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overview

IMMUNOLOGY

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Immunology Overview

Definitions

Cells Lymphocytes

Antigen-presenting cells Effector cells

Responses The innate immune response

Capturing and displaying antigens

Cell-mediated immunity

Humoral immunity

Immunologic memory

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Immunology Overview

Definitions

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Definitions

Immunity = protection against infections

Immune system = collection of cells and moleculesthat defend us against microbes

Immune deficiencies infections

Immune excesses autoimmune diseases

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Innate (Natural) Immunity

Always present (innate); doesnt change over time

First line of defense when bugs come

Major components: Epithelial barriers (skin, GI, respiratory) NK cells

Complement

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Adaptive (Acquired) Immunity

Second line of defense

More specific (adaptive) and powerful than innate

Major components: Lymphocytes Lymphocyte products

Two types of adaptive immunity: Humoral immunity (mediated by antibodies) Cellular immunity (mediated by T cells)

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Immunology Overview

Definitions

Cells Lymphocytes

Antigen-presenting cells

Effector cells

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White Blood Cell Development

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10/74White blood cells

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Immunology Overview

Definitions

Cells

Lymphocytes

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Lymphocytes

Present in lymphoid organs and in blood

Groups T-lymphocytes (grow up in thymus)

B-lymphocytes (grow up in bone marrow)

Each one has receptors for a specific antigen

Recognize millions of different antigens!

Diversity generated by:

rearrangement of antigen receptor genes

differentjoining of the gene segments

Gene rearrangement studies

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13/74Lymphocyte (could be B cell or T cell!)

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Lymphoid tissues

Lymphocytes grow up in primary organs, then

travel to secondary organs, searching for

antigens.

Primary organs

thymus

bone marrow

Secondary organs lymph nodes

spleen

mucosal and cutaneous lymphoid tissues

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Lymph node

Interfollicular area (brown)

Follicle

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T-Lymphocytes

Live in blood, bone marrow, lymphoid tissues

Two basic functions:

kill stuff

help other cells do their jobs

T-cell receptor (TCR) complex recognizes antigens binds antigen

sends signals to the T cell

Antigens must be:

displayed by other cells

AND bound to an MHC receptor

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The T-Cell Receptor

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The T-Cell

Receptor

Bound to

Antigen

Antigen-presenting cell

T cell

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T-Lymphocytes

Helper T cells

CD4+ (and CD8-)

help B cells make antibodies

help macrophages eat bugs

Cytotoxic T cells

CD8+ (and CD4-)

kill virus-infected cells and tumor cells

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Helper T cell Cytotoxic T cell

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Cytotoxic T cells surrounding tumor cell

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MHC

Collection of genes on chromosome 6

Three regions: class I, class II, class III

Highly polymorphic!

Gene products:

class I molecules class II molecules

class III molecules (and other stuff)

Major histocompatibility (MHC) complex

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class I MHC moleculeclass II MHC molecule

class II MHC genes class I MHC genesclass III MHC genes

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MHC

Encoded by three loci: HLA-A, HLA-B, HLA-C

Display antigens from within the cell(e.g., viral antigens) to CD8+ T cells.

Present on all nucleated cells! (Good idea.)

Class I MHC molecules

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MHC

Encoded by three loci: HLA-DP, HLA-DQ, HLA-DR

Display extracellular antigens (e.g., bacterialantigens the cell has eaten) to CD4+ T cells

Present mainly on antigen presenting cells, like

macrophages! (Makes sense.)

Class II MHC molecules

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B-Lymphocytes

Live in blood, bone marrow, lymphoid tissues

Basic function: make antibodies (immunoglobulins)

B-cell receptor complex recognizes antigens binds antigen

sends signals to T cells

Antigens can be free and circulating (dont have tobe bound to MHCs or displayed by other cells to berecognized!)

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The B-Cell Receptor

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The B-Cell Receptor Bound to Antigen

B cell

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Natural Killer Cells

Belong to innate immunity arm

No highly variable receptors like T and B cells

Main job: recognize and kill damaged or infected cells

Antigens can be free and circulating (dont have to be

bound to MHCs or displayed by other cells to berecognized!)

