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What are the features of an immune response against pathogens?

1. Physical barriers and preformed chemicals to prevent entry

2. If a breach occurs; recognition of pathogen as foreign and
dangerous (don't want us to eliminate commensal bacteria that
are in competition with the pathogenic species)

3. An early INNATE (non-specific) response triggered by recognition:
broad-acting and fast responding

4. A slower ADAPTIVE response to a particular antigen that forms
part of the pathogen - gives us specificity in our response: 4
hours to 4 days after infection, forms coordinated specific
response, kickstarted by the innate immune system, but can
also use the innate immune system to amplify response.
Adaptive response allows memory of the specific immune
response, to provide a quicker/larger response if pathogen is

5. Augmentation and resolution of these responses


What are our defences at the epithelial barrier sites (the respiratory tract)?

The respiratory tract is a tightly packed system that prevents pathogens passing through - viruses can be quite good at this. This is made up of several distinct features:

- at the tips of the cilliated cells is loose mucous adept at controlling
microbes and commensal bacteria
- the crypts of the villi contain paneth cells and stem cells and
have a dense mucose to control the ph gradient
- the villi themselves contain goblet cells for mucosa production
- Innate immune cells waiting beyond the epithelial cell membrane
to mount an innate response if there's a breach
- In respiratory tract there are cilia that flush cells out or further in where
the alkaline/acidic environment kills invading pathogens


What is the normal function of epithelial barriers in the airway?

Low permeability

Exclude pathogens and allergens from tissue

Intercellular junctions adhere the epithelial cells to each other and to the cytoskeleton of the cell

Secretion of mucus by Goblet cells

Actin prevents deformity, and hold cell in structural shape

Goblet cells secrete mucosa which prevent cells entering body


What is the role of the epithelial barrier if there is a breach?

Components of the immune system co-operate to form a co-ordinated response:

- To protect us from infectious agents at the point of arrival

- Act as a surveillance system to monitor tissue integrity - look for damage, whether cells are dangerous (can be non-self, or self- eg cancerous) and whether they are non-self

Recognise and eliminate foreign organisms that penetrate host defences

Discriminate between self vs. non-self


What are the differences between the INNATE and the ADAPTIVE immune system?

- Broad-acting and non-specific
- Less efficient - lots of components targeting different attacks.
- Pattern recognition receptors (PRRs) recognise pathogen associated
molecular patterns (PAMPs) - i.e. features of pathogens, but are
active across lots of systems.
- Humoral component = the complement pathway, readily active and
ready to go, non-specific.
- Immediate response (0-4 hours) - preformed by mediators
- Early-induced response (4-96 hours)
- Germline-encoded - don't mutate, constant from one infection to next

- Highly specific to the pathogen
- Mediated by LYMPHOCYTES
- Driven by antigen - very specific to the pathogen
- Humoral components are the antibodies
- Late response (>96 hours), because it is specific it is responsible for
generating memory
- Individually unique via controlled somatic mutations, particularly in B


What are the cellular components of the adaptive and the innate response?

- B cells -> antibodies
- T cells -> CD4+ T helper cells and CD8+ T killer cells

- dendritic cells
- mast cells
- macrophages
- natural killer cells
- complement proteins
- granulocytes: neutrophil, eosinophil, basophil

Natural killer cells
T cells


Where do immune cells come from?

All immune cells come from haemopoeitic progenitor cell in bone marrow.

| |
Common lymphoid progenitor Common myeloid progenitor
| | | | | |
Pre NK | Pre T Pre B Granulocyte/ Megakaryocyte
| | | | monocyte |
NK | T B progenitor |
| | | _/\_
| plasma cell |
| _________________________|___________________________
| | | | | |
Pro-dendritic Neutrophil basophil/mast Eosinophil Monocyte
| pro cell pro pro pro
| | | | | |
| | basophil mast | mono
| | pro cell pro | |
| | | | | |
Dendritic neutro baso mast cell eosinophil macrophage


Which cell lines belongs to which immune response pathway?

NK cells produced in the lymphoid linage are INNATE
T and B cells in the lymphoid linage are ADAPTIVE
The whole amyloid linage is INNATE


What are the features of neutrophils?

