overview

IMMUNOLOGY

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

Immunology Overview

Definitions

Definitions

Immunity = protection against infections

Immune system = collection of cells and molecules that defend us against microbes

Immune deficiencies infections

Immune excesses autoimmune diseases

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

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)

Immunology Overview

Definitions

Cells Lymphocytes Antigen-presenting cells Effector cells

White Blood Cell Development

White blood cells

Immunology Overview

Definitions

Cells Lymphocytes

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

different joining of the gene segments

Gene rearrangement studies

Lymphocyte (could be B cell or T cell!)

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

Lymph node

Interfollicular area (brown)

Follicle

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

The T-Cell Receptor

The T-Cell Receptor Bound to Antigen

Antigen-presenting cell

T cell

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

Helper T cell Cytotoxic T cell

Cytotoxic T cells surrounding tumor cell

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

class I MHC molecule class II MHC molecule

class II MHC genes class I MHC genes class III MHC genes

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

MHC

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

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

Present mainly on antigen presenting cells, like macrophages! (Makes sense.)

Class II MHC molecules

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 to be bound to MHCs or displayed by other cells to be recognized!)

The B-Cell Receptor

The B-Cell Receptor Bound to Antigen

B cell

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 be recognized!)

Natural killer cell

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

Immunology Overview

Definitions

Cells Lymphocytes

Antigen-presenting cells

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 to

T cells, which tell macrophages to kill bugs

B cells present antigens to helper T cells, which tell B cells to make antibodies

Dendritic cell surrounded by lymphocytes

Dendritic cell (right) talking to lymphocyte (left)

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

Macrophage Monocyte

Macrophage reaching for bacterium

Macrophage gorging on bacteria

Immunology Overview

Definitions

Cells Lymphocytes

Antigen-presenting cells

Effector cells

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)

Plasma cell

Neutrophil

Immunology Overview

Definitions

Cells Lymphocytes Antigen-presenting cells Effector cells

Responses The innate immune response

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

Immunology Overview

Definitions

Cells Lymphocytes Antigen-presenting cells Effector cells

Responses The innate immune response Capturing and displaying antigens

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 innate immune response trigger proliferation and differentiation of B and T cells

Immunology Overview

Definitions

Cells Lymphocytes Antigen-presenting cells Effector cells

Responses The innate immune response Capturing and displaying antigens Cell-mediated immunity

Cell-Mediated Immunity Humoral Immunity

Cell-Mediated Immunity Humoral Immunity

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?

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?

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 into cytotoxic 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?

Matt Damon and the asset

Cell-Mediated Immunity

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 Immunity Humoral Immunity

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

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

Bind to and 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

What is complement? Just give me the bottom line.

Humoral immunity

Its a bunch of proteins that poke holes in cells.

Okay, give me a little more information.

Humoral immunity

Consists of about 20 plasma proteins (C1, C2, etc.)

Can be activated in a few different ways by antigen-antibody complexes

by bacterial LPS

by bugs that have mannan on their surfaces

Activation proceeds in a cascade fashion

End results: cell lysis

chemotaxis

opsonization

Complement, ridiculously oversimplified

Humoral Immunity

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

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

Summary of the Adaptive Immune Response

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