Lecture 2: innate immunity

Question 1

• The innate immune system recognizes a limited number of antigenic determinants
• Innate immune cells recognize pathogen associated molecular patterns (PAMPS)

Answer 1

Specificity of innate immune system

Question 2

• ds RNA in replicating viruses
• unmethylated CpG DNA sequences found in bacteria
• N-formyl-met (initiation of bacterial protein synthesis)
• LPS (found in OM of gram (-) bcteria
• teichoic acids in gram (+) bacteria
• mannose rich oligosaccharides

Answer 2

Key PAMPS

Question 3

• neutrophils (PMNs)
• macrohages
• dendritic cells
• NK cells

Answer 3

Cells of the innate immune system

Question 4

• Precursors are band cells
• they’re small
• short lived
• they’re the major cells of acute inflammation
• they’re first on the scene and die early
• they phagocytize very well
• they’re the predominant white blood cells
• they have primary, azurophillic, (love azure stain) granules which contain enzymes such as myeloperoxidase, and cationic proteins
• they also have secondary granules which contain lactoferrin, which binds iron so bacteria can’t get it
• they’re first line of defense against pyogenic bacteria, such as strep pyogenes

Answer 4

neutrophils (PMNs)

Question 5

• they’re large long lived, and have a bilobed nucleus
• they have different names if found in different tissues: Osteoclasts in bone, migcroglia in brain, kupfer cells in liver, and splenic _____ in spleen
• they’re a type of mononuclear phagocyte
• they live in tissues
• they arrive later than neutrophils at site of infection
• They’re activated by IFN-gamma released by Th1 cells
• once activated they become more potent

Answer 5

macrophages

Question 6

• IL-6- systemic effects: it induces fever and acute-phase protein production by hepatocytes
• TNF-alpha- local effects: it activates vascular endothelium and increases vascular permeability, which leads to increased entry of complement and cells to tissues and increased fluid drainage to lymph nodes. systemic effects: it induces fever, mobilization of metabolites, and shock
• IL-1ß-local effects: it activates vascular endothelium , it activates lymphocytes, it causes local tissue destruction, and increases access of effector cells. systemic effects: it induces fever and IL-6 production
• IL-8 (CXCL8)- it’s a chemokine. local effects: it’s a chemotactic factor that recruits neutrophils and basophils to site of infection.
• IL-12-local effects: it activates NK cells

Answer 6

Cytokines secreted by macrophages

Question 7

1. F-Met-Leu-Phe- a by-product of bacterial protein synthesis
2. C5a-complement component generated by activation of the classical pathway and the alternatve pathways of complement
3. Leukotriene B4- arachadonic acid metabolite
4. Chemokines-e.g. IL-8 and others produced by activated macrophages

Answer 7

Key chemotactic factors for phagocytosis

Question 8

1. acidification- lower PH inside phagosome/phagolysosome to Ph=3.5-4.0
2. toxic nitric oxides-NO, NO2, and HNO2
3. antimicrobial peptides- defensins and cationic proteins
4. enzymes- lysozyme-dissolves cell walls of some gram (+) bacteria, acid hydrolases- further digest bacteria
5. competitors-lactoferrin- binds Fe and vit B12 binding protein-binds B12
6. Cellular proteins- TNF-alpha produced by macrophages

Answer 8

Non-oxidative mechanisms of killing after phagocytosis

Question 9

1. NADPH oxidase converts O2 molecules to superoxide anion, O2-.
2. superoxide dismutase (SOD) converts O2- to H2O2.
3. peroxidase and iron convert hydrogen peroxide to hypochlorite ions and hydroxyl radicals.

Answer 9

Oxidative mechanisms of killing: the use of reactive oxygen intermediates (ROIs) to kill bacteria

Question 10

• It’s an XL disease (found in male infants)
• It’s due to defect in NADPH oxidase
• Patients are unable to generate respiratory burst
• They often suffer from frequent lung infections

Answer 10

Chronic granulomatous disease

Question 11

• they’re large granular lymphocytes
• they’re not antigen specific
• they recognize absence of MHC I (HLA-A, B, and C) on target cell via KIR
• they use perforin and granzymes to induce apoptosis of virally infected cells and tumor cells
• they produce cytokines such as IFN-gamma
• they can also be activated by IL-2 and IFN-gamma
• Some of them express CD8 and others don’t
• IL-2, IL-12, IFN-ß, and IFN-alpha enhance their activity
• they’re induced to kill when exposed to a nonspecific activation signal on a target cell and/or to an absence of MHCI (HLA-A,B, and C) on target cell surface

Answer 11

NK cells

Question 12

• they’re cells of the innate immune system
• they’re called basophils when found int he blood, and ______ when found in tissues
• they’re involved in inflammation
• they release histamine, the predominant pre-formed molecule of _______.

Answer 12

mast cells

Question 13

• they’re cells of the innate immune system
• they’re important in parasitic disease and allergies
• People with allergies have lots of _____
• people with tape worms have lots of ____

Answer 13

Eosinophils