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Immunology Exam Study Notes

Antigens and Receptors

  • T cells and B cells need receptors to see antigens before mounting an antigen response.
  • Genetic rearrangement for these receptors occurs in the bone marrow for both cell types.
  • T cells then mature.

Chemokines

  • CCL19 and CCL20 are chemokines that facilitate the movement of T cells and B cells out of lymph node zones.
  • This movement requires chemokine receptors.

T Cell Memory

  • Memory T cells develop after antigen encounter and activation, resulting in a faster response compared to naive T cells.
  • T cell memory does not require germinal center reactions or persistent antigen presence.
  • Memory T cells reside in the bone marrow, providing long-term immunity.

Immune Cell Interactions

  • LFA-1 (integrin) binds to ICAM-1, aiding in signal integration into cells.
  • C9 forms the membrane attack complex, creating holes in target cells.
  • Perforin, from CD8 T cells, also creates holes in the target cell membrane.

MHC Class II Deficiency

  • MHC class II deficiency leads to decreased CD4 T cells and decreased antibody production.
  • Class switching is impaired; patients primarily produce IgM and IgD.
  • CD4 T cells recognize MHC class II.

T Cell Recognition

  • T cells must have antigens chopped into peptide sequences to recognize them.
  • Cytokines help activate T cells.
  • Co-stimulation involves CD28 on T cells binding to CD80/86 (B7) on dendritic cells.
  • TCR must bind with MHC for T cell activation.
  • CD40 ligand on activated T cells interacts with CD40 on B cells.
  • ITAMs (immunoreceptor tyrosine-based activation motifs) are critical for signaling.
  • MHC class I restricted T cells are CD8 T cells.
  • T cells cannot directly recognize antibodies.
  • CD40 expression on B cells and CD40 ligand on T cells facilitate interaction.
  • CD28 is a co-stimulatory molecule on T cells, and E-selectin is on the epithelium.

Dendritic Cells (DCs)

  • DCs are professional antigen-presenting cells, presenting via both MHC class I and class II.
  • DCs activate various cell types and produce numerous cytokines.

T Cell Activation Steps

  • First step: Antigen recognition involving MHC presenting a peptide to the TCR.
  • Second step: Signaling through CD3 and zeta chains, activating adaptive proteins.
  • Third step: Adhesion molecules (e.g., LFA-1 on T cells binding to ICAM-1 on dendritic cells) to stabilize interactions.
  • Fourth step: Co-stimulation via B7 (CD80/86) to change phosphorylation events of the adaptive proteins.

Antibody Types

  • IgM antibodies neutralize polysaccharide antigens without T cell help (T cell-independent).
  • IgA, IgE, and IgG require T cell help (T cell-dependent).

Transcription Factors

  • Phosphorylation of LAT leads to activation of NF-κB (Nuclear Factor kappa B).
  • Other transcription factors include NFAT (Nuclear Factor of Activated T-cells).
  • T-bet is important for CD4 differentiation but not primary T cell activation.

T Helper Cell Differentiation

  • Dendritic cells producing IL-12 and IFN-γ skew CD4 T cells to differentiate into TH1 cells.
  • This response is crucial for bacterial infections.

CD4 T Cell Function

  • CD4 T cells kill via cytokines that activate macrophages.
  • Interferon-gamma (IFN-γ) activates macrophages and B cells.
  • Antibodies opsonize and neutralize, especially against endotoxins and venoms.
  • Macrophages have Fcγ receptors for IgG.
  • The complement system is activated to help clear infections.

Vaccine Response

  • A TH2 response to a vaccine against an intracellular bacterial infection is not ideal.
  • Vaccinated individuals might experience enhanced disease due to the wrong type of immune response, which should be TH1.

T Regulatory Cells (Tregs)

  • Tregs regulate T cells to prevent unwanted reactions against self-cells.
  • IL-10 dampens down the immune system.
  • IL-2 supports T cell proliferation; Tregs suppress IL-2 by expressing CD25 (high-affinity IL-2 receptor).
  • CTLA-4 on Tregs binds to CD80/86, turning off transcription factors in activated T cells.
  • Tregs also produce TGF-β.