- Multi-lobed nucleus and granular cytoplasm
- 40-95% of total WBCs; approximately 1.6 – 7.5 xE9/L
- 12-17μM
- Very short lived - circulate in blood (~10 hours) then migrate into
tissues, react then die by apoptosis.
- Accumulate in sites of tissue injury and bacterial infection via
chemotaxis (when a tissue is injured it releases chemokines)
- Major role as phagocytes
- When enveloped, produce reactive oxygen and nitrogen species in
process called respiratory burst
- Have a role in cytokine production and produce antimicrobial peptides
to combat infection
- Express adhesion molecules and receptors involved in phagocytosis

A band cell is an immature neutrophil, in an infection bone marrow kicks out underdeveloped neutrophils - evidence the body is fighting an active infection.


What are the features of eosinophils?

- Bi-lobed nucleus and protein-containing granules
- 1-5% of blood leucocytes; approximately 0.1 – 0.5 x E9/L
- 12-17μM
- Weakly capable of phagocytosis
- Granules can kill larger pathogens, which very important when there are
multicellular pathogens in and around cells in tissue
- Release pro-inflammatory mediators (peroxidase, major basic
protein, cationic protein - really reactive proteins and enzymes to break
down a parasites surface)
- Activated by IgE cross-linkage of FcεRI - links to innate response
- Important in parasitic infection
- Inappropriate activation in allergic response - people with allergies
often have lots of these in locations where allergies affect, eg
bronchioles in respiratory allergies.


What are the features of basophils?

- Densely granulated
- 0.2% leukocytes
- (14-16μM)
- Similar functionally to mast cells, the blood version
- Express FcεRI, secrete Th2 cytokines
- Can't see nucleus in stain die to excess granules
- Fewer granules but larger, their release opens up blood vessels making
them leaky so that other cells can get in.
- Toxic degranulation releases histamine, heparin and leukotrienes
- Circulate in periphery, but can infiltrate tissues in inflammation
- Express cytokine and chemokine receptors
- IgE + antigen activation releases mediators


What are the features of mast cells?

- Round nucleus and large dense cytoplasmic granules
- Tissue-resident cells (skin, connective tissue, respiratory/ digestive/
genitourinary mucosal epithelium)
- Release of pre-formed mediators from cytoplasmic granules
- Toxic granule contents include: histamine, tryptase, peroxidase
and serotonin
- Risk of severe allergic reactions, particularly analphylaxis - will
always ccheck for mast cell tryptase release
- Allergic response; IgE bound to FcεRI at rest, then cross-linked by
- Mastocytosis – skin lesions, nausea/ vomiting/ diarrhoea/ flushing/

Resident in tissues ready to be activated, compared to basophils which circulate in blood)


What are the features of monocytes?

- Circulate in blood; approximately 0.1 – 1.0 x E9/L
- Large (10-18μM)
- Horseshoe shaped nucleus
- Recruited to tissues and differentiate into tissue-specific
macrophages (~8 hours)
- Macrophage colony-stimulating factor
- Part of the Mononuclear Phagocyte System
- Clear pathogens and resolve inflammation
- Contain lysosomes (small name range bound vesicles in
cytoplasm, containing active enzymes that break down
pathogens); contents include peroxidases and hydrolases
- Activated by LPS (CD14) and IgG (FcγRI/II)
- Express MHC Class II
- Some migrate to lymph nodes


What are the features of macrophages?

- Derived from monocytes or embryonic cells during development,
always have a steady supply in tissue
- Resident throughout the body’s tissues, first responder if a pathogen
gets in through skin then activates rest of innnate response
- Activated by IFNγ and GM-CSF
- Main function is phagocytosis
- Activated via recognition of microbial molecules, T helper-secreted
cytokines, inflammatory mediators, complement proteins
- Secrete cytokines: TNF, IL-6, IL-8, IL-12
- Antigen presentation via MHC Class II – activate T-lymphocytes
- Role in tissue repair (muscle, wound healing)
- Kuppfer / Langerhans / Microglial cells


What are the features of dendritic cells?

- Potent antigen-presenting cell - function isn't to kill bacteria but to
express it to allow adaptive response to form the correct response.
- Constitutively expresses MHC Class II
- Different types can derive from either myeloid or lymphoid
- Capture antigen by phagocytosis and pinocytosis
- Act as sentinels continuously sampling the local tissue
- Recognise danger through expression of various receptors
(e.g. Toll-like)
- Activated by microbial products and inflammatory cytokines

Follicular DCs found in secondary lymphoid organs (diff to dendritic cells), actually just hold antigens on their surface in the dentrites, helping it to present it to adaptive immune response


What are the features of natural killer cells?

