Chapter_1_BW_(1)

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Parham Ch. 1: An overview of the immune system

Introduction: Us vs. them: pathogens (Fig. 1.3) pathogen = an organism that causes disease eg: Bacteria

Viruses Fungi Parasites (unicellular protozoa,

multicellular invertebrates)

Us vs. us: cancer

cancer: unregulated / ill-regulated cell growth

Macrophages and Natural Killer cells have roles in combating malignant cells

1o (primary) barriers to infection

skin: numerous layers of keratinized cells form a strong barrier to invading microorganisms

mucosal membranes (mucosa):

continuous with the skin

line respiratory, gastrointestinal and urogenital tracts

secrete mucous

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1o (primary) barriers to infection

Innate immunity

innate = “not acquired” i.e. present at birth

recognizes certain classes of molecules but not specific organisms

rapid response, but constant (does not vary)

provides no “memory” of the pathogen

Innate immunity

The complement protein system is used in innate immunity to attack bacteria

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Innate immunity The innate response is also responsible for inflammation

Adaptive immunity

has a delayed response (cells require stimulus for activation (see lectures on clonal stimulation)

hugely variable (e.g. see antibody diversity)

why is this a concern? how is this possible (given our limited genome size)?

response is specific, and further tuned during the response itself (see somatic hypermuation)

provides long term “memory” to pathogens - up to lifetime immunity (memory B cells)

Compare and contrast adaptive vs. innate immunity (Fig 1.9)

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Adaptive immunity entails selective lymphocyte activation (Fig. 1.10)

Adaptive immunity entails selective lymphocyte activation (Fig. 1.10)

(Fig. 1.11)

- all blood cells arise through the determination and differentiation of hematopoietic stem cell progeny - mechanisms?

Leukocytes (white blood cells) Hematopoiesis (Fig 1.14)

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Lymphocytes – Fig. 1.12

Small lymphocytes B Cells - produce cell-surface immunoglobins, secrete soluble form after activation (antibody) T Cells - produce T-cell receptor

NK Cells

- destroy virus-infected cells - involved in cancer defense

Granulocytes - Neutrophils - “disposable” (single-use) macrophages - engulf invaders to destroy them

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- Neutrophils are released from bone marrow as part of innate response - contribute to inflammation

Granulocytes Eosinophils - act in parasitic infections, secrete granules Basophils – (rare) – act in parasite response?

Macrophages - resident in tissues (derived from monocytes) - initiate the innate response (cytokine signaling) - recruit neutrophils

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Macrophages - resident in tissues (derived from monocytes) - initiate the innate response (cytokine signaling) - recruit neutrophils

Macrophages act in the inflammatory response

Dendritic Cells similarities with macrophages in that they are resident in tissues act as initiators of the adaptive response (compared to the inflammatory response for macrophages) travel from sites of infection with pathogens / antigens to lymphoid tissues

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Mast Cells resident in connective tissue carries histamine granules a major contributor to inflammation

Lymphoid tissues 1o lymphoid organs Fig 1.18 bone marrow site of hematopoiesis B cells remain and mature here thymus T Cells migrate from bone marrow to thymus and mature here

Determination? Differentiation?

Lymphoid tissues 2o lymphoid organs - lymphatic system and lymph nodes Figures 1.18 – 1.25

- lymph nodes

lymph vessels pick up excess plasma system has one-way valves

excess plasma returns to vascular system through lymph nodes

lymph nodes house macrophages that filter out pathogens (prevent sepsis)

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- lymph nodes are also sites for pathogen: lymphocyte interactions (adaptive immunity)

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2o lymphoid tissue: spleen

- acts like a lymph node for the blood stream: filters out pathogens that gain direct entry into the bloodstream

- also functions to removed damaged / spent erythrocytes

Mucosa associated lymphoid tissue (MALT) - in the gut (GALT) - Peyer’s patches

- M cells sample gut contents and deliver antigens / pathogens to the lymphoid tissue