Immune Response to Pathogens Flashcards
Give four components of the immediate defence
- Complement
- Antibodies
- Phagocytic cells
- Antimicrobial peptides
How fast does the immediate defence act?
0-4 hours
What pathway of complement opsonises pathogens for phagocytosis?
Alternative mainly
Also maybe lectin
When can the classical pathway be used?
If natural or specific antibody is present
Where is the membrane attack complex used?
Directly destroying Gram-negative bacteria
What genetic defects in complement predispose to immune complex disease?
C1q C1r C1s C2 C4
What genetic defects in complement predispose to recurrent pyogenic infections?
C3
Factor H
Factor I
What genetic defects in complement predispose to Neisseria infections?
C5 C6 C7 C8 Properdin Factor D
How do macrophages and neutrophils recognise pathogens?
Complement, scavenger and other receptors
What infection is associated with leukocyte adhesion deficiency (LAD)?
- Staphylococcus species
- Enteric gram-negative bacteria
- Fungal infections, esp. C. albicans
What is natural antibody?
IgM
Made without previous exposure to antigens
What produces natural antibody?
B-1 cells
What are defensins?
Major group of human antimicrobial peptides
What do defensins do?
Disrupt cell membranes
What are defensins effective against?
- Gram-negative and Gram-positive bacteria
- Fungi
- Parasites
- Enveloped viruses
What produces defensins?
Epithelial cells in skin, respiratory and urogenital tracts
Paneth cells in small intestine
Neutrophils
Where are β-defensins produced?
Urogenital tract
Where are α-defensins produced?
Paneth cells in small intestine
How fast does the induced innate response act?
4 hours to 4 days
What is the main component of the induced innate response?
Macrophages
What do macrophages do in the induced innate response?
Activated PRRs signal production of pro-inflammatory cytokines
What are the pro-inflammatory cytokines?
- IL-1
- IL-6
- IL-12
- TNF-α
What are the six functions of TNF-α?
- Induces adhesion molecule expression on vascular endothelium
- Increases vascular permeability
- Triggers platelet activation and blood clotting
- Stimulates dendritic cell activation and migration to lymph nodes
- Stimulates acute phase response
- Primes newly recruited neutrophils
What is the result of increased vascular permeability?
- Neutrophil migration
2. Inflammatory exudate
What pathogens do interferons deal with?
Viruses
What is the role of RIG-1-like receptors?
- Detect presence of viral nucleic acid in cytoplasm of infected cells
- Induce expression of type 1 interferons
What are the type 1 interferons?
IFNα and IFNβ
What is the effect of type 1 interferons?
- Induce antiviral state in surrounding cells by interfering with viral replication
- Activate natural killer cells
What is the role of IFNγ?
Macrophage activation
What proportion of lymphocytes do NK cells make?
5-25%
What is the role of NK cells?
- Kill infected host cells
2. Secrete cytokines that act on macrophages to upregulate phagocytosis and inflammatory cytokine production
Which cytokines recruit NK cells to sites of infection?
- IFNα and IFNβ
2. IL-12
What is the relationship between macrophages and NK cells?
Activate each other
What is the effect of NK cells on dendritic cells?
Signals need for initiation of adaptive immunity
How fast is the adaptive response?
4 days onwards
What four things does the adaptive response require?
- Dendritic cell activation and migration to secondary lymphoid organs
- Activation of low frequency T cells
- Activation and proliferation of antigen-specific B cells by activated T cells
- B cell differentiation into plasma cells for antibody production, B cell isotype switching and affinity maturation
What do CTLs kill?
Cells harbouring intracellular viruses and parasites
MHC class I restricted
What is the role of TH1 cells?
Activate macrophages via IFNγ
What is the role of TH2 cells?
- Direct IgE production
- Help eosinophils, basophils, mast cells and B cells resist parasite infections
via IL-4
What is the role of TH17 cells?
Help neutrophils respond to extracellular bacterial and fungal infections
Via IL-17
When does specific antibody appear?
5 days post infection
What is the first antibody isotype to be produced?
Specific IgM
What does IgM do?
- Recruits complement
2. Compensates for low affinity with high avidity
What does IgE do?
Eosinophil recruitment
What does IgG do?
Neutralisation
What does IgG1 do?
Opsonisation
What does IgA do?
- Neutralisation
2. Epithelial transport
What are the principle innate mechanisms against extracellular bacteria?
- Complement activation
- Phagocytosis
- Acute inflammatory response
What is the principle adaptive mechanism against extracellular bacteria?
Specific antibody
What is the role of secretory IgA?
Block binding to epithelial cells
What three roles do the CD4+ helper T cells assist with?
- TH17 cells stimulating neutrophil recruitment
- TH1 cells activating macrophages
- Helper T cells required for thymus-dependent antibody production
What type of T cell response do helminths induce?
TH2
What does the TH2 response involve?
- IgE
- IgG1
- IgG4
- Eosinophils
- Expansion of basophils, mast cells and alternatively activated macrophages
What do natural killer cells do?
- Kill virally infected cells
2. Secrete inflammatory cytokines
What does the cell-mediated response to viruses mainly rely on?
- Cytotoxic T cells
2. Helper TH1 cells
How is protective immunity to viruses established?
Neutralising antibody produced following vaccination or natural infection
What do CD4-TH1 cells express to activate macrophages?
CD40L
How does Leishmania prevent MAC formation?
Uses a surface protease (gp63) to cleave C3b to iC3b
However this increases macrophage uptake as iC3b is an opsonin
What is the main innate response to protozoa?
Phagocytosis