- Classic lymphoid cell morphology but lack the expression of
cell-surface molecules (lineage-negative - most other cells have
a protein on their surface allowing you to tell them apart, these are
negative on every test which allows you to distinguish anyway)
- ILC1 are cytotoxic – best characterised are natural killer cells (100 –
600 cells/μl)
- Activated by IFNα, IFNβ, TNF
- Inhibitory molecules; NKG2 and CD94 (recognise MHC class I, if it is
present these cells wont mount a response as it thinks it is a host cell)
- Perform antibody-dependent cell cytotoxicity via FcγRIII
- Cytolytic action through granzyme (enzymes which break down
proteins) and perforin release (puts pores in cells that prevents a cell
controlling what enters)


What are the features of cytotoxic T killer lymphocytes?

- Express CD3 (T-cell) and CD8 on cell surface
- Effector cells circulating in peripheral blood and lymphatic
systems but primarily reside in lymphoid organs until initial activation
- 200 – 900 cells/μl
- Respond to antigens presented on MHC Class I using antigen-specific
T-cell receptor
- Activated by presence of fragment of foreign peptide in MHC Class I
and co-stimulation by dendritic cell
- Effector cells migrate to site of infection
- Kill infected host cells through release of perforin and granzymes


What are the features of helper T lymphocytes?

- Express CD3 (T-cell) and CD4 (as opposed to CD8) on cell surface
- 400 – 2100 cells/μl
- Interact with antigen presented on MHC Class II (key difference
between CD4 and CD8 T cells) using antigen-specific T-cell
- Activated by presence of fragment of foreign peptide in MHC Class II
and co-stimulation by dendritic cell
- Generally enhance other parts of the immune response


What are the features of B lymphocytes that develop into plasma cells?

- Express CD19 and CD20 on cell surface
- 100 – 500 cells/μl
- Develop and mature in the bone marrow
- Naïve B lymphocytes migrate to spleen and lymph nodes
- Activated by presence of antigen binding to B-cell receptor (surface
=> B cells are mature when they come out of the bone marrow
but are still naive until they meet cells that would allow them to
mount an adaptive response.
- Can present antigen to T-lymphocytes via MHC Class II -
activate T lyphocytes

- Adapt to generate high-affinity antibody
- Differentiate into plasma cells which are responsible for high level
antibody secretion; long-lived, PCs return to bone marrow


Where are lymphocytes produced?

Primary lymphoid organs are responsible for lymphocyte production:

- Produced in bone marrow but then migrate to the thymus for
- 98% immature thymocytes die as undergo positive and negative
- Positive = must be able to bind to MHC
- Negative = must not bind to self antigens

- Produced and selected in the bone marrow

Secondary lymphoid organs are regions where lymphocytes come into first contact with foreign antigen, here they:
- Undergo clonal expansion
- Mature into effector cells

E.g. Lymph nodes; connected to lymphatic vessels
Spleen; connected to blood vessels


What are the humoral mediators: antibodies and immunoglobulins?

- Soluble glycoproteins that occur mainly in plasma, recognise and
bind foreign antigens specifically
- Form immune complexes with pathogen to limit spread and activate
host responses, coated in antibodies to produce these complexes
- Secreted by plasma cells
- There are 5 classes: IgM, IgG, IgA, IgE and IgD
- Antigen-binding site is located in the hypervariable region
- Constant regions are able to bind to Fc receptors on: mononuclear cells,
neutrophils, NK cells, mast cells.
- Constant region binds to and activate complement


What are the humoral mediators: complement?

- Key component of innate immune system AND enhance
adaptive immune responses
- Over 50 soluble plasma proteins and membrane-bound proteins
- Active enzymes are formed by cleavage
- Opsonise microorganisms to enhance (complement) antibody-
mediated responses
- Opsonisation also attracts and activation of phagocytes for microbial
- Performs direct microbial killing by cell lysis, clearance of immune
complexes and apoptotic cells and triggers and amplifies inflammatory


What are the humoral mediators: cytokines?

- Small soluble proteins that act as intercellular messengers to enable
communication between immune cells
- Controls amplification and duration of a targeted immune
- Biologically active at low concentrations
- Act transiently and locally; bind to receptors on target cell
- Multiple effects on target cells; often redundant and tightly-controlled

Producers: Monocytes, Macrophages, Th1, DCs, MCs, NKs, B cells.
Affects: Macrophage activation, induces E-selectin on endothelium,

Producers: Th1
Affects: T- and B-lymphocyte proliferation, NK cytotoxicity