Cells of the immune system

Hematopoisis

the formation and development of both red blood cells (erythrocytes) and white blood cells (leukocytes)

leukocytes

White blood cells (most have high turnover rates)

erythrocytes and how are they made

red blood cells, erythropoiesis

where do leucoytes come from?

hematopoietic stem cells in the bone marrow

list the types of white blood cells and how are they made

• granulocytes (granulopoiesis)

• monocytes (monocytopoiesis)

• lymphocytes (lymphopoiesis)

how are platelets made

thrombopoiesis

characteristics of hematopoietic stem cells (HSC)

• self renewal with multilineage differentiation potential (pluripotent)

• rare - fewer than 1 in 50000 bone marrow cells

• maintained at steady state levels throughout adulthood

• high proliferative capacity - a very small amount can recreate the whole system in a transplant patient 

hematopoiesis in a fetus - where

yolk sac, liver, spleen

hematopoiesis in an infant - where

bone marrow in practically all bones

hematopoiesis in adults - where

bone marrow in vertebrae, ribs, sternum, skull, sacrum, pelvis, ends of femurs

hematopoetic growth factors characteristics

• glycoproteins at low concentrations 

• produced by stromal cells, monocytes, lymphocytes

• show synergistic or additive action with other growth factors

• active on stem cells / functional end cells 

Types of granulocytes

• neutrophil

• eosinophil

• basophil

• mast cell

neutrophil

• granulocyte

• 50-70% of leukocytes are neutrophils - most abundant

• usually first responders to infection and to inflammatory molecules

• segmented nucleus: 3-4 segments

• phagocytosis of bacteria, proteins to kill bacteria and remodel tissue, 

• dead neutrophils = pus

• oxygen dependent and oxygen independent method for killing ingested bacteria

eosinophil

• granulocyte

• rare: 1-3% of leukocytes 

• lots in small intestine 

• segmented nucleus: 2 lobes with spherical granules, pink

• anti parasitic function, allergy and asthma

• release cytokines for adaptive immune response, coordinate immune responses against multicellular parasites

• makes cells lyse

basophil

• granulocyte

• very rare: less than 1% in circulation

• segmented nucleus: 2 lobes, purple

• non-phagocytic, attach to parasitic surface

• kill extracellular parasites, multicellular worms

• release antibody/antigen complexes, then granule contents

mast cells

• granulocyte

• very rare: less than 1% of leukocytes

• made in bone marrow > immature precursors released in blood > enter tissue > differentiate at interface between body and environment eg skin, mucus

• 2 types: connective tissue mc and mucosal mc

• initiate inflammation, defend against parasite, fight allergic reactions

macrophage

• sentinel/sensor cells

• travel around body through tissues 

• in embryonic development, tissue resident macropaheges arise: named according to where they are found 

• in adults: circulation monocytes in blood > migrate into tissues > differentiate into macrophages 

• self renewing: maintain a population

name the tissue-resident macrophages

• Alveolar macrophage: lung

• histiocytes: connective tissues

• kupffer cells: liver

• mesangial cells: kidney

• microglial cells: brain

• osteoclasts: bones

macrophages are activated by:

• phagocytosis

• Inflammatory T_H1 cytokines

• inflammatory mediators

• bacterial components

what do macrophages do after getting activated?

• enhance phagocytic activity

• increased killing ability

• increased secretion of inflammatory mediators > invite and activate other immune cells

• increased migration

• increased ability to activate t cells

dendritic cells (dc)

• subtypes and subsets from different lineages: myeloid and lymphoid 

• most potent in antigen presenting cells

• take up potential antigens by phagocytosis, pinocytosis, receptor mediated endocytosis

• sit in tissues > capture antigens from invading pathogens > load them into MHC class I and II molecules > migrate to lymphodes and hand over the antigens to the t cells to activate them

• produce cytokines to polarize immune responses

Lymphocytes

• 20-40% of leukocytes

• subsets: B cells, T cells, innate lymphoid cells (includes natural killer cells), Natural killer-T cells

B-cells

• 10-20% of lymphocytes

• develop in bone marrow

• Antibody producing factory

• B-cell receptors are and membrane bound immunoglobulins formed by the same gene that encodes antibodies

• BCRs 2 regions: constant and variable regions

• constant region is also called the fragment crystallizable region

• variable region contains the antigen binding site

• B-cell > antigen recognition and activation > differentiate into plasma B cells to make and release antibodies

T-cells

• develop in bone marrow > migrate to thymus > finish cooking in thymus

• T-cell receptor: membrane bound proteins composed of Ig like domains

• TCR 2 regions:

• Constant = membrane bound

• variable = has antigen binding site

• 2 subsets: CD4⁺ and CD8⁺ T cells (2:1 ratio in healthy blood)

• naive, activated, memory cells

CD4⁺ and CD8⁺ T cells

• effector cells

CD8⁺ Cytotoxic T cells (CTL

• kill virus infected cells and cancer cells 

• source of cytokines like interferon gamma 

CD4⁺ helper T cells (T_H1 and T_H2) 

• help to activate CD8⁺ T cells, B cells, macrophages, and other immune cells, also regulate immune responses 

• function by producing a range of different cytokines

Regulatory T cells

• Mostly CD4⁺ 

• control immune response, generally by regulating T cell activity

Innate lymphoid cells

• cells with lymphoid characteristics with no antigen specificity

• 10-15% of lymphocytes 

• develop in bone marrow from common lymphocyte progenitor > migrate to lymphoid tissues and peripheral organs 

Innate lymphocyte subgroups

Group 1 (ICL1)

• ILC1 and natural killer cells

• NK cells are present in tissues and in circulation, need IL-15 and Nfil3 & EOMES transcription factors

• ILC1 present mainly in tissue-resident cells and need IL-7 & Tbet transcription factors

Group 2 (ILC2) 

• participate in mucosal immunity and produce IL-5 and IL-13

Group 3 (ILC3)

• produce several cytokines which induce production of chemokines and antimicrobial peptides against extracellular bacteria and fungi 

Natural Killer cells (NK cells)

• major subset of ILC 

• develop in bone marrow

• large lymphocyte-like cells with granular cytoplasm

• mediate cytotoxic function

• possess memory-like abilities

• produce cytokines, perforin, and granzyme to kill certain  cancer cells and virus infected cells

NKT cells

• develop in bone marrow > mature in thymus

• similar to NK cells but express a functional T-cell receptor 

• kill virus-infected cells and cancer cells

• produce pro-inflammatory cytokines to direct to other immune cells