Lecture 1 - Intro to Immunology Flashcards
Blood smear (types and importance)
Types:
1) complete blood count (CBC) 2) Differential Leukocyte count (DIFF)
Together, both provide a complete hematological profile of a case in terms of structure and morphology —– diagnostic clues of a disease
How to make a blood smear
1) One end thick, other thin
2) Zone of morphology (area of optimal thickness for light microscope) is 2cm in length
Giemsa Stain
-Stain of basic stain “methylene blue” and acidic stain “eosin”, which allows you to see and differentiate different types of leukocytes
WBC components and percentage
- Neutrophils: 40-70
- Eosinophils: 1-4
- Basophils: 0.5-1
- Monocytes: 2-8
- Lymphocytes: 20-40
Cluster of Differentiation
- CDs. - surface cell markers
- Allows one to differentiate B, T and NK cells under a microscope where specific antigens (CDs) are identified on the cell and selectively expressed
-Direct and Indirect fluorescence Microscopy is used
Leukocytes cell markers for CDs (and nomenclature)
Tcell - CD3, CD4, CD8
Bcell - CD19, CD20
NKcell - CD56
Macrophage/monocyte - CD14
-If Ag for CD4 is present on a Tcell, it would be “CD4+T-cells” and if expression is high, a “hi” would follow the name
Phagocytes
-Neutrophils and monocytes (blood) and macrophages (tissue — but from monocytes)
Functions:
1) Ingest and destroy microbes, then get rid of damaged tissues
2) Secrete cytokines for immune regulation
Scavenger function
Phagocytes tendency to get rid of damaged microbe tissue
Phagocyte functional response
1) Recruitment - of cell to infection site
2) Recognition – of microbes
3) Ingestion – via phagocytosis
4) Destruction – of microbes
Neutrophils
- Nucleus with 3-5 lobules
- highest abundance circulating WBC
- Mediate early inflammation via cytokine, etc. release
- Contain cytoplasmic granules
- apoptosis after hours or days
Cytoplasmic granules
- In NK and cytotoxic T cells
- Contain peroxidase, lysozyme, degradative enzymes, defensins
Leukocytosis
- WBC count above 11k cell/mcL
- Neutrophilia is most common type but can also be due to basophils, eosinophils, etc
-Sign of infection, 2-3 fold increase in circulating WBC during inflammation
Causes of Leukocytosis
Mild
- inflammation - necrosis - stress - drugs - pregnancy
Red flags (for malignant cause)
- unwell person
- severe neutrophilia
- left shift
Left shift
Greater than 5% circulating immature neutrophils — bone marrow releasing more immature WBC due to need
Leukopenia
- WBC count less thank 4k cells/mcL
- Neutrophenia
Neutropenia
- aka Agranulocytosis/Granulocytopenia
- reduction in circulating neutrophils
- increased risk of infection
- often caused by radiation therapy
Neutrophil Killing Mechanisms
- Intra or extracellular
1) Phagocytosis - engulfed, killed by digestive enzymes
2) Degranulation - enzymes released from granules, killed extracellularly (bow and arrow)
3) NETs
NETs
- Neutrophil extracellular traps
- Released by neutrophils to kill microbes
- Contain DNA, histones, proteins, enzymes
- Paralyze pathogen and facilitate phagocytosis
KEY: Neutrophils continue activities after NET formation
Monocytes
- Primary mononuclear phagocytes in blood (macrophages in tissue)
- From bone marrow, M-CSF
- 3-8% WBC in blood
- Can live few days or much longer if needed for inflammation
Dendritic cells
- Similar to macrophages in function –> capture and process antigens
- Best of APC (antigen presenting cells)
Monocytosis
- Increase # of monocytes in blood
- Response to:
- Chronic infection
- Autoimmune disorder
- Sarcoidosis (growth of macrophage and others in tissues)
Monocytopenia
- Low # of blood monocytes
- Common in people getting chemotherapy
Tissue-residing macrophages
- Long-lived cells from embryonic, fetal hematopoietic organs as stem cell (Must be since they wouldn’t be able to cross Blood-brain barrier in formed human)
- Heterogeneous population (serve diverse, specific functions - osteoclast, microglial cell, kupffer cell, etc.)
