IMMUNOLOGY

overview

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

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

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

nterfollicular 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

MHC
Major histocompatibility (MHC)
complex

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)

class II MHC genes

class II MHC

class III MHC genes

class I MHC genes

class I MHC

MHC
Class I MHC
molecules

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.)

MHC
Class II MHC
molecules

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.)

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

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

Dendritic cell (orange) talking to T lymphocytes

Monocyte

Macrophage

Macrophage reaching for

Macrophage gorging on

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)

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

Responses

Lymphocytes
Antigen-presenting cells
Effector cells
The innate immune response
Capturing and displaying antigens
Cell-mediated immunity

Humoral Immunity

Cell-Mediated Immunity

Humoral Immunity

Cell-Mediated Immunity

Cell-mediated immunity

How does the process work?

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

Cell-mediated immunity
What are cytokines?
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

Cell-mediated immunity
What kinds of effector T cells are
there?
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.

Cell-Mediated Immunity

Immunology Overview

Definitions

Cells

Responses

Lymphocytes
Antigen-presenting cells
Effector cells

The innate immune response

Capturing and displaying antigens
Cell-mediated immunity
Humoral immunity

Humoral Immunity

Cell-Mediated Immunity

Humoral immunity
How does the process work?

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

Humoral immunity
What is an antibody again?

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

Humoral immunity
What do antibodies do?
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 is complement?
Just give me the bottom line.

Humoral immunity
Its a bunch of proteins that poke holes in
cells.

Humoral immunity

Okay, give me a little more

information.
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

Responses

Lymphocytes
Antigen-presenting cells
Effector cells
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