Extracellular immunity

What are the main types of unicellular protozoa

• Amoebae

• Flagellates

• Ciliates

• Apicomplexa

What are the main types of multicellular helminths

• Nematodes

• Trematodes

• Cestodes

What are common ectoparasites

• Ticks

• Fleas

• Lice

• Mites

Why are most parasites difficult for the immune system to eliminate

• They are extracellular

• Too large for phagocytosis

• Have thick coats that resist complement and T cell perforins

How can the immune system effectively target parasites

By attacking weak spots such as the parasites digestive tract

Which immune pathway mainly responds to parasite infections

Th2 driven immune responses

How do worms trigger immune responses in epithelial cells

• Worms damage epithelial cells causing release of alarmins

• Parasite molecules act on dendritic cells to promote a Th2 response

How do dendritic cells process helminth antigens

1. They take up helminth antigens

2. Process them for MHC class II presentation

3. Migrate to lymph nodes to activate CD4+ T cells

What type of immune response is generated at mucosal surfaces against worms

A Th2 driven type 2 response

What happens after antigen recognition by T cells in helminth infection

Clonal expansion of T cells and differentiation towards the Th2 lineage

How do dendritic cells promote Th2 responses

Signals received by dendritic cells in infected tissue instruct them to promote Th2 differentiation

What crucial cytokine is needed for Th2 induction that dendritic cells do not produce

IL-4

What are innate lymphoid cells and how do they differ from T and B cells

They do not express TCR and BCR and do not require specific antigen recognition for activation

How do ILCs support Th2 responses

They respond to alarmins by producing IL-13 and IL-4

How does ILC-derived IL-4 influence Th2 responses

It supports the differentiation of Th2 cells

What is the role of ILC-derived IL-13 in immune responses

It promotes the migration of dendritic cells to lymph nodse

What effect does Th2-derived IL-4 have on antibody class switching

It mediates class switching to IgE or IgG1

What is the role of IgE in parasite immunity

Triggers mast cell degranulation and eosinophil antibody-dependent cellular cytotoxicity

What is the role of IgG1 in parasite immunity

• Promotes immune cell degranulation

• Enhances phagocytosis

• ADCC

• Helps trap tissue migrating larvae via macrophages

How do goblet cells contribute to worm expulsion during a type 2 response

Goblet cell hyperplasia increases mucus production helping expel worms

What is the role of RELMβ in helminth infections

It reduces worm feeding ability on host  tissues lowering their fecundity

How do Th2 cytokines and mast cell proteases affect epithelial barriers during helminth infection

They increase fluid leakage across the epithelium

What effect does IL-13 have on intestinal smooth muscle

It drives muscle hypercontractility

How does IL-13 affect epithelial turnover

It stimulates increased epithelial turnover forming an epithelial escalator

What immune pathway do helminth infections promote

A Th2 response with strong IgG and IgE antibody producing an activation of eosinophils and mast cells

What drives the choice toward a Th2 response in helminth infection

IL-4

How do Th2 cells influence macrophages

They cause alternative activation which blocks Th1 actions

Why is a Th2 response effective against helminths

It targets large extracellular pathogens using IgE/IgE, eosinophils, mast cells and alternative macrophage activation

What cytokines drive classical M1 macrophage activation

IFNy which activates TNFa, IL-1b and iNOS

What cytokines drive alternative M2 macrophage activation

IL4/IL13 which activates IL-10, TGFb, Arginase, RELMa

What are the functions of M2 macrophages

• Promote ECM deposition

• Wound repair

• Worm encapsulation

• Down regulate inflammation

What are the early roles of mast cells in helminth infection

• Sentinel function

• Production of alarmin IL-33

• Initiation and amplification of the Th2 response

How do mast cells become activated later in the response

• They expand in response to IL-9

• Express Fc receptors for IgE

• Degranulate when IgE bound to their surface is cross linked by antigen

What do mast cells release during degranulation and what are the effects

• Histamine, proteases and cytokines

• Serine proteases can directly kill helminths and open tight junctions to allow fluid egress

What cytokine drives eosinophil accumulation during helminth infection

IL-5 drives eosinophilia in blood and tissues

What receptor do eosinophils express for IgE

The high affinity IgE receptor FcεRI

How do eosinophils kill helminths

1. IgE binds to the helminth surface

2. FcεRI on eosinophils binds IgE

3. Eosinophils degranulate

4. Toxic granules damage the helminth cuticle

How do eosinophils and mast cells recognise helminths

They react to antigen complexed IgE and release vasoactive anti-worm molecules

What is the role of mast cells in parasite immunity

They stimulate worm expulsion via increased mucus production

In ruminants what aids worm expulsion

Goblet cells and IgA

What is the main function of eosinophils in helminth infection

Killing worms through toxic granule release

What helminth components do T-cells target

Tegument, coat and secreted parasite proteins

How does helminth size help with immune evasion

Large size and thick extracellular coat reduce immune effectiveness

How do helminths mask their presence

• Absorbing host proteins

• Molecular mimicry

• Shedding surface antigens

How do helminths avoid immune detection through location

Anatomical seclusion

How do helminths interfere with immune activation

Interference with antigen presentation and induction of immunosuppression

What active strategies do helminths use to evade immunity

Migration and production of enzymes that degrade Ig or C5a

What drives the choice of a Th2 response

IL-4

What type of antibodies do Th2 cells promote

Neutralising IgGs

How do Th2 cells affect macrophages

They suppress macrophage activation

What pathogens are best targeted by a Th2 response

Extracellular pathogens

What are the key roles of antibody-mediated protection against extracellular bacteria

• Neutralise toxins

• Kill bacteria

• Opsonize bacteria

• Intracellular killing by macrophages

• Essential protection for neonates