Cells of the Immune System and Antigen Recognition

Jennifer Nyland, PhDOffice: Bldg#1, Room B10

Phone: 733-1586Email: jnyland@uscmed.sc.edu

Teaching objectives

• To review the role of immune cells in protection from different types of pathogens

• To discuss the types of cells involved in immune responses

• To describe the nature of specificity in adaptive immune responses

• To understand the role of lymphocyte recirculation in immune responses

Overview of the immune system

• Purpose:– Protection from pathogens• Intracellular (viruses, some bacteria and parasites)• Extracellular (most bacteria, fungi, and parasites)

– Eliminate modified or altered “self”• Cancer or transformed cells

• Sites of action:– Extracellular– Intracellular

Overview- extracellular pathogens

• Ab are primary defense– Neutralization– Opsonization– Complement activation

Overview- intracellular pathogens

• Cell-mediated responses are primary defense– Ab are ineffective– Two scenarios:• Pathogen in cytosol

– Cytotoxic T cell (CD8)

• Pathogen in vesicles– Th1 (CD4) releases cytokines– Activates macrophages

Cells of the immune system

Development of the immune system

NK cell

Stem cell

Macrophage

Lymphoidprogenitor

Myeloidprogenitor

T cell

B cell

Plasma Cell

Granulocyte

Monocyte

Mast cell

Dendritic cell

Cells of the immune system

Granular Agranular (35% in circulation)

Basophil

Eosinophil

Plasma cell

Lymphocyte (T, B, NK)

Neutrophil Dendritic cell

Monocyte

Phagocytosis and Intracellular killing

Neutrophils and Macrophages

Phagocytes – neutrophils (PMNs)

• Characteristic nucleus, cytoplasm

• Granules• CD66 membrane

marker protein

Geimsa stainSource: www.dpd.cdc.gov

Neutrophil

Characteristics of neutrophil granules

Primary granules Secondary granules

Azurophilic; young neutrophils Specific for mature neutrophils

Contain:cationic proteins, lysozyme, defensins, elastase and

Contain:Lysozyme, NADPH oxidase components and

myeloperoxidase Lactoferrin and B12-binding protein

Phagocytes – macrophages

• Characteristic nucleus• lysosomes• CD14 membrane

marker proteinMacrophage

Source: Dr. Peter Darben, QueenslandUniversity of Technology, used with permission

Non-specific killer cells

NK cellsEosinophils

Natural killer (NK) cells

• Also known as large granular lymphocytes (LGL)

• Kill virus-infected or transformed cells

• Identified by the CD56+/CD16+/CD3-

• Activated by IL-2 and IFN-γ to become LAK cells

Eosinophils

• Characteristic bi-lobed nucleus

• Cytoplasmic granules, stain with acidic dyes (eosin)– Major basic protein

(MBP)– Potent toxin for

helminths• Kill parasitic worms

Source: Bristol Biomedical Image Archive,used with permission

Mast cells

• Characteristic cytoplasmic granules

• Responsible for burst release of preformed cytokines, chemokines, histamine

• Role in immunity against parasitesSource: Wikimedia

Cells of the immune system: innate

• Phagocytes– Monocytes/macrophages– PMNs/neutrophils

• NK cells• Basophils and mast cells• Eosinophils• Platelets

Cells of the immune system: APC

• Cells that link the innate and adaptive arms– Antigen presenting cells (APCs)• Heterogenous population with role in innate immunity

and activation of Th cells• Rich in MHC class II molecules (lec 11-12)

– Examples• Dendritic cells• Macrophages• B cells• Others (Mast cells)

Cells of adaptive immune response

T cells and B cells

Cells of the immune system: adaptive

• Lymphocytes– B cells• Plasma cells (Ab producing)

– T cells• Cytotoxic (CTL)• Helper (Th)

– Th1– Th2– Th17– T-reg

Major distinguishing markersMarker B cell CTL T-helper

Antigen R BCR (surface Ig) TCR TCR

CD3 -- + +

CD4 -- -- +

CD8 -- + --

CD19/ CD20 + -- --

CD40 + -- --

Specificity of adaptive immune response

• Resides with Ag R on T and B cells

• TCR and BCR – both specific for only ONE antigenic determinant

• TCR is monovalent• BCR is divalent

T cellTCR Ag

B cellBCR

Ag

Ag

Specificity of adaptive immune response

• Each B and T cell has receptor that is unique for a particular antigenic determinant on Ag

• Vast array of different AgR in both T and B cell populations

• How are the receptors generated?– Instructionist hypothesis

• Does not account for self vs non-self– Clonal selection hypothesis

• AgR pre-formed on B and T cells and Ag selects the clones with the correct receptor

Four principles of clonal selection Hθ

1. Each lymphocyte has a SINGLE type of AgR2. Interaction between foreign molecule and

AgR with high affinity leads to activation3. Differentiated effector cell derived from

activated lymphocyte with have the same AgR as parental lymphocyte (clones)

4. Lymphocytes bearing AgR for self molecules are deleted early in lymphoid development and are absent from repertoire

Specificity of adaptive immune response

• Clonal selection Hθ can explain many features of immune response– Specificity– Signal required for activation– Lag in adaptive immune response– Discrimination between self and non-self

Development of the immune system

NK cell

Stem cell

Macrophage

Lymphoidprogenitor

Myeloidprogenitor

T cell

B cell

Plasma Cell

Granulocyte

Monocyte

Mast cell

Dendritic cell

Bone Marrow ThymusTissues

2° Lymphoid

Lymphocyte recirculation

• Relatively few lymphocytes with a specific AgR– 1/10,000 to 1/100,000

• Chances for successful encounter enhanced by circulating lymphocytes– 1-2% recirculate every

hour

Lymphocyte recirculation• Lymphocytes

enter 2° lymphoid organs via high endothelial venules (HEVs)

• Ag is transported to lymph nodes via APC

• Upon activation, lymphocytes travel to tissues

T cell B cellMonocyteDC

APC

T cell

T cell B cell

B cell

B cellT cell

Bone marrow

Thymus

Tissues

Virginlymphocytes

Spleen and lymph nodes

Primed lymphocytes

Lymphocyte recirculation• After activation,

new receptors (homing R ) are expressed to direct to tissues

• R on lymphocytes recognize CAMs on endothelial cells

• Chemokines at infection help attract activated lymphocytes

T cell B cellMonocyteDC

APC

T cell

T cell B cell

B cell

B cellT cell

Bone marrow

Thymus

Tissues

Virginlymphocytes

Spleen and lymph nodes

Primed lymphocytes