Inmune Response

What are the 4 steps of the immune response?

Identification, Designation, Recruitment, Elimination

What is the overall goal of the immune response?

Kill the pathogen and don't harm the host

Innate immune response timeframe

0–96 hours

Innate immune response cell types

Monocytes, neutrophils, basophils, eosinophils

Innate immune response characteristics

Rapid, short, non-specific (generic)

Acquired immune response timeframe

After 96 hours

Acquired immune response characteristics

Delayed, specific, memory

Acquired immune response cell types

B lymphocytes, T lymphocytes, NK cells

PAMP

Pathogen-associated molecular pattern (e.g. mannose, LPS, phosphatidylcholine, zymosan, flagellin)

PRR

Pattern recognition receptor (e.g. MBL, LBP, TLR4, CRP, TLR2, TLR5)

Innate "Designation" step = what?

Opsonization

What 3 things does opsonization activate?

B lymphocytes (antibody production), Complement system, Phagocytes

IL-8

Cytokine released by infected tissue that recruits phagocytes to the infection site

ICAM-1

Expressed by endothelial cells around infected tissue; binds LFA-1

LFA-1

Expressed by activated phagocytes; binds ICAM-1 to allow migration to infected tissue

5 steps of phagocytosis

Binding/absorption, phagosome formation, phagosome+lysosome→phagolysosome, digestion, release of microbial products

Pro-inflammatory cytokines

Cause inflammation

Anti-inflammatory cytokines

Stop inflammation

Chemokines

Recruit neutrophils and macrophages to infection site

Adhesion molecules

Allow neutrophils/macrophages to stick to vessel walls and migrate to infection site

Local release of TNFα does what?

Recruits phagocytes/lymphocytes, increases platelet adhesion, promotes phagocytosis, causes local vessel occlusion, drains plasma/cells to lymph node

What causes septic shock (sepsis)?

Activated macrophages in liver/spleen release TNFα into the bloodstream systemically

Effects of systemic TNFα in sepsis

Systemic edema, decreased blood volume, vessel collapse, disseminated intravascular coagulation (DIC), organ failure, death

4 treatments for sepsis

Antibiotics/antifungals, IV fluids, vasopressors, inotropic therapy

Two branches of acquired immunity

Humoral (B lymphocytes) and Cell-mediated (T lymphocytes)

BCR

B-cell receptor; a membrane-bound antibody that identifies antigen

Humoral immune response — Identification/Designation

B cell binds antigen via BCR and differentiates into an antibody-secreting plasma cell

Clonal selection → expansion → differentiation

Antigen selects matching B cell clone → clone expands → differentiates into plasma cells (antibody-secreting) and memory B cells

Antibody Fab fragment function

Recognizes a specific antigen by its 3D structure (binds antigen)

Antibody Fc fragment function

Distinguishes antibody isotype, binds Fc receptors on phagocytes (opsonization), activates complement

IgM

First antibody produced upon antigen exposure; pentamer; on B cell surface; no exposed Fc (can't bind phagocytes but can activate complement)

IgG

Produced after class-switching from IgM; only antibody that crosses the placenta; memory B cells make it immediately on 2nd exposure

IgA

Found in tears, saliva, mucosal secretions, and breastmilk; a dimer

IgD

Found on B lymphocyte surface; function unknown; possible role in autoimmune disease

IgE

Binds Fc receptors on mast cells; triggers histamine release; eliminates parasites; drives allergies

Primary antibody response

Slow and small (first exposure)

Secondary antibody response

Immediate and strong — memory B cells make IgG right away

5 functions of antibodies

Opsonization, virus neutralization, toxin neutralization, complement activation, ADCC

ADCC

Antibody dependent cell cytotoxicity — neutrophils, eosinophils, macrophages, or NK cells lyse antibody-coated cells

Complement system

~35 blood plasma proteins that opsonize/lyse pathogens and act as chemotaxis factors

Classical complement pathway trigger

C1 binding to the Fc portion of antibodies

Antigen (cell-mediated context)

A molecule the immune system identifies as foreign (non-self)

APC

Antigen presenting cell — presents antigen to B and T lymphocytes

Professional APCs

Macrophages, dendritic cells, B lymphocytes — present exogenous (extracellular) antigen via MHC Class II

Atypical APCs

Almost any infected cell — present endogenous (intracellular) antigen via MHC Class I

MHC Class I presents to

CD8 T cells (cytotoxic)

MHC Class II presents to

CD4 T cells (helper)

Co-stimulatory signal for T cell activation

B7 (CD80/CD86) on APC binds CD28 on T cell

Th1 cells

Induced by IL-12; secrete IFN-γ, TNF-α; activate macrophages, IgG-producing B cells, cytotoxic T cells; fight intracellular bacteria/viruses

Th2 cells

Induced by IL-4; secrete IL-4, IL-5, IL-13; activate mast cells/eosinophils, IgE-producing B cells; fight extracellular parasites

Th17 cells

Induced by TGF-β + IL-6; secrete IL-17A, IL-17F, IL-22; recruit neutrophils/macrophages; linked to autoimmune disease

Treg cells

Induced by TGF-β; secrete TGF-β, IL-10; suppress immune responses (peripheral tolerance)

2 ways CTLs kill target cells

Perforin (forms pores → apoptosis); FasL binds Fas receptor → apoptosis

How does HIV evade the immune system?

Tat protein inhibits production of MHC Class I

How does Herpesvirus evade the immune system?

Prevents viral peptides from binding to MHC Class I

Tuberculoid leprosy immune profile

Th1-dominant: IgG, macrophages, CTLs — controls intracellular bacteria, low infectivity

Lepromatous leprosy immune profile

Th2-dominant: IgE, mast cells, eosinophils — fails to control intracellular bacteria, disseminated infection

How do vaccines work?

Antigen activates dendritic cells/APCs → present antigen to naive T cells → T cell help activates B cells → antibody-secreting plasma cells + memory T/B cells form