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Natural killer cell

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Natural killer cell (top) killing infected cell (bottom)

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Immunology Overview

Definitions

Cells

Lymphocytes

Antigen-presenting cells

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Antigen-presenting cells

Main job: catch antigens and display them to lymphocytes

Dendritic cells

Have fine cytoplasmic projections

Present all over body: skin, lymph nodes, organs

Capture bug antigens, display to B and T cells

Other APCs

Macrophages eat bugs and present antigens toT cells, which tell macrophages to kill bugs

B cells present antigens to helper T cells, which tell

B cells to make antibodies

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Dendritic cell surrounded by lymphocytes

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Dendritic cell (right) talking to lymphocyte (left)

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Dendritic cell (orange) talking to T lymphocytes (green)

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MacrophageMonocyte

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Macrophage reaching for bacterium

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Macrophage gorging on bacteria

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Immunology Overview

Definitions

Cells

Lymphocytes

Antigen-presenting cells

Effector cells

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Effector cells

These guys carry out the ultimate immune

system task: eliminate infection

Types of effector cells

NK cells

Plasma cells

T cells (both CD4+ and CD8+)

Macrophages

Other leukocytes (e.g., neutrophils)

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Neutrophil

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Immunology Overview

Definitions

Cells

Lymphocytes

Antigen-presenting cells Effector cells

Responses

The innate immune response

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The Innate Immune Response

Main bug barriers: skin, mucosa

If bugs make it through epithelium, they

encounter innate immune system

What happens in the innate immune system?

Phagocytes eat bugs, kill them

Cytokines are released

Complement is activated The adaptive immune system is activated

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Immunology Overview

Definitions

Cells

Lymphocytes

Antigen-presenting cells Effector cells

Responses

The innate immune response

Capturing and displaying antigens

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Capturing and displaying antigens

Dendritic cells in epithelium capture bug antigens,

transport them to lymph nodes

APCs in lymph nodes eat antigens, display them

(using their MHC receptors) to T cells

B cells in lymph nodes also recognize antigens

Antigens and molecules produced during innateimmune response trigger proliferation and

differentiation of B and T cells

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Immunology Overview

Definitions

Cells

Lymphocytes

Antigen-presenting cells Effector cells

Responses

The innate immune response

Capturing and displaying antigens Cell-mediated immunity

Cell-Mediated ImmunityHumoral Immunity

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Cell-Mediated ImmunityHumoral Immunity

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Cell-mediated immunity

Nave T cells are activated by antigen and

costimulators in lymph nodes

then they proliferate and differentiate into

effector cells that go find the antigen.

CD4+ T cells help macrophages eat bugs

CD8+ T cells kill infected cells directly

All these steps are dependent upon cytokines

How does the process work?

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Cell-mediated immunity

Polypeptides that do lots of different things:

help leukocytes grow and differentiate

activate T cells, B cells and macrophages help leukocytes communicate

recruit neutrophils

Made by lymphocytes and macrophages

Examples: TNF, the interleukins, interferon

What are cytokines?

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Cell-mediated immunity

CD4+ T cells differentiate into two kinds of effector cells:

TH1 cells(activate macrophages, cause B cells to secrete Ab)

TH2 cells(activate eosinophils, cause B cells to secrete IgE)

These guys go to the site of infection, and with the

help of macrophages and cytokines, do their thing.

CD8+ T cells differentiate intocytotoxic T cells These guys kill cells that have microbes in their cytoplasm.

They are like little assassins.

What kinds of effector T cells are there?

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Matt Damon and the asset

Cell Mediated Immunity

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Cell-Mediated Immunity

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Immunology Overview

Definitions

Cells

Lymphocytes

Antigen-presenting cells Effector cells

Responses

The innate immune response

Capturing and displaying antigens Cell-mediated immunity

Humoral immunity

Cell-Mediated ImmunityHumoral Immunity

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B cells get activated by exposure to antigens

(sometimes with the help of CD4+ T cells)

B cells differentiate into plasma cells (that make

antibodies)

The antibodies do nasty things to bugs

How does the process work?

Humoral immunity

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Y-shaped glycoprotein

2 light chains (or )

2 heavy chains (, , , , or )

Constant regions of heavy chain form the Fc fragment

binds to APCs

defines isotype (immunoglobulin class: IgA, IgE, etc.)

Variable regions of both chains form the Fab fragments

binds to antigen

defines idiotype

What is an antibody again?

Humoral immunity

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Bind toand neutralize bugs, so they cant

infect cells.

Coat (opsonize) bugs, making them yummy to

macrophages and neutrophils (which have

receptors for the Fc portion of IgG! How

handy!).

Activate complement.

What do antibodies do?

Humoral immunity

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What is complement?Just give me the bottom line.

Humoral immunity

Its a bunch of proteins that poke holes in cells.

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Complement, ridiculously oversimplified

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Complement, ridiculously oversimplified

Humoral Immunity

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y

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Immunology Overview

Definitions

Cells

Lymphocytes

Antigen-presenting cells Effector cells

Responses

The innate immune response

Capturing and displaying antigens

Cell-mediated immunity

Humoral immunity

Immunologic memory

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Immunologic memory

Most effector lymphocytes die after killing the bug.

A few memory cells live on for years. expanded pool of antigen-specific lymphocytes

respond faster, better than nave cells

vaccines depend on these guys

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Immunology Overview

Definitions

Cells

Lymphocytes

Antigen-presenting cells Effector cells

Responses

The innate immune response

Capturing and displaying antigens

Cell-mediated immunity

Humoral immunity

Immunologic memory