Monocyte-derived inflammatory tissue macrophage
-Monocyte is only cell to migrate to tissues during inflammation
-Differentiate upon arrival
Functions:
1) inflammatory rxns
2) repairing tissues damaged during body defense
What are the names of macrophages from the: bone, CNS, Lungs, Liver and Connective Tissue?
osteoclast, microglial cell, alveolar macrophage, kupffer cell, histiocyte
Dendritic Cells
- DC’s
- Professiomnal antigen presenting cells
- Do not travel, activate interferons
- Innate Immune System
- Two types: Myeloid DCs and plasmacytoid DCs
Interferon
Protein released by host cells in response to virus in order to stop pathogen
Myeloid DCs
- dendritic cells derived from monocytes
- Similar to tissue macrophages
- capture, process and present antigens to T cells
Plasmacytoid DCs
- Subset of IFN-producing DCs (interferon)
- Circulate through blood and peripheral tissues
Langerhans cells (LCs)
- Another subpopulation of DC
- Resides in skin epidermis (think Langer-hands…hands and skin)
Mast cells, basophils, esoinophils
- Innate immune system
- Protect against helminthes, cause allergic rxns
- Possess cytoplasmic granules (contains inflammatory and antimicrobial weapons/signalers)
Helminthes
worm-like parasites
Mast Cells
- Polymorphic granulocytes
- Large, oval, densely packed, live months
- Fixed to tissues
- Defend against microbes
- Allergetic/anaphalactic response
- Grnules w/ histamine, serotonin, cytokines, chemokines
Basophils
- Polymorphic granulocytes
- small, round, low count, live days
- Circulating in blood (Baso = blood)
- Defend against microbes
- Allergetic/anaphalactic response
- Grnules w/ histamine, serotonin, cytokines, chemokines
Biology of Mast Cells
- From mast cell progenitors (leaves marrow young - diff from other cells)
- Differentiate/mature once in tissue
- Present throughout variety of tissues
- Quickly respond to allergens, pathogens, toxins
- SENTINEL CELLS!!
Sentinel Cells
- First line of defense, embedded in peripheral tissues
- Release granules to initiate granulocyte response
- THEY ARE NIGHT WATCHMEN!!
Mastocytosis
- Increase in tissue Mast Cells
- Susceptible to itching, hives, anaphylactic shock due to HISTAMINE release
- Localized to the skin (typically)
Cutaneous Mastocytosis
- mastocytosis localized to the skin
- Urticaria Pigmentosa is most common
Eosinophils
- Polymorphonuclear granulocytes
- Fight pathogens/involved in allergic rxns (involved in epithelial cell damage, exfoliation, bronchospasm)
- Contain large and small granules w/ basic proteins
Large secondary granules
- Present in Eosinophils
- Contain four basic proteins
Small granules
Contain histamine, peroxidase, lipase and major basic protein
Basic proteins
-Involved in anti-parasitic defense as toxins against parasitic worms
Eosinophilia
- count over 500/mcl
- due to allergic disorders, infection, certain tumors
Natural Killer cells (NK)
- Generated from marrow precursor in lymphoid
- involved in innate immunity
- Constant surveillance – attacks infected and precancerous cells
- NO ANTIGEN SPECIFICITY or IMMUNOLOGICAL MEMORY — any difference from host antigens and it attacks
Lymphocytes (name cells)
1) B cells (MAJOR)
2) T cells (MAJOR)
3) Plasma cell
4) T lymphocyte
Types of Adaptive Immunity
1) Humoral
2) Cell-mediated
Cell-mediated immunity
1) Controlled by T Lymphocytes (work with APC and phagocytes)
2) Mediates defense against pathogens that aren’t able to be reach by Abs
3) Function: kill infected HOST cells and rid of infection
Humoral Immunity
-Caused by the activation of a B cell, which was developed and matured in the bone marrow and spleen
T Helper cells (roles)
- Assist B cells in making Abs that are HIGH AFFINITY to the specific antigens
- Activate macrophages or cytotoxic T lymphocytes to destroy infected cells
B lymphocytes (in response to microbes
secrete Abs
Clonal Selection/Expansion
1) Prior to exposure, we have many cells with a diversity of Ag specificity
2) exposure to Ag cause lymphocytes specific to it to bind and proliferate.
3) Clonal cells (army) either attack antigen or some become memory cells for adaptive immunity.