CD8 T Cell Activation

  • Activation of CD8 T cells leads to upregulation (increased production) of enzymes and perforins.
  • Upregulation of integrins and selectins facilitates movement out of lymph nodes.

TH17 Cells

  • TH17 cells produce IL-17 and IL-22.
  • IL-22 is important for maintaining tissue homeostasis.

Extracellular Bacteria

  • Extracellular bacteria replicate outside of host cells and produce endotoxins.
  • Gram-negative bacteria produce LPS (lipopolysaccharide), leading to sepsis in high amounts.
  • Gram-positive bacteria also release toxins.

Immune Response to Extracellular Bacteria

  • Sentinel cells sense bacteria breaching barriers and secrete cytokines to initiate inflammation.
  • Leukocytes and granulocytes are recruited to the blood.
  • The complement system is activated.
  • B cells produce IgG to opsonize bacteria and activate the complement system.
  • Neutrophils are also recruited.

Immune Response to Open Wounds

  • In the first few minutes, mast cells in the tissue secrete cytokines.
  • Granulocytes phagocytose and undergo NETosis, releasing chromatin DNA to trap bacteria.
  • DNA fragments act as damage-associated molecular patterns (DAMPs).
  • DAMPs, such as mitochondrial DNA and ATP, activate innate immune cells.
  • After one week, exudate and pus indicate an ongoing immune response.
  • Depending on the pathogen (bacteria, parasites, viruses), different immune cells respond.

Complement Cascade

  • The complement system involves floating proteins, with C3 being the most abundant.
  • The classical pathway is activated by antibody-coated bacteria.
  • The lectin pathway binds to lectins and mannans on the surface.
  • The alternative pathway is activated by C3 tick-over, where C3 spontaneously breaks down into C3a and C3b.
  • C3b binds to bacteria, activating the pathway.

Outcomes of Complement Pathways

  • All three complement pathways lead to the production of C3a, C3b, C5a, C5b, and the membrane attack complex (MAC).
  • MAC causes cell lysis.
  • C3b opsonizes bacteria, enhancing phagocytosis.
  • C3a and C5a contribute to inflammation by recruiting leukocytes.

Complement Activation by IgM

  • IgM antibodies activate the classical pathway.
  • IgG1 and IgG3 also activate the classical pathway.

C3 Deficiency

  • C3 deficiency results in the inability to activate any complement pathway.
  • This leads to decreased opsonization, less macrophage activation, and increased susceptibility to infections.

Cytokine Groups

  • Five simplified groups: chemokines, interferons, tumor necrosis factors (TNFs), interleukins, and growth factors.
  • Chemokines are involved in cell movement.
  • Interferons interfere with viral replication.
  • TNFs are involved in cellular proliferation, survival, and apoptosis.
  • Interleukins are a broad group involved in various immune functions.
  • Growth factors promote cell growth and differentiation.

Pathogen Recognition

  • Immune cells recognize pathogen-associated molecular patterns (PAMPs) on pathogens.
  • Examples include LPS.
  • Toll-like receptors (TLRs) are on the cell surface or in endosomes.
  • Nod-like receptors (NLRs) are in the cytoplasm.

Innate Immune System Hallmarks

  • Hallmarks include rapid response, repetitiveness, and short duration. It is not reactive to host.

Neutrophil and Mast Cell Features

  • Both can perform extracellular traps.

Leukocyte Migration

  • Cytokines induce the expression of adhesion molecules on endothelial cells.
  • Integrins arrest lymphocytes.

Dendritic Cell Function

  • Inflammatory cytokines increase the expression of adhesion molecules on human endothelial cells.

Somatic Hypermutation

  • Increases the affinity for the antigen occurs after antigen exposure.

T Cell-Independent Activation

  • IgM antibodies can bind and neutralize antigens that contain polysaccharides without additional T cell help.

Complement Regulation

  • C1 inhibitor is an example of a complement regulator.

Blood Filtration

  • Macrophages in the spleen filter the blood.

T Cell Egress

  • S1PR1 on T cells interacts with S1P to facilitate egress.