Introduction to Immune System System Part 1 (Lecture 4)

Question 1

What are Neutophils?

Answer 1

• Comprise the majority of white blood
cells (60–70%).

• Professional phagocytes, engulfment
of bacteria.

• 100X reserve in bone marrow;
released at a rate of 7 million per min.

• Short-lived cells (2–3 days).
• The main function is the phagocytosis.

• Produce inflammatory mediators -
cytokines, prostaglandins, and
leukotrienes.

• Named granulocytes because of
prominent cytoplasmic granules
which contain:

! peroxidase
! lysozyme
! degradative enzymes
! defensins

Question 2

What are Eosinophils?

Answer 2

• Comprise 2–5% of white blood cells.

• Contain eosinophilic (red-pink)
granules with:
> Basic proteins
> Peroxidases
> Antimicrobial substances

• Important function in allergic
reaction and defense against
parasitic infections.

• Eosinophils secrete granules for
extracellular digestion of infectious
pathogens.

• Produce inflammatory mediators -
cytokines, prostaglandins and
leukotrienes.

Question 3

What are Mast Cells and Basophils?

Answer 3

• Mast cells are tissue-fixed.

• *• Basophils are circulating in the
  blood. **

• Contribute to the elimination
of parasites.

• Play key pathogenic role in
allergic and anaphylactic
reactions.

• Contain basophilic (purpleblack)
granules with:
– histamine, serotonin, heparin
– cytokines and chemokines

Question 4

What are Monocytes?

Answer 4

Monocytes Are Blood Precursor Cells of
Tissue Macrophages

• Mononuclear cells present in
the blood (3-8%).

• Monocytes are important
phagocytes.

• Monocytes differentiate into
macrophages when

transmigrating from the blood
into the tissue.

• The main functions of
macrophages is phagocytosis
and destruction of particulate
material.

Question 5

What is a Macrophage?

Answer 5

Macrophages (Mφ)
• Phagocytic cells.
• Antigen-presenting cells.

• Ubiquitous cells in the tissue -
serve various functions and
show various morphologies
depending on tissue:
– histocytes in connective
tissue
– Kupffer cells in the liver
– alveolar macrophages in
the lungs
– microglial cells in the CNS

Question 6

What are NK cells?

Answer 6

• Recognize and destroy a
variety of target cell types
without any prior stimulation or
immunization.

• Targets:
– virus infected cells
– cancer cells
– transplant cells

• Cytotoxic mechanism:
– secretion of perforin

• No specific Ag receptor
(recognition).

• Because of this broad cytotoxic
activity NK cells belong to innate
immunity.

Question 7

What is complement?

Answer 7

Innate immunity (Complement)

• The complement system consists of a
set of serum proteins which
normally exist as soluble inactive
precursors.
• Upon activation, each precursor is
cleaved into two or more fragments.
• Large fragments have enzymatic
properties and activate the
downstream components resulting in
formation of Membrane Attack
Complexes (MACs) – disrupt the
membranes of certain pathogens.

• Small fragments serve as:
– Opsonins – deposited on microbes and
enhance their uptake by phagocytes
bearing complement receptors.
– Chemotactic factors – attract
immune cells.
– Anaphylatoxins – cause
degranulation of mast cells/basophiles
and release vasoactive substances.

Question 8

What are the pathways for complement?

Answer 8

• Complement activation is
based on an enzymatic
amplifying cascade.

• Activation can be triggered
by one of three pathways:
– classic pathway is activated
by antigen–antibody (Ag-Ab)
complexes
– alternative pathway
activated by microbial-cell
walls
– lectin pathway by the
interaction of microbial
carbohydrates with
mannose-binding protein
in the plasma.

Question 9

What are acute-phase proteins?

Answer 9

• *• Several blood circulating proteins are involved in defense against
  infections. **

• These plasma proteins are induced rapidly by cytokines after
infection and called Acute-Phase Proteins.

Examples:
– Plasma mannose-binding lectin (MBL) is a protein that recognizes
microbial carbohydrates. MBL activates the complement cascade
through the lectin pathway.
– C-reactive protein (CRP) binds to phosphorylcholine on microbes and
coats the microbes for phagocytosis by macrophages.

Question 10

What are cytokines and chemokines?

Answer 10

• Cytokines are small proteins secreted by many cell types.
• Cytokines produced by immune cells mediate inflammation, immunity
and hematopoiesis.
• Can operate over a long range on distant cells (endocrine), over a short
range on neighboring cells (paracrine), or on cells which produce those
cytokines (autocrine).
• Can have multiple functions and their function can be dependent on the
cell type to which they bind.
• Cytokines of innate immunity are sub-divided into two classes:
– Pro-inflammatory cytokines (stimulate inflammation)
– Anti-inflammatory cytokines (inhibit inflammation)
• Chemokines are small protein chemoattractants important for trafficking
of immune cells.