Physiology 1, Fall 2008, LPC

Chapter 24 – Immune System

I – Overview

A. Functions:

  1. Protect body from disease-causing invaders & other foreign molecules
  2. Removes dead or damaged cells
  3. Tries to recognize & remove abnormal cells

B. Pathologies of immune system

  1. incorrect response (autoimmunity)
  2. overactive responses (allergies)
  3. lack of response – immunodeficiency diseases

II – Pathogens

  1. Bacteria

1. Cells, usually surrounded by cell wall. Some encapsulated
2. Can survive & reproduce outside host, if in required conditions
3. Susceptible to antibiotics

2. Viruses

1. DNA or RNA in a capsid of viral proteins. Some also have phospholipid/protein envelope
2. Must use the intracellular machinery of host to replicate
3. Some susceptible to antiviral drugs, none to antibiotics

III – Immune Response
            Takes over after physical & chemical barriers have failed
            Steps:

      1. detection & identification of foreign substance
      2. communication with other immune cells to rally an organized response
      3. recruitment of assistance & coordination of the response
      4. destruction or suppression of the invader

Vocabulary

Antibodies – proteins secreted by certain immune cells, bind antigens & make them more visible to the immune system
Cytokines – protein messengers released by one cell that affect the growth or activity of another cell
Innate immunity – present from birth, nonspecific, clears infection or contains it until acquired immune response activated
Nonspecific immune response – does not target a particular pathogen
Inflammation – red, warm, swollen area
Acquired immunity – directed at specific invaders. Is body’s specific immune response
See Table 24-2: chemotaxins, cytokines, opsonins, antibodies, complement, heparin, histamine, interferons, major histocompatibility complex (MHC), perforin, T-cell receptors

IV – Anatomy

Lymph nodes throughout body, especially in areas with a lot of exposure to the environment.
Lymph nodes have clusters of immune cells in a capsule that monitor blood and lymph fluid and remove foreign invaders
Spleen also traps & removes aging RBCs    

Cells

  1. Neutrophils

most numerous
ingest & destroy invaders

2. Lymphocytes

Specific responses to invaders, including antibody production
B lymphocytes & plasma cells
T lymphocytes = cytotoxic T (Tc)cells & Helper T (Th) cells
Natural killer cells (NK cells)
Memory cells

3. Monocytes (in blood) -> macrophages, wander through tissues, scavenge bacteria, old RBCs, dead neutrophils

Ingest & destroy invaders
Antigen presentation

4. Eosinophils

Destroy invaders, particularly antibody-coated parasites

5. Basophils & mast cells

Release chemicals that mediate inflammation & allergic responses

V – Innate Immunity: Nonspecific Responses
            Physical & Chemical barriers – 1st line of defense

Skin, mucous linings of GI and genitourinary tracts, ciliated epithelium of respiratory tract

Phagocytes
            Mainly macrophages & neutrophils
            Pathogen can bind directly to phagocyte receptors

Encapsulated bacteria must be coated with antibody before phagocytes can bind & ingest them
Opsonins convert unrecognizable particles in “food” for phagocytes

Natural Killer lymphocytes        

 Induce virus-infected cells to commit suicide

Secrete antiviral cytokines, including interferons


               Inflammatory Response

Activated tissue macrophages release cytokines, -> attract other immune cells, increase capillary permeability, cause fever                      

Histamine                      

Found in granules of mast cells & basophils
Opens pores in capillaries, allowing plasma protein into interstitial space, -> edema
Dilates blood vessels, -> increased blood flow in area                  

Complement Proteins = opsonins & chemotaxins

         Complement cascade -> membrane attack complex

Membrane attack complex- proteins that insert themselves into cell membranes or pathogens & virus-infected cells -> pores. Pores -> cells swell & lyse    

VI – Acquired Immunity: Antigen-Specific Responses
            Mediated primarily by lymphocytes

1. activated B lymphocytes -> plasma cells -> antibodies
2. activated T lymphocytes -> either cells that attack & destroy virus-infected cells or into cells that regulate other immune cells
3. Natural killer (NK) cells – attack & destroy virus-infected cells & tumor cells     

Active immunity – from exposure to pathogen & produce antibodies
Passive immunity – from mother to fetus or gamma globulin shot

Lymphocytes that are specific for a given ligand = clone. Clonal expansion -> more identical cells.  Can become effector cells, -> immediate response OR -> memory cells that will respond quickly after next exposure to ligand

B lymphocytes insert antibody molecules into their cell membranes, antibodies become surface receptors. When B cells activated, -> plasma cells -> antibody secretion.

Antibodies

Y-shaped protein – Y is heavy chain, lower part = Fc (constant) region.  
Upper part = Fab (antibody binding) region.
Outer part of upper part = light chain.

 Functions
        Opsonins – mark or tag pathogens so phagocytes can find and ingest them
        Cause antigen clumping, inactivation of bacterial toxins
        Antibody-dependent cell-mediated cytotoxicity

Mast cell degranulation -> release chemicals that mediate inflammatory response

Antigen-bound antibodies use the Fc end of antibody molecule to activate complement

Antigen binding to antibody activates antibody to bind to immune cell. Fc region constant, allowing immune cells to have a single Fc receptor.

       T lymphocytes

T cells bind to cells that display foreign antigen fragments on a major histocompatibility complex (MHC) on their surface

MHC protein complexes encoded by a specific set of genes

MHC-I “platform” + virus or bacterial fragments recognized & killed by cytotoxic T cell (Tc cell)
MHC-II + antigen fragments helper T cell (Th cell) responds by secreting cytokines, -> enhanced immune response

Tc cells release pore-forming molecules (perforin) -> channels for enzymes -> apoptosis

Th cells -> cytokines -> activation of macrophages, activate antibody production & Tc cells, enhance leukocyte production, support actions of mast cells & eosinophils. Bind to B cells & promote differentiation into plasma cells & memory B cells.

VII – Immune Response Pathways
24 17 L – immune responses to extracellular bacteria – very good
            Extracellular bacterial infection

      1. activation of complement system

      chemotaxins attract leukocytes
      degranulation of mast cells -> histamine -> dilate blood vessels & increase capillary permeability
      formation of Membrane Attack Complex molecules -> ion entry -> H2O entry -> lyse bacteria

    2. macrophages ingest unencapsulated bacteria. If bacteria are encapsulated, must be coated with antibody before being ingested.

    3. If antibody present, enhance response. Memory B cells, if present, -> antibody. Novel infection -> B cell clonal expansion, antibody production by plasma cells, formation of memory B and Th cells.

    4. Initiate repair

            Viral Infection

    Macrophages ingest virus, chop them into fragments & puts fragments onto MHC-II platforms

    1. cytokines that activate NK cells
    2. cytokines for inflammatory response
    3. activation of helper T cells which activate B lymphocytes to become Plasma cells -> secrete antibodies

    Virus infects host cells which chop them into fragments & puts fragments onto MHC-I platforms

    attack by NK cells and cytotoxic T cells -> aptosis & death

    Viruses mutate quickly, subsequent infections of same virus (like flu) are different enough to cause infection

Allergic response to pollen

An allergy is an inflammatory immune response to a nonpathogenic antigen.  Antigen called allergen

Allergen ingested by antigen-presenting cell, chopped into fragments & put on MCH-II platforms
Antigen-presenting cell activates helper T cell
Helper T cell activates B lymphocyte, -> plasma cell -> antibodies
Reexposure -> activation of complement proteins, cytokines, histamine, etc -> inflammation, vasodilation, brochoconstriction, increased vascular permeability
Anaphylaxis – severe allergic reaction, massive release of histamine & other cytokines -> widespread vasodilation, circulatory collapse, & severe bronchoconstriction

     Transfusion of incompatible blood

RBCs have antigens on membrane, different ones for different blood types
Plasma has antibodies to antigens not on person’s RBCs. (Type O can donate any blood. Type AB can receive any blood.)

If blood type given to person with antibodies, RBCs will clump & activate complement system -> transfused cells swell & leak hemoglobin -> renal failure

Important to know self from non-self so can eliminate invaders and sick cells.
If mistake self as foreign, -> autoimmune disease (destroy organ or tissue type)

The brain, immune system, and endocrine system communicate among themselves.  All three affect same tissues.