Immunity and Immune System Disorders

Altered Immunity and Immune Defense

Immune System Fundamentals

Third Line of Defense
- Recognition and neutralization of foreign substances.
- Specific immune response.
- Immunologic memory.
Key Terms
- Function: Protects the body from antigens/immunogens, foreign substances, and abnormal cells. Recognizes foreign invaders and non-self.
- Immunity: Protection from disease, especially infectious diseases.
- Immune Response: Collective, coordinated response of immune cells and molecules.
- Antigens (Immunogens/Pathogens): Substances foreign to the host that elicit an immune reaction.
- Antibodies (Immunoglobulins): Immune cells and proteins secreted in response to an antigen.
- Antigenic Determinants (or Epitopes): Unique molecular shapes on an antigen that an antibody recognizes and has a specific receptor for.

Cellular Components of Immunity

Classification by Granules
- Granulocytes:
  - Neutrophil
    - Main Function: Phagocytize bacteria and fungi (first responders).
    - Notes: Most abundant white blood cell ( $50-70\%$ ).
  - Eosinophil
    - Main Function: Fight parasites; involved in allergic responses.
    - Notes: Contain granules with toxic proteins.
  - Basophil
    - Main Function: Release histamine during allergic reactions.
    - Notes: Rare; similar to mast cells.
- Agranulocytes:
  - Lymphocyte
    - B cell
      - Main Function: Produce antibodies (humoral immunity).
      - Notes: Mature in bone marrow.
    - T cell
      - Main Function: Cell-mediated immunity (kill infected cells, regulate other immune cells).
      - Notes: Mature in thymus.
        Helper T ( $CD4^+$ ): Activate B cells, other T cells, and macrophages. Target of HIV.
        Cytotoxic T ( $CD8^+$ ): Kill virus-infected and tumor cells. Important in antiviral defense.
        Regulatory T: Suppress excessive immune response. Maintains immune tolerance.
  - NK cell (Natural Killer cell)
    - Main Function: Destroy virus-infected and cancerous cells.
    - Notes: Part of innate immunity.
  - Monocyte
    - Main Function: Phagocytosis; differentiate into macrophages and dendritic cells.
    - Notes: Largest white blood cell.
      - Macrophage (Derived from monocyte): Engulf pathogens; tissue repair; antigen presentation. Long-lived.
      - Dendritic cell (Derived from monocyte): Present antigens to T cells to activate immunity. Key in adaptive immunity initiation.

Lymphopoiesis

The process of lymphocyte development:
- Hematopoietic Stem Cell origin.
- In the Bone Marrow, develop into Common Lymphoid Progenitor Cells.
- These differentiate into:
  - Immature B cells in the bone marrow, then mature into Mature B cells (e.g., in the spleen).
  - Thymocytes in the thymus, which mature into Mature T cells.
Cellular Components (Summary):
- Lymphoid progenitor cells.
- T lymphocytes (Cytotoxic, Helper, Suppressor).
- B lymphocytes (differentiate into plasma cells for antibody production).
- Natural killer cells.

Innate and Adaptive Immunity

Immune Defense Concept Map
- Nonspecific (Innate Immunity)
  - Involves inflammatory processes.
  - Components: Neutrophil, Natural killer cell, Dendritic cell, Monocyte, Macrophage.
  - Functions: Phagocytosis, Nonspecific cellular antigen destruction, Antigen presentation.
- Specific (Adaptive Immunity)
  - Targeted to a specific antigen.
  - Involves T and B lymphocytes.
  - Components:
    - B lymphocytes: Plasma cells (secretion of antibody/immunoglobulin (Ig)), Memory cells (efficient, rapid antibody response to subsequent antigen recognition).
    - T lymphocytes: Cytotoxic T cell ( $CD8$ ) (specific cellular antigen destruction), Helper T cell ( $CD4$ ) (activation of antigen-specific T cell).

Adaptive Immunity Details

Active Immunity
- Development of antibodies to an antigen.
- Achieved by having a specific disease or vaccination.
Passive Immunity
- Immunity transfer from host to recipient.
- Achieved via mother-infant transfer (placenta or breast milk) or injection of antibody.
Humoral Immunity
- Mediated by B lymphocytes.
- Involves antibodies (IgA, IgD, IgE, IgG, IgM) secreted from plasma cells.
- Involves memory cells.
- Primary Adaptive Immune Response: Activation with the first recognition of a specific antigen.
- Secondary Adaptive Immune Response: Reactivation with later recognition of the same antigen; characterized by a faster and stronger antibody production.
  - The secondary response shows a significantly higher and more sustained IgG titer, and a quicker, smaller IgM peak compared to the primary response.
Cell-Mediated Immunity
- Mediated by Cytotoxic T lymphocytes (CD8) and Helper T lymphocytes ( $T<em>H1$ , $T</em>H2$ ) (CD4).
- Major Histocompatibility Complex (MHC), also known as Human Leukocyte Antigen (HLA).
  - MHC Class I molecules ( $CD8$ ): Bind with intracellular pathogen antigens and are found on nucleated infected cells.
  - MHC Class II molecules ( $CD4$ ): Associated with antigen peptide fragments and are found on antigen-presenting cells (APCs).
- Process Overview (Cell-Mediated):
  - Pathogen enters.
  - Phagocytosis of antigen by an antigen-presenting cell (APC), which presents the antigen via MHC II to a $CD4$ T-helper cell.
  - A nucleated infected cell presents viral epitopes via MHC I to a $CD8$ T lymphocyte.
  - The $CD8$ T lymphocyte's TCR (T-cell receptor) associates with the antigen/MHC I complex, leading to the destruction of the infected cell.
  - This pathway also generates Cytotoxic T memory cells.
  - In parallel, activated T-helper cells can stimulate B lymphocytes, leading to plasma cell differentiation and antibody production, as well as B memory cells.

The Lymphatic System

Importance: Critical in establishing the immune response.
Organs:
- Central Organs: Bone marrow and Thymus.
- Peripheral Organs: Spleen, lymph nodes, and lymphoid tissue.
Detailed Organ Functions:
- Bone Marrow: Soft, spongy tissue in the center of bones; vital for making white blood cells, red blood cells, and platelets.
- Thymus: Located in the upper chest; most active before puberty; where T-cells fully mature to fight invaders.
- Lymph Nodes: Bean-shaped glands monitoring and cleansing lymph; clear damaged cells and cancer cells; store lymphocytes and other immune cells; about $600$ scattered throughout the body (e.g., armpits, groin, neck).
- Spleen: Largest lymphatic organ, located under the left ribs; filters blood, removes old/non-functioning cells, keeps red blood cells and platelets available.
- Mucosa-Associated Lymphoid Tissue (MALT): Mucus membrane lining tonsils, airways, small intestine, appendix; detects and destroys germs.
- Lymph (Lymphatic Fluid): Extra fluid draining from cells and tissues not reabsorbed into capillaries; contains proteins, minerals, fats, damaged cells, cancer cells, germs; transports infection-fighting white blood cells (lymphocytes).
- Lymphatic Vessels: Network of tubes (from capillaries to larger tubes); pulsing of nearby arteries/muscles and one-way valves move lymph.
- Collecting Ducts: Two main ducts (right lymphatic duct, thoracic duct) in the upper chest empty lymph into subclavian veins, rejoining the bloodstream.
- Tonsils and Adenoids: Trap pathogens from food and air; part of the body's first line of defense; tonsils in the back of the throat, adenoids behind the nasal cavity (active during childhood).

Processes of Altering Immune Function

Host Defense Failure
- Antigenic variation.
- Viral latency.
- Immunodeficiency.
Hypersensitivity
- Type I (Immediate):
  - Mediator: IgE, mast cells.
  - Target: Allergens.
  - Onset: Immediate.
  - Example: Anaphylaxis, asthma, food allergy.
- Type II (Antibody-Mediated):
  - Mediator: IgG/IgM + complement.
  - Target: Specific cells.
  - Onset: Minutes-hours.
  - Example: Transfusion reaction, hemolysis.
- Type III (Immune Complex–Mediated):
  - Mediator: Immune complexes.
  - Target: Tissues (kidney, joints).
  - Onset: Hours-days.
  - Example: Lupus, RA, serum sickness.
- Type IV (Cytotoxic T Lymphocyte–Mediated):
  - Mediator: T cells.
  - Target: Self or contact antigens.
  - Onset: $2-3$ days.
  - Example: TB test, contact dermatitis, MS.
- Includes direct cell-mediated toxicity and delayed hypersensitivity reactions.
Autoimmunity
Alloimmunity

Complete Blood Count (CBC) Examples

(Note: Some values are marked 'H' for High or 'L' for Low, indicating deviation from reference ranges.)

Example 1 (Page 5):
- WBC: $20.96 imes 10^3/\mu L$ (H)
- RBC: $3.42 imes 10^3/\mu L$
- HGB: $9.3$ g/dl
- HCT: $29.4\%$
- MCV: $96.0$ fL
- MCH: $27.3$ pg
- MCHC: $31.8$ g/dl
- CHCM: $31.1$ g/dl
- CH: $26.7$
- RDW: $13.9\%$
- HDW: $3.04$ g/dl
- PLT: $671 imes 10^3/\mu L$
- MPV: $7.4$ fL
- NEUT: $18.60 imes 10^3/\mu L$
- LYMPH: $1.37 imes 10^3/\mu L$
- MONO: $0.65 imes 10^3/\mu L$
- EOS: $0.17 imes 10^3/\mu L$
- BASO: $0.7 imes 10^3/\mu L$
- LUC: $0.10 imes 10^3/\mu L$
Example 2 (Page 6):
- WBC count: $13.75$ ( $H$ ) $10^3/\mu L$ (Reference Range: $4.17-10.16$ )
- Hemoglobin: $9.9$ ( $L$ ) g/dL (Reference Range: $11.3-14.8$ )
- Hematocrit: $29.9$ ( $L$ ) $%$
  (Reference Range: $34.7-44.5$ )
- MCV: $89$ fL (Reference Range: $81-97$ )
- MCH: $29.3$ pg (Reference Range: $26.8-34.3$ )
- MCHC: $53.1$ g/dL (Reference Range: $31.4-37.4$ )
- RDW: $15.0\%$
  (Reference Range: $11.6-15.1$ )
- Platelet count: $322 imes 10^3/\mu L$ (Reference Range: $150-350$ )
- Segs: $60\%$
  (Reference Range: $45-77$ )
- Lymphocytes: $19\%$
  (Reference Range: $14-44$ )
- Monocytes: $5\%$
  (Reference Range: $4-12$ )
- Eosinophils: $15$ ( $H$ ) $%$
  (Reference Range: $0-6$ )
- Basophils: $1\%$
  (Reference Range: $0-1$ )
- Absolute neutrophil: $8.25$ ( $H$ ) $10^3/\mu L$ (Reference Range: $1.88-7.82$ )
- Absolute lymph: $2.60$ $10^3/\mu L$ (Reference Range: $0.58-4.47$ )
- Absolute mono: $0.69$ $10^3/\mu L$ (Reference Range: $0.17-1.22$ )
- Absolute eos: $2.06$ ( $H$ ) $10^3/\mu L$ (Reference Range: $0.00-0.61$ )
- Absolute baso: $0.14$ ( $H$ ) $10^3/\mu L$ (Reference Range: $0.00-0.10$ )

Immunoglobulin Ascriptions (as presented)

IgA: allergic reaction
IgD: found in respiratory secretions
IgG: first to challenge antigen
IgM: first to challenge antigen

Organs with Immune Relevance (as presented)

Spleen
Liver
Thymus
Bone marrow
Bloodstream

Additional Points

Adaptive immunity involves memory and is a relatively slow and specific process.
Immune cells include B cells, T cells, Plasma cells, and Memory cells.
Examples of immune interventions/exposures: injection of gamma-globulin, flu vaccine, allergy shots, exposure to poison ivy.

External Resources

Introduction to Immune System: https://www.youtube.com/watch?v=gR84OJ_EGxk (Osmosis video)
Innate & Adaptive Immunity: https://www.osmosis.org/learn/Immune_response_-_Innate:_Nursing (Osmosis video)
Hypersensitivity Reactions - Type I: https://www.osmosis.org/learn/Hypersensitivity_reactions_-_Type_I:_Nursing (Osmosis video)