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Immunology Kristine Krafts, M.D. Overview
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01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Jun 21, 2020

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Page 1: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

ImmunologyKristine Krafts, M.D.Overview

Page 2: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Immunology Overview

DefinitionsCells• Lymphocytes • Antigen-presenting cellsResponses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity• Immunologic memory

Page 3: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Immunology Overview

Definitions

Page 4: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Definitions

• Immunity = protection against infections

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

• Immune deficiencies → infections

• Immune excesses → autoimmune diseases

Page 5: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

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)• Phagocytes • NK cells• Complement

Page 6: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Adaptive (Acquired) Immunity

• Second line of defense

• More specific (adaptive) and powerful than innate

• Major components:• Lymphocytes• Lymphocyte products (like antibodies)

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

Page 7: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response
Page 8: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Immunology Overview

DefinitionsCells• Lymphocytes

Page 9: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

White Blood Cell Development

Page 10: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

White blood cells

Page 11: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

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!

Page 12: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Lymphocyte (could be B cell or T cell!)

Page 13: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

• Lymphocytes grow up in primary organs, then travel to secondary organs, where they get exposed to antigens.

• Primary organs• Thymus• Bone marrow

• Secondary organs• Lymph nodes• Spleen• Mucosal and cutaneous lymphoid tissues

Lymphoid Tissues

Page 14: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

B cells are in follicles; T cells are in interfollicular areas

Lymph Node

Page 15: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

T Lymphocytes

• Two basic functions:• Kill stuff (cytotoxic T cells)• Help other cells do their jobs (helper T cells)

• 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 molecule (receptor)

Page 16: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Cytotoxic T cells surrounding tumor cell

Page 17: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

The T-Cell Receptor Bound to AntigenAntigen-presenting cell

T cell

Page 18: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Class I MHC moleculeClass II MHC molecule

class II MHC genes class I MHC genesclass III MHC genes

Major Histocompatibility Complex (MHC)

Page 19: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Class I and II MHC Molecules

Class I molecules

• Display antigens from within the cell

(e.g., viral antigens) to cytotoxic (CD8+) T cells.

• Present on all nucleated cells! (Good idea.)

Class II molecules

• Display extracellular antigens (e.g., bacterial

antigens the cell has eaten) to helper (CD4+) T cells.

• Present only on antigen-presenting cells, like

macrophages! (Makes sense.)

Page 20: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

B Lymphocytes

• Basic function: make antibodies

• B-cell receptor complex recognizes antigens• Binds antigen• Sends signals to B cells

• Antigens can be free and circulating (don’t have to be bound to MHC molecules or displayed by other cells to be recognized!)

Page 21: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Natural Killer (NK) Cells

• Belong to innate immunity arm

• Receptors are not highly variable (like T and B cell receptors are)

• Main job: recognize and kill damaged or infected cells

Page 22: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Natural killer cell

Page 23: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

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

Page 24: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Immunology Overview

DefinitionsCells• Lymphocytes • Antigen-presenting cells

Page 25: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Antigen-Presenting CellsDendritic cells• Present mostly in two places: under epithelia and in

germinal centers of lymph nodes• Capture bug, present antigens to B and T cells• Super important in activating the adaptive system

Macrophages• Present all over the body• Eat bugs and present antigens to T cells• Their role in activating the adaptive system is not as

pivotal though!

Page 26: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response
Page 27: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Dendritic cell surrounded by lymphocytes

Page 28: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Dendritic cell (right) talking to lymphocyte (left)

Page 29: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

MacrophageMonocyte

Page 30: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Macrophage reaching for bacterium

Page 31: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Macrophage gorging on bacteria

Page 32: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Immunology Overview

DefinitionsCells• Lymphocytes • Antigen-presenting cellsResponses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity• Immunologic memory

Page 33: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Immunology Overview

DefinitionsCells• Lymphocytes • Antigen-presenting cellsResponses• The innate immune response

Page 34: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

The Innate Immune Response

• If bugs make it through epithelium, they encounter cells of the innate immune system

• What happens in the innate immune system?• Phagocytes eat bugs• Complement is activated • NK cells find and kill infected cells • Dendritic cells migrate to lymph nodes to

activate the adaptive immune system

Page 35: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response
Page 36: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

What is complement?Just give me the bottom line.

It’s a bunch of proteins that poke holes in cells.

Page 37: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Okay, give me a little more information.

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

• Can be activated by bacterial components

• Activation proceeds in a cascade fashion

• End results:• Cell lysis• Chemotaxis (attraction of neutrophils)• Opsonization (coating of cells to make them

“yummy” to macrophages)

Page 38: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Complement, ridiculously oversimplified

Page 39: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Immunology OverviewDefinitionsCells• Lymphocytes • Antigen-presenting cells• Effector cellsResponses• The innate immune response• Capturing and displaying antigens

Page 40: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Capturing and Displaying Antigens

• Dendritic cells in epithelium capture bug antigens, transport them to lymph nodes

• Dendritic cells display antigens to B and T cells

• Antigens and cytokines trigger proliferation and differentiation of B and T cells

Page 41: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Immunology Overview

DefinitionsCells• Lymphocytes • Antigen-presenting cellsResponses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity

Page 42: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

The Main Players in Cell-Mediated Immunity

Helper (CD4+) T cells• These guys help macrophages eat bugs.• They also call in neutrophils.

Cytotoxic (CD8+) T cells• These guys kill infected cells.• They are like highly-trained assassins.

Page 43: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Matt Damon and the �asset�

Page 44: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Cell-Mediated Immunity

Page 45: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Immunology Overview

DefinitionsCells• Lymphocytes • Antigen-presenting cellsResponses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity

Page 46: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Humoral Immunity

Bacteria enter body

B cells make antibodies against

bacteria

Antibodies bind to bacteria

Phagocytes ingest bacteria

Page 47: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

What is an antibody?

• Y-shaped glycoprotein • 2 light chains (κ or λ)• 2 heavy chains (α, γ, δ, ε, or μ)

• Fab fragments• Upper part of Y (the arms)• Binds to antigen

• Fc fragment• Lower part of Y (the stem)• Binds to cells like macrophages, neutrophils.

Page 48: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response
Page 49: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response
Page 50: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

What happens when antibodies bind to bugs?

• Bugs are neutralized (they can’t infect cells).

• Antibody-coated bugs are �opsonized,” making them yummy to macrophages and neutrophils (which have receptors for the Fc portion of IgG! How handy!).

• Complement is activated (bad news for bugs).

Page 51: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Immunology Overview

DefinitionsCells• Lymphocytes • Antigen-presenting cellsResponses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity• Immunologic memory

Page 52: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Immunologic Memory

• After an infection is over, most immune cells die.

• A few memory cells remain and live on for years.• Expanded pool of antigen-specific lymphocytes• Respond faster, better than naïve lymphocytes• Vaccines depend on these guys

Page 53: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Summary of the Adaptive Immune Response

Page 54: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Immunology Overview

DefinitionsCells• Lymphocytes • Antigen-presenting cellsResponses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity• Immunologic memory

Page 55: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Summary of the Adaptive Immune Response

Page 56: 01 Immunology overview - WordPress.com · 2019/5/1  · Immunology Overview Definitions Cells • Lymphocytes • Antigen-presenting cells Responses • The innate immune response

Immunology Overview

DefinitionsCells• Lymphocytes • Antigen-presenting cellsResponses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity• Immunologic memory