are altered
    by initial encounter with antigen and persist
  • Subsequent responses are faster, bigger and
    better - anamnestic
  • Responses are usually directed against foreign
    antigens (non-self) and not against self antigens

23
Summary - adaptive/acquired immunity
  • Specificity
  • Diversity
  • Memory
  • Self/non-self discrimination
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