Immunology overview

Immunology overview

Dendritic cell

A hairy person (or someone who doesn’t mind being hairy)

Dendritic cell

• Hairy projections

• Eats bugs

• Presents antigens

Natural killer cell

An indiscriminate bully

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

Natural killer cell

• A brute

• Indiscriminate killer

• Part of innate immune system

Helper T cell

A person who is always helpful

Helper T cell

• Helps other cells do their jobs

• Recognizes MHC II

• Part of adaptive immunity

Cytotoxic T cell

A highly trained, expert killer

Cytotoxic T cell

• Deadly, accurate killer

• Recognizes MHC I

• Part of adaptive immune

system

B cell

An extremely productive person

B cell

• Turns into plasma cell

• Makes antibodies


system

Macrophage

Someone who likes to eat

Macrophage

• Eats bugs

• Presents antigen


system

Neutrophil

Someone filled with toxic chemicals

Neutrophil

• Eats stuff

• Releases toxic stuff


system

Infected cell

A sick person

Infected cell

• Virus laden

• Expresses MHC I

• Gets killed by cytotoxic T

cell

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); doesn’t 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


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 (don’t 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 (don’t 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


• 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


• 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


• 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


• 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


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

Cell-Mediated Immunity Humoral Immunity


Cell-mediated immunity

• Naïve 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?


• 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 γ

What are cytokines?


• 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?

Cell-Mediated Immunity

Immunology Overview

• Definitions


• Responses • The innate immune response • Capturing and displaying antigens • 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 (κ or λ)

• 2 heavy chains (α, γ, δ, ε, or μ)

• 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 can’t 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

• It’s 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



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 naïve cells

• vaccines depend on these guys

Summary of the Adaptive Immune Response

Immunology Overview

• Definitions



Innate immunity

1. Dendritic cell eats bugs

Innate immunity


• Displays antigen to naïve T cells (which MHC?)

Innate immunity



• T cells mature (put on costumes, and get ready to do their jobs)

Innate immunity




2. Neutrophil eats bugs; kills with toxic chemicals

Innate immunity




2. Neutrophil eats bugs; kills with toxic chemicals

3. NK cell kills bugs

Adaptive immunity: Cell-mediated

1. Helper T cell does stuff



• Tells macrophage to eat bugs




• Tells B cell to make antibodies





2. Cytotoxic T cell does stuff





2. Cytotoxic T cell does stuff

• Finds and kills infected cell (how?)

Adaptive immunity: Humoral

1. B cell makes antibodies, which coat bugs

• “Neutralizes” bugs

• Opsonizes bugs (yummy for who?)

Immunology overview

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