Immune System

Section: Critical care Curriculum: Curriculum, page 48

Innate Immune System

Non-specific and rapid first line defense mechanisms against microbial molecular components
Features
- Non-specific
- Immediate
- No memory
Components
- Physical
  - Skin, mucosa, tight junctions
  - Environment - acid, enzymes (lysozymes in saliva)
  - Microbiome
- Cellular
  - Phagocytes
    - Macrophages, Neutrophils, Dendritic cells
  - Natural Killer cells
  - Phagocytes - neuts, mono, macro
  - Mast cells, eosinophils, and basophils: Involved in allergic responses and defense against parasites.
Functions
- Detect microbes
- First line defense against invasion and infection
- Maintain immunological homeostasis - pro vs anti inflammatory mechanisms
- Cardinal signs of inflammation due to it
- Pattern recognition receptors - PRR’s → pathogen-associated molecular patterns (PAMPs) and DAMPS
  - Which then trigger the Inflammatory cascade and the activate adaptive immune response

Brocken down in to Humoral and Cellular systems
Key Features:
- Specific: Targets specific antigens on pathogens.
- Slower response: Takes days to develop during the first exposure.
- Immunological memory: Faster and stronger response upon re-exposure to the same pathogen.
Important cells
- T Cells
  - Each express a single unique antigen-binding receptors on their membrane, known as the T-cell receptor (TCR)
- Antigen presenting cells (APCs)
  - Usually dendritic cells, but also macrophages, B cells, fibroblasts and epithelial cells
  - Surfaces of APCs express Class 2 (and Class 1) MHCs
- Major histocompatibility complex (MHC)
  - Class 1 - found on all nucleated cells
    - Present endogenous (intracellular) peptides
    - After activation leads to the differentiation of Cytotoxic T cells (CD8+ cells)
  - Class 2 - found only on certain immune cells
    - Present exogenous (extracellular) peptides to T cells
    - After T cells activation leads to the formation of CD4+ helper cells
  - Note this terminology is slightly misleading (but it is the accepted short hand) - MHC is a region of genes that incode HLA proteins. So it is actually the HLA proteins that present antigens to T-Cells.
    - Class I: HLA-A, HLA-B, HLA-C Class II: HLA-DR, HLA-DP, HLA-DQ
- B cells
  - B cells can recognise antigens directly unlike T cells
  - Function is the production of antibodies
  - Differentiate into plasma cells which secrete an antibody specific to the antigen and memory B cells

Overview
- Antibody mediated
- Results in plasma cells that secrete specific antibodies
  - Opsonization
- Although this is good for acute phase it cannot eleminate intra-cellular virus -the advaptive cell-mediate immunity is required
Process
- Antigen presenting cells (APCs) ingest pathogen
- Present the pathogen on Major Histocompatibility Complex Class II (MHC-II)
- T cell is activated after binding to the MHC-II
- Cytokines released by APC to guide differentiation of T cell to T-helper (Th) cells (CD4+ cells)
  - Effector cells are created the carry out the function, these die when the infection is resolved but memory T cells remain
- T helper cells active B cells which differentiate into plasma cells which secrete an antibody specific to the antigen and memory B cells
  - This is why it is called Humoral - antibody-mediated immunity

Function
- Does not involve antibodies
- Activation of antigen-specific cytotoxic T cells that induce apoptosis of cells displaying foreign antigens or derived peptides on their surface
- The activation of macrophages and NK cells, enabling them to destroy intracellular pathogens
- This type of immunity is most effective in eliminating virus-infected cells and cancer cells, but can also participate in defending against fungi, protozoa, cancers, and intracellular bacteria. Cell-mediated immunity also plays a major role in transplant rejection.
Process
- Infected cell displays antigen on MHC-1
- T cell is activated after binding to the MHC-I
- Cytokines released to guide differentiation of T cell into Cytotoxic T cells (CD8+ cells)
- Cytotoxic T cells then can cause apoptosis of infected cells

Passive vs Active
- Passive
  - Transfer of antibodies - i.e in-utero or via milk
- Active
  - In adults
Primary vs Secondary Phases
- Primary
  - First exposure
- Secondary
  - Memory B cells put out ABs more effectively upon subsequent antigen exposure
  - Germinal centres in secondary lymphoid tissue (e.g. LN) = where humoral response mainly occurs