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Ch8 Immune System

Overview

  • The immune system is a distributed set of cells in blood, lymph fluid, tissues, and organs.
  • It can distinguish self vs non-self.

  • Core functions:

  • protect against infections

  • isolate and remove foreign substances
  • remove cancer cells

Leukocytes (WBC)

  • Leukocytes = white blood cells (WBC)
  • immune responses rely heavily on cell–cell interactions and communication

Innate Immune Response

  • defends without distinguishing identities (no antigen specificity)
  • distinguishes self vs non-self primarily via pattern recognition

Self vs non-self recognition

  • Pattern Recognition Receptors (PRRs) recognize conserved pathogen patterns.
  • own cells express proteins that inactivate complement system (e.g., against C3b via ComplementReceptor1, etc.)

  • NK cells use a combination of:

  • activating receptors (self protein)

  • inhibitory receptors (non-self or stress protein)
  • these inputs occur in a specific balance

Major components of innate immunity

  1. Physical barriers

  2. skins, hair, mucus, stomach acid, antimicrobial chemicals

  3. Phagocytes

  4. engulf pathogens and cellular debris (phagocytosis) and merge with lysosomes

  5. includes:

    • neutrophils (chemotaxis)
    • macrophages (PRRs and complement system)
    • Natural killer (NK) cells

  6. recognition and destruction of cancer cells / virally infected cells

  7. Complement system

  8. circulating proteins in plasma that assist destruction of pathogens

  9. Inflammation

  10. local response to infection and injury that destroys potential pathogens

Example: response to a splinter

  1. cells (including epithelial and leukocytes) sense tissue damage and release signal molecules

  2. increases capillary permeability and dilates local arterioles

  3. causes edema (swelling)

  4. neutrophils (and other phagocytes) move out of blood to inflamed area

  5. multistage movement

  6. “chemotaxis” = directed migration of a cell in response to a chemical signal

  7. killing of pathogens via:

  8. engulfment by phagocytes

  9. complement system

Complement system effect (example)

  • C3b interacts with pathogen membrane and marks it for destruction via:

  • phagocytosis, or

  • activation of MAC

Adaptive Immunity

  • depends on recognizing specific pathogens

  • key cell type: lymphocytes

  • from bone marrow

  • found in lymphatic system and blood

Main lymphocyte types

  • B cells (plasma cells, memory B cells)
  • helper T cells
  • cytotoxic T cells

Antigens

  • any kind of marker the immune system can recognize

  • examples:

  • proteins or sugars on the outside of viruses

  • immune system reads antigens with specificity

  • antigens can exist on:

  • viruses, bacteria, allergens, parasites

  • proteins, tumor cells, normal cells

B Cells

  • each B cell expresses one antigen receptor
  • the receptor is an immunoglobulin (multi-subunit protein)

When antigen binds:

  • B cell undergoes division (clonal expansion) → gives rise to:

  • antibody-secreting plasma cells

  • memory B cells

Antibody Fc function :

  • the stem (Fc) portion interacts with receptors on phagocytes:

  • stimulates phagocytosis

  • can also activate complement system

Helper T Cells

  • bind antigen complexed with MHC Class II molecules made by some cells (including macrophages and B cells)
  • requires co-stimuli to fully activate

  • secretes signals that:

  • further activate itself

  • paracrine effects to B cells, cytotoxic T cells, and NK cells

Cytotoxic T Cells

  • activated with MHC Class I (expressed by all cells)
  • require signal from helper T cells for activation

Mechanism :

  • cytotoxic T cells are activated by antigen complexed with MHC Class I

  • target cancer and virally infected cells

  • leads to apoptosis

Note :

  • “except red blood cell, present virus to the outside”

After an infection

  • most activated lymphocytes undergo apoptosis
  • antibodies can last for days–months
  • memory B cells remain
  • some helper T and cytotoxic T cells remain as memory cells

Primary vs secondary response

  • first antigen exposure: small amount of specific antibody, about 7–10 days after infection
  • second exposure: significantly more specific antibody, about 2–5 days after infection

Roles of adaptive immunity

  • encounter and antigen recognition
  • lymphocyte activation
  • coordinate attack
  • memory

Active vs Passive Immunity

  • Active: resistance due to exposure to pathogens or vaccinations
  • Passive: transfer of antibodies from gestation, breast feeding, therapy

Tolerance (self-nonself control)

Central tolerance

  • during early development
  • B and T cells with high affinity to self antigen undergo apoptosis
  • process: clonal deletion

Peripheral tolerance

  • regulatory T cells modulate immune response to prevent attacking self

Example mechanism :

  • regulatory T cells recognize MHC class II and signal to autoreactive B-cell → apoptosis

Autoimmune disease

Immune system attacks self cells, e.g.:

  • multiple sclerosis (myelin in CNS)
  • type 1 diabetes mellitus (beta islet cells in the pancreas)

Causes

  1. failure of clonal deletion of lymphocytes
  2. problem with regulatory T cells
  3. exposure to pathogens with antigens similar to our own proteins → cross-reactivity

Innate vs Adaptive (comparison)

  • innate: rapid, no specificity, no memory
  • adaptive: slower, specificity, with immunological memory

Interaction between innate and adaptive immunity

  • antibodies can recruit complement (C1b) system and phagocytes
  • inflammation recruits lymphocytes
  • macrophages present MHC class II to helper T cells
  • helper T cells increase activity of natural killer